Journal of Pharmacy & Pharmacognosy Research E-ISSN: 0719-4250 [email protected] Asociación de Académicos de Ciencias Farmacéuticas de Antofagasta Chile
RESÚMENES Journal of Pharmacy & Pharmacognosy Research, vol. 2, núm. 1, mayo, 2014, pp. sxi- s357 Asociación de Académicos de Ciencias Farmacéuticas de Antofagasta Antofagasta, Chile
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© 2014 Journal of Pharmacy & Pharmacognosy Research, 2 (Suppl. 1), S1-S357 ISSN 0719-4250
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RESÚMENES / ABSTRACTS
«LATINFARMA Habana 2013» / «LATINFARMA Havana 2013»
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LATINFARMA 2013 Índice/Index
ÍNDICE / INDEX
CONFERENCIAS PLENARIAS INAUGURALES / OPENING PLENARY LECTURES (PL) 1 Lunes, Octubre 21 / Monday, October 21st 1 Martes, Octubre 22 / Tuesday, October 22nd 1 PL 001: BIOLOGICAL AND THERAPEUTIC RELEVANCE OF THE DISCOVERY OF PROSTACYCLIN AND NITRIC OXIDE: Moncada S 1 PL 002: IMMUNOTHERAPY AND COMPLEXITY: OVERCOMING THE BARRIERS FOR THE CONTROL OF ADVANCED CANCER: Lage Dávila A 1 PL 003: TRENDS OF RESEARCH IN THE 21RST CENTURY: Moncada S 1 Taller sobre Inmunofarmacología y Biotecnología. Sesión: Inmunofarmacología / Workshop on Immunopharmacology and Biotechnology. Session; Immunopharmacology 2 CO 001: TOWARDS CLINICAL TRANSLATION OF T-CELL RECEPTOR GENE EDITING TO MEDIATE ADOPTIVE ANTI-TUMOR IMMUNOTHERAPY: Ciceri F et al. 2 CO 002: HUMAN ANTIBODIES REACTIVE TO NEUGCGM3 GANGLIOSIDE HAVE CYTOTOXIC ANTITUMOR PROPERTIES: Rodríguez-Zhurbenko N et al. 2 CO 003: PHARMACOLOGIC INTERVENTION OF CASEIN KINASE 2 (CK2)-MEDIATED PRO-SURVIVAL AND PROLIFERATIVE SIGNALING ON T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (T- 3 ALL): Perera Y et al. CO 004: In Silico DESIGN AND FUNCTIONAL CHARACTERIZATION OF A TGFβ1 MUTEIN, ANTAGONISTIC OF TGFβ SIGNALING, WITH ANTITUMOR AND IMMUNEMODULATORS 3 PROPERTIES: Corría Osorio J et al. CO 005: MOLECULAR MECHANISMS INVOLVED IN THE INHIBITION OF TUMOR CELLS PROLIFERATION EXPOSED TO ELEVATED CONCENTRATIONS OF EPIDERMAL GROWTH FACTOR 4 (EGF): Camacho H et al. CO 006: CONCENTRATION OF MMP-3 AND IL-6 IN PATIENTS WITH SEPSIS AND MULTIORGAN FAILURE: Ricarte Bratti JP et al. 4 CO 008: IMMUNOTRANS-ARTERIAL CHEMOEMBOLIZATION (ITACE) IN HEPATOCELLULAR CARCINOMA PATIENTS TREATED WITH ANTI-EGFR MAB NIMOTUZUMAB PLUS ADRIAMYCIN. 5 PHASE I CLINICAL TRIAL, FINAL RESULTS: Ramos-Suzarte M et al. CO 009: A NOVEL PEPTIDE SELECTED FROM AN ALA-SCANNING REGULATES THE ONCOGENIC ACTIVITY OF NFKB IN CANCER CELLS: Oliva B et al. 5 CO 010: NEOPLASTIC transformation of human mesenchymal stem cells CONCERTS IMmune-evasion and pro-iNflaMmatory programs IN THE ABSENCE OF IMMUNe-EDITION MEDIATED 6 PREASSURE: Miranda-Rodríguez A et al. CO 011: PRECLINICAL EVIDENCES OF P3 MAB IMMUNORESTORATION CAPACITY ON SUPPRESSED BALB/c MICE: Martínez D et al. 6 CO 012: PANUSIN, A NEW DEFENSIN-LIKE ANTIMICROBIAL PEPTIDE FROM THE HEMOCYTES OF SPINY LOBSTER Panulirus argus: Pacios-Michelena A et al. 7 CO 013: BIOMODULINA T: IMMUNOMODULATOR NATURAL PRODUCT OF THE LIFE´S QUALITY: Aznar García E et al. 7 Simposio de Ensayos Clínicos /: Symposium on Clinical Trials 8 CO 015: ETHICAL CONSIDERATIONS IN DEVELOPING COUNTRIES IN HIV VACCINE TRIALS: Ellis G. 8 CO 016: CANCER CLINICAL TRIALS: STATE OF THE ART AND THE CUBAN EXPERIENCE: Crombet-Ramos T. 8 CO 017: PHARMACODYNAMICS AND PHARMACOKINETICS OF TWO FORMULATIONS CONTAINING SYNERGISTIC PROPORTIONS OF INTERFERONS ALPHA-2B AND GAMMA IN HEALTHY 9 MALE VOLUNTEERS (SOFIA STUDY): García I et al. CO 019: SERUM LEVELS OF INFLAMMATORY MARKERS IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION DURING A 6 MONTH FOLLOW UP: Brizuela NY et al. 9 CO 020: SUBJECT: NATIONAL BIOETHICS NETWORK AND RESEARCH IN PERU - RENABIP: Socualaya P et al. 10 CO 021: CLINICAL TRIAL DESIGNS THAT CAN SPEED UP NEW DRUG DEVELOPMENT: López-Saura PA et al. 10 MR 001: CLINICAL TRIALS: PERSPECTIVE AND UPDATING: Pascual López MA et al. 11 CO 022: EFFICACY AND SAFETY OF RECOMBINANT STREPTOKINASE VERSUS HYDROCORTISONE ACETATE-BASED SUPPOSITORIES IN THE TREATMENT OF HEMORRHOIDAL DISEASE. 11 RANDOMIZED, CONTROLLED TRIAL (THERESA-4 Study): Hernández-Bernal F et al. CO 023: TRIMETAZIDINE INHIBITS THE RENAL FIBROSIS INDUCED BY CYCLOSPORIN A: De la Cruz Rodríguez L et al. 12 Taller de Métodos Alternativos (3Rs) en Farmacología, Toxicología y Enseñanza / Workshop on 3Rs Alternatives in Pharmacology, Toxicology and Teaching. 13 C 003: INTERNATIONAL VALIDATION AND REGULATORY ACCEPTANCE OF ALTERNATIVE METHODS: PROGRESSES AND PROSPECTS: Eskes C. 13 CO 024: ALTERNATIVE METHODS IN THE SAFETY EVALUATION OF COSMETIC: EUROPEAN SITUATION: Vinardell MP. 13 CO 025: PRINCIPLE OF REDUCTION AND THE VALIDITY AND EFFICIENCY OF ANIMAL ASSAYS: Rosenkranz A. 14 CO 026: ALTERNATIVE METHODS AND THE SAFETY ASSESSMENT OF HEALTH PRODUCTS: EXPERIENCE OF NATIONAL INSTITUTE OF QUALITY CONTROL IN HEALTH, BRAZIL: Fernandes 14 Delgado I et al. CO 027: PROPOSED METHODS AND ESPECIALLY STEM CELLS AS POTENTIAL REPLACEMENT METHODS TO STUDY HUMAN PATHOLOGIES: Bercovier H. 15 CO 028: BASIC ASPECTS OF THE TOXICOLOGICAL EVALUATION OF NANOMATERIALS: Vinardell MP et al. 15 Taller de Métodos Alternativos (3Rs) en Farmacología, Toxicología y Enseñanza / Workshop on 3Rs Alternatives in Pharmacology, Toxicology and Teaching. 16 CO 029: BEST PRACTICE AND ALTERNATIVES TO ANIMAL EXPERIMENTS IN EDUCATION: Jukes N. 16 CO 031: ALTERNATIVES TO THE USE OF ANIMALS IN VETERINARY MEDICINE EDUCATION: Torres M et al. 16 CO 032: SUPER-SELECTIVE OPHTHALMIC ARTERY CATHETERIZATION IN THE PIG AS A TRAINING MODEL WITH POSSIBLE IMPLICATIONS FOR RETINOBLASTOMA TREATMENT: Asprea 17 M et al. CO 033: USING VIDEOS AND PLASTINATED MURINE MODELS FOR TRAINING: Streber ML et al. 17 CO 034: DISSECTION OF THE VENTRAL NERVE CORD-DEEP ABDONIMAL FLEXOR MUSCLE SYSTEM OF THE FRESHWATER LOBSTER OF THE Cherax GENUS: AN IN SITU MODEL FOR 18 TEACHING PHARMACOLOGY: Islas V et al.
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Taller de Farmacoepidemiología / Workshop on Pharmacoepidemiology 19 C 004: THE DISCREET FASCINATION OF THE DRUGS: Pérez J. 19 CO 036: DRUG USE IN PREGNANT WOMEN: Viroga S et al. 19 CO 037: MEDICAL PRACTICE CONFIRMS CLINICAL TRIAL RESULTS OF THE USE OF INTRALESIONAL HUMAN RECOMBINANT EPIDERMAL GROWTH FACTOR IN ADVANCED DIABETIC 20 FOOT ULCERS: López-Saura PA et al. CO 038: FREQUENCY OF USE OF THE MONOCLONAL ANTIBODY RITUXIMAB ON THE NATIONAL CANCER INSTITUTE OF MEXICO: ONE YEAR EXPERIENCE: López-Gamboa M et al. 20 C 005: PHARMACOKINETIC CHANGES INDUCED BY SPINAL CORD INJURY: Castañeda G. 21 CO 039: RATIONAL USE OF MEDICINES IN PRIMARY HEALTH CARE: POLYPHARMACY IN PEOPLE AGED 60 YEARS AND OLDER: Ponce LN et al. 21 CO 040: EDUCATIVE INTERVENTION ON ESSENTIAL MEDICATIONS TO BE USED IN DISASTERS BY FAMILY DOCTORS IN ARROYO NARANJO MUNICIPALITY, IN 2012: López Aguilera AF et 22 al. CO 041: EFFECTIVENESS OF ANTIRETROVIRAL TREATMENT IN COLOMBIA: Machado-Alba JE et al. 22 CO 042: IMPACT OF AN ANTIBIOTIC POLICY ON ANTIMICROBIAL CONSUMPTION AT COMANDANTE MANUEL FAJARDO UNIVERSITY HOSPITAL, 2011: Morejón M et al. 23 CO 043: CLINICAL PHARMACIST PERFORMANCE IN MULTIPROFESSIONAL TEAM IN A TEACHING HOSPITAL: Amaral Pedroso L et al. 23 CO 044: LIPID-LOWERING THERAPY EFFECTIVENESS IN A SAMPLE OF COLOMBIAN PATIENTS: Machado-Alba JE et al. 24 CO 045: NSAID AND GASTROPROTECTIVE AGENTS PRESCRIPTION AT THE CLINICAL HOSPITAL “DR. MANUEL QUINTELA”: Cuñetti L et al. 24 Simposio de Farmacología del Dolor / Symposium on Pharmacology of Pain 25 C 006: BETWEEN HYPERTENSION AND PAIN: Henrique Ferreira S. 25 CO 046: MANGIFERIN FOR THE MANAGEMENT OF PAIN: ADVANTAGES OF ITS TRANSCIENT AND LONG TERM NEUROMODULATORY EFFECTS: Garrido BB et al. 25 CO 047: ANTINOCICEPTIVE ACTIVITY OF MANGIFERIN IN FORMALIN PAIN: Espinoza de los Monteros-Zuñiga A et al. 26 CO 048: ANTI-HYPERALGESIC EFFECT OF A NEUROPROTECTIVE COMPOUND IN ANIMAL MODELS OF PAIN: Castro M et al. 26 C 007: PHENOTYPIC MODIFICATIONS OF PRIMARY AFFERENT NEURONS INNERVATING OSTEOARTHRITIC JOINTS: Castro-Lopes JM et al. 27 C 008: THE RATIONALE OF ANALGESIS COMBINATIONS: Granizo E. 27 C 009: CARDIOVASCULAR RISK OF NONSTEROIDAL ANTI-INFLAMMATORY DRUG FREQUENTLY USED: Prozzi GR. 28 CO 051: OPIOIDS UPDATE IN 2013. PAIN FREE HOSPITALS, IMPORTANCE OF ITS DEVELOPMENT IN CUBA: Yera-Nadal JL. 28 Simposio sobre Epigenética / Symposium on Epigenetics 29 C 010: FLAVANOLS MODULATE THE TRANSCRIPTION OF GENES INVOLVED IN ATHEROSCLEROSIS WITH HETEROGENIC EPIGENETIC CHANGES OF THEIR DNA METHYLATION STATE: 29 Weseler AR et al. C 011: EPIGENETIC DEREGULATION IN CANCER: THERAPEUTIC APPLICATIONS: Berdasco M. 29 C 012: EPIGENETIC REGULATION OF BREAST CANCER METASTASIS BY STEROIDAL LACTONE WITHAFERIN A: Szarcvel Szic K et al. 30 C 013: PROMISES & CHALLENGES OF MICRORNAS IN MULTIPLE MYELOMA THERAPY: Palagani A et al. 30 C 015: EFFECT OF DNA DEMETHYLATION ON CYP1A1 GENE EXPRESSION IN RAT CELLS: Olguín-Reyes S et al. 31 Taller de Nanofarmacología / Workshop of Nanopharmacology 32 CO 052: CRITICAL POINTS TO CONSIDER WHEN DEVELOPING PHARMACEUTICAL PRODUCTS BASED ON MICROSPHERES CONTAINING PROTEINS: Saez V. 32 CO 053: SYNTHESIS, CHARACTERIZATION AND DRUG DELIVERY PROFILE OF MAGNETIC PLGA-PEG-PLGA/MAGHEMITE NANOCOMPOSITE: Pereira ED et al. 32 CO 054: AFFINITY MATURATION AND FINE FUNCTIONAL MAPPING OF AN ANTIBODY FRAGMENT AGAINST A NOVEL NEUTRALIZING EPITOPE ON HUMAN VASCULAR ENDOTHELIAL 33 GROWTH FACTOR: Lamdan H et al. CO 055: NANOEMULSION PREPARATIONS FROM A PLANT LIPID EXTRACT WITH WIDE RANGE OF APPLICATIONS IN MEDICINE: Turiño L et al. 33 C 017: LOW LEVEL LASER THERAPY (LLLT): THERAPEUTIC EFFECTS, DOSES, INDICATIONS AND CONTRAINDICATIONS, SIDE EFFECTS: Fornaini et al. 34 CO 056: DEVELOPMENT AND CHARACTERIZATION OF MANGIFERIN NANOCAPSULES: Moura UJ et al. 34 CO 057: COMBINATION EFFECT OF SONOPHORESIS AND IONTOPHORESIS ON ANTIPYRINE TRANSDERMAL PENETRATION: Aoyagi T et al. 35 CO 058: NANOPARTICLES AS DRUG CARRIERS: CHARACTERISTICS AND PERSPECTIVES: Oropesa-Nuñez R et al. 35 CO 059: NOVEL PEGYLATION TECHNOLOGIES FOR THE DEVELOPMENT OF NEXT GENERATION BIODRUGS: Ikeda Y et al. 36 CO 060: PEGYLATION: AN EFFECTIVE TOOL FOR BIOMASKING: Ramón JA et al. 36 CO 061: NANOSTRUCTURE: SURFACE MODIFICATIONS BY LASER BEAM: Guastaldi AC. 37 MR 002: DRUG REGULATORY AUTHORITY OF CUBA. YEAR 25: Sánchez C et al. 37 Sesión para la Constitución de la Red Latinoamericana - Iberoamericana de Alternativas Basadas en las 3Rs / Session for the Constitution of the Latin-American - Iberoamerican Network for 38 3 Rs Alternatives CO 062: THE ROLE OF THE BRAZILIAN CENTER FOR VALIDATION OF ALTERNATIVE METHODS (BraCVAM) IN THE PROCESS OF VALIDATION IN BRAZIL: LOOKING TO THE FUTURE: 38 Presgrave O et al. CO 063: ALTERNATIVE METHODS AT THE END OF THE WORLD: Asprea M. 38 CO 064: CUBAN EXPERIENCE IN THE DEVELOPMENT OF 3RS IN THE FIELD OF TOXICOLOGY AND METABOLISM OF DRUGS: Rodeiro I. 39 CO 065: WHY AND FOR WHAT CREATING A LATINAMERICAN-IBEROAMERICAN NETWORK FOR ALTERNATIVES?: Chovel ML. 39 MIÉRCOLES, OCTUBRE 23 / WEDNESDAY, OCTOBER 23rd: SESIÓN PLENARIA / PLENARY SESSION 40 PL 005: PERSONALIZED CANCER VACCINES: WHO SHOULD PICK THE TARGET?: Overwijk WW. 40 PL 006: DRUG METABOLISM IN THE BRAIN AND HOW IT CAN ALTER DRUG RESPONSE: Tyndale R. 40 Taller Inmunofarmacología y Biotecnología. Sesión: Inmunofarmacología / Workshop on Immunopharmacology and Biotechnology. Session; Immunopharmacology 41 CO 066: CIGB-814, A PEPTIDE AS IMMUNOMODULATOR FOR THE TREATMENT OF RHEUMATOID ARTHRITIS: Domínguez MC et al. 41 CO 067: ENHANCEMENT OF THE INHIBITORY EFFECT OF AN IL-15 ANTAGONIST PEPTIDE BY ALANINE SCANNING: Rodríguez Y et al. 41 CO 068: THE LONG PENTRAXIN PTX3: A NON-REDUNDANT COMPONENT OF THE HUMORAL INNATE IMMUNITY AND A PROMISING BIOMARKER IN INFLAMMATORY CONDITIONS: 42 Garlanda C et al. CO 069: LEVELS OF SOLUBLE IL-15, IL-6, TNFΑ AND IL-15RΑ IN SYNOVIAL FLUID AND MEMBRANE BOUND IL-15 ON SYNOVIAL CELLS FROM PATIENTS WITH RHEUMATOID ARTHRITIS 42 AND OSTEOARTHRITIS: Machado-Díaz AC et al.
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CO 070: IMMUNOMODULATING AND ENHANCING ACTIVITIES OF SOLUBLE GLUCANS FROM Sacharomyces cerevisiae ASSESED BY MONOCYTE ACTIVATION TEST: Pardo-Ruiz Z et al. 43 CO 071: EARLY PHASE OF SYSTEMIC REACTION TO ORAL ASPIRIN CHALLENGE IS RELATED TO AN INCREASE IN THE LEVELS OF IL-6 AND THE PERCENTAGE OF EFFECTORS MEMORY T- 43 CELLS: Pérez-Novo CA et al. Taller Inmunofarmacología y Biotecnología. Sesión: Desarrollo e Investigación sobre Vacunas / Workshop on Immunopharmacology and Biotechnology. Session; Development and Research 44 on Vaccines CO 073: CONJUGATE VACCINE CANDIDATE AGAINST Neisseria meningitidis: Acevedo R et al. 44 CO 074: A Salmonella typhi POLYSACCHARIDE VI- DIPHTHERIA TOXOID (VI-DT) CONJUGATE VACCINE AGAINST TYPHOID FEVER: Fernández S et al. 44 CO 075: FORMULATION, CHARACTERIZATION AND RELEASING OF A LIVE-ATTENUATED 638 Vibrio cholerae ORAL VACCINE: Tamayo Y et al. 45 CO 076: DEVELOPMENT OF NOVEL THERAPEUTIC HEPATITIS B VACCINE: NASVAC: Guillén G et al. 45 CO 077: HEPTAVALENT CONJUGATE VACCINE AGAINST THE MOST PREVALENT SEROTYPES OF Streptococcus pneumoniae IN LATINOAMERICA: PRECLINICAL EVALUATION: García-Rivera 46 D et al. CO 078: ADVANCES IN THE CHARACTERIZATION OF A Bordetella pertussis DERIVED PROTEOLIPOSOME AS VACCINE CANDIDATE AGAINST WHOOPING COUGH: Pérez JL et al. 46 Taller sobre Estrés Oxidativo y Ozonoterapia / Workshop on Oxidative Stress and Ozonetherapy 47 C 019: OZONE´S THERAPEUTICAL TARGETS. BASIS OF THEIR PLEIOTROPIC EFFECTS: León Fernández OS et al. 47 CO 079: THE EFFECT OF OZONE ACTIVATED AUTOLOGOUS PLATELET-RICH PLASMA INJECTION ON PATTERN HAIR LOSS: A PRELIMINARY STUDY: Martínez-Sánchez G et al. 47 CO 080: OZONE OXIDATIVE POSTCONDITIONING AMELIORATES JOINT DAMAGE AND DECREASES PROINFLAMMATORY CYTOKINES LEVELS AND OXIDATIVE STRESS IN PG/PS-INDUCED 48 ARTHRITIS IN RATS: Dranguet J et al. CO 081: OZONE THERAPY AMELIORATES NERVOUS SYSTEM DISORDERS AND OXIDATIVE STRESS IN PATIENTS DURING ETHANOL WITHDRAWAL—A PILOT STUDY: Díaz M et al. 48 C 020: OZONE CONDITIONING EFFECT, NRF2 PATHWAY AND EPRE. AN IN VIVO STUDY DURING MAYOR AUTHO-HEMOTHERAPY: Re L et al. 49 CO 082: EVALUATION OF INHIBITION CAPACITY TO LIPIDIC PEROXIDATION AT BRAIN LEVEL OF FREE AND ESTERIFIED PHYTOSTEROLS: Hernández R et al. 49 CO 083: CHARACTERIZATION OF OXIDATIVE STRESS IN DIFFERENT CLINICAL CONDITIONS AND INTERVENTIONS, USING REDOX INDEXES WITH DIAGNOSTIC VALUE: Gil del Valle L et al. 50 CO 084: EFFECT ANTIPROLIFERATIVE OF (-)-EPICATECHIN AND ITS RELATIONSHIP WITH REACTIVE OXYGEN SPECIES IN BREAST CANCER CELL LINES: Perez AG et al. 50 CO 085: THE TREATMENT WITH CHP3R99-LALA MONOCLONAL ANTIBODY REDUCES OXIDATIVE STRESS AND PROINFLAMMATORY CYTOKINE EXPRESSION IN EXPERIMENTAL MODELS 51 OF ATHEROSCLEROSIS: Delgado L et al. CO 086: CONTRIBUTION OF OXIDATIVE STRESS AND INFLAMMATION TO THE HYPERTENSION INDUCED BY INTERMITTENT HYPOXIA IN A RAT EXPERIMENTAL MODEL OF 51 OBSTRUCTIVE SLEEP APNEA: Iturriaga R et al. CO 087: DETERMINATION OF STRUCTURAL ALERTS TO PREDICT CLASTOGENIC ACTIVITY OF PRO-OXIDANT FLAVONOID COMPOUNDS: QUANTITATIVE STRUCTURE-ACTIVITY 52 RELATIONSHIP STUDY: Molina E et al. CO 088: CLUSIANONE, A NATURAL OCCURRING NEMOROSONE’S REGIOSOMER, UNCOUPLED MITOCHONDRIA AND INDUCED CELL DEATH: Pardo-Andreu GL et al. 52 CO 089: LEARNING OF CELLULAR REDOX BALANCE IN PHARMACY AND FOOD INSTITUTE OF THE UNIVERSITY OF HAVANA, CUBA: León Fernández OS et al. 53 Simposio de Productos Naturales / Symposium of Natural Products 54 CO 090: MECHANISMS INVOLVED IN THE ANTITUMOR/ANTIMETASTATIC ACTIVITIES OF PROTEOLYTIC FRACTION DERIVED FROM Vasconcellea cundinamarcensis LATEX: Lemos FO et al. 54 CO 091: PROTEOLYTIC FRACTION FROM VASCONCELLEA CUNDINAMARCENSIS LATEX STIMULATES MACROPHAGES ACTIVITY AGAINST INFLAMMATORY BREAST CANCER CELLS: Braga 54 AD et al. CO 092: MECHANISTIC EFFECTS OF Ganoderma lucidum (REISHI) ON INFLAMMATORY BREAST CANCER PROGRESSION: Martínez-Montemayor MM et al. 55 CO 093: RJLB-14 PEPTIDE: EXPERIMENTAL EVIDENCES AND POTENTIAL IN CANCER TREATMENT: Díaz-García A et al. 55 CO 094: ANTI-CANCER ACTIVITY OF Thalassia testudinum EXTRACT REGULATES ATF4, P53 AND HIF1 DEPENDENT GENE EXPRESSION PROGRAMS RELATED TO CELL DEATH AND 56 SURVIVAL, CELLULAR DEVELOPMENT AND GROWTH AND PROLIFERATION: Hernandez I et al.
CO 095: Xanthium strumarium L. SHOWS ANTIPROLIFERATIVE ACTIVITY THROUGH INDUCING CELL CYCLE ARREST AT G2/M CHECKPOINT: Pérez CL et al. 56 CO 096: Xanthium strumarium L. A POTENTIAL ANTI-TUMOUR AGENT: Piloto J et al. 57 CO 097: ANTIPROLIFERATIVE ACTIONS OF THREE Hypericum SPECIES: EFFECTS OF LEAVE AND FLOWER EXTRACTS OF H. perforatum, H. montbretii AND H. origanifolium: Öztürk Y et al. 57 CO 102: EXTRACTS AND FRACTIONS FROM Cryptostegia grandiflora L. EXHIBITED ANTI-INFLAMMATORY EFFECTS IN VIVO AND INHIBITED NITRIC OXIDE AND PGE2 PRODUCTION IN 58 LPS-STIMULATED RAW 264.7 MOUSE MACROPHAGES IN VITRO: Castro J et al. CO 103: EVALUATION OF THE PROTECTIVE EFFECT OF ETHANOL EXTRACT OF Dracontium SP. ON LETHAL AND COAGULANT ACTIONS INDUCED BY VENOM OF Bothrops asper: Franco L 58 et al. CO 104: ANTIOXIDANT ACTIVITY OF ETHANOL EXTRACT OF THE FRUIT OF THE SPECIES Syzygium samarangense (WAX APPLE): Fonseca A et al. 59 CO 105: PROTECTOR EFFECT OF THE PHYTO-THERAPEUTIC Piper aduncum (MATICO) IN BREAST CANCER INDUCED IN RATS: Arroyo J et al. 59 Taller de Farmacoeconomía / Workshop on Pharmacoeconomy 60 C 021: CRITERIA FOR THE REGULATION OF THE PRICE OF MEDICINES: Rovira J. 60 MR 003: ECONOMIC IMPLICATIONS IN SAFETY AND DRUG USE. CUBAN EXPERIENCE: Gálvez González AM et al. 60 CO 106: NATIONAL PROGRAMME CHILDREN’S IMMUNIZATION IN CUBA. ECONOMICS AND HEALTH IMPACTS IN THIS COUNTRY 1962-2012: Collazo Herrera M et al. 61 CO 107: HEALTH TECHNOLOGY ASSESSMENT (HTA): A BROAD ECONOMIC PERSPECTIVE: Rovira J. 61 CO 108: CONSUMPTION OF ANTINEOPLASTIC AND SUPPORT DRUGS IN LAS TUNAS PROVINCE , FROM 2009 TO 2012: Pérez JE et al. 62 CO 109: EFFICIENCY OF TWO TREATMENT MODALITIES FOR ANXIETY CAUSED BY NEUROSIS: Casas Gross S et al. 62 CO 110: ASSESSING FEASIBILITY IN THE DEVELOPMENT AND MARKETING OF PHYTOMEDICINES: THE CASE OF A Lippia alba (VERBENACEAE) ANTI-INFLAMMATORY GEL IN THE COSTA 63 RICAN MARKET: Segura S. CO 111: COST-EFFECTIVE OPTIONS IN THE MANAGEMENT OF DIABETES IN A DEVELOPING COUNTRY: Wynter-Adams D et al. 63 CO 112: ANALYSIS FROM A CUBAN POINT OF VIEW: Pérez Ojeda L et al. 64 CO 113: MEASURING THE PRICES OF MEDICINES FOR NATIONAL SYSTEM OF HEALTH IN CUBA: De la Cruz Pérez CB et al. 64 Taller sobre Daño Cerebral y Neuroprotección: Un Enfoque Básico y Clínico / Workshop on Brain Injury and Neuroprotection; A Basic and Clinical Approach 65 C 022: THE GUANINE-BASED PURINERGIC SYSTEM AS A NEW TARGET FOR NEUROPROTECTION AGAINST GLUTAMATERGIC EXCYTOTOXICITY: Souza DO. 65 CO 114: THE ROLE OF ASTROCYTES IN METABOLISM AND NEUROTOXICITY OF THE PYRROLIZIDINE ALKALOID MONOCROTALINE, THEMAINTOXIN OF Crotalaria retusa: Lima Costa S. 65 CO 115: RESVERATROL PREVENTS CA1 NEURONS AGAINST ISCHEMIC INJURY BY MODULATION OF BOTH GSK-3Β AND CREB THROUGH PI3-K/AKT PATHWAYS AND THE 66 INFLAMMATORY RESPONSE: Simão F et al.
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CO 116: ACTION OF FATTY ACIDS ON GABAA RECEPTORS: IMPLICATIONS FOR THEIR ANXIOLYTIC-LIKE EFFECTS IN WISTAR RATS: Rodríguez-Landa JF et al. 66 C 023: PRECLINICAL STUDIES OF A NEW HYBRID MOLECULE WITH NEUROPROTECTIVE EFFECTS IN THE TREATMENT OF CEREBRAL ISCHEMIA: Nuñez Y et al. 67 CO 117: A MIXTURE OF FATTY ACIDS PRODUCES ANXIOLYTIC-LIKE BEHAVIOR IN THE WISTAR RAT: COMPARISON WITH DIAZEPAM: García-Ríos RI et al. 67 C 024: Achyrocline satureioides (LAM) D.C. (MARCELA): PROTECTIVE EFFECTS IN PRIMARY NEURONAL CULTURES AND AGAINST AN ISCHEMIC INJURY IN VIVO: Rivera F et al. 68 CO 118: CHARACTERIZATION OF A MODEL OF GLOBAL STROCK INDUCED BY PERMANENT OCCLUSION OF THE ARTERIES COMMON CAROTIDS: Pavón N et al. 68
CO 119: ORGANO SELENO COMPOUNDS AS NEUROPROTECTIVE AGENTS: EMPHASIS IN DIPHENYL DISELENIDE (PHSE)2: Rocha JBT et al. 69 CO 120: NEUROPROTECTION AND CLINICAL TRIAL IN AUTISTIC DISORDER: Robinson-Agramonte MA et al. 69 Simposio de Farmacogenética y Farmacogenómica / Symposium of Pharmacogenetic and Pharmacogenomic 70 C 025: GENETIC VARIATION IN SMOKING AND LUNG CANCER: Tyndale R. 70 C 026: PHARMACOGENETICS: CLINICAL IMPLICATIONS FOR EATING DISORDERS AND SUICIDE: Llerena A et al. 70 CO 121: POPULATION PHARMACOKINETIC OF CYCLOSPORINE IN THE EARLY PERIOD THE POST RENAL TRANSPLANT IN PAEDIATRIC PATIENTS: Lares-Asseff I et al. 71 CO 122: ASSOCIATION OF POLYMORPHISMS OF THE CYP2C9*2,*3 AND CYP2C19*2,*3, THE NUTRITIONAL STATUS AND CONCOMITANT TREATMENT, WITH PHENYTOIN 71 PHARMACOKINETICS AND TREATMENT RESPONSE, IN PATIENTS WITH EPILEPSY: Gutiérrez Álvarez O et al. CO 123: PHARMACOGENOMIC AND PHARMACOKINETIC PARTICULARITIES OF THE MEXICAN POPULATION: NECESSITY OF LOCAL CLINICAL PHARMACOLOGY STUDIES IN LATIN 72 AMERICA: Castañeda G. CO 124: DETERMINATION OF MUTATIONS WITH CLINICAL IMPLICATION OF THE NAT2, ABCB1, CYP2C9 AND CYP4F2 ON DRUG RESPONDS IN PERUVIAN SETTLERS: Salazar-Granara A et 72 al. CO 125: DISTRIBUTION OF CYP2C19 POLYMORPHISMS IN EIGHT AMERINDIAN GROUPS FROM NORTHWEST MEXICO: Sosa-Macías M et al. 73 CO 126: ASSOCIATION OF CYP1A1*2C WITH HEPATIC FUNCTION AND HYPERLIPIDEMIA IN A MEXICAN TEPEHUANO INDIGENOUS GROUP: Galaviz-Hernández C et al. 73 CO 127: METABOLIC PHENOTYPES OF DEBRISOQUINE AND GENOTYPIC OF CYP2D6 IN THE NICARAGUAN POPULATION: Ramírez Roa R. 74 CO 129: POLYMORPHISMS OF THE BIOTRANSFORMATION AND ELIMINATION SYSTEMS OF THE MEDICINES: ON OVERVIEW TO STUDIES PERFORMED IN CUBA: Rodeiro I et al. 74 CO 130: FROM PHARMACOGENETICS TO PERSONALIZED MEDICINE: A CUBAN REGULATORY PERSPECTIVE: Remirez D. 75 CO 131: PHARMACOGENETICS LEARNING IN MEDICAL STUDENTS USING ICTs AND PBL METHODOLOGY: AN ACTION RESEARCH STUDY IN A PUBLIC UNIVERSITY. LIMA-PERÚ: Placencia 75 M et al. CO 132: PHARMACOEPIDEMIOLOGY AND PHARMACO-GENETICS OF SCHIZOPHRENY: Fariñas H et al. 76 PL 013: THE ROLE OF ENVIRONMENT AND EPIGENETIC IN HYPERTENSION: Lopez-Jaramillo P. 76 JUEVES, OCTUBRE 24 / THURSDAY, OCTOBER 24th: SESIÓN PLENARIA / PLENARY SESSION 77 PL 007: SEPSIS, INFLAMMATION AND CELL RESPONSE: Salomao R. 77 PL 008: OLD REMEDIES FOR NEW AILMENTS - PRESENT TIME OF THE PHYTOMEDICINES (Enlarge abstract): Alonso J. 77 Taller Inmunofarmacología y Biotecnología. Sesión: Vacunas de Tuberculosis / Workshop on Immunopharmacology and Biotechnology. Session; Tuberculosis vaccines 79 C 027: ANCIENT DNA STUDIES BRING NEW LIGHT ON THE EPIDEMIOLOGY OF TUBERCULOSIS: Bercovier H. 79 C 028: DEVELOPMENT OF EXPERIMENTAL STRATEGIES FOR THE PROPHYLAXIS AND TREATMENT OF TUBERCULOSIS: Acosta A et al. 79 CO 134: IMMUNOLOGICAL EVALUATION OF A PROTEOLIPOSOME DERIVATE FROM Mycobacterium bovis BCG AS A POTENTIAL VACCINE CANDIDATE AGAINST TUBERCULOSIS: Alvarez N 80 et al. Taller Inmunofarmacología y Biotecnología. Sesión: Preclínica y Control de Calidad de Vacunas / Workshop on Immunopharmacology and Biotechnology. Session; Preclinical Studies and 81 Quality Control of Vaccines CO 136: 3RS FOR VACCINES: OPPORTUNITIES AND HURDLES: Hendriksen C. 81 CO 138: DEVELOPMENT OF ALTERNATIVE METHODS FOR QUALITY CONTROL ON IMMUNOBIOLOGICAL PRODUCTS: EXPERIENCE OF NATIONAL INSTITUTE OF QUALITY CONTROL IN 81 HEALTH, BRAZIL: Chaves Leal E et al. CO 139: EVALUATION OF WHOLE PERTUSSIS VACCINES BY COMBINING RELEVANT IMMUNOLOGICAL AND BIOLOGICAL ASSAYS AS STRATEGY FOR DETERMINING THE ROLE OF TOTAL 82 AND SPECIFIC ANTIBODIES FOR PROTECTION: Chovel ML et al. CO 140: EXPERIENCE ON THE DEVELOPMENT OF BIOMODELS FOR Haemophilus influenzae TYP B INFECTION: Infante Bourzac JF et al. 82
CO 141: REPEATED DOSE TOXICITY STUDY OF THE MENINGOCOCCAL SEROGROUP AW135 OUTER MEMBRANE VESICLE VACCINE IN SPRAGUE DAWLEY RATS: Oliva R et al. 83 CO 142: DEVELOPMENT AND VALIDATION OF METHOD FOR QUANTIFICATION MULTIVALENT POLYSACCHARIDES VACCINES BY CAPILLARY ZONE ELECTROPHORESIS: Merchán Y et al. 83 Taller de Farmacología Básica / Workshop on Basic Pharmacology 84 C 029: NEW PROMISING CANDIDATES FOR DIABETES TYPE 2 TREATMENTS OBTAINED FROM NATURAL SOURCES: INHIBITORY EFFECTS ON PTP1B, DPPIV AND GLUCOSE UPTAKE IN 84 VITRO ASSAYS: Marrero Faz E et al. CO 143: TRANSIENT MIDDLE CEREBRAL ARTERY OCCLUSION-INDUCED CHANGES ON VASCULAR PROPERTIES ARE ABOLISHED BY URIC ACID: Onett Y et al. 84 CO 144: LACTOFERRIN IN ACTINOMYCETOMA GRAINS: Castrillón RL et al. 85 CO 145: SURFACEN DOWN-REGULATED THE Staphylococcus aureus-INDUCED TNF-Α AND IL-6 IN MONOCYTES AND NOT AFFECT OXIDATIVE BURST IN VITRO: Lugones Y et al. 85
CO 146: REPETITIVE EXPOSURE OF NORADRENALINE INDUCES FACILITATION OF THE RAT TESTICULAR CAPSULE CONTRACTION THROUGH THE INTERACTION BETWEEN α1D- AND β- 86 ADRENERGIC RECEPTORS: Silva Júnior ED et al. CO 147: MUSCARINIC RECEPTOR SUBTYPE AND CALCIUM SIGNALLING INVOLVED IN THE CONTRACTIONS INDUCED BY ACETYLCHOLINE OR CARBACHOL IN RAT TESTICULAR CAPSULE: 86 Silva Júnior ED et al. C 030: DIFFERENTIAL REGULATION BY P1 AND P2 PURINOCEPTORS OF ATRIAL CONTRACTION IN NORMOTENSIVE AND SPONTANEOUSLY HYPERTENSIVE RATS: Jurkiewicz A et al. 87 CO 148: LOWER DENSITY OF L-TYPE AND HIGHER DENSITY OF P/Q-TYPE CALCIUM CHANNELS IN CHROMAFFIN CELLS OF HYPERTENSIVE, COMPARED WITH NORMOTENSIVE RATS: 87 Miranda-Ferreira R et al. CO 149: EFFECT OF PHOSPHATIDYLETHANOLAMINE ON THE ACTIVITY OF PEPTIDES StII1-30 AND StII11-30, DERIVED FROM THE PORE-FORMING TOXIN STICHOLYSIN II: Mesa Galloso H 88 et al. CO 150: COUPLING BETWEEN THE ENDOPLASMIC RETICULUM AND MITOCHONDRIA, IN CONTROLLING CATECHOLAMINE RELEASE FROM RAT EMBRYO CHROMAFFIN CELLS, 88 COMPARED WITH ITS MOTHER: Musial DC et al. CO 151: ALTERATION FUNCTION OF P1 RECEPTOR COULD CONTRIBUTE TO THE HIGH ACTIVITY OF ACE (ANGIOTENSIN-CONVERTING ENZYME) AND TO DEVELOP THE HYPERTENSION 89 IN STREPTOZOTOCIN-INDUCED DIABETIC RATS: Musial DC et al. CO 152: IN VITRO ANTIPROLIFERATIVE EFFECT OF INDOLE PHYTOALEXINS: Mojzis J et al. 89
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CO 153: UNCOMPLETE INDIVIDUAL PROFILES (SPARSE DATA) IN NONCLINICAL RESEARCH. COMBINING COMPARTMENTAL ANALYSIS, IMAGING THECNIQUES AND POPULATION 90 PHARMACOKINETIC: Hernández I et al. CO 154: IN VITRO EVALUATION OF THE ANTI-PROLIFERATIVE EFFECT OF A SERIES OF SYNTHETIC COMPOUNDS ON HUMAN PROSTATE CANCER CELLS: Roa J et al. 90 CO 155: SIMVASTATIN EFFECT ON THE EXPRESSION OF ENDOTHELIAL CELL ADHESION MOLECULES AND INFECTION INDUCED BY Trypanosoma cruzi: Campos-Estrada C et al. 91 Simposio de Productos Naturales / Symposium of Natural Products 92 C 031: INHIBITION OF CYTOCHROME P450 BY NATURAL PRODUCTS AS AN ANTIMUTAGENESIS MECHANISM: Espinosa-Aguirre JJ. 92 CO 156: THE AQUEOUS EXTRACT OF Montanoa frutescens PRODUCES ANTI-STRESS-LIKE EFFECTS IN MALE WISTAR RATS IN THE FORCED SWIM TEST: Flores-Aguilar LA et al. 92 CO 157: Montanoa grandiflora EXTRACT PRODUCES ANTI-STRESS-LIKE BUT NOT ANTI-DESPAIR-LIKE EFFECTS IN WISTAR RATS: COMPARISON WITH FLUOXETINE: Rosas-Sánchez GU et 93 al. CO 158: EVALUATION OF ANXIOLYTIC ACTIVITY OF AQUEOUS EXTRACTS OF Plantago major L. AND Mentha viridis L.: PLANTS USED IN THE TRADITIONAL MEDICINE OF COLOMBIAN 93 CARIBBEAN COAST: Caro D et al. CO 159: Montanoa grandiflora EXTRACT PRODUCES ANXIOLYTIC-LIKE EFFECTS SIMILAR TO DIAZEPAM IN CYCLING FEMALE WISTAR RATS: Vicente-Serna J et al. 94 CO 160: ANXIOLYTIC-LIKE EFFECT OF Montanoa frutescens EXTRACT IN THE METESTRUS-DIESTRUS PHASE OF THE OVARIAN CYCLE IN WISTAR RATS: Rodríguez-Blanco LA et al. 94
CO 161: HEPATOPROTECTIVE EFFECT OF SOLIDS LIPIDS NANOPARTICLES WITH VANILLIN AGAINST CCL4-INDUCED ACUTE LIVER INJURY IN MICE: Castan L et al. 95 CO 162: PHARMACOLOGY OF ANTIASTHMATIC NATURAL PRODUCTS FROM MEXICAN MEDICINAL PLANTS: Navarrete A et al. 95 CO 163: ANTIBACTERIAL ACTIVITY OF MEDICINAL PLANTS OF THE COLOMBIAN NORTHERN COAST: Barrios L et al. 96 CO 164: Rosmarinus officinalis L. SECONDARY METABOLITES CHARACTERIZATION IN PLANTS GROWN IN CUBA AND MEXICO: Fung Boix Y et al. 96 CO 165: HUMAN CELLS PHOTOPROTECTION BY FRACTIONS OBTAINED FROM Phyllanthus orbicularis Kunth: Vernhes M et al. 97 CO 166: NEW INDICATION OF SURFACEN A PORCINE NATURAL SURFACTANT IN THE TREATMENT OF THE ACUTE RESPIRATORY DISTRESS SYNDROME: Fernández Limia O et al. 97 Simposio Actualización Terapéutica en Oncoterapética / Symposium of Therapeutic Updating on Cancer 98 C 032: CHEMO-IMMUNOTHERAPY FOR CANCER: A RATIONAL SCIENTIFIC AND THERAPEUTIC: Soriano García JL. 98 CO 167: RADIO-IMMUNOTHERAPY FOR MALIGNANCIES: Batista Albuerne N. 98 C 033: IMMUNOTHERAPY FOR NON HODGKIN’S LYMPHOMAS. ADVANCES IN THE USE OF MONOCLONAL ANTIBODIES: Gracia Medina E. 99 CO 168: IMMUNOTHERAPY COMBINATIONS: Crombet T. 99 CO 169: REVIEW OF TARGETED THERAPIES IN HER2 POSITIVE BREAST CANCER: Falla R. 100 CO 170: CHEMO-IMMUNOTHERAPY FOR GASTRO-INTESTINAL MALIGNANCIES: Lima Pérez M. 100 CO 171: TARGETED THERAPIES AGAINST SOFT-TISSUE SARCOMAS (OR THE DEVIL IN THE DETAILS): Cubedo R. 101 CO 172: FAMILY HAPLOIDENTICAL STEM CELL TRANSPLANTATION OUTCOME IS NOT INFERIOR TO STANDARD MATCHED RELATED AND UNRELATED DONOR TRANSPLANTATION: AN 101 INTENTION-TO-TREAT ANALYSIS OF 611 PATIENTS WITH ACUTE LEUKEMIAS: Ciceri F. CO 173: LOSS OF MISMATCHED HLA AT LEUKEMIA RELAPSE AFTER HEMATOPOIETIC STEM CELL TRANSPLANTATION IS SIGNIFICANTLY ASSOCIATED WITH CLINICAL AND IMMUNO- 102 GENETIC HALLMARKS OF DONOR-VERSUS-HOST ALLOREACTIVITY: Ciceri F. Taller sobre Daño Cerebral y Neuroprotección: Un Enfoque Básico y Clínico / Workshop on Brain Injury and Neuroprotection; A Basic and Clinical Approach 103 C 034: EPIDERMAL GROWTH FACTOR AND GROWTH HORMONE-RELEASING PEPTIDE-6: COM-BINED THERAPEUTIC APPROACH FOR NEURODEGENERATIVE DISEASES: García del Barco 103 D et al. CO 174: THERAPEUTIC EFFECT OF THE COMBINED USE OF GROWTH HORMONE RELEASING PEPTIDE-6 AND EPIDERMAL GROWTH FACTOR IN A PROXIMAL NEUROPATHY MODEL: 103 García del Barco D et al. CO 175: REDUCING ALZHEIMER’S DISEASE Β-AMYLOID BY MANIPULATING IL-12/IL-23 SIGNALING: Lopategui Cabezas I et al. 104 CO 176: NEW EVIDENCES FROM NASAL NEUROEPO IN ALZHEIMER NON-TRANSGENIC ANIMAL MODEL: García Rodríguez JC et al. 104 C 035: EXPERIMENTAL HYPOTHYROIDISM DURING LACTATION ALTERS NEUROENERGETIC IN RAT CEREBELLUM: de Assis AM et al. 105 CO 177: BEHAVIOUR OF IMMUNOLOGIC HUMORAL MARKERS IN NOT INFECTIOUS NEUROLOGIC ENTITIES: León-Toirac EJ et al. 105 CO 178: PARTICIPATION OF THE MEDIAL AMYGDALA-HIPPOCAMPUS CIRCUIT ON THE DETECTION OF AN ALARM PHEROMONE ASSOCIATED TO AN AVERSIVE STIMULUS: Molina- 106 Jiménez T et al. CO 179: EFFECTS OF BACLOFEN AND VIGABATRIN ON GABAERGIC TRANSMISSION IN THE RAT NUCLEUS ACCUMBENS DURING COCAINE WITHDRAWAL: Pastrana A et al. 106 CO 180: A NEW ANTICONVULSANT COMPOUND PREVENTS THE OXIDATIVE DAMAGE INDUCED BY PENTYLENETETRAZOLE AND EXERTS ANTIDEPRESSANT-LIKE EFFECTS IN MICE: 107 Pastore V et al. CO 181: NEW NEUROPROTECTOR THERAPIES FOR MULTIPLE SCLEROSIS AND STROKE: Pentón-Rol G et al. 107 Simposio: Perspectivas de las Drogas Huérfanas en Latinoamérica: Desde la Investigación a la Accesibilidad / Symposium; Perspectives of Orphan Drugs in Latin America; From the Research 108 to the Accesibility C 036: IMPACT OF RARE DISEASES IN THE HEALTH POLICIES IN COUNTRIES UNDER DEVELOPMENT. EXPERIENCES AT LATIN-AMERICA AND CARIBBEAN (LA&C): Llera VA. 108 C 037: ORPHAN DRUGS: DEFINITIONS, RESEARCH & DEVELOPMENT, MASTER PLANS, ACCESIBILITY AND BIOETHICAL ASPECTS: Roldán E. 108 C 038: ECONOMIC EVALUATION AND ORPHAN DRUGS: Gálvez González AM. 109 C 039: INTERNATIONAL COOPERATION AND ACTIONS FOR ORPHAN DRUGS. INCLUDING LATIN- AMERICA AND CARIBBEAN WITHIN THE INTERNATIONAL LANDSCAPE: Llera VA. 109 Simposio de Farmacogenética y Farmacogenómica / Symposium of Pharmacogenetic and Pharmacogenomic 110 C 040: USE OF GENETICALLY MODIFIED MOUSE MODELS TO STUDY MECHANISMS OF CHEMICALLY-INDUCED LIVER CANCER RISK: Grant DM. 110 CO 182: IMMUNOGENETICS AND BIOINFORMATICS IN THE PHARMACOGENETIC PROFILE OF VACCINES AND BIOTECHNOLOGICAL PHARMACEUTICALS: Serrano-Barrera OR. 110 CO 183: PROTEIN-PROTEIN INTERACTIONS AND GENE EXPRESSION STUDIES IDENTIFY MOLECULAR MECHANISMS DRIVING THE CYTOTOXIC EFFECT OF CIGB-552: Fernández Massó JR 111 et al. CO 184: APPLICATION OF DNA MICROARRAYS TECHNOLOGY FOR STUDY IN HUMAN BLOOD SAMPLES THE SPECIFIC GENE EXPRESSION PROFILE FOR GENDER: Guillén I et al. 111 CO 185: EARLY SAT1 AND FAS GENE EXPRESSION IN SUBJECTS TREATED WITH HEBERPAG FORMULATION: Bello C et al. 112 CO 186: EXPLORATION OF A SET OF THE ANTITUMOR PEPTIDE CIGB-300-REGULATED GENES IN AML CELL LINES: Vázquez-Blomquist D et al. 112 CO 187: OAS-1 AS PHARMACODYNAMIC BIOMARKER OF ACTION OF CIGB-128 IN MYFIC AND SOFÍA CLINIC TRIALS: Izquierdo Y et al. 113 VIERNES, OCTUBRE 25 / FRIDAY, OCTOBER 25th: SESIÓN PLENARIA / PLENARY SESSION 114 PL 009: CEIBA: PHARMACOGENETICS IN IBEROAMERICANS AND ITS CLINICAL IMPLICATIONS: Llerena A. 114
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PL 010: PHARMACOLOGICAL MANAGEMENT OF NEUROPATHIC PAIN: Granizo E. 114 Taller Inmunofarmacología y Biotecnología. Sesión: Biotecnología / Workshop on Immunopharmacology and Biotechnology. Session; Biotechnology 115 C 041: THE USE OF ENZYMES FOR POLYMER CONJUGATION: Pasut G. 115 C 042: SIMULATION OF PLASMID RECOVERY PROCESS FOR A DNA VACCINE: Limonta M et al. 115 CO 188: PRODUCTION OF SCFV ANTIBODY FRAGMENT IN RECOMBINANT Pichia pastoris UNDER DIFFERENT CONCENTRATIONS OF COBALT SULFATE: Weinacker DF et al. 116 CO 189: COMPARISON OF DIFFERENT CULTURE CONDITIONS OF GENETICALLY –MODIFIED Pichia pastoris TO PRODUCE SCFV ANTIBODY FRAGMENT ANTI-LDL (-): Zepeda AB et al. 116 CO 190: EFFECTS OF TEMPERATURE AND CONCENTRATION OF METHANOL ON THE EXPRESSION OF OXIDATIVE DAMAGE BIOMARKER IN MEMBRANES OF Pichia pastoris 117 RECOMBINANT: Figueroa CA et al. Taller Inmunofarmacología y Biotecnología. Sesión: Vacunas / Workshop on Immunopharmacology and Biotechnology. Session; Vaccines 118 C 043: CONTROVERSIAL POINTS ABOUT VA-MENGOC-BC: Ochoa Azze R. 118 CO 191: AN ADVERSE EVENTS FOLLOWING IMMUNIZATION’S (AEFI) INVESTIGATION: Lammer M et al. 118 CO 192: POTENTIAL OF THE SINGLE INSERTION MUTANT TATC FOR THE PRODUCTION OF THE Mycobacterium tuberculosis APA ANTIGEN IN Streptomyces lividans: Rodríguez C et al. 119 CO 193: NEW VACCINE STRATEGIES AGAINST Nesisseria meningitidis serogroup X: Zayas C et al. 119 CO 194: STABILITY AND PRECLINICAL STUDIES OF THE TETANUS DIPHTHERIA VACCINE IN ADULTS AND ADOLESCENTS: Hernández León D et al. 120 Simposio de Farmacología Básica / Symposium of Basic Pharmacology 121 C 044: NOVEL MODEL FOR “CALCIUM PARADOX” IN SYMPATHETIC TRANSMISSION OF SMOOTH MUSCLES: ROLE OF CYCLIC AMP PATHWAY: Bergantin LB et al. 121 CO 197: ISOLATION, IDENTIFICATION AND TOXICOKINETICS OF AN ANTIMICROBIAL PHOSPHOLIPASE A2 OF Bothrops asper VENOM: Fernández M et al. 121 CO 198: ORGANOMETALLIC COMPLEXES WITH IRON AS POTENTIAL CANCER THERAPEUTICS: Mojzisova G et al. 122 CO 199: EFFECTS OF SOME ANGIOTENSIN-CONVERTING ENZYME INHIBITORS AND ANGIOTENSIN II RECEPTOR BLOCKERS ON EXPERIMENTAL INFLAMMATION: Magyar I et al. 122 C 045: SELECTIVE CYTOTOXIC ACTIVITY OF 1-O-UNDECYL GLYCEROL: Hernández-Colina M et al. 123 CO 200: EFFECT OF GESTATIONAL AGE ON PHARMACOKINETICS OF RANITIDINE IN NEWBORNS: Lares Asseff I et al. 123 CO 201: ANXIETY AND STRESS BEHAVIOR ON ZEBRAFISH (Danio rerio): A NEW WAY FOR DRUGS DISCOVERY: Iturriaga-Vásquez P et al. 124 CO 202: EFFECT OF ESCULETIN IN EXPERIMENTAL MODEL OF INFLAMMATORY BOWEL DISEASE: Witaicenis Fantinati A et al. 124 CO 203: POPULATION PHARMACOKINETIC ANALYSIS OF TACROLIMUS IN MEXICAN PEDIATRIC RENAL TRANSPLANT PATIENTS: Jacobo C et al. 125 CO 204: ENDOTHELIAL INVOLVEMENT ON THE INDUCED RELAXATION BY ROSUVASTATIN, IN OBESE RAT AORTIC RINGS: Aranda-Zepeda L et al. 125 CO 205: ANTIANGIOGENIC EFFECT OF CHALCONE DERIVATIVES: Mirossay L et al. 126 CO 206: EFFECT OF IBUPROFEN AND IBUPROPHENYL-IBUPROPHENATE ON GASTRIC MUCOSA LESIONS AND ACUTE TOXICITY: López A et al. 126 CO 207: COAGULATION FACTOR Xa (FXa) AND ITS ZYMOGEN FX INHIBIT ANGIOGENESIS: Valenzuela R et al. 127 Simposio de Productos Naturales / Symposium of Natural Products 128 CO 208: THE USE OF MEDICINAL PLANTS AND OTHER DIETARY SUPPLEMENTS FOR THE TREATMENT OF PAIN IN INTEGRATIVE CLINICS IN THE UNITED STATES: Kiefer D. 128 CO 209: THE OVERLAP OF TRADITIONAL AND ALLOPATHIC MEDICINE: A STUDY FROM MIDWESTERN UNITED STATES: Kiefer D et al. 128 CO 210: HERBAL MEDICINES: NEW PARADIGM FOCUS: Chico S et al. 129 CO 211: PROJECT FUNDING MODELS FOR RDI IN MEDICINAL PLANTS IN LATIN AMERICA: Desmarchelier C. 129 CO 212: EFFECT OF MANGIFERIN (Mangifera indica L.) ON THE GASTRIC MUCOSA OF CD-1 MICE: Cervantes F et al. 130 CO 213: NEUROTOXICOLOGICAL EVALUATION OF AQUEOUS EXTRACTS OF Turnera diffusa (TURNERACEAE) AND Chrysactinia xviexicana (Asteraceae) IN MICE, PLANTS USED AS 130 TRADITIONAL APHRODISIAC REMEDIES. “DAMIANA DE CALIFORNIA AND FALSA DAMIANA”: Ferreyra-Cruz O et al. C 046: METABOLIC SYNDROME AND PLANT DRUGS: Alonso J. 131 CO 214: SCREENING MEDICINAL PLANTS FROM GUANAJUATO (MEXICO) FOR THE DETECTION OF NOVEL ANTIPROTOZOAL PRODUCTS: Osegueda MS et al. 132 CO 215: ANTI-Trypanosoma cruzi EFFECT OF ESSENTIAL OIL FROM Thymus vulgaris L (THYME) AND ITS MAIN CONSTITUENT, THYMOL, IN MICE: Rojas Armas JP. 132 CO 216: MANGIFERIN: A NATURAL GLUCOSILXANTHONE AND ITS THERAPEUTIC POTENTIALITIES: Delgado-Hernández R et al. 133 CO 217: CYTOPROTECTOR EFFECT OF METHANOLIC EXTRACT FROM THE LEAF OF Erythroxylum coca IN GASTRIC INJURY INDUCED IN RATS: Palomino de la Gala R et al. 133 CO 218: PHYTOCHEMICAL EVALUATION, ACUTE TOXICITY AND ANALGESIC, ANTI-INFLAM-MATORY AND PROKINETIC EFFECTS OF Maytenus macrocarpa (CHUCHUHUASI) LEAVES ON 134 RODENTS: Salazar-Granara A et al. Taller de Farmacovigilancia / Workshop on Pharmacovigilance 135 CO 220: REGULATORY REQUIREMENTS COMPARISON OF MINISTRIES OF HEALTH AND ETHICS COMMITTEES FOR SAFETY REPORTS IN CLINICAL RESEARCH IN CENTRAL AMERICA AND 135 CARIBBEAN: Ramírez N et al. CO 221: CHARACTERIZATION OF ADVERSE DRUG REACTIONS OF LOW FREQUENCY OF APPERANCE IN THE CUBAN DRUG SURVEILLANCE SYSTEM, 2004-2012: Santos L et al. 135 CO 222: COMPETENCE IN REPORTING ADVERSE DRUG REACTIONS AND MEDICATION ERRORS BY REGISTERED NURSES IN A SPANISH TEACHING HOSPITAL: Salcedo-Diego I et al. 136 CO 223: CHAGAS DISEASE: PHARMACOLOGICAL ALTERNATIVES FOR VECTOR CONTROL: Marin GH et al. 136 CO 225: IMPLEMENTATION OF A PROGRAM OF ADVERSE EFFECTS NOTIFICATION FOR PATIENT. GUANTÁNAMO. JUNE 2009 – FEBRUARY 2010: Trabanca Beltrán YA et al. 136 CO 226: ADVERSE REACTIONS TO ANTIMICROBIAL AGENTS. CUBAN PHARMACOLOGICAL SURVEILLANCE SYSTEM, 2003-2012: Alfonso Orta I et al. 136 CO 227: CHARACTERIZATION OF ADVERSE REACTIONS TO NSAIDs IN ELDERLY IN BOGOTA DC 2012: Chaves M. 138 CO 228: ADVERSE DRUG REACTIONS NOT DESCRIBED IN THE ELDERLY. PHARMACOVIGILANCE SYSTEM. CUBA, 2008-2012: Furones JA et al. 138 CO 229: PHARMACOVIGILANCE OF HEBERPROT-P®: Yera I et al. 139 CO 231: WHY IS THERE A NEED TO SET UP A SPANISH-LATIN AMERICAN DILI NETWORK?: Bessone F et al. 139 CO 232: THE SPANISH-LATIN AMERICAN DILI NETWORK: PRELIMINARY RESULTS FROM A COLLABORATIVE STRATEGIC INITIATIVE: Bessone F et al. 140 Simposio de Cronobiofarmacología / Symposium of Chronobiopharmacology 141 C 047: CHRONOPHARMACOLOGY: Valdés Y. 141 C 048: THE ROLE OF ACTIGRAPHY IN THE STUDY OF THE SLEEP-WAKE CYCLE: Meira e Cruz M. 141 MR 005: SPORT’S CHRONOBIOLOGY: León A et al. 142
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LATINFARMA 2013 Índice/Index
Taller de Medicamentos Genéricos / Workshop on Generic Drugs 143 CO 233: A ROLE OF INNOVATION IN CUBAN PHARMACEUTICAL INDUSTRY: Carralero M et al. 143 CO 234: BIOEQUIVALENCE (OR BIOINEQUIVALENCE) OF GENERIC IMMUNOSUPPRESSIVE DRUGS: PHARMACO-DYNAMIC CONSIDERATIONS: Castañeda G. 143 CO 237: CARBON NANOTUBES AS PARACETAMOL CARRIERS FOR CONTROLLED DRUG DELIVERY: A THEORETICAL STUDY: Hernández Valdés D et al. 144 CO 238: SIMPLIFYING AND STREAMLINING THE MARKETING AUTHORIZATION PROCESS IN CUBA: Suárez Y et al. 144 CO 239: DRUGS DEVELOPMENT VS NEEDS OF HEALTH. A XXI CENTURY CHALLENGE: Rodríguez AJR et al. 145 Taller de Enseñanza de la Farmacología / Workshop on Teaching of Pharmacology 146 C 049: PERMANENT PHARMACOLOGY UPDATING, INHERENT COMPETENCE TO PHARMA-CEUTICAL CARE: Sedeño C. 146 CO 240: HISTORY OF PHARMACOKINETICS AND BIOPHARMACY IN CUBA: ROLE OF THE UNIVERSITIES: Fernández-Sánchez E. 146 CO 241: APPLICATION OF PBL, ICTs AND ITS EFFECT ON ACADEMIC ACHIEVEMENT IN THE COURSE OF BASIC PHARMACOLOGY-2011, MEDICAL SCHOOL OF UNMSM: Placencia M et al. 147 CO 242: “SIMULA EXPERIMENTAL PHARMACOL”: SOFTWARE TO TEACH AND LEARN EXPERIMENTAL PHARMACOLOGY WITHOUT USE LABORATORY ANIMALS: Balderas JL et al. 147 CO 243: CURRICULAR IMPROVEMENT OF THE SUBJECTS PHARMACOLOGY I AND II IN THE CURRICULUM OF MEDICINE: Rodríguez Ezcurdia R et al. 148 CO 244: TEACHING PHARMACOLOGY AS A MEANS OF PROMOTING RATIONAL DRUG USE. AN EXPIERENCE WITH UNDERGRADUATE STUDENTS: López M et al. 148 C 050: IMPLEMENTATION OF VIRTUAL SIMULATION SOFTWARE Microlab® and RAT CARDIO-VASCULAR in PHARMACOLOGY 2012, MEDICAL SCHOOL OF UNMSM: Placencia M et al. 149 CO 246: ASSESSMENT OF THE GENERAL PHARMACOLOGY LEARNING/TEACHING PROCESS IN THE YEAR 2012: Demurtas SL et al. 149 CO 247: TEACHING OF PHARMACOLOGY IN THE MODULAR SYSTEM: CONSTRUCTION OF THE TRANSFORMATION OBJECT: Izquierdo-Sánchez T. 150 CO 248: THE GAME IN PHARMACOLOGY: ANOTHER WAY OF LEARNING TO LEARN: Yodú Ferral N et al. 150 CO 249: COMPARATIVE ANALYSIS OF CLINICAL PHARMACOLOGY TRAINING PROGRAMS ACROSS THE WORLD: Domínguez V et al. 151 PL 014: CAUSES OF DISEASES AND THEIR BOARDING FROM THE PERSPECTIVE OF ORTHOMOLECULAR MEDICINE: Llorente JR. 151 CARTELES / POSTERS (P) 152 Inmunofarmacología y Biotecnología / Immunopharmacology and Biotechnology (PIF-BT) 153 PIF-BT 001: CHARACTERIZATION OF DRY POLYSACCHARIDES FROM NEISSERIA MENINGITIDIS SEROGROUPS A, C, Y AND W135 TO BE USED AS INTERNAL CONTROLS: Diaz D et al. 153 PIF-BT 002: DEVELOPMENT AND VALIDATION OF A SEROLOGICAL TEST (ELISA) FOR DETERMINING TETANUS ANTIBODIES AS A POTENCY MEASUREMENT IN MICE SERA: Gutiérrez N et 153 al. PIF-BT 003: PRODUCTION OF AN STANDARD SERUM IN MICE FOR THE DETERMINATION OF Salmonella typhi ANTI POLYSACCHARIDE VI IgG: Valmaseda T et al. 154 PIF-BT 004: SDS-PAGE AND RELATIVE QUANTIFICATION BY DENSITOMETRY OF RELEVANT PROTEINS PRESENT IN THE OMV FROM N. meningitides, SEROGROUPS A AND W135: Alvárez 154 M et al. PIF-BT 005: IMMUNOHISTOCHEMICAL ANALYSIS OF B23/NUCLEOPHOSMIN (NPM) PROTEIN IN TUMOR BIOPSIES FROM PATIENTS WITH CERVICAL CANCER STAGE IB2/II: Reyes V et al. 155 PIF-BT 006: MOLECULAR AND KINETIC CHARACTERIZATION OF PANULIRIN, A NOVEL TRYPSIN INHIBITOR FROM THE HEMOLYMPH OF THE SPINY LOBSTER Panulirus argus: Perdomo R 155 et al. PIF-BT 007: THERAPEUTIC EFFECT OF AN ALTERED PEPTIDE LIGAND DERIVED FROM HEAT-SHOCK PROTEIN 60 BY SUPPRESSING OF INFLAMMATORY CYTOKINES SECRETION IN TWO 156 ANIMAL MODELS OF RHEUMATOID ARTHRITIS: Lorenzo N et al. PIF-BT 008: EXPRESSION OF THE EPIDERMAL GROWTH FACTOR RECEPTOR AND N-GYCOLYL GM3 GANGLIOSIDE AS RECOGNIZED BY IOR EGF/R3 AND 14F7 MABS IN TRIPLE-NEGATIVE 156 BREAST CANCER: Alvárez I et al. PIF-BT 009: IMMUNOLOGICAL BIOMARKERS IN THE PROGNOSIS OF PATIENTS WITH COLON CANCER: Lahera T et al. 157 PIF-BT 010: CR3-HBcAg INTERACTION TRIGGERS HIV-SPECIFIC TH1 AND CTL IMMUNE RESPONSE AFTER TERAVAC IMMUNIZATION IN MICE: Rodríguez-Alonso I et al. 157 PIF-BT 011: INDUCTION OF DE NOVO HCV CORE-SPECIFIC CELL-MEDIATED IMMUNE RESPONSES AND ENHANCEMENT OF NEUTRALIZING ANTIBODIES RESPONSE BY CIGB-230, A DNA- 158 BASED VACCINE CANDIDATE, ON TRIPLE THERAPY WITH IFN-Α PLUS RIBAVIRIN: Amador-Cañizares Y et al. PIF-BT 012: THE IL-2 MUTEIN IS BETTER TOLERATED IN BALB/C MICE THAN wtIL-2: Fuentes D et al. 158 PIF-BT 013: DETECTION OF ERYTHROPOIETIN AND ITS ANOLOGOUS BY ISOELECTRIC FOCUSING AND DOUBLE-BLOTTING TECHNIQUE: Domínguez R et al. 159 PIF-BT 014: DEVELOPMENT OF A POLYSTYRENE LATEX-BASED DIAGNOSTIC SYSTEM FOR RHEUMATOID FACTOR: Marrero G et al. 159 PIF-BT 015: ASSESSMENT OF THE IN VIVO GENOTOXICITY OF THE 1E10 MONOCLONAL ANTIBODY BY MEANS OF THE BONE MARROW MICRONUCLEUS TEST: Curbelo A et al. 160 PIF-BT 016: SYNERGISTIC EFFECT EVALUATION ON THE COMBINATION OF THE CIGB-552 PEPTIDE WITH CONVENTIONAL ANTINEOPLASIC DRUGS ON LUNG AND COLON CANCER CELL 160 LINES: Gómez Y et al. PIF-BT 017: EXPRESSION AND CHARACTERIZATION OF A RECOMBINANT MOUSE ANTI-CD20 ANTIBODY: Harteman O et al. 161 PIF-BT 018: CD4+ T LYMPHOCYTES AND VIRAL LOAD IN HIV PATIENT WITH PREMIERE OF AIDS THAT RECEIVE ANTIRETROVIRAL TREATMENT: Hernández D et al. 161 PIF-BT 019: EFFECT OF BLOCKADE OF EGF SYSTEM ON WOUND HEALING IN PATIENTS VACCINATED WITH CIMAVAX® EGF: Fernández A et al. 162 PIF-BT 020: HOMOLOGOUS RECOMBINATION INDUCED BY RADIATION, ASSAYED BY DIRECT REPEATS DUPLICATION ASSAY: Cuétara Lugo E et al. 162 PIF-BT 021: CLONING, EXPRESSION AND SEMI-PURIFICATION OF A CHIMERIC PROTEIN ENCOMPASSING HEPATITIS C VIRUS EPITOPES: Aguilar-Noriega D et al. 163 PIF-BT 022: RESULTS OF THE SAFETY EVALUATION OF CANCER VACCINES DEALING WITH NOVEL TARGETS FOR CANCER IMMUNOTHERAPY: Mancebo A et al. 163 PIF-BT 023: TOXICOLOGICAL SAFETY EVALUATION OF ACM T1H BY INTRAVENOUSLY ROUTE IN CENP: BEAG DOGS: González Y et al. 164 PIF-BT 024: PROCESS DEVELOPMENT OF Dermatophagoides siboney PURIFIED PROTEIN ALLERGENS AS THE ACTIVE PHARMACEUTICAL INGREDIENT FOR AN ADJUVANTED ALLERGY 164 VACCINE: Martínez D et al. PIF-BT 025: IMMUNOLOGICAL CHARACTERIZATION OF MEN X CONJUGATED AS CANDIDATE VACCINE IN BALB/C MICE: Espinosa-Viñals C et al. 165 PIF-BT 026: GENERATION OF MOUSE MONOCLONAL ANTIBODIES AGAINST SEVERAL SEROTYPES OF STREPTOCOCCUS PNEUMONIAE USING A HEPTAVALENT CONJUGATED VACCINE: 165 Rodríguez Y et al. PIF-BT 027: EVALUATION OF IMMUNE RESPONSE IN DOSIS STUDIES OF CONJUGATED HEPTAVALENT VACCINE OF Streptococcus pneumoniae IN RABBIT: Martín Y et al. 166 PIF-BT 028: IMMUNOGENICITY OF MONOVALENT CONJUGATES AGAINST SEROTYPES 7F, 9V AND 19A OF Streptococcus pneumoniae: Pérez A et al. 166 PIF-BT 029: ACUTE DOSE INTRAMUSCULAR TOXICITY OF Streptococcus pneumoniae VACCINE IN CENP: SPRD RATS: Luque Y et al. 167 PIF-BT 030: PHYSICOCHEMICAL AND IMMUNOLOGICAL PARAMETERS OF THE ANTI-ALLERGIC ADJUVANT HOUSE-DUST-MITE VACCINE: Más A et al. 167 PIF-BT 031: CHARACTERIZATION OF THE CONJUGATES OF VI POLYSACCHARIDE OF Salmonella typhi: Padrón MA et al. 168 PIF-BT 032: CONJUGATES FROM Streptococcus pneumoniae CAPSULAR POLYSACCHARIDE SEROTYPE 5PIF-BT 032: PREPARATION AND CHARACTERIZATION OF: Mariño D et al. 168
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PIF-BT 033: INFLUENCE OF PHOSPHATE SALTS AND ALUM CONTENT ON TO THE IMMUNOGENICITY OF A Dermatophagoides siboney AFPL1-ADJUVANTED VACCINE: Samalea R et al. 169 PIF-BT 034: PHYSICOCHEMICAL AND IMMUNOLOGICAL COMPARISON OF VI POLYSACCHARIDE CONJUGATES AGAINST TYPHOID FEVER: Soubal JP et al. 169 PIF-BT 035: PURIFICATION AND CHEMICAL CHARACTERIZATION OF IMMUNOGENIC PNEUMOCOCCAL CAPSULAR POLYSACCHARIDES TYPES 19F AND 23F: Martínez Rodríguez JC et al. 170 PIF-BT 036: OBTENTION OF PEPTIDES DISPLAYED ON M13 PHAGE RECOGNIZING A MAB AGAINST MENINGOCOCCAL GROUP A POLYSACCHARIDE: Blaín K et al. 170 PIF-BT 037: PREPARATION OF GLYCOCONJUGATES FROM Streptococcus pneumoniae SEROTYPE 14 TO TETANUS TOXOID BY TWO METHODS OF CONJUGATION: Serrano Y et al. 171 PIF-BT 038: PHARMACOLOGICAL EVALUATION OF A VEGF BASED IMMUNOTHERAPY IN NON HUMAN PRIMATES: Morera Y et al. 171 PIF-BT 039: IMMUNOGENICITY AND REACTO-GENICITY OF A BOOSTER DOSE OF TETANUS VACCINE, VAX-TET®-5 IN TEENAGERS: Baró M et al. 172 PIF-BT 040: IMMUNOTHERAPY WITH HOUSE DUST MITE ALLERGEN VACCINES IN PEDIATRIC PATIENTS WITH PERSISTENT MODERATE ALLERGIC RHINITIS: González JV. 172 PIF-BT 041: IDENTIFICATION OF ANTIGENIC COMPOSITION OF OUTER MEMBRANE VESICLES FROM NEISSERIA Meningitidis SEROGROUP X: Rodríguez Y et al. 173 PIF-BT 042: ANTI-EGF/EGFR THERAPEUTIC ANTI-CANCER DRUGS AND THE WOUND HEALING PROCESS: Casacó A et al. 173 PIF-BT 043: PILOT TRIAL OF IMMUNOGENICITY AND PRECLINICAL TOXICITY OF Salmonella VACCINE CONJUGATE IN SPRAGUE DAWLEY RATS: Fariñas M et al. 174 PIF-BT 044: BREASTFEEDING AND HUMORAL IMMUNE RESPONSE AGAINST Tetanus AND Diphtheria TOXOID IN CHILDREN OF 2 YEARS OLD: La Rosa D et al. 174 PIF-BT 045: DESIGN OF A SEMIPURIFICATION STEP BASED IN A TWO AQUEOUS PHASES SEPARATING SYSTEM FOR THE PHB-01 EXTRACTION FROM TOBACCO LEAVES: Ferro W et al. 175 PIF-BT 046: RESULTS OF A PHASE II CLINICAL TRIAL CONDUCTED IN NON-SMALL CELL LUNG CANCER (NSCLC) PATIENTS TREATED WITH 1E10 MAB-ALUM, AN ANTI-IDIOTYPIC 175 VACCINE: Valdés A et al. PIF-BT 047: HUMORAL IMMUNE RESPONSE INDUCED IN EARLY STAGE BREAST CANCER PATIENTS INCLUDED IN A PHASE III CLINICAL TRIAL USING A GANGLIOSIDE-BASED VACCINE: 176 Valdés A et al. PIF-BT 048: PRELIMINARY RESULTS OF IMMUNOLOGICAL BIOMARKERS IN PATIENTS WITH PSORIASIS TREATED WITH ITOLIZUMAB: Aira Diaz LE. 176 PIF-BT 049: EGF CANCER VACCINE: TOWARDS A SCHEDULE OPTIMIZATION AND A BIOMARKER OF CLINICAL RESPONSE: Popa X et al. 177 PIF-BT 050: DIFFERENT STRATEGIES FOR THE RECOMBINANT EXPRESSION OF THE DOMAIN 1 OF CD6, A HUMAN TARGET RECEPTOR INVOLVED IN AUTOIMMUNE DISEASES USING 177 BACULOVIRUS EXPRESSION SYSTEM: Álvarez Y et al. PIF-BT 051: INTRAMUSCULAR AND INTRANASAL IMMUNIZATION WITH NEW ANTI-MENINGOCOCCAL NANOPARTICULATE VACCINE FORMULATIONS AS PROTEO-LIPOSOMES AND 178 COCHLEATES INDUCE AT-A- DISTANCE CELLULAR RESPONSE: Tamargo B et al. PIF-BT 052: IMMUNOPROTECTOR POTENTIAL OF CELLULAR VACCINE FORMULATIONS DEVELOPED FROM LEPTOSPIRA INTERROGANS BALLUM USING MESOCRICETUS AURATUS AS 178 BIOMODEL: Batista Santiesteban N et al. PIF-BT 053: PHARMACOLOGIC INHIBITION OF CASEIN KINASE 2 (CK2)-MEDIATED SIGNALING TO INDUCE APOPTOSIS IN ACUTE MIELOID LEUKEMIA (AML) CELLS: Cruz Y et al. 179 PIF-BT 054: DELINEATING THE FUNCTIONAL MAP OF THE INTERACTION BETWEEN NIMOTUZUMAB AND THE EPIDERMAL GROWTH FACTOR RECEPTOR ANTIBODY: Tundidor Y et al. 179 PIF-BT 055: RESULTS IN THE IMPLEMENTATION OF QUALITY MANAGEMENT SYSTEM DEVELOPMENT STAGE IN THE CIGB: Apezteguia I et al. 180 Métodos Alternativos / 3Rs Alternatives Methods (PMA) 181 PMA 001: IN VITRO CELL-BASED APPROACHES TO ASSESS THE MECHANISMS UNDERLYING ANTITUMORAL ACTIVITY OF METHOTREXATE VIA pH-SENSITIVE CHITOSAN 181 NANOPARTICLES: Nogueira DR et al. PMA 002: SIMILARITIES AND DIFFERENCES BETWEEN THE GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS AND THE MEXICAN NORM NOM-062-ZOO-1999: Streber ML et al. 181 PMA 003: E-LEARNING AS A STRATEGY TO REDUCE THE NUMBER OF ANIMALS USE IN PHARMACOLOGY: Mourelle AC et al. 182 PMA 004: ZEBRAFISH NEUROTRANSMITTER SYSTEMS AS POTENTIAL PHARMACOLOGICAL AND TOXICOLOGICAL TARGETS: Rico EP. 182 PMA 005: DEVELOPMENT OF A SEROLOGICAL TEST FOR DETERMINING BIOLOGICAL ACTIVITY OF THE WHOLE CELL COMPONENT IN DPT VACCINES FOR PRECLINICAL STUDIES: Blanco 183 A et al. PMA 006: DEVELOPMENT OF A VERO CELL METHOD FOR DETERMINING SPECIFIC TOXICITY AND REVERSION TO TOXICITY FOR DIPHTHERIA TOXOID IN VACCINES: Herrera L et al. 183 PMA 007: IGY TECHNOLOGY: USE OF EGG YOLK ANTIBODIES FOR DIAGNOSTIC, PREVENTION AND THERAPY OF DISEASES: Geoghegan P et al. 184 PMA 008: ALTERNATIVE METHODS FOR TRAINING PROSTATE PALPATION AND URETHRAL CATHETERIZATION FOR DOGS IN VETERINARY TEACHING: Capilé K et al. 184 Nanofarmacología / Nanopharmacology (PNM) 185 PNM 001: DETERMINATION OF ELASTIC PROPERTIES OF CANCEROUS CELLS BY ATOMIC FORCE MICROSCOPY: Ramos JR et al. 185 PNM 002: SYNTHESIS OF SELF-ASSEMBLED AMPHIPHILIC PEG-PLA COPOLYMERS BY UGI FOUR COMPONENT CONDENSATION AS A POTENTIAL CONTROL RELEASE SYSTEM FOR CANCER 185 TREATMENT: Peña L et al. PNM 003: DEXAMETHASONE RELEASE FROM CHITOSAN MICROSPHERES OBTAINED BY SPRAY DRYING AND COATED WITH A NOVEL PH DEPENDENT INTERPOLYMER COMPLEX: García J 186 et al. PNM 004: SYNTHESIS, CHARACTERIZATION AND IN VITRO EVALUATION OF CHITOSAN/APATITE NANOSTRUCTURED COMPOSITES AS PROMISING BONE SUBSTITUTE MATERIALS: Solís Y 186 et al. PNM 005: THE ISO TC 229/IEC TC 113, ESSENTIAL TOOL IN CONFORMITY ASSESSMENT OF RESEARCH AND PRODUCTION OF NANO-SCALE DEVICES: Valdés G et al. 187 PNM 006: IRON OXIDES NANOPARTICLES FOR MEDICAL APPLICATION: Díaz C. 187 PNM 007: CHITOSAN-ALGINATE POLYELECTROLYTE COMPLEX NANOPARTICLES AS DRUG CARRIERS FOR ORAL ADMINISTRATION: Becherán L et al. 188 PNM 008: PH-SENSITIVE MICROPARTICLES BASED ON POLYELECTROLYTE COMPLEXES FOR ANTIBIOTIC DELIVERY: Agüero L et al. 188 PNM 009: ORGANIC-INORGANIC THIN FILMS CONTAINING NANOCRYSTALLINE HYDROXY-APATITE PARTICLES: Peón Avés E et al. 189 PNM 010: STUDY OF COMPOSITION POLYMERIC INFLUENCE ON THE CONTROLLED DRUG DELIVERY CAPACITY OF A HYDROPHILIC COMPOSITE: Campos Y et al. 189 PNM 011: SYNTHESIS AND CHARACTERIZATION OF NANOMATERIALS CONTAINING NATURAL ACTIVE INGREDIENTS FOR BIOMEDICAL APPLICATIONS; Soriano J et al. 190 PNM 012: DENTAL MATERIALS’ MODIFICATION BY CARBON NANOPARTICLES: Ageev O et al. 190 PNM 013: THE SCANNING TUNNELLING MICROSCOPY IN THE CHARACTERIZATION OF MOLECULES STRUCTURES WITH APPLICATION IN PHARMACOLOGY: Herrera JA et al. 191 PNM 014: NOVEL SOLIDS DISPERSION OF CYCLOSPORIN A FOR IMMUNOSUPPRESSION THERAPY: Salomón S et al. 191 Estrés Oxidativo y Ozonoterapia / Oxidative Stress and Ozonetherapy (PEO) 192 PEO 001: OXIDATIVE STRESS IN OBESES CHILDREN: Fernández D et al. 192 PEO 002: LEVELS OF SOME ANTIOXIDANTS IN CHILDHOOD HYPERTENSION: Alfonso J et al. 192 PEO 003: OXIDATIVE STRESS INDICATORS IN PROGRESIVE RENAL DISEASE: Heredia D et al. 193 PEO 004: GLYCEMIC CONTROL AND OXIDATIVE DAMAGE IN TYPE 2 DIABETES MELLITUS: Céspedes E et al. 193 PEO 005: PHENOLIC CONTENT AND IN VITRO ANTIOXIDANT ACTIVITY OF Pleurotus SP EXTRACTS: Beltrán Y et al. 194
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PEO 006: EVALUATION IN HIV-INFECTED PATIENTS OF ANTIRETROVIRAL CONCENTRATION, REDOX INDEXES AND PROGRESSION MARKERS ON BLOOD SAMPLES: Gravier R et al. 194 PEO 007: ANTIOXIDANT ACTIVITY OF THE EXTRACTS OF THE LEAVES OF Terminalia muelleri: González Pérez M et al. 195 PEO 008: ANTIOXIDANT ACTIVITY OF FLAVONOID – RICH FRACTION FROM Dichrostachys cinerea (MIMOSACEAE) LEAVES: Ribalta V et al. 195 PEO 009: URIC ACID AND LIPID PEROXIDATION IN HYPERTENSIVE PATIENTS WITH CARDIOVASCULAR DISEASE: Peña M et al. 196 PEO 010: EXPERIMENTAL EVALUATION OF 5-AMYNOSALICYLIC ACID AS A FREE RADICAL SCAVENGER AND MYELOPEROXIDASE INHIBITOR, IN A TYPE 2 DIABETES MELLITUS MODEL: 196 Alemán González Duhart D et al. PEO 011: ANXIOLYTIC EFFECT AND ANTIOXIDANT POTENTIAL OF A SEMI-SYNTHETIC DERIVATIVE OF LIMONENE: Cardoso de Almeida AA et al. 197 PEO 012: VIRTUAL SCREENING TO PREDICT THE CLASTOGENIC ACTIVITY OF PHENOLIC ACIDS: Guardado E et al. 197 PEO 013: RECOVERY FROM IRON DEFICIENCY ANEMIA WITH DIFFERENT IRON SOURCE: EFFECTS ON LIPID PEROXIDATION AND ANTIOXIDANT ENZYMATIC DEFENSE: García Y et al. 198 PEO 014: DETERMINATION OF DPPH FREE RADICAL SCAVENGING ACTIVITY OF VIMANG CONSTITUENTS: Nuevas Paz L et al. 198 PEO 015: Phalaris canariensis EFFECT IN THE PREVENTION AND CONTROL OF METABOLIC SYNDROME INDUCED FOR HYPOCALORIC DIET. MODULATION OXIDATIVE STRESS IN RAT: 199 Alvarado Acosta JL et al. Farmacología de Productos Naturales / Pharmacology of Natural Products (PPN) 200 PPN 001: Cardiospermum corindum (SAPINDACEAE) INHIBITS HYPERACTIVITY GASTROINTESTINAL ON RATS IN VIVO AND IN VITRO: Silva VA et al. 200 PPN 002: Bidens pilosa L. (ASTERACEAE) INHIBITS HYPERACTIVITY GASTROINTESTINAL ON RATS IN VIVO AND IN VITRO: Costa LA et al. 200 PPN 003: INHIBITORY EFFECT FROM HYDROMETHANOLIC EXTRACT OF Struthanthus venetus (BLUME) LEAVES,ON THE PROLIFERATION OF HUMAN BREAST CANCER CELLS (MCF-7) IN 201 CULTURE: Lorenzana- Jiménez M et al. PPN 004: HYDROMETHANOLIC EXTRACT OF Struthanthus venetus (BLUME) LEAVES ATTENUATES THE METABOLIC SYNDROME INDUCED BY HIGH FRUCTOSE DIET IN WISTAR RATS: 201 Lorenzana-Jiménez M et al. PPN 005: ANTIHYPERTENSIVE AND VASORELAXANT EFFECTS OF A METHANOLIC EXTRACT FROM Chiranthodendron pentadactylon (LARREAT) IN RATS: Magos Guerrero GA et al. 202 PPN 006: USE OF TRADITIONAL MEDICINE AS AN ALTERNATIVE METHOD FOR THE TREATMENT OF DIABETES MELLITUS IN PATIENTS IN THE COMMUNITY OF YAXCABÁ, YUCATÁN, 202 MEXICO: Cen J et al. PPN 007: DRUG INTERACTIONS OF HERBAL MEDICINES USED IN URUGUAY: Moreale J et al. 203 PPN 008: THE ROLE OF Bidens pilosa L. AND Physalis angulata L. IN OBESE MICE: Ribeiro JR et al. 203 PPN 009: CYTOTOXIC ACTIVITY OF AN AVOCADO SEEDS EXTRACT (Persea americana Mill.) IN A PANEL OF CANCER CELL LINES: Martínez M et al. 204 PPN 010: Valeriana officinalis ATTENUATES THE ROTENONE-INDUCED TOXICITY IN Drosophila melanogaster: Vargas N et al. 204 PPN 011: PRELIMINARY EVALUATIONOF Brassica campestris AND Coffea arabica EFFECTS IN OBESITY: Del Ben A et al. 205 PPN 012: CONTRIBUTIONS TO THE QUALITY OF MEDICINAL PLANTS NEGOTIATED IN THE STATE OF RIO DE JANEIRO, BRAZIL: Marques CA et al. 205 PPN 013: HYPOGLYCEMIC EFFECT OF SWEET LIME (Citrus limetta) PEEL: Padilla E et al. 206 PPN 014: ANTI-Helicobacter pylori, ANTI-INFLAMMATORY, AND TOXICOLOGICAL EVALUATION OF ROOT EXTRACTS FROM Hippocratea celastroides: García G et al. 206 PPN 015: ACUTE TOXICITY AND HYPOCHOLESTEROLAEMIC EFFECT OF A HYDROALCOHOLIC EXTRACT OF Eryngium heterophyllum IN C57BL/6 MICE: Castro-Torres IG et al. 207 PPN 016: ANTIDIABETIC ACTIVITY OF Annona cherimola MILL. (ANNONACEAE) ON TYPE 2 DIABETIC RATS: Solares JI et al. 207 PPN 017: ANTI-INFLAMMATORY ACTIVITY IN MICE BY ETHANOLIC EXTRACT OBTAINED BY GRAPE SEED OIL: Flores L et al. 208 PPN 018: CONSUMPTION STUDY ON RED QUINOA AREQUIPA PROVINCE, AREQUIPA, PERU-2013: Reyes Schultz R et al. 208 PPN 019: THE THERAPEUTIC POTENTIAL AND TOXICOLOGICAL PROFILE OF Pimenta dioica (pimento): Campbell-Shelly J. 209 PPN 020: MECHANISMS OF ACTION INVOLVED IN THE GASTROPROTECTIVE EFFECT OF THE ESSENTIAL OIL OF Hyptis martiusii BENTH. (LAMIACEAE): Almir GW et al. 209 PPN 021: EFFECTIVENESS OF A CREAM MADE OF PLANTAIN, NETTLE, AND FLAXSEED COMPARED WITH THE CREAM CALMARTRIT IN ELDERLY (DISTRICT OF SELVA ALEGRE - 210 AREQUIPA): Burgos Macedo C et al. PPN 022: CARNOSOL QUANTIFYING IN ROSEMARY (Rosmarinus officinalis L.) EXPLANTS CULTIVATED UNDER A TEMPORARY IMMERSION SYSTEM (TIS): Villegas E et al. 210 PPN 023: TOXICOLOGICAL ANALYSIS OF ROSEMARY BIOACTIVES WITH POTENTIAL USE IN CLINICAL APPLICATIONS AGAINST BACTERIA-RESISTANT IN RABBITS: Ojeda-Sana AM et al. 211 PPN 024: GASTRIC HEALING PROPERTIES OF PROTEOLYTIC FRACTIONS FROM Vasconcellea cundinamarcensis LATEX: Araujo e Silva A et al. 211 PPN 025: PHARMACOVIGILANCE STUDY OF UNREGISTERED PRODUCTS COMMERCIALIZED IN COSTA RICA, THE CASE OF MANZINOP™ CONTAINING CHAMOMILE (Matricaria chamomille) 212 AND TETRAHYDROZOLINE: Castillo M et al. PPN 026: Lopezia racemosa Lag, MEXICAN MEDICINAL PLANT WITH ANTINOCICEPTIVE ACTIVITY: Velázquez-González C et al. 212 PPN 027: SYNTHESIS OF MASTICADIENONIC ACID DERIVATIVES: Marrero JG et al. 213 PPN 028: INHIBITION OF NARINGENIN ON CYP1A1 ACTIVITY: Santes-Palacios R et al. 213 PPN 029: ANTIDIABETIC EFFECT OF AQUEOUS EXTRACT AND FRACTIONS FROM Allophylus cominia (L) SW LEAVES: Sánchez J et al. 214 PPN 030: COMBIFER: NEW FORMULATION WITH HEM AND NO HEM IRON FOR ANAEMIA PREVENTION IN PREGNANT WOMEN. COMPARISON OF THE BIOAVAILABILITY OF FERROUS 214 SELTS: González Hernández R et al. PPN 031: SUPPLEMENTAL SAFETY PHARMACOLOGICAL STUDIES OF BM-21, AN AQUEUS-ETHANOLIC EXTRACT FROM THE SEA GRASS Talassia testudinum: Morales RA et al. 215 PPN 032: HYPOLIPIDEMIC EFFECTS OF CHITOSAN AND CHITOSAN ACIDS SALTS ON TWO MODELS OF INDUCED HYPERLIPIDEMIA IN MICE: Bellma Menendez A et al. 215 PPN 033: BIOCHEMICAL CHARACTERIZATION AND IN VITRO CYTOTOXIC EFFECT OF A POLYPEPTIDE AND PROTEIN MIS DERIVED FROM THE Rophalurus junceus: Rodríguez A et al. 216 PPN 034: ANTIOXIDANT ACTIVITY OF THE EXTRACTS OF THE LEAVES OF Spondias mombin L. (JOBO): Perez-Portero Y et al. 216 PPN 035: CHEMICAL COMPOSITION, ANTIOXIDANT PROPERTIES OF THE ESSENTIAL OIL OF Piper angustifolium LEAVES: Monteagudo Romero U et al. 217 PPN 036: ANTIOXIDANT ACTIVITY OF THE EXTRACTS OF Capraria biflora L.: Cadenas-Perez X et al. 217 PPN 037: ANTIOXIDANT, ANALGESIC AND TOXICOLOGICAL EVALUATION OF AN HYDROALCOHOLIC EXTRACT OBTAINED FROM Piper ossanum Trel (PIPERACEA): Gutiérrez Gaitén Y et al. 218 PPN 038: PHYTOCHEMICAL AND PHARMACO-TOXICOLOGICAL STUDIES OF AN EXTRACT FROM Syringodium filiforme A MARINE PLANT WITH PROMISSORY RESULTS TO BE USED AS A 218 NATURAL DRUG: Fernández Pérez MD et al. PPN 039: IMMUNOSTIMULATING EFFECTS AND PHARMACOLOGICAL POTENTIAL OF THE EDIBLE MUSHROOM Pleurotus SP.: Aguirre R et al. 219 PPN 040: ANTI-INFLAMMATORY EFFECTS OF Zuelania guidonia SP.: Puente E et al. 219 PPN 041: PROTEOLYTIC ACTIVITY EVALUATION ON Morinda citrifolia L. FRUITS: Álvarez Jiménez E et al. 220 PPN 042: THEORETICAL MODELING OF THE CHEMICAL INTERACTION BETWEEN THE 2,4-DITERBUTILPHENOL AND PROMUTAGENIC AROMATIC AMINES: METAPHENYL-ENEDIAMINE, 220 4-AMINOBIPHENYL AND 2-AMINO-1-METHYL-6-PHENYLIMIDAZO [4,5 B] PYRIDINE AS DNA PROTECTIONS MECHANISM: Marrero-Gutiérrez J et al.
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PPN 043: ACUTE INFLAMMATORY EVALUATION OF VEGETABLE OIL Cucurbita moschata DUCH: Sueiro-Oyarzun ML et al. 221 PPN 044: DETERMINATION OF DIURETIC POTENTIAL OF Commelina elegans HBK AND Bryophylum pinnatum LAM: Valdovinos N et al. 221 PPN 045: TOPICAL ANTI-INFLAMMATORY ACTIVITY OF FIVE FRACTIONS OF FRESH AERIAL PARTS OF Phania matricarioides (CHAMOMILE LAND): García AI et al. 222 PPN 046: PRECLINICAL VALIDATION OF THE TRADITIONAL USE OF Cordia martinicesis: Martínez I et al. 222 PPN 047: EVALUATION OF ANTI-INFLAMMATORY AND ANALGESIC PROPERTIES OF AN ORGANIC EXTRACT OF RED SEAWEED Galaxaura rugosa: Duménigo A et al. 223 PPN 048: PRECLINICAL VALIDATION OF ANTI-INFLAMMATORY EFFECT OF Hibiscus rosa sinensis (Marpacífico): Brito G et al. 223 PPN 049: ANTIPYRETIC ACTIVITY OF A WATERY EXTRACT OF Cecropia peltata L. IN RATS OF THE WISTAR SPECIES EXPERIMENTAL MODEL: Hernández Río M et al. 224 PPN 050: EVALUATION OF THE HYPOGLYCEMIC ACTIVITY OF EXTRACTS FROM Boldoa purpurascens CAV.: González D et al. 224 PPN 051: ANTIVIRAL ACTIVITY EVALUATION OF Laurencia obtusa AGAINST HERPES SIMPLEX VIRUS AND DENGUE VIRUS: Rojas L et al. 225 PPN 052: CLINICAL TRIAL PHASE IV WITH SURFACEN IN NEONATE POPULATION: Barrese Y et al. 225 PPN 053: THE IMPACT OF PHARMACEUTICAL SCIENCE LOOKING THROUGH TECHNOLOGY: WEB PAGE OF EXPERIMENTAL STATION OF MEDICINAL PLANTS "DR. JUAN TOMAS ROIG": 226 Elizagaray-Fernández B et al. PPN 054: TOPICAL TREATMENT FOR MYCOTIC VAGINITIS WITH GARLIC EXTRACT: Izquierdo M et al. 226 PPN 055: BACH FLORAL THERAPY IN TYPE 2 DIABETIC PATIENTS AND ITS EFFECT ON T LYMPHOCYTE FUNCTION: Mahía M et al. 227 PPN 056: EFFECTIVENESS OF OZONIZED SUNFLOWER OIL (ORAL OLEOZON®) COMBINED WITH GIARDINUM IN THE TREATMENT OF GIARDIASIS: Marcel Llovet A et al. 227 PPN 057: EFFECT OF A NATURAL SOLUTION OF THE Rhopalurus junceus SCORPION VENOM IN PATIENTS WITH BRAINSTEM GLIOMA. CASE´S REPORT: Cruz N et al. 228 PPN 058: USE OF VIDATOX® 30CH IN INFLAMMATORY, ONCOLOGICAL AND AUTOIMMUNES DISEASES: Casamayor Z et al. 228 PPN 059: ETNOMEDICAL USE OF A NATURAL SOLUTION OF Rhopalurus junceus SCORPION VENOM IN COLORECTAL CANCER PATIENTS: Morales C et al. 229 PPN 060: EFFICACY OF BACH´S FLORAL THERAPY IN THE TREATMENT OF ACADEMIC STRESS: Maceo O et al. 229 PPN 061: AURICULAR MICROSYSTEM THERAPY AND FLORAL THERAPY COMBINATION IN THE TREATMENT OF ESSENCIAL HYPERTENSION. BAYAMO 2011- 2012: Ramos K et al. 230 PPN 062: BACH FLOWER THERAPY IN THE TREATMENT OF FEMALE CLIMACTERIC SYNDROME: López Suárez JC et al. 230 PPN 063: Cymbopogon citratus FRACTIONS, PROTECTIVE ACTIVITY AGAINST UVC LIGHT IN Caulobacter crecentus: Fuentes-León F et al. 231 PPN 064: PROGRESS OF ELDERLY WITH ANEAMIA DUE TO NUTRITIONAL DEFICIT TREATED WITH APIASMIN: Morfi R et al. 231 PPN 065: PHYTOCHEMISTRY DETERMINATION OF TWO SPECIES OF ALGAE GROWN UP IN CUBAN COAST: Cabrera H et al. 232 PPN 066: BIOACTIVE COMPOUNDS AND PHARMACOLOGICAL PROPERTIES OF A HYDROSOLUBLE CRUDE EXTRACT OF Pleurotus SPP. MYCELIUM: Morris H et al. 232 PPN 067: ASSESSMENT OF ANTI-INFLAMMATORY ACTIVITY OF Agave brittoniana POLAR FRACTION IN ULCERATIVE COLITIS EXPERIMENTAL MODEL: González Y et al. 233 PPN 068: USE OF VIDATOX® 30CH IN PATIENTS WITH ADVANCED TUMORS: González S et al. 233 PPN 069: DIURETIC EFFECT OF THE PEPEROMIA PELLUCIDA IN RATS WISTAR: Dranguet Y et al. 234
PPN 070: HEPATOPROTECTIVE EFFECTS OF AN AQUEOUS ETHANOLIC EXTRACT FROM Thalassia testudinum IN THE DAMAGE CCL4-INDUCED IN RATS: Rodeiro I et al. 234 PPN 071: Tilia americana VAR. MEXICANA: A SPECIES WITH HIGH ANTIOXIDANT POTENTIAL: Coballase-Urrutia E et al. 235 PPN 072: ETHNOPHARMACOLOGY OF Moringa oleifera Lam: DEVELOPMENT OF A NEW TABLET FORMULATION: Lemus Z et al. 235 PPN 073: HARVEST, POSTHARVEST AND LAB QUALITY CONTROL MONITORING SYSTEM FOR AROMATIC ESSENTIAL OILS: Abuín A et al. 236 PPN 074: MAIN ITEMS IN THE PRODUCTION OF NATURAL MEDICINES IN PINAR DEL RIO, 1990-2009: Callava C et al. 236 PPN 075: ACUTE TOXICOLOGICAL EVALUATION OF TWO EXTRACTS OBTAINED FROM LEAVES OF GUANÁBANA (Annona muricata L.) IN MICE: Isidrón M et al. 237 PPN 076: ANALGESIC ACTIVITY OF A WATERY EXTRACT OF Matricaria recutita L. USING TWO ALGESIC MODEL IN SPRAGUE DAWLEY RATS: Valido Díaz A et al. 237 PPN 077: ANTI-DIABETIC, ANTIOXIDANT AND ANTI-INFLAMMATORY EFFECTS OF A Momordica charantia L. PLANT EXTRACT: Menéndez R et al. 238 PPN 078: SYNTHESIS OF TRITERPENOID URSOLIC ACID DERIVATIVES: Alonso MM et al. 238 PPN 079: SAFETY ASSESSMENT OF A MEDICINAL EXTRACT FROM Caesalpinia paraguariensis BARK IN A SUB-CHRONIC ORAL TOXICITY STUDY IN RODENTS: Sgariglia M et al. 239 PPN 080: Vernonanthura patens’ LEAVES AND STEMS’ CHEMICAL - BIOLOGICAL CHARACTE-RIZATION OF OBTAINED ETHANOL EXTRACTS. PRELIMINARY STUDIES: Manzano Santana P et 239 al. PPN 081: CLINICAL TRIAL PHASE III WITH SURFACEN IN PEDIATRIC POPULATION: Barrese Y et al. 240 Neuroinmunomodulación / Neuroimmunomodulation (PNF) 241 PNF 001: NEUROPROTECTIVE EFFECT OF JM-20 ON EXPERIMENTAL STROKE MODELS INVOLVES MITOCHONDRIAL STABILIZATION AND REDUCTION OF EXTRACELLULAR EAA LEVELS: 241 Ramírez-Sánchez J et al. PNF 002: EFFECTS OF JM-20 ON RATS BRAIN MITOCHONDRIA AND SYNAPTOSOMES. UNCOVERING ITS NEUROPROTECTIVE MECHANISM (PART I): Núñez Y et al. 241 PNF 003: THE EFFECTS OF JM-20 ON [3H] GLUTAMATE UPTAKE BY SYNAPTIC VESICLES, SYNAPTOSOMES, AND ASTROCYTES FROM RAT BRAIN. UNCOVERING ITS CELLULAR 242 MECHANISMS OF NEUROPROTECTION (PART II): Núñez Y et al. PNF 004: SCREENING OF A NOVEL SERIES OF SYNTHETIC ANTI-GLUTAMATERGIC STEROIDS AS CYTOPROTECTIVE AND MODULATORS OF IN VITRO INFLAMMATORY RESPONSES: García- 242 Pupo L et al. PNF 005: PHYCOCYANOBILIN INDUCES A PROTECTIVE GENE EXPRESSION PROFILE AND RESTORES THE REDOX BALANCE IN A MODEL OF ACUTE CEREBRAL HYPOPERFUSION IN 243 WISTAR RATS: Marín-Prida J et al. PNF 006: C-PHYCOCYANIN AND INTERFERON BETA: MOLECULAR MECHANISMS ASSOCIATED TO A NEW COMBINED THERAPY FOR MULTIPLE SCLEROSIS IN THE EXPERIMENTAL 243 AUTOIMMUNE ENCEPHALOMYELITIS MODEL: Nazabal-Gálvez M et al. PNF 007: MULTIPLE SCLEROSIS PATIENT’S TREG CELLS MARKERS ARE UP-REGULATED IN-VITRO AFTER IFN-γ AND C-PHYCOCYANIN STIMULATION: Cervantes-Llanos M et al. 244 PNF 008: EGF AND GHRP6 CO-ADMINISTRATION FOR CEREBRAL ISCHEMIA: DOSE RESPONSE AND THERAPEUTIC TIME WINDOW STUDIES: Subirós-Martínez N et al. 244 PNF 009: THERAPEUTIC EFFECT OF ZINC AND NEURO EPO IN TRANSGENIC MICE WITH ATAXIA TYPE 2: González Triana C et al. 245 PNF 010: PROLONGED ORAL ADMINISTRATION OF BM-21, AN AQUEOUS-ETHANOLIC EXTRACT OF THE MARINE PLANT Thalassia testudinum, ENHANCES REFERENCE SPATIAL MEMORY 245 PERFORMANCES IN MICE: García T et al. PNF 011: NEUROPROTECTION IN A MODEL OF QUINOLINIC ACID TRANSPLANTED WITH BONE MARROW CELLS: Serrano-Sánchez T et al. 246 PNF 012: BRAIN INSULIN RESISTANCE AND COGNITIVE FUNCTION IN AGING RATS: NEUROMODULATORY AND NEUROTROPHIC EFFECTS OF INSULIN ADMINISTRATION: Haas CB et al. 246 PNF 013: NEUROPROTECTIVE EFFECT OF BERBERINE ON BRAIN ISCHEMIA IN VITRO MODEL: INVOLVMENT OF SURVIVAL AND APOPTOSIS PATHWAY: Simões Pires E et al. 247 PNF 014: A LOW DOSE OF DIAZEPAM REDUCES ANXIETY-LIKE BEHAVIOR IN WEANLING RATS IN THE ELEVATED PLUS-MAZE TEST: Guillén-Ruiz G et al. 247
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PNF 015: GUANOSINE IMPROVES FUNCTIONAL RECOVERY AND DECREASES BRAIN OXIDATIVE STRESS AFTER SENSORIMOTOR CORTICAL ISCHEMIA IN RATS: Hansel G et al. 248 PNF 016: CHARACTERIZATION OF L TYPE CA2+ CHANNELS IN SPONTANEOUS DIFFERENTIATED OLFACTORY NEURONS IN CULTURE, OBTAINED FROM BIPOLAR DISEASE AND 248 SCHIZOPHRENIA PATIENTS: Solís-Chagoyán H et al.
PNF 017: ACTION OF FATTY ACIDS ON GABAA RECEPTORS: IMPLICATIONS FOR THEIR ANXIOLYTIC-LIKE EFFECTS IN WISTAR RATS: Rodríguez-Landa JF et al. 249
PNF 018: METHYLPHENIDATE AMPLIFIES LONG-TERM POTENTIATION IN THE HIPPOCAMPUS THROUGH β-ADRENERGIC AND D1/D5 RECEPTORS: Carreño M et al. 249 PNF 019: HEPTANOIC ACID INCREASES ACTIVE BEHAVIOR IN THE FORCED SWIM TEST IN WISTAR MALE RATS: Saldivar-Lara M et al. 250 PNF 020: COMPARISON BETWEEN TRICAINE AND BENZOCAINE IN THE BEHAVIORAL PROFILE OF EPILEPTIC SEIZURE CAUSED BY ADMINISTRATION OF KAINIC ACID IN ZEBRAFISH 250 ADULT: Rico EP et al. PNF 021: CYTOCHROME P450 2J3 AND 2C11 REGULATION IN A LPS-INDUCED MODEL OF NEUROINFLAMMATION IN ASTROCYTES: Navarro-Mabarak C et al. 251 PNF 022: IN VITRO MODEL OF MILD HYPERHOMOCYSTEINEMIA CAUSES MODULATION IN REDOX STATE IN CEREBRAL CORTEX AND HEART: Longoni A et al. 251 Ensayos Clínicos / Clinical Trials (PEC) 252 PEC 001: CONTROLLED CLINICAL TRIALS: AN ACTIVITY IN INCREASE IN VILLA CLARA: Rodríguez M et al. 252 PEC 002: SAFETY OF ANTI-IDIOTYPIC 1E10/ALUMIN VACCINE. RESULTS OF 6 FASE II CLINICAL TRIALS: García E et al. 252 PEC 003: RESULTS OF CLINICAL TRIALS WITH RECOMBINANT HUMAN ERYTHROPOIETIN IN CUBA: Vargas A et al. 253 PEC 004: EVALUATION OF THE ACCEPTABILITY OF METERED DOSE INHALATOR SALBUTAMOL HFA, 100 MICROGRAMS IN THE TREATMENT OF PRESISTENT BRONCHIAL ASTHMA: 253 Bermudez Y et al. PEC 005: EFFICACY AND SECURITY OF CRANIOPUNCTURE VERSUS BACLOFEN IN PATIENTS WITH SPASTICITY: Saumell Y et al. 254 PEC 006: EXPERIENCES IN THE CONDUCTION OF A CLINICAL TRIAL IN PRIMARY ATTENTION IN VILLA CLARA, CUBA: Lorenzo G et al. 254 PEC 007: PERFORMANCE EVALUATION OF GOOD CLINICS PRACTICE AT THE CLINIC PREVISORA OF CAMAGUEY: Infante E et al. 255 PEC 008: INTEGRATION OF MONITORING BASED ON RISK IN THE MANAGEMENT OF BIOLOGICAL SAMPLES IN LABORATORY: Bueno E. 256 PEC 009: AUDITS OF GOOD CLINICAL PRACTICE: TOOL TO IMPROVE THE QUALITY OF A CLINICAL TRIAL: Alvarez S et al. 257 PEC 010: CLINICAL TRIALS: FEASIBILITY´S EVALUATION: Rodriguez J. 257 PEC 011: PLANNING QUALITY IMPROVEMENT REPORT ADVERSE EVENTS IN CLINICAL TRIAL: Martín Y et al. 258 PEC 012: THERAPEUTIC EQUIVALENCE BETWEEN IOR LEUKOCIM, HEBERVITAL AND NEUPOGEN AS TREATMENT OF SEVERE NEUTROPENIA AFTER CHEMOTHERAPY IN PATIENTS 258 WITH ACUTE LEUKEMIA: Mendoza I et al. PEC 013: TEACHING PROPOSAL FOR RESEARCHERS IN CANCER CLINICAL TRIALS: Valls AR et al. 259 PEC 014: QUALITY OF LIFE IN PATIENTS WITH NON-SMALL CELL LUNG CARCINOMA TREATED WITH EGF VACCINE: Saborido L et al. 259 PEC 015: CHARACTERIZATION OF DETECTION AND REPORTING OF ADVERSE EVENTS IN CLINICAL TRIALS: Garcés O et al. 260 PEC 016: USE OF IMMUNOTHERAPEUTIC PRODUCTS TREATMENT OF PATIENTS WITH CANCER IN CLINICAL TRIALS PERFORMED IN SANTIAGO OF CUBA: Griñan D et al. 260 PEC 017: APPROACH TO THE EPIDEMIC SITUATION OF THE WHOOPING COUGH IN CUBA DURING THE 2010 – 2011: Muñoz Y et al. 261 PEC 018: EVALUATION OF NO-INFERIORITY WITH CORRELATED TIME-TO-EVENT OUTCOME. A RANDOMIZED TRIAL OF TREATMENTS IN LEUKEMIA PATIENTS: Robaina-García M et al. 261 PEC 019: BIOTECHNOLOGICAL PRODUCTS FOR THE TREATMENT OF ADVANCED NON-SMALL-CELL LUNG TUMORS IN THE PROVINCE OF LAS TUNAS: Montes de Oca N et al. 262 PEC 020: BEHAVIOR OF HEMATOLOGICAL VARIABLES WITH USE OF FERRICAL IN FEMALE BASKETBALL SPORTSMEN: Espronceda M et al. 262 PEC 021: IMPLANTATION AND EVALUATION OF A LOGISTICAL SYSTEM FOR THE INVESTIGATIONAL PRODUCT IN CLINICAL TRIAL: Martínez L et al. 263 PEC 022: SIDE EFFECTS ASSOCIATED TO THE EGF VACCINE IN PATIENTS WITH NON-SMALL CELLS LUNG CANCER: Peacok Aldana S et al. 263 PEC 023: QUALITY LIFE OF PATIENTS WITH CANCER INCLUDED IN CLINICAL OF TRIALS: Viada C et al. 264 PEC 024: RECURRENT SQUAMOUS CARCINOMA OF CONJUNCTIVE IN PATIENTS WITH AIDS AND NEW MODALITY OF THERAPEUTIC CONTROL. PRELIMINAR RESULTS: Carnesoltas Lázaro 264 D et al. PEC 025: CIMvaxEGF VACCINES IN PATIENTS WITH NON–SMALL CELL LUNG CANCER TREATED IN THE PRIMARY HEALTH CARE IN CIENFUEGOS: Fernández D et al. 265 PEC 026: CLINICAL TRIALS REGISTRY, WHO ARE RESPONSIBLE FOR COMPLIANCE?: Jiménez G. 265 PEC 027: A BAYESIAN APPROACH TO OVERCOME SMALL SAMPLE SIZE IN AN EXPLORATORY CLINICAL TRIAL: Uranga R et al. 266 PEC 028: CLINICAL EVOLUTION OF PATIENTS WITH DIABETIC FOOT ULCER TREATED WITH HEBERPROT-P®: Álvarez Crespo A et al. 266 PEC 029: SAFETY AND EFFICACY OF GRANULOCYTE COLONY-STIMULATING FACTOR (IOR®-LEUKOCIM) IN ONCOHEMATOLOGY PATIENTS. PHASE IV: Cachimaille Y et al. 267 PEC 030: CLINICAL EVALUATION DEVELOPMENT STRATEGY OF RECOMBINANT STREPTOKINASE IN CUBA: Marrero Miragaya MA et al. 267 PEC 031: THE ETHITCS IN THE DESIGN, THE CONDUCTION AND THE MONITORING OF CLINICAL TRIALS IN THE CUBAN UNITS OF INTENSIVE CARES: Avila Y et al. 268 PEC 032: VQV CLINICAL EVALUATION SCHEME WITH EGF IN THE TREATMENT OF PATIENTS WITH PROSTATE CANCER: Ills D et al. 268 PEC 033: THERAPEUTIC DRUG MONITORING IN CUBAN PATIENTS WITH ANTI-RETROVIRAL THERAPY: Tarinas A et al. 269 PEC 034: ANALYSIS OF HEMATOLOGY AND BLOOD CHEMISTRY’S ADVERSE EVENTS DOCUMENTED IN SPONSOR’S DATABASES: Wilkinson B et al. 269 PEC 035: TREATMENT PEGYLATED INTERFERON (PEG-IFN) AND RIBAVIRIN FOR THE TF CHRONIC HEPATITIS C (CHC). A CASE REPORT: Hernandez E et al. 270 PEC 036: SAFETY OF NIMOTUZUMAB IN THE TREATMENT OF HEAD AND NECK TUMORS IN ADVANCED STAGES FROM OCTOBER, 2012 THROUGH APRIL, 2013: Del Toro Rúa M. 270 PEC 037: SAFETY, EFFICACY AND PHARMACOKINETIC EVALUATION OF INTRAVENOUS CIGB-300 IN PATIENTS WITH SOLID TUMORS, REFRACTORY TO ONCOSPECIFIC TREATMENTS: 271 González L. PEC 038: CLINICAL STUDY RESULTS FROM A RANDOMIZED CONTROLLED TRIAL OF THERAPEUTIC CLINICAL EVALUATION OF THE Plectranthus amboinicus LOUR SPRENG (FRENCH 271 OREGANO) TABLETS IN PATIENT WITH COMMON COLD: Jimenez D et al. PEC 039: NIMOTUZUMAB, IN THE TREATMENT OF TUMORS OF EPITHELIAL ORIGIN: NEW KNOWLEDGE: Ramos Suzarte M. 272 PEC 040: MANAGEMENT SYSTEM FOR BIOLOGICAL SAMPLES OF PATIENTS INCLUDED IN MULTICENTER CLINICAL TRIALS: Troche M et al. 272 PEC 041: THE THERAPEUTIC PSYCHOPHARMACOLOGY OF THE DEPRESSION: CHALLENGES AND CONFLICTS: Zarragoitia Alonso I. 273 PEC 042: CLINICAL TRIAL RESULTS OF THE RECOMBINANT STREPTOKINASE IN THE HEMORRHOIDAL DISEASE IN CUBA: Pelaez Y et al. 273 Farmacoepidemiología / Pharmacoepidemiology (PFep) 274 PFep 001: EVALUATION OF DRUGS AUTHORIZED OUTSIDE VADEMECUM IN A FIRST LEVEL CARE PUBLIC HEALTH PROVIDER OF URUGUAY: Santurio A et al. 274 PFep 002: LOW FREQUENCY OF PROPHYLAXIS PRESCRIPTION FOR OSTEOPOROSIS IN PATIENTS RECEIVING CHRONIC TREATMENT WITH CORTICOSTEROIDS IN COLOMBIA: Machado- 274 Alba J et al.
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PFep 003: UTILIZATION OF ERGOTAMINE ¿DO PHYSICIANS KNOW IN COLOMBIA AS PRESCRIBE?: Morales-Plaza C et al. 275 PFep 004: ANTIPSYCHOTIC PRESCRIPTION PATTERNS IN PATIENTS AFFILIATED TO THE SOCIAL SEGURITY SYSTEM IN HEALTH OF COLOMBIA: Morales-Plaza C et al. 275 PFep 005: THE ESTABLISHMENT OF A STRATEGY FOR THE RATIONAL USE OF INJECTABLE OMEPRAZOLE: Moreira Da Costa J et al. 276 PFep 006: PHARMACEUTICAL ORIENTATION AT THE TIME OF HOSPITAL DISCHARGE: STRENGTHENING ADHERENCE AND PROVIDING CONTINUITY OF CARE: Pedroso L et al. 276 PFep 007: PRELIMINARY RESULTS BENZODIAZEPINES PRESCRIPTION: Martínez E et al. 277 PFep 008: DRUG PRESCRIBING IN INTERNAL MEDICINE AT A UNIVERSITY HOSPITAL: Mendez G et al. 277 PFep 009: PRELIMINARY RESULTS OF AN ANALGESIC UTILIZATION STUDY IN A HOSPITAL IN HIDALGO, MEXICO: Reynoso-Vázquez J et al. 278 PFep 010: COMPARISON OF NON-PHARMACOLOGICAL TREATMENT GUIDELINES OF ADULT HIV/AIDS PATIENTS IN GUYANA AND JAMAICA TO THAT OF BRITISH GUIDELINES: Moncreiffe 278 S et al. PFep 011: PHARMACOEPIDEMIOLOGY OF PSYCHOACTIVE MEDICATION IN ADULT PATIENTS IN THE PSYCHIATRIC DEPARTMENT OF DURANGO, MEXICO GENERAL HOSPITAL: Cano- 279 Torres E et al. PFep 014: WORKING SYSTEM AND EVALUATION OF PHARMACOTHERAPEUTIC COMMITTEES. CUBA 2012: Calvo D et al. 279 PFep 015: PRESCRIBING BEHAVIOR OF NPH INSULIN IN PATIENTS WITH DIABETES MELLITUS. CUBA 2012: Broche Villarreal L et al. 280 PFep 016: ANTIMICROBIALS PRESCRIPTION IN ADMITTED PATIENTS WITH BACTERIAL PNEUMONIA: Legón Pérez T. 280 PFep 017: DETECTION OF POTENTIAL DRUG-DRUG AND DRUG-DISEASE INTERACTIONS ON PRESCRIBED MEDICATIONS FOR ELDERLY PATIENTS IN A COMMUNITY: Peña C et al. 281 PFep 018: CONSUMER PHARMACEUTICAL MARKET SEGMENTATION OF DRUGS IN CUBA: García Milián AJ et al. 281 PFep 019: DRUG CONSUMPTION IN SELECTED CITIES OF CUBA: García Milian AJ et al. 282 PFep 020: PHARMACO-EPIDEMIOLOGICAL STRATEGIES FOR THE IMPROVEMENT OF THE CONTINOUS MEDICAL PRESCRIPTION, GENERAL HOSPITAL “JUAN BRUNO ZAYAS ALFONSO”: 282 Acosta E et al. PFep 021: DRUG USE IN THE HOSPITAL PHARMACY SERVICES AND EVALUATION THROUGH QUALITY INDICATORS: Cuba MM. 283 PFep 022: CHARACTERIZATION OF THE ANTMICROBIANS COMSUMPTION IN TWO CONSECUTIVE YEARS IN THE HOSPITAL MANUEL FAJARDO: Peña A et al. 283 PFep 023: BIBLIOMETRIC CHARACTERIZATION OF SCIENTIFIC PUBLICATIONS STUDY DRUG USE: García Milian AJ et al. 284 PFep 024: ANTIHYPERTENSIVE DRUG UTILIZATION STUDY IN PRIMARY HEALTH CARE: Arias Gallardo AI et al. 284 PFep 025: ANTIMICROBIAL DRUG UTILIZATION STUDIES IN PATIENTS WITH PNEUMONIA IN THE INTERNAL MEDICINE SERVICE: Arias Gallardo A et al. 285 PFep 026: RECURRENT APHTHOUS STOMATITIS. HOMEOPATHIC TREATMENT PATIENTS AT GASTROENTEROLOGY INSTITUTE: Quintero M. 285 PFep 027: ANTIBIOTICS CONSUMPTION IN THE ARTEMISA PROVINCE HOSPITALS, 2012: Cabrera Cepero JR et al. 286 PFep 028: ANTIMICROBIAL RESISTANCE AGAINST Shigella SPP. IN THE PROVINCE OF CAMAGUEY: Ferrándiz D et al. 286 PFep 029: KNOWLEDGE MANAGEMENT STUDY OF THE DRUG IN NURSING. SERVICE OF RESUSCITATION. GYNECOLOGICAL AND OBSTETRIC HOSPITAL IN GUANABACOA 2011: Montero 287 Vizcaíno Y et al. PFep 030: INAPPROPRIATE MEDICATIONS IN OLDER ADULTS PATIENTS: Ortega IL et al. 287 PFep 031: DETECTED ERRORS IN MEDICAL PRESCRIPTIONS IN ST. ANN’S BAY HOSPITAL PHARMACY, JAMAICA: Barroso A et al. 288 PFep 032: STUDY ABOUT THE USE OF ANTIMICROBIALS IN CRITICALLY ILL PEDIATRIC PATIENTS WITH LOWER RESPIRATORY INFECTIONS: Hernández Núñez A et al. 288 PFep 033: STRATEGY FOR THE IMPLEMENTATION OF THE PHARMACEUTICAL CARE IN SANTIAGO OF CUBA HOSPITALS: Reyes I et al. 289 PFep 034: PSYCHOTROPIC MEDICATION CONSUMPTION IN PATIENTS BELONGING TO THE FAMILY DOCTOR’S CONSULTATION #16 FROM “JULIO ANTONIO MELLA” UNIVERSITY 289 POLYCLINIC: Serrano Y et al. PFep 035: BEHAVIOR OF THE CONSUMPTION OF PARENTERAL ANTIMICROBIAL DRUGS IN “HERMANOS CORDOVÉ “PEDIATRIC HOSPITAL FROM MARCH TO AUGUST, 2012: Arceo Naranjo 290 R. PFep 036: ANTIMICROBIAL RESISTANCE OF Staphylococcus AND GRAMNEGATIVE GERMS IN THE INTENSIVE CARE UNIT. GUANTÁNAMO, 2011: Cazull I et al. 290 PFep 037: IMPACT OF POST GRADUATE COURSE IN THE SELECTION AND MANAGEMENT WITH ANTIMICROBIALS IN RESPIRATORY AND URINARY INFECTIONS: Fernández D et al. 291 PFep 038: PROFICIENCY OF THE DRUG INFORMATION SERVICE OF CEDIMED – VC.: González N et al. 291 PFep 039: RISK OF ENVIRONMENTAL DAMAGE DUE TO ANTIBIOTIC RESIDUES IN THE BELICO RIVER AREA IN SANTA CLARA, CUBA: Hernández E et al. 292 PFep 040: USE OF ACAMPROSATE IN THE TREATMENT OF ALCOHOL DEPENDENCE DISORDER: Galán L et al. 292 PFep 041: ERECTILE SEXUAL DYSFUNCTION AND RESPONSE TO SILDENAFIL IN HYPERTENSIVE PATIENTS: Brito Ferrer Y et al. 293 PFep 042: SEXUAL DYSFUNCTION IN PATIENTS UNDER HYPOTENSIVE DRUG THERAPY: Armada Esmores Z et al. 293 PFep 043: FEMALE SEXUAL DYSFUNCTION IN HYPERTENSIVE PATIENTS: González Caballero Y et al. 294 PFep 044: DRUG USE IN THE ADULT FEMALE POPULATION OF CUBA: García Milian AJ et al. 294 PFep 045: CHARACTERIZATION OF SCIENTIFIC PUBLICATIONS DRUG consumption: García Milian AJ et al. 295 PFep 046: CHARACTERIZATION OF ANTIMICROBIAL PRESCRIBING IN THE INSTITUTE OF CARDIOLOGY AND CARDIOVASCULAR SURGERY, 2012: Pavón J et al. 295 PFep 047: CLIMATIC CHANGE AND MEDICATIONS: López Aguilera AF et al. 296 PFep 048: RESEARCH METHODOLOGY IN HEALTH SYSTEMS AND SERVICES FOR ASSESSING QUALITY OF PRESCRIPTION DRUG: Gross Fernandez C et al. 296 PFep 049: EVALUATION OF THE SATISFACTION LEVEL OF THE MEMBERS OF THE MAILING LIST FARMEPI-L, 2012-2013: López M et al. 297 PFep 050: STRATEGY OF INTERVENTION FOR THE ADDICTIONS PREVENTION IN AN UNIVERSITY COMMUNITY: Pupo Perera E. 297 PFep 051: IMPACT OF EDUCATION SERVICE TO DIABETIC PATIENTS: Bermúdez I et al. 298 PFep 052: CHARACTERIZATION OF THE PEPTIC ULCER IN THE HOSPITAL MANUEL FAJARDO IN THE YEAR 2011: Tawfiq M et al. 298 PFD 001: EFFECT OF METFORMINA ON MICE NOCICEPTION ACCORDING TO ABDOMINAL CONTORTION TEST AND IMMERSION OF THE TAIL: Salazar Granara A et al. 299 PFep 053: INTERVENTION STRATEGY ABOUT CLOPIDOGREL PRESCRIBING IN A CARDIOLOGY SERVICE: Ramos Hernández L et al. 299 PFD 002: ANALGESIC ACTIVITY OF Renealmia alpinia (ROTTB.) MAAS, IN EXPERIMENTAL ANIMALS: Díaz Henao GP et al. 300 Farmacoeconomía / Pharmacoeconomy (PFEc) 301 PFEc 001: ECONOMIC EVALUATION OF THE ANTIBIOTICS TREATMENT IN HYSTERECTOMISED PATIENT FOR UTERINE MIOMA. HOSPITAL "DR. AGOSTINHO NETO", GUANTANAMO: 301 Romero K et al. PFEc 002: ESTABLISHMENT OF QUALITY IMPROVEMENT SYSTEM FOR RECEPTION PROCESS IN THE DRUG MARKETING AND DISTRIBUTION COMPANY OF HOLGUIN: Walton CT. 301 PFEc 003: IBUPROFEN IN THE TREATMENT OF THE ARTERIAL PERMEABLE DUCTUS, HOSPITAL “RAMON GONZALEZ CORO”, 2010-2012: Duro E et al. 302
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PFEc 004: COST-CONSEQUENCES EVALUATION PROPHY-LACTIC ANTIBIOTIC USED IN ONCOLO-GICAL HOSPITAL OF SANTIAGO DE CUBA: Perrand M et al. 302 PFEc 005: COST EFFECTIVENESS OF TWO STRATEGIES FOR ANESTHESIA IN PATIENTS WITH TUMOR SURGERY AT THE INSTITUTE OF NEUROLOGY AND NEUROSURGERY IN HAVANA: 303 Turro Fuentes M et al. PFEc 006: TRACEABILITY OF PLANNING, ARRIVAL AND DISTRIBUTION OF REAGENTS. CUBA 2013: Garriga Rodríguez Y. 303 Farmacovigilancia / Pharmacovigilance (PFV) 304 PFV 001: PATIENTS KNOWLEDGE, ATTITUDES AND PRACTICES ABOUT REMAINING DRUG DISPOSAL, AN ECOPHARMACOVIGILANCE APPROACH. BOGOTÁ 2013: Quijano D et al. 304 PFV 002: PHARMACOVIGILANCE IN CHILDREN. CAMAGUEY, CUBA: Bárzaga Z et al. 304 PFV 003: ASSESSMENT OF ADVERSE EVENTS REPORTING. NATIONAL ONCOLOGY INSTITUTE (INOR). MAY 2011 - APRIL 2013: Pérez Noya AL et al. 305 PFV 004: ADVERSE DRUG REACTIONS OF LOW FREQUENCY OF APPEARANCE IN PREGNANT WOMEN. CUBAN PHARMACOVIGILANCE SYSTEM. 2003 – 2009: López L et al. 305 PFV 005: PHARMACOVIGILANCE WEB SITE ON PRIMARY HEALTH CARE ASSISTANCE: López M et al. 306 PFV 006: PREVENTABLE ADVERSE REACTIONS BY THE CONSUMPTION OF HERBAL MEDICINES. CUBA 2003 - 2010: Ruiz Salvador K et al. 306 PFV 007: KNOWLEDGE AND PRACTICES ON PHARMACO-VIGILANCE IN DENTISTRY STAFF: Ruiz A et al. 307 PFV 008: EVALUATION OF THE IMPACT OF IMPLEMENTATION OF A DRUG SURVEILANCE SYSTEM IN EMERGENCY SERVICES IN THE QUALITY PHARMACOVIGILANCE SYSTEM. 307 SATURNINO LORA HOSPITAL: Boizant LM et al. PFV 009: A CUBAN NATION-WIDE PHARMACOVIGILANCE STUDY OF ALLERGEN IMMUNOTHERAPY FOR ASTHMA USING ALLERGEN VACCINES FROM TROPICAL RELEVANT HOUSE-DUST- 308 MITE SPECIES: Mateo M et al. PFV 010: ADVERSE DRUG REACTIONS SURVEILLANCE IN A HOSPITAL LUCÍA IÑIGUEZ. HOLGUÍN 2009 - 2012: Rodríguez S et al. 308 PFV 011: PHARMACOVIGILANCE FROM LIORAD PHARMA-CEUTICAL LABORATORY: Burguet N et al. 309 PFV 012: BEHAVIOR OF ADVERSE DRUG REACTION REPORTS AT THE INSTITUTE OF NEUROLOGY AND NEUROSURGERY. 2011 - FIRST QUARTER 2013: Cordero A. 309 PFV 013: QT PROLONGUED SYNDROME IN OPHTHALMOLOGY: Egaña Arucas M et al. 310 PFV 014: BEHAVIOR OF ADVERSE REACTIONS AFFECTING THE CENTRAL NERVOUS SYSTEM, NOTIFIED BY THE CUBAN SYSTEM OF DRUG IN 2012: Viña Pérez G et al. 310 PFV 015: USE OF MIDRIATICS IN PEDIATRIC AGE. REPORT OF CASE: Otero Alba I. 311 PFV 016: CHARACTERIZATION OF THE ADVERSE DRUG REACTIONS IN ERNESTO GUEVARA HOSPITAL, 2008 - 2012: Gallardo A et al. 311 PFV 017: ADVERSE REACTIONS RELATED TO CONSUMPTION OF CONTRACEPTIVE HORMONE FROM A FAMILY PLANNING CONSULTATION: Aguilar M et al. 312 PFV 018: CHARACTERIZATION OF THE SIDE EFFECTS TO ANTIBIOTICS IN ELDERLY PATIENTS IN A HOSPITAL SERVICE: Echavarría M et al. 312 PFV 019: CHARACTERIZATION OF THE ADVERSE DRUG REACTIONS ACCORDING TO THEIR EVITABILITY IN ELDERLY PATIENTS, GRANMA 2005 - 2012: Aguilera Aguilera O et al. 313 PFV 020: EPIDEMIOLOGICAL SURVEILLANCE OF DRUGS USE DURING PREGNANCY AND CONGENITAL MALFORMATIONS IN VILLA CLARA: Herrera Martínez M et al. 313 PFV 021: BEHAVIOR OF ADVERSE DRUG REACTIONS REPORTS AT THE CLINIC DR MARIO MUÑOZ MONROY, 2011: Sánchez LI et al. 314 PFV 022: CHARACTERIZATION OF THE POLYPHARMACY AT THE EMERGENCY ROOM IN THE HOSPITAL MANUEL FAJARDO, 2011: Pacheco F et al. 314 PFV 023: CONSIDERATIONS ON THE ADVERSE REACTIONS OF HEBERTRANS®: Cruz MA et al. 315 PFV 024: ADVERSE DRUG REACTIONS NOT DESCRIBED IN THE CHILDREN. PHARMACO-VIGILANCE SYSTEM. CUBA, 2005-2012: Furones JA et al. 315 PFV 025: ADVERSE DRUG REACTIONS TO DRUGS IN CHILDREN OF THE GRANMA PROVINCE. JANUARY 2010 TO DECEMBER 2012: Casate ML et al. 316 PFV 026: PHARMACOVIGILANCE STUDY OF HEBERVITAL® TREATMENT TO PREVENT OR CURE NEUTROPENIA. REPORT OF 250 CYCLES OF TREATMENT: González T et al. 316 PFV 027: BEHAVIOR OF ADVERSE DRUG REACTIONS IN INTERNAL MEDICINE SERVICE FOR 6 MONTHS: Salgado Rodríguez CA et al. 317 PFV 028: TERAZOSIN: AN OPTION FOR THE BENIGN PROSTATIC HYPERPLASIA IN HYPERTENSIVE PATIENTS: Acosta C et al. 317 PFV 029: ENDOTHELIN: ITS ROLE IN HYPERTENSION: Acosta C et al. 318 PFV 030: BEHAVIOR OF ADVERSE DRUG REACTIONS MORE COMMON IN THE COMMUNITY HEALTH AREAS. TUMEREMO. VENEZUELA. JANUARY TO OCTOBER 2012: Diaz MA et al. 318 Cronobiofarmacología / Chronobiopharmacology (PCB) 319 PCB 001: MELATONIN AND MELATONIN-ANALOGUES: Rosales Mesa Y et al. 319 PCB 002: VARIABILITY OF LIPIDS AND MODIFIABLE RISK FACTORS IN TYPE 2 DIABETIC PATIENTS WITH ACUTE MYOCARDIAL INFARCTION: Valle Rodríguez RA. 319 PCB 003: CHRONOTHERAPY VS. CONVENTIONAL THERAPY IN TREATMENT OF SPORTS INJURIES ON THE NATIONAL SOCCER TEAM: León Lobeck A. 320 Enseñanza de la Farmacología / Teaching of Pharmacology (PEF) 321 PEF 002: DETERMINING THE NEEDS AND PROJECTIONS OF TEACHERS’ TRAINING FOR PHARMACOLOGY CONTENTS IN MEDICINE STUDIES: Milián Vázquez PM et al. 321 PEF 003: SYSTEM OF PROFESSIONAL CONTINUOUS STUDY OF THE MEDICINE PROFESSOR FOR THE TEACHING OF PHARMACOLOGY: Milián Vázquez PM et al. 321 PEF 005: LINKING OF THE CONTENTS OF PHARMACOLOGY II WITH THE WARD ROUND ACTIVITIES OF THE STUDENTS IN MEDICAL STUDIES: López Guerra RL et al. 322 PEF 006: ACTION PLAN FOR PEDAGOGICAL FORMATION OF PHARMACOLOGY RESIDENTS: Ortiz Y et al. 322 PEF 007: PROFESSIONAL TRAINING OF PHYSICIANS TO DEVELOP DRUG UTILIZATION RESEARCH: Cisneros Nápoles Y et al. 323 PEF 008: METHODOLOGICAL CONSIDERATIONS REGAR-DING THE TEACHING OF PHARMACOLOGY DISCIPLINE TO A MULTICULTURAL GROUP OF STUDENTS IN FACULTY OF MEDICINE 323 "JULIO TRIGO LOPEZ”: Tasé Martínez MJ et al. PEF 009: VIRTUAL COURSE: PROMOTION OF RATIONAL USE OF ANTIMICROBIAL AGENTS IN PRIMARE HEALTH CARE: Pereira E et al. 324 PEF 010: SATISFACTION AND RESULT OF STUDENTS WITH GENERAL PHARMACOLOGY SUBJECT: Álvarez González R et al. 324 PEF 011: IMPLEMENTATION OF THE CURRICULUM STRATEGIES IN PHARMACOLOGY I AND ITS INFLUENCE ON THE TEACHING PROCESS AT THE MEDICAL UNIVERSITY OF MATANZAS 325 DURING 2011-2013: Romero MB et al. PEF 012: INFLUENCE OF THE COURSE CLINICAL EVALUATION OF HERBAL DRUGS IN HEALTH PROFESSIONALS: Castañedo Z et al. 325 PEF 013: FORMATION OF THERAPEUTICAL COMPETENCE THROUGH THE SUBJECT PHARMACOLOGY ON STUDENTS OF PHARMACEUTICAL SERVICES: Hernández D et al. 326 PEF 014: METHODOLOGICAL GUIDELINES PROPOSAL FOR THE INVOLVEMENT OF DRUGS TOPICS IN THE SUBJECT OF MORPHOPHYSIOLOGY III: Alfonso Hidalgo A et al. 326 PEF 015: METHODOLOGICAL PROPOSITION FOR THE DEVELOPMENT OF CLINICAL PHARMACIST´S GRADUATE IN THE HOSPITAL’S PHARMACEUTICAL SERVICES IN PINAR DEL RIO, 2013: 327 Sanchez R et al. PEF 016: CONSOLIDATION OF LOGICAL ANALYSIS PROCEDURES IN PHARMACY STUDENTS BY LEARNING DRUGS MECHANISMS OF ACTION IN PHARMACOLOGY SUBJECTS: Hernández M 327 et al. Medicamentos Genéricos / Generic Drugs (PPG) 328 PPG 001: DEVELOPMENT AND VALIDATION OF A HIGH PERFORMANCE LIQUID CHROMATOGRAPHY METHOD FOR QUANTIFICATION OF DOCETAXEL FOR INYECTION OF 80 MG/BULB: 328
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Izquierdo A et al. PPG 002: VALIDATION OF A CHROMATOGRAPHIC METHOD FOR QUANTITATION OF 50 µg/mL LATANOPROST IN A CUBAN EYE DROPS: García CM et al. 328 PPG 003: ADMINISTRATION AND COST DETERMINATION OF AMANTADINA IN “CIREN”: Díaz AE et al. 329 PPG 004: DEVELOPMENT AND VALIDATION OF A HIGH PERFORMANCE LIQUID CHROMATOGRAPHY METHOD FOR QUANTIFICATION OF CYCLOSPORINE IN TABLETS OF 20 MG: Romero J 329 et al. PPG 005: SIMPLIFYING AND STREAMLINING THE MARKETING AUTHORIZATION PROCESS IN CUBA: Suárez Y et al. 330 PPG 006: EVALUATION IN VITRO ACTIVITY OF VITROFURAL AGAINST PATHOGENIC STRAINS OF Clarias gariepinus: Morales Y et al. 330 PPG 007: KINETIC OF RELEASE OF CEFALEXINE, CIPROFLOXACINE, CEFTAZIDIME, CEFAZOLINE, CEFTRIAXONE AND MEROPENEM FROM ACRYLIC BONE CEMENTS: López M et al. 331 PPG 008: PRECLINICAL SAFETY EVALUATION OF ERYTHROPOIETIN WITH LOW SIALIC ACID CONTENT (NEURO EPO): Lagarto A et al. 331 PPG 009: QUALITY CONTROL AND STABILITY STUDY OF 100 mg/mL PARACETAMOL ORAL DROPS: García CM et al. 332 Farmacología Básica / Basic Pharmacology (PFB) 333 PFB 001: IMAGE ANALYSIS SYSTEM IN THE DETERMINATION OF THE ACTIVITY ANTIDREPANOCYTIC OF O-VANILLIN IN HUMAN ERYTHROCYTES: Alonso-Moreno Y et al. 333 PFB 002: USE OF PHYTOTHERAPY IN DERMATOLOGIC DISEASES: Miranda M et al. 333 PFB 003: VASCULAR INTEGRITY IN AORTIC SAMPLES ISOLATED UNDER AIREATION CONDITIONS: Hernández E et al. 334 PFB 004: ANTI-INFLAMMATORY ACTIVITY AND CHEMOINFORMATIC ANALYSIS OF NEW POTENT 2-SUBSTITUTED 1-METHYL-5-NITROINDAZOLINONES: Siverio-Mota D et al. 334 PFB 005: LUTETIUM-177 RADIOLABELING OF THE HUMANIZED MONOCLONAL ANTIBODY hR3 USING MACROCYCLIC AND ACYCLIC LIGANDS: Leyva R et al. 335 PFB 006: MINIMAL STRUCTURAL CHANGES DETERMINE NICOTINIC AGONIST OR ANTAGONIST ACTIVITY FOR NICOTINIC ANALOGUES: Iturriaga-Vásquez P et al. 335 PFB 007: EFFICACY OF A 2-IMINOTHIAZOLIDIN-4-ONE LpQM18 AS ANTI-Trypanosoma cruzi AGENT IN INFECTED MICE: Leite ACL et al. 336 PFB 008: ACUTE EFFECTS OF SIBUTRAMINE ON ADRENERGIC RESPONSE ON YOUNG RAT VAS DEFERENS: Souza BP et al. 336 PFB 009: POPULATION PHARMACOKINETICS OF CYCLOS-PORINE IN THE EARLY PERIOD OF POST RENAL TRANSPLANT (RT) IN MEXICAN PEDIATRIC RECEPTORS: Lares-Asseff I et al. 337 PFB 010: USE OF FRESHLY ISOLATED RENAL CELLS TO STUDY RENAL UPTAKE OF SELECTED ANTIVIRALS: Trejtnar F et al. 337 PFB 011: CHEMICAL COMPOSITION AND PHARMACOLO-GICAL EFFECTS OF MEXICAN PROPOLIS ON EXPERIMENTAL GASTRIC ULCERS IN RATS: Hernández-Delgadillo GP et al. 338 PFB 012: CARDIOPROTECTOR EFFECT OF NIFEDIPINE AND RUTHENIUM RED AGAINST CARDIAC ISCHEMIA AND REPERFUSION INJURY IN RATS: Tavares JGP et al. 338 PFB 013: LUNG EMPHYSEMA: EXPERIMENTAL MODELS: Dantas R et al. 339 PFB 014: EFFECTS OF ETOH INGESTION IN VAS DEFERENS CONTRACTILITY, SPERMATOGENESIS AND CONSEQUENCES ON THE MALE REPRODUCTIVE SYSTEM IN THE RAT: Jurkiewicz 339 NH et al. PFB 015: ANTI HYPER-GLYCAEMIA EFFECT AND THE SAFETY OF THE ZEOLITA: FE2+-CLINOPTI-LOLITA (FZ) IN ANIMAL’S EXPERIMENTATION: Fleitas AS et al. 340 PFB 016: BIODISTRIBUTION AND PHARMACOKINETICS OF T1h MONOCLONAL ANTIBODY AND ITS ANTI MURINE CD6 COUNTERPART 10D12 IN HEALTHY ANIMALS AND IN AN 340 ARTHRITIS MODEL: Aldana L et al. PFB 017: COMPARATIVE STUDY OF SEVERAL DOSES OF PARACETAMOL IN RATS EXPERIMENTAL MODEL: Jiménez Martínez MC et al. 341 PFB 018: PREVENTATIVE AND THERAPEUTIC ANTI-ALLERGIC EFFECT OF A NOVEL HOUSE-DUST-MITE VACCINE BASED ON A COMBINATION ADJUVANT: Ramírez W et al. 341 PFB 019: CORRELATION BETWEEN SEROTONIN CONCENTRATION VARIATIONS AND CLINICAL COURSE IN PATIENTS WITH ALCOHOL WITHDRAWAL SYNDROME TREATED WITH 342 CLOMETIAZOLE: Llinás S et al. PFB 020: CHARACTERIZATION OF THE PROTEINS Mtl2p AND Wsc1p LIKE POSSIBLE SENSORS OF THE CELLULAR WALL IN Schizosaccharomyces pombe: Cruz S et al. 342 PFB 021: PROTEOME AND BIOLOGICAL CHARACTERIZA-TION OF Bothrops punctatus VENOM. ISOLATION AND IDENTIFICATION ONE BRADYKININ-POTENTIATING PEPTIDES: Fernández 343 M et al. PFB 022: DISSOLUTION PROFILES OF CAPTOPRIL SIMULATING CONDITIONS POST-SURGICAL IN PATIENTS UNDERGOING TO BARIATRIC SURGERY IN "Y" OF ROUX: Alviz A et al. 343 PFB 023: ORAL AND INTRAVENOUS BIOAVAILABILITY OF QUERCETIN AND RELATIONSHIP WITH THE HYPOGLYCEMIC EFFECT: González A et al. 344 PFB 024: EFFECTS OF METFORMIN IN LOCAL AND SYSTEMIC ANTIHYPERALGESIC ACTION OF INDOMETHACIN, DICLOFENAC AND PARECOXIB: Torres-López JE et al. 344 PFB 025: DETECTION OF INSULIN POLYMERS IN PLASMA FROM OBESE PATIENTS AND ITS RELATIONSHIP WITH INSULIN RESISTANCE: García JR et al. 345 PFB 026: IS 15-EPI-LIPOXIN A4 THE MEDIATOR OF THE EFFECT OF ASPIRIN ON EXPERIMENTAL INFECTION WITH Trypanosoma cruzi?: Campos-Estrada C et al. 345 PFB 027: SEARCH OF NEW THERAPEUTIC AGENTS: PYRIDO[2,3-d]PYRIMIDINES: Acuña J et al. 346 PFB 028: IN VIVO ANTITUMORAL EFFECT OF TRIPHENIL-PHOSPHONIUM-GALLIC ACID DERIVATIVES: Peredo L et al. 346 PFB 029: ALTERATIONS IN THE SYMPATHETIC NEUROTRANSMISSION OF VAS DEFERENS FROM PRE-HYPERTENSIVE AND HYPERTENSIVE RATS: Peña M et al. 347 PFB 030: DEVELOPMENT AND VALIDATION OF ANALYTICAL PROCEDURES TO DETERMINE LOSARTAN POTASSIUM IN TABLETS AND PLASMA FOR THERAPEUTIC EQUIVALENCE 347 STUDIES: Baudrit O et al. PFB 031: Nocardia brasiliensis AS BIOFILM GROWING ON VARIOUS INERT SURFACES: Monroy G et al. 348 PFB 032: STUDY ON POSSIBLE MECHANISM OF ACTION OF OZONE INDUCES SEIZURES PENTYLENETETRAZOL: Donoso Cedeño R et al. 348 PFB 033: TRISULFATED HEPARIN DISACCHARIDE CONFERS CARDIOPROTETION AGAINST CARDIAC ISCHEMIA AND REPERFUSION INJURY IN RATS: Caricati-Neto A et al. 349 PFB 034: POPULATION PHARMACOKINETIC ANALYSIS OF NIMOTUZUMAB IN COMBINATION WITH CHEMOTHERAPY IN PATIENTS WITH BREAST CANCER: Rodríguez L et al. 349 PFB 035: HSG CELLS CULTURED IN 3D EXPRESSING SYNAPTOTAGMIN I AND SECRETE AMYLASE: MODEL TO STUDY THE OVEREXPRESSION OF SYNAPTOTAGMIN I IN SJÖGREN'S 350 SYNDROME: Cortés J et al.
PFB 036: ROLE OF HISTAMINE H3 RECEPTORS IN THE INHIBITION OF THE CARDIO-ACCELERATOR SYMPATHETIC OUTFLOW IN PITHED RATS: Pinacho-García LM et al. 350 PFB 037: EFFICIENCY OF THE ARJ-DH12 AS ANALGESIC IN PATIENTS WIHT ACUTE ARTICULAR PAIN: Bermúdez MI et al. 351 PFB 038: BIODISTRIBUTION AND PHARMACOKINETIC OF 1E10 MONOCLONAL ANTIBODY AFTER SUBCUTANEOUS ADMINISTRATION IN HEALTHY MICE: León M et al. 351 PFB 039: EFFECTS OF 17β-IMINOESTROGENS ON THE SEXUAL BEHAVIOR OF FEMALE RATS: Jiménez L et al. 352 PFB 040: LONG-TERM INHIBITION OF CRAC CHANNELS ACTIVITY AND ALLERGIC ASTHMA IN EXPERIMENTAL CONDITIONS: Sutovska M et al. 352 PFB 041: ROLE FOR THE TRPV1 CHANNEL IN GLUCOSE HOMEOSTASIS: Díaz-García CM et al. 353 PFG 001: CYP1A1, GSTM1 AND GSTT1 METABOLIZING GENE POLYMORPHISMS AND SUSCEPTIBILITY TO CORONARY ARTERY DISEASE AMONG CIGARETTES SMOKERS: Belkhiria MN et al. 353 POt 001: PTAQUILOSIDE RESIDUALITY CANCER COMPOUND IN MILK FROM CATTLE FARMS INVADED BY Pteridium arachnoideum (KAULF.) MAXON IN THE PROVINCE OF BOLÍVAR, 354 ECUADOR: Calderón A et al. POt 002: DESIGN AND EVALUATION OF L-ARGININE PELLETS TO IMPROVE DEVELOPMENT AND REPRODUCTION IN RUMINANTS: Sánchez Z et al. 354
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POt 003: PATENTABILITY TEST IN COSTA RICA: CRITERIA USED IN PHARMACY AND COMPARISON WITH FOREIGN GUIDELINES: Vargas R. 355 POt 004: RETROSPECTIVE STUDY ON DRUG’S PATENTABILITY IN COSTA RICA: Madrigal G. 355 POt 005: PHARMACOKINETICS AND TISSUE PENETRATION OF CEFTAZIDIME ADMINISTERED DURING ABDOMINAL HYSTERECTOMY AND OOPHORECTOMYIN BITCHES: De Gatica L et al. 356 POt 006: PHARMACOKINETICS AND TISSUE DAMAGE EVALUATION OF TWO PREPARATIONS OF CEFTAZIDIME ADMINISTERED VIA INTRAMUSCULAR ROUTE IN GOATS: Lacunza J et al. 356 POt 007: STRATEGIC PROJECT MANAGEMENT IN THE PHARMACEUTICAL INDUSTRY: THE ROLE OF THE CONTRACT RESEARCH ORGANIZATIONS: Slaninka Miceska M et al. 357 POt 008: INTERACTIONS BETWEEN CUBA AND BRAZIL: PRODUCTION SCIENCE, HUMAN RESOURCES TRAINING IN NEUROSCIENCE: Calabró L et al. 357
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LATINFARMA 2013 Resúmenes/Abstracts
CONFERENCIAS PLENARIAS INAUGURALES / OPENING PLENARY LECTURES (PL)
Lunes, Octubre 21 / Monday, October 21st
PL 001: BIOLOGICAL AND THERAPEUTIC RELEVANCE OF illustrate the limitation of the strategy, due to the fast appearance of THE DISCOVERY OF PROSTACYCLIN AND NITRIC OXIDE resistance. Moncada S. The complexity of regulatory networks will demand simultaneous intervention on several molecular targets and capacity to handle the The Wolfson Institute for Biomedical Research, University College London, ¨dual effects¨. Patient to patient heterogeneity and cell to cell United Kingdom. heterogeneity will demand personalized medicine and clinical trials in smaller patient niches. Mutation rates will need the mobilization of biologic mechanisms, such as the immune system, which could evolve In this lecture I will explain how the mechanism of action of aspirin together with the tumor. Finally these mechanisms should act in a and other non-steroidal anti-inflammatory drugs were discovered and genetic background which has not been selected by evolution for will also describe the discovery of prostacyclin and nitric oxide. protecting health in the post-reproductive period of human life. Neither classic screening strategies of pharmacology, nor the current I will discuss the biological relevance of those discoveries to our regulatory context for drug development are well suited for facing understanding of the physiology and pathophysiology of various these challenges. organs and tissues and their implications for the therapy and prevention of different diseases. Biotechnology drugs offer the possibility of innovative approaches. Recent evidences related to the effect of monoclonal antibodies and Finally I will consider the possibilities of future research in these areas therapeutic vaccines, and data related to the control of the immune of research. response, epitope spreading, pathways of apoptosis, oncogene addiction and immuno-senescence point out the possibility to stepwise transform the clinical course of advanced cancer into that of a chronic PL 002: IMMUNOTHERAPY AND COMPLEXITY: OVERCOMING disease compatible of years of quality life. THE BARRIERS FOR THE CONTROL OF ADVANCED CANCER
Lage Dávila A. Director General, Centro de Inmunología Molecular, Cuba. Martes, Octubre 22 / Tuesday, nd October 22 Age-adjusted cancer mortality rates are showing a slow, but clear trend to decline in some countries. However, such decline is mostly due to reduction in tobacco smoking and to earlier diagnosis of some PL 003: TRENDS OF RESEARCH IN THE 21RST CENTURY tumors. Long term control of advanced cancer continue to be a goal very hard to attain: Survival gains over the last three decades for many Moncada S. tumors are measured in months, not years. The Wolfson Institute for Biomedical Research, University College London, Four major barriers prevent a faster progress: the complexity of United Kingdom. networks for the control of cell proliferation; the heterogeneity of cancer cells; the mutation rate; and our genome-environment mismatch. They challenge the classic pharmacology paradigm of “one The current tendencies in the development of research in a molecular target/one specific drug¨. globalised world will be analyzed. The position of Latin America in terms of investment and success of the research enterprise will be Targeted therapy, the most recent acquisition for the treatment of discussed in relation to the world effort. The impact of science in social advanced cancer, together with its impressive short term effects, and economic development will also be considered.
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LATINFARMA 2013 Resúmenes/Abstracts
SIMPOSIOS Y TALLERES / SYMPOSIA AND WORKSHOPS CONFERENCIAS Y COMUNICACIONES ORALES / CONFERENCES AND ORAL COMMUNICATIONS
Taller Inmunofarmacología y Biotecnología. Sesión: Inmunofarmacología / Workshop on Immunopharmacology and Biotechnology. Session: Immunopharmacology
CO 001: TOWARDS CLINICAL TRANSLATION OF T-CELL CO 002: HUMAN ANTIBODIES REACTIVE TO NEUGCGM3 RECEPTOR GENE EDITING TO MEDIATE ADOPTIVE ANTI- GANGLIOSIDE HAVE CYTOTOXIC ANTITUMOR PROPERTIES TUMOR IMMUNOTHERAPY Rodríguez-Zhurbenko N, Martínez D, Blanco R, Rondón T, Griñán T, Ciceri F, Mastaglio S, Bonini C. Hernández AM.
Experimental Hematology Unit, San Raffaele Scientific Institute, Milan, Italy. Center of Molecular Immunology, Havana, Cuba. E-mail: [email protected]
Introduction: The genetic addition of a tumor specific receptor into T Introduction: NeuGcGM3 ganglioside is not naturally expressed in cells yielded already substantial clinical results in patients affected by normal human tissues but is overexpressed in several tumors and has hematological malignancies. immunosuppressive capacity, contributing to cancer progression. These features make NeuGcGM3 an attractive candidate for tumor Methods: To completely substitute T cell specificity, we recently immunotherapy; however, little is known about the naturally occurring developed the TCR gene editing approach, based on the combination anti-NeuGcGM3 antibody response in healthy humans. Aims of this of: i. Somatic knockout of the endogenous TCR genes (achieved by study were to analyze and characterize the antibody responses against transient exposure to β- and α-chain specific Zinc Finger Nucleases- this ganglioside in healthy donors and cancer patients. ZFN), and ii. Introduction of a tumor-specific TCR by lentiviral vectors (LV). By avoiding competition for surface expression between Material and methods: The study comprised 100 healthy donors and exogenous and endogenous TCR β- and α-chains, and by abrogating the 55 age-matched untreated non small cell lung cancer (NSCLC) patients. risk of inappropriate TCR pairing, the TCR editing approach In all the subjects, specific anti-NeuGcGM3 antibody response was permanently overcomes the major limitations of TCR gene transfer assessed by ELISA. The functionality of these antibodies was tested as (Provasi, Genovese et al., Nat. Med. 2012). their ability to bind and kill tumor cell lines expressing NeuGcGM3. Results: To promote an effective and persistent therapeutic effect, and Results: 65 healthy donors had antibodies that specifically recognized to facilitate its clinical application, we established a scalable protocol of NeuGcGM3 and kill tumor cells expressing this antigen by a TCR single editing, applicable within a single round of T cell complement mediated mechanism. Interestingly, even after stimulation. This approach completely and permanently abrogates complement inactivation, 17% of the positive sera showed a direct expression of the endogenous TCR repertoire of donor T cells, which is cytotoxic effect on the tumor cells. This cytotoxicity was dependent on responsible of GvHD. In addition, we validated the TCR editing the presence of the antigen on the tumor cells and resembles an approach on NY-ESO-1, expressed by solid tumors and hematological oncotic kind of cell death. Both, the levels of anti-NeuGcGM3 antibodies malignancies. We observed similar high levels of TCR expression, in the sera of healthy donors as well as the percentage of donors with measured by NY-ESO-1 specific dextramer binding, in single edited and this natural immunity decrease with age. Furthermore, we could only transferred T cells (RFI 73 vs. 66). Single edited cells efficiently detect low reactivity against NeuGcGM3 in the sera of 6 NSCLC recognized and killed NY-ESO-1+ myeloma cell lines, without aberrant patients. - response to NY-ESO-1 targets, and displayed improved tumor Conclusions: Healthy human sera contain naturally occurring anti- specificity than unedited TCR-transferred cells in co-culture assays NeuGcGM3 antibodies with cytotoxic anti-tumor properties, (99% of elimination of target cells in both single edited and transferred reinforcing the importance of NeuGcGM3 ganglioside as an important cells; 0% vs. 45.9% of elimination of unspecific targets, respectively). target for cancer immunotherapy. Treatments that boosted this anti- Conclusions: These results suggest that the TCR gene editing approach NeuGcGM3 antibody response should be considered an important can mediate Graft versus Tumor and overcome the risk of GvHD in immunotherapeutic regimen against NeuGcGM3 containing tumors as patients with hematological malignancies undergoing allo-HSCT. elderly donors and NSCLC patients lacked this natural anti-tumor response.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S2
LATINFARMA 2013 Resúmenes/Abstracts
CO 003: PHARMACOLOGIC INTERVENTION OF CASEIN CO 004: In Silico DESIGN AND FUNCTIONAL CHARACTERIZA- KINASE 2 (CK2)-MEDIATED PRO-SURVIVAL AND PROLI- TION OF A TGFβ1 MUTEIN, ANTAGONISTIC OF TGFβ FERATIVE SIGNALING ON T-CELL ACUTE LYMPHOBLASTIC SIGNALING, WITH ANTITUMOR AND IMMUNOMODULA- LEUKEMIA (T-ALL) TORS PROPERTIES
Perera Y1, Melao A2, Miranda J3, Perea SE1, Barata JT.2 Corría Osorio J, Pérez Rodríguez S, Carmenate Portilla T, León Monzón K. 1Laboratory of Molecular Oncology, Division of Pharmaceuticals, Center for Genetic Engineering and Biotechnology (CIGB), P.O. Box 6162, CP 10600, C. System Biology Department. Center of Molecular Immunology, Havana, Cuba. E- Habana, Cuba. E-mail: [email protected] mail: [email protected] 2Cancer Biology Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa Ed. Egas Moniz - P3-C48 Av. Prof. Egas Moniz 1649-028 Lisboa, Portugal. 3Bioinformatics Department, CIGB, Havana, Cuba. Introduction: Transforming growth factor β (TGFβ) is pleiotropic cytokine that affects tumor growth, metastasis, stroma, and immune response. There are three isoforms: TGFβ1, TGFβ2, and TGFβ3. They Introduction: Despite sustained advances in the treatment of T-cell interact on the cell surface with the TβRII receptor, TβRIII receptor Acute Lymphoblastic Leukemia (T-ALL) mortality rates are still and several of the type I receptors that have been described (ALK5, unacceptable high, stressing the necessity to develop new therapeutic ALK1, ALK2, ALK3); ALK5 is the clasic type I receptor of these ligands. compounds. The role of CK2 on T-ALL biology has been recently It has been proposed that the ligands bind first to TβRIII and then this addressed by experimental and clinical data. Such findings uncover the receptor transfers them to TβRII receptor. TGFβ1 and TGFβ3 can bind relevance of CK2-mediated phosphorylation on PTEN inactivation, to TβRII receptor with high affinity (5-30 pM) whereas TGFβ2 has leading to an aberrant PI3K/Akt signaling and increasing T-ALL 1000 fold less affinity. ALK5 is recruited and activated in a highly survival and proliferation. Importantly, emerging evidences also cooperative manner by the TβRII/TGFβ complex, forming the connect CK2 activity with IL-7-mediated signaling, a cytokine with heterotrimeric signaling complex. The ALK5 signaling plays a pivotal leukemia supportive effect. Here, we analyzed the impact of CIGB-300 role in regulating the pathogenesis of a wide variety of disorders peptide, a molecule designed to block CK2-mediated phosphorylation including cancer. Blockade of TGFβ signaling has been reported to be by direct binding to conserved phosphoaceptor domain on its efficacious in the suppression of tumor growth and metastasis in substrates, on T-ALL biology. animal models and clinical trials. In the present work we described for first time, a TGFβ1 mutein that behave as an antagonistic of the TGFβ Methods: CIGB-300´s antiproliferative effect was assessed on T-ALL signaling and has antitumor and immunemodulators effects in vitro. cell lines representing common genetic lesions and differentiation stages (n=8) using Alamar blue and H3-thymidine assays. Cytotoxicity Material and methods: This mutein was designed using several and cell cycle distribution were determined by FACS using AnnexinV- bioinformatics tool such as 3DCoffee and clustalX for the evolutionary 7AAD and PI staining, respectively. IL7-mediated activation on analysis, the web server Protein Interaction Calculator was used to primary-like TAIL7 (IL7-dependend) and HPB-ALL (IL7-responsible) determine principals interactions in the interface, and Rosetta to cells was determined by FSC vs. SSC analysis. CIGB-300´s cytotoxic determine hot spot residues and destabilizing mutations This mutein effects was verified in co-culture experiments using transfected murine was fused to a human IgG1 Fc region with a set of mutations in the the stromal cells (OP9DL1) and primary leukemia cells from patients Cγ2 domain that abrogates the binding with Fc gamma receptors (n=6). Signaling experiments were performed by western blot. except the neonatal. The fusion to Fc region was useful for expressing, for first time, the TGFβ domain without its latency associated Results: CIGB-300´s exerted a dose-response antiproliferative effect propeptide (LAP) that is very important because the mutein can be on T-ALL cells (IC50 mean= 24 µM) which can be explained by direct obtained in its active form to interact with TβRII receptor. TGFβ1 induction of cell death. Such effect overcomes IL7-mediated activation mutein.Fc was obtained using a lentiviral transduction protocol in and viability boost, both in cell lines and patient samples, while CHO-K1 cells. Evaluation of the antagonistic effects was done in IL-2– prevents stromal support in vitro. Signaling experiments point to two dependent CTLL-2 cell proliferation assay, TGFβ1-induced Treg described CK2 substrates as potential targets for CIGB-300 on T-ALL differentiations assays and in vitro tumor cell migration assay. (i.e. NPM/B23 and P27) while in the context of IL7-stimulation putative new unexpected target(s) emerge upstream in JAK-STAT Results: TGFβ1Mut_Fc had less biological activity than recombinant signaling axis (i.e. JAK1). TGFβ1 and blocked TGFβ1-stimulated inhibition of IL-2–dependent CTLL-2 cell proliferation. Also, TGFβ1Mut_Fc inhibited the generation Conclusion: Our data support the suitability of anti-CK2 of foxp3 positive CD4+ T cells induced by wtTGFβ1. Finally, pharmacologic interventions to impair T-ALL survival and TGFβ1Mut_Fc inhibited tumor cell migration in vitro. proliferation even in the context of aberrant IL7-IL7R signaling. Conclusions: The TGFβ1 mutein.Fc behaves as an antagonistic of TGFβ signaling and that suggest that the destabilizing mutations predicted by using bioinformatics tool affect interaction between TGFβ1 and ALK5. These data provide a foundation to support using TGFβ1 mutein_Fc as a therapeutic agent for TGFβ-dependent cancer with metastatic and immuneregulatory capacity.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S3
LATINFARMA 2013 Resúmenes/Abstracts
CO 005: MOLECULAR MECHANISMS INVOLVED IN THE CO 006: CONCENTRATION OF MMP-3 AND IL-6 IN PATIENTS INHIBITION OF TUMOR CELLS PROLIFERATION EXPOSED WITH SEPSIS AND MULTIORGAN FAILURE TO ELEVATED CONCENTRATIONS OF EPIDERMAL Ricarte Bratti JP, Montrull HL, Meirovich CI, Jaime NJ, Demurtas SL, GROWTH FACTOR (EGF) Brizuela NY.
Camacho H, Guillen IA, Berlanga J, Fernández-de-Cossio ME, Pérez L, Universidad Nacional de Córdoba – Fac Cs Medicas – Catedra de Farmacologia. Palenzuela D, Díaz T, Guillen GE, Herrera L, Cosme K, Gorovaya L, Santa Rosa 1085, Córdoba, Argentina. E-mail: [email protected] Mendoza O, Fernández JR, Ancizar JA, Suarez J, Tuero A, Ochagavia ME, Roca J, Gavilondo J, García del Barco D, Martin J and Novoa LI.
Center for Genetic Engineering and Biotechnology, CIGB, Havana, Cuba. E-mail: Introduction: Sepsis is the leading cause of mortality in intensive care. [email protected] The study of its pathophysiology is essential to try to change the high mortality that this syndrome presents. The multiple organ dysfunction Syndrome (MODS) is a high mortality syndrome caused by sepsis. Introduction: The EGF promotes inhibition of cell proliferation in Cytokines are the main responsible for the inflammatory response in vitro and in vivo models depending on its concentration, application sepsis and MODS, including IL-1, 6 and TNF alpha. MMP-3 is a molecule schema and the type of tumor cells on which it acts. Our research relatively recent that has not been studied in sepsis yet. hypothesis was based on the fact that the EGF varies the expression of genes involved in a negative regulation of tumor cell lines proliferation Aim: To assess the predictive power of cytokines on MODS and death. carrying high levels of its receptor (EGFR). Our objectives were, to obtain information about the effect of EGF on tumor cell proliferation Material and methods: 48 patients older than 18 years with sepsis in vitro and in vivo models and, know the gene expression patterns of a criteria who were attended the Hospital Nacional de Clínicas of group of genes involved in cancer signaling pathways and EGFR. Cordoba-Argentina have been included. Upon admission blood samples were drawn for the dosage of cytokines. Material and methods: We used six cancer cell lines (K562, MCF-7, U1906, LS-174T, H125 and A431) with different concentrations of Results: Patients with MODS had a mean value of IL-6 of 210.10 ± EGFR. An animal model was obtained in Nude mice xenografts with the 30.82 pg/mL and for patients without MODS of 155.32 ± 20.84 pg/mL cell line A431 over-expressing the levels of EGFR The real time PCR (p=0.135). For MMP-3 MODS patients had an average of 14.57 ± 0.63 technique was used to explore in models in vitro and in vivo, the mg/mL whereas patients who did not develop MODS reached an differential expression of 44 genes involved in EGF signaling pathway average of 9.8 ± 0.83 mg/mL (p<0.0001). Evaluating mortality IL-6 in and cancer in cells treated with EGF and controls. Relative death patients was a medium term of 203.65 ± 26.64 pg/mL in slight quantification of gene expression was performed using the software contrast to the survivors, whose average was 161.88 ± 24.38 pg/mL, REST 2009 v2.0.13 (QIAGEN GmbH All rights reserved). giving a difference without statistical significance (p = 0.26). Values of MMP-3 in survivors had an average of 10.55 ± 0.76 mg/mL, whereas Results: The results showed that EGF at nanomolar concentrations the average of the deceased was 13.77 ± 0.98 mg/mL (p=0.012). inhibits the tumor cells proliferation bearing high levels of EGFR and, promotes the survival of treated animals, establishing a direct Conclusions: MMP-3 has shown that if at the time of admission it´s in a relationship between the inhibition of cell proliferation, high high value (Beyond 12 mg/mL) has a prognostic value since it predicts concentrations of EGF and, high amount of EGFR in the cells. The death and organ failure. IL-6 has a tendency to the above, but with non- differential gene expression profile showed a variation in a group of significant results, so more studies are needed with larger numbers of genes which exert a powerful control over the cell cycle progression, patients. gene transcription and apoptosis. Conclusions: The inhibition of tumor cell proliferation by the action of EGF is due to activation of molecular mechanisms controlling cell cycle progression.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S4
LATINFARMA 2013 Resúmenes/Abstracts
CO 008: IMMUNOTRANS-ARTERIAL CHEMOEMBOLIZATION CO 009: A NOVEL PEPTIDE SELECTED FROM AN ALA- (ITACE) IN HEPATOCELLULAR CARCINOMA PATIENTS SCANNING REGULATES THE ONCOGENIC ACTIVITY OF TREATED WITH ANTI-EGFR MAB NIMOTUZUMAB PLUS NFKB IN CANCER CELLS ADRIAMYCIN. PHASE I CLINICAL TRIAL, FINAL RESULTS Oliva B, Fernandez Jr, Gil J, Garay H, Reyes O, Guillen G, Ramos-Suzarte M1, Hernández JC2, Roque A2, Ugarte JC2, Jordán J2, Vallespi GM. Samada M2, Lorenzo P1, Fernández A1, Catalá M2, Fermín E2, Frías A1, Center for Genetic Engineering and Biotechnology (CIGB), P.O.Box. 6162, 1 1 1 1 1 Izquierdo M , Cedeño M , Rengifo E , Frómeta M , Crombet T. Cubanacan, Playa, La Habana, Cuba. E-mail: [email protected] 1Center of Molecular Immunology, Havana, Cuba. E-mail: [email protected] 2Center for Medical and Surgical Research, Havana, Cuba. Introduction: The nuclear factor NFkB plays a critical role in diverse cellular processes associated with proliferation, cell death, as well as Introduction: Hepatocellular carcinoma (HCC) is a common inflammation. Starting from a LPS-binding peptide from Limulus anti- complication of chronic liver disease. EGFR is well validated as a LPS factor, with powerful immunostimulatory activity, we have done primary contributor of different tumor of epithelial origin included alanine substitutions of particular residues and obtained a novel liver cancer in initiation and progression. Nimotuzumab is a synthetic peptide (CIGB-552) that has lost its LPS binding capacity and humanized monoclonal antibody (mAbs) that recognizes the EGFR is a powerful in vitro and in vivo cytotoxic agent. The potential extracellular domain. While it has similar preclinical and clinical mechanism responsible for the antitumor activity of CIGB-552 is based activity when compared to other anti-EGFR mAbs, it does not induce on a specific degradation of RelA (p65) and inhibition of NFkB skin toxicity or hypomagnesaemia. regulated genes. Methods: Phase I prospective clinical trial (RPCEC00000022) to Material and methods: Cell lines: HT-29 (human colon cancer) and evaluate safety and optimal biological doses of immunotrans-arterial D122 (Lewis lung carcinoma). Female Balb/c mice were purchased chemoembolization (ITACE) with nimotuzumab in patients with from CENPALAB, Cuba. The peptide was synthesized manually using unresectable HCC. In this trial were enrolled 3 patients in 4 different Fmoc/tBu solid phase. level doses of Mab: 50 mg, 100 mg, 200 mg and 400 mg maintaining the same concentration of cytostatic drug per level, just one Results: Here we demonstrate that treatment of tumor cells with the administration per patients. The principal endpoint was evaluate peptide CIGB-552 promotes the degradation of RelA (p65) and safety and Optimal or Maxima Biological Doses in the treatment of HCC induces cell cycle arrest and apoptosis. In addition, the peptide by Trans arterial chemoembolization (ITACE) by injecting inhibits gene products activated by NFkB, such as the anti-apoptotic nimotuzumab an doxorubicin mixed with a radiopaque contrast (e.g. protein Bcl-2. Here, we demonstrate that the CIGB-552 stabilizes a key Lipiodol) and an embolic agent Gel foam into hepatic artery. protein in tumor cells, it which inhibits the transcription activity of NFkB. These findings provide evidence to support the regulation of Results: The maximum tolerable dose was 200 mg of nimotuzumab, transcription factor NFkB by the peptide CIGB- 552 in cancer cells. was impossible complete the administration in 400 mg because the Furthermore, we demonstrate that CIGB-552 decrease tumor growth administration rout was intra-arterial and the limiting factor was the and increase survival in the human colon cancer xenograft HT-29 and final volume. Was confirmed a gain for these patients, since the life shows anti-metastatic activity in a spontaneous metastatic model of expectancy of them were about 6 months however median survival of the Lewis lung carcinoma. 13.01 months was found to be above expected. Nimotuzumab was safe in terms of intra-arterial administration and the combination with Conclusion: Our finding points out to a novel mechanism by which the doxorubicin. Not anti-idiotipic response was detected in any treated anti-apoptotic activity of NFkB can be regulated in cancer cells. Better patients. Was the first time that nimotuzumab was administered by understanding of the regulation of NFkB will provide a platform for intra-arterial rout but is a perfect way to be used in this tumor. development of specific therapeutic agents targeted towards the cancer-associated inflammation. Conclusions: The maxima tolerated dose was 200 mg of nimotuzumab for ITACE. The administration of nimotuzumab was safety, increasing patient survival, which provides a longer period for the possibility for patients to receive a liver transplant. The combinations with chemotherapy not increase the toxicity of therapy.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S5
LATINFARMA 2013 Resúmenes/Abstracts
CO 010: NEOPLASTIC TRANSFORMATION OF HUMAN CO 011: PRECLINICAL EVIDENCES OF P3 MAB MESENCHYMAL STEM CELLS CONCERTS IMMUNE-EVASION IMMUNORESTORATION CAPACITY ON SUPPRESSED AND PRO-INFLAMMATORY PROGRAMS IN THE ABSENCE BALB/C MICE OF IMMUNE-EDITION MEDIATED PREASSURE Martínez D, Rodríguez-Zhurbenko N, Griñan T, Rondón T, Vázquez Miranda-Rodríguez A1, Sánchez-Castellanos N1, Funes-Quesada JM2, AM, Hernández AM. Pérez-Rodríguez R1, de León-Delgado J1. Center of Molecular Immunology, P.O. Box 16040, Playa, Havana, Cuba. E-mail: 1Centro de Inmunología Molecular, La Habana, Cuba. E-mail: [email protected] [email protected] 2UCL-Cancer Institute, London, United Kingdom.
Introduction: The presence of altered molecular pathways associated Introduction: A fast reconstitution of T cell dependent immunity is a with oncogenes and tumor suppressor genes as cancer hallmark not critical issue for patients treated with lymphodepleting regimens. only support the self-sufficiency on tumor cells proliferation but also Prolonged period of T cell dysfunction may have serious consequences determine the interaction of neoplastic cells with the host, allowing for the patients, like higher susceptibility to infections, reduced cells to escape from homeostatic control mechanisms. The aim of this response to vaccines and easier tumor relapse. P3, a murine IgM mAb, research is to assess the direct impact of cancer progression driven by recognize N-glycolilated gangliosides, sulphatides and antigens genetic alterations over immune-surveillance evasion and tumor expressed in several human tumors. This antibody has the ability to related inflammation, in a context independent on immune-edition trigger an IgG antibody response in the syngeneic Balb/c model, even mediated pressure. We took advantage of a model based on in vitro when it is administered without adjuvant or carrier protein. Although step-wise neoplastic transformation induced on human mesenchymal the mechanism by which the P3 activates the immune system is stem cells (hMSC). The genetic lesions introduced to transform hMSC unknown, previous experiments show that it is capable of stimulate T included hTERT, c-Myc and H-Ras activity while p53 and pRb cells populations. expression were reduced. Material and methods: We evaluate the importance of T cell Methods: MSC immunogenicity was evaluated by HLA-ABC gene and populations in the P3 mAb immunogenicity and the capacity of P3 to protein expression. In vitro co-culture experiments were performed to recover T cells populations on immunosuppressed Balb/c mice, due to determine hMSC inhibitory capacity on T cells proliferation. Immune- tumor or cyclophosphamide treatment. suppressive mediators, pro-inflammatory molecules and IFNγ Results: We show that the high immunogenicity of P3 mAb depends signaling were assessed on hMSCby qPCR, western blot, flow not only on CD4+ but also on CD8+ T cells, since the depletion of CD8+ cytometry, ELISA, gene micro-array and immune-fluorescence assays. or CD4+ T cells led to the loss of P3 mAb immunogenicity in the Neoplastic hMSC with reduced expression of IL-beta were obtained by syngeneic model. Furthermore, the immunization with P3 mAb lentiviral infection encoding shRNA targeting IL-beta mRNA. enhanced the recovery of the CD8+ T cell population in mice treated Anchorage independent growth in soft agar was assayed as surrogate with an anti-CD8a antibody. Additionally, the immunization with P3 of cells tumorigenicity. In vivo tumorigenicity was evaluated by mAb restored the capacity of immunosuppressed mice to reject xenogenic transplantation in athymic nude mice. allogeneic tumors, a mechanism mediated by the action of CD8+ T cells. Results: In vitro step-wise neoplastic transformation reduces hMSC Finally, in mice with cyclophosphamide induced lymphopenia, the + immunogenicity and progressively increases the inhibitory capacity of administration of P3 mAb accelerated the recovery of both CD4 and + hMSC on T cell proliferation, whereas a modification in the immune- CD8 T cells. suppressive mechanism is detected. Transformation leads to the Conclusions: These results show new possibilities for B and CD8+ T generation of a pro-inflammatory phenotype characterized by cells interactions during the immune response elicited by a self-protein. increased expression of IL-beta, a mediator that concert tumorigenic Furthermore they point to P3 mAb as a potential interesting candidate and immune-suppressive potential of fully transformed cells. for the treatment of immunosuppressed patients. Conclusions: Overall results suggest that neoplastic transformation can stimulate oncogenic inflammation and immune-surveillance evasion as an intrinsic feature of cancer cells, even in the absence of the immune-edition pressure exerted at tumor microenvironment.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S6
LATINFARMA 2013 Resúmenes/Abstracts
CO 012: PANUSIN, A NEW DEFENSIN-LIKE ANTIMICROBIAL CO 013: BIOMODULINA T: IMMUNOMODULATOR NATURAL PEPTIDE FROM THE HEMOCYTES OF SPINY LOBSTER PRODUCT OF THE LIFE´S QUALITY Panulirus argus Aznar García E1, Pereira Y1, Súarez Fundora S1, Batista Speranza G2, Pacios-Michelena A1, Montero-Alejo V1, Perdomo-Morales R1, Corzo Leyva B.3 G2, Pardo-Ruiz Z1, Vega-Hurtado Y1 1Clinical Study and Sanitaries Register. Centro Nacional de Biopreparados. 1Center for Pharmaceuticals Research and Development, Ave. 26 No. 1605, BioCen. Carretera de Beltrán Km 1 ½ Bejucal, La Habana, Cuba. Nuevo Vedado, CP 10600, Havana, Cuba; Telephone number: 881-1944. E-mail: 2Hosp. Oncológico GB Grassi Costia, Roma, Italia. [email protected] 3Centro Iberoamericano para la Tercera Edad. MINSAP, La Habana, Cuba. 2Institute of Biotechnology, UNAM, Av. Universidad 2001, Cuernavaca, Morelos 62210, Mexico. Roundtable is will include a groups of lecture and free topics of one thematic: The role of the Biomoduline T, pharmaceuticals Introduction: Naturally occurring antimicrobial peptides are compositions based a natural polypeptide compound made up of component of first line of host defense against pathogens as part of the specific thymus fractions and include the formulation for the humoral innate immune response in crustacean. Marine invertebrates parenteral administration. Others clinical application will be analyzed lack an acquired immune system, and must rely mainly on innate in oncology; experience in Oncology Hospital Roma, immunity mechanisms encompassed by cellular and humoral Quality specification and stability was defined. The non clinical and responses. In the spiny lobsters Panulirus argus, there are yet any clinical assay was demonstrated effectiveness and safety in geriatrics reports concerning the isolation and characterization of these patient, inflammatory and autoimmune diseases. Study in geriatrics biomolecules from hemolymph. patients with respiratory disease was evaluated clinical and Material and methods: Hemocytes were analyzed after in vivo immunological cellular test before and after the beginning of the challenged of juvenile lobsters with LPS. The TFA acid precipitation treatment. This medication is recommended for the immunological was used as fractionation procedure and the acid lysate extract dysfunction. showing antimicrobial activity was further purified by cation exchange The study about the effect of Biomodulin T in children present with chromatography. Purity was evaluated using RP-HPLC and Tricine- recurrent infection and a decrease of thymic area showed that after the Urea-PAGE electrophoresis. The minimal inhibitory concentration treatment decreases of infections and increases the thymic area. (MIC) was evaluated by broth microdilution assay against Gram positive and Gram negative microorganisms, while the susceptibility The others clinical applications are evaluated: Cancer patient with assay was assessed by radial diffusion. Complete amino acid sequence chemotherapy treatment, rheumatoid arthritis, multiple sclerosis, AIDS, was established by a combination of Edman degradation, mass and immunodeficiency atypical. spectrometry and transcriptome analysis. Results: the sequence analysis demonstrated for the first time a defensin-like antimicrobial peptide isolated from crustacean. This defensin shows potent antimicrobial activity against gram-positive and gram-negative bacteria, it is not haemolytic or LPS-binding activity. Besides, it enhances LPS-induced pro-inflammatory cytokines IL-6, IL- 1β and TNFα as shows in the Monocyte Activation Test (MAT). Conclusion: A defensin-like antimicrobial peptide was identified with potent antimicrobial activity.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S7
LATINFARMA 2013 Resúmenes/Abstracts
Simposio de Ensayos Clínicos / Symposium on Clinical Trials
CO 015: ETHICAL CONSIDERATIONS IN DEVELOPING CO 016: CANCER CLINICAL TRIALS: STATE OF THE ART AND COUNTRIES IN HIV VACCINE TRIALS THE CUBAN EXPERIENCE Ellis G. Crombet-Ramos T.
Strategies for Well-Being, LLC, Philadelphia, PA, USA. E-mail: Center of Molecular Immunology, La Habana, Cuba. [email protected]
The old paradigm for oncology drug development was based on the Since no disease of global proportions has been eradicated or experience of classical cytotoxic agents. According it, antitumor activity effectively controlled without a vaccine, implementing a successful is connected to toxicity and therefore, treatments must be scaled up to AIDS vaccine program is critical. The effort poses not only scientific maximal tolerated dose; pharmacokinetics is relevant to define the challenges, however, but also critical ethical issues. optimal schedule; an active drug should produce rapid tumor shrinkage; the response rate is a predictor of survival and tumor At issue is the ethical principle of “beneficence,” the obligation to progression indicates treatment failure. However, the unique minimize possible harms and maximize possible benefits of medical characteristics of biologics challenge these dogmas and demand novel intervention. Informed consent presents other ethical issues with trials developmental guidelines. For immunotherapy, the optimal biologic in developing countries. In resource--poor areas, access to the medical dose can be far below the maximal tolerated dose, mechanisms of care provided to trial participants can be seen as undue inducement to action can be indirect and therefore not related to pharmacokinetics, participate in a clinical trial. effect in survival can be seen without tumor shrinkage and therapeutic Scientists may understandably also wish to minimize risk to study effect could be delayed in time and continue beyond progression. The participants, and it has been shown that HIV can be prevented by new emerging paradigm recommends finding the optimal biologic dose reductions in high-risk behaviors. However, if this ethical imperative is in a “proof of principle trial” according to a pre-defined biological followed and counseling and contraceptives provided, the study results endpoint or biomarker; followed by an efficacy assessment in a could be jeopardized. randomized trial with long term treatment and survival as the main endpoint. CIM has now 10 projects in clinical development, including When a developed country enters a developing country to conduct a biosimilars and proprietary drugs. The original product pipeline clinical trial, its actions are closely scrutinized because of the concentrates around 3 main targets: the Epidermal Growth Factor disparities that exist between the home nation of the researchers and Receptor (EGFR) system, the gangliosides and the regulatory loops of the local trial population. If regulatory authorities and institutional the immune system. Four of the innovative products have already review boards (IRBs) are not well developed in host countries, political transited through clinical trials and received registration in several and economic interests can influence which vaccines proceed in countries: the anti-EGFR humanized monoclonal antibody clinical trials. nimotuzumab, the anti-CD6 antibody (itolizumab), the EGF conjugated therapeutic vaccine CimaVax-EGF and the anti-idiotypic vaccine This leads to the following question: if the ethical norms and standards racotumomab. The clinical experience with these products illustrates of care differ between countries, whose rules prevail - those of the the application of the new development paradigm intended to country which has developed the vaccine and is holding the clinical transform cancer into a chronic disease. trial, or those of the host country? This presentation will examine considerations to enhance and accelerate the development of an HIV vaccine in a manner sensitive to ethical concerns of subjects and their communities.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S8
LATINFARMA 2013 Resúmenes/Abstracts
CO 017: PHARMACODYNAMICS AND PHARMACOKINETICS CO 019: SERUM LEVELS OF INFLAMMATORY MARKERS IN OF TWO FORMULATIONS CONTAINING SYNERGISTIC PATIENTS WITH ACUTE MYOCARDIAL INFARCTION PROPORTIONS OF INTERFERONS ALPHA-2B AND GAMMA DURING A 6 MONTH FOLLOW UP IN HEALTHY MALE VOLUNTEERS (SOFIA STUDY) Brizuela NY, Ricarte Bratti JP, Vergottini JC, Ponce LN and Menara A. García I1, Díaz A2, Tuero AD1, González CA2, Pérez S2, García Y1, Campos Cátedra Farmacología General. Facultad de Ciencias Médicas. Universidad 1 1 1 1 2 3 R , Valenzuela CM , Cruz A , Cervantes M , Martín A , Vásquez DM , Nacional de Córdoba. Santa Rosa 1085. (5000), Córdoba. Argentina. E-mail: Howland I4, Bello I1. [email protected], [email protected] 1Clinical Investigation Department, Center for Genetic Engineering and Biotechnology (CIGB), Ave 134 e/ 23 and 25, Cubanacán, Playa, P.O. Box 6332, Havana 10600, Cuba. Telephone: +53 (7) 2087379; 2087465; Fax: +53 (7) Introduction: The inflammation plays a fundamental role in 2736008. Email: [email protected] pathogenesis and complication of the atherosclerosis. Cytokines and 2 National Center for Toxicology, “Carlos J. Finlay” University Hospital, Ave. 31 and adhesion molecules are key components of these events that 114, Marianao, Havana 11400, Cuba. 3Genomics Department, CIGB, Ave 134 e/ 23 and 25, Cubanacán, Playa, Havana contribute to the development of an atherosclerotic plaque. Their 10600, Cuba. determination of plasma levels provides an excellent reflection of the 4Clinical Laboratory, Center for Medical-Surgical Research, 216 and 11-B, underlying inflammatory process, since it is positively correlated with Siboney, Playa, Havana 10600, Cuba. other markers such as pro-inflammatory cytokines. The cytokine Tumor necrosis factor alpha (TNF-α), the interleukin-6 (IL-6) and vascular adhesion molecule-1 (VCAM-1) are indicators of basal Introduction: A sustained full Interferon (IFN)-receptor interactions inflammation. This study reports on the follow-up of 27 patients, aged with more potent antiproliferative activity are desired in the treatment 42–82 years with confirmed acute myocardial infarction (AMI group) of cancer. This is possible to obtain combining IFN-alpha and IFN- and a matched control group of 10 patients without coronary artery gamma that synergize for their biological activities. The aim of this disease (control group). study was to characterize pharmacodynamics, pharmacokinetics and Material and methods: Blood samples for determination of biological safety of two formulations (CIGB-128 and CIGB-128-A) inflammatory markers were taken on the 3rd day and after 6 months. based on the combination of IFNs alpha-2b and gamma in healthy male Concentrations of cytokines and adhesion molecules were measured volunteers. using commercial Immunoassay (ELISA) kits (Amersham Sciences). Material and methods: A randomized, crossover, double-blind study Results: The serum level of VCAM-1 in the AMI group was significantly 6 with a 3-weeks washout period, was done. A single 24.5 x 10 IU IFN higher than in control groups (P<0.01). In the acute phase of mixture dose was administered intramuscularly. Thirteen apparently myocardial infarction (MI) the levels of TNF-α and IL-6 were higher healthy male subjects were included. Classical IFN-inducible serum than in the control group (P0.01). Six months later the levels of TNF- markers, neopterin, beta2-microglobulin (β2M), and 2’-5’ α, IL-6 and ICAM-1 normalized (P0.001). oligoadenylate synthetase (2'-5' OAS), were used as indicators of their pharmacodynamic action. Serum IFN concentration was measured Conclusions: The present study showed that in the acute phase of AMI during 48 hours by enzyme immunoassay. Adverse events were increased activation of pro inflammatory markers. In the course of rigorously checked. healing within 6 months after the infarction the inflammatory reaction disappears. It is necessary to carry out further studies to clarify the role Results: Neopterin levels at 24-48 hours post-administration were 9 of adhesion molecules in acute coronary syndrome. Future studies of times superior to the initials. This high increment has not been the prediction of recurrent vascular events after AMI should described before in the literature with any subtype or variant of IFN. At concentrate on clinical variables and different blood inflammatory the same time mean serum β2M peaked around the double from markers. baseline. The concentrations of the enzyme 2'-5' OAS were still elevated at the eighth day post-injection. Concerning pharmacokinetics, no interferences by simultaneous administered IFNs were observed in their typical similar systemic profiles; parameters as Tmax (7-10 hours) and t1/2 (6 hours) were within the reported ranges for these conventional IFNs. Both products were well tolerated. The most frequent adverse reactions were fever, headache, arthralgias and lymphopenia, mostly mild. Serum IFN concentrations has a direct, strong correlation with body temperature. Conclusions: The potent synergistic IFN mixture possesses improved pharmacodynamic properties without additional toxicity that may useful in the oncologic setting leading to less frequent injections, and a better patient’s compliance and quality of life.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S9
LATINFARMA 2013 Resúmenes/Abstracts
CO 020: SUBJECT: NATIONAL BIOETHICS NETWORK AND CO 021: CLINICAL TRIAL DESIGNS THAT CAN SPEED UP NEW RESEARCH IN PERU - RENABIP DRUG DEVELOPMENT Socualaya P, Minaya G, Ayala B and Fuentes D. López-Saura PA, Valenzuela-Silva CM.
Instituto Nacional de Salud – Perú. Calle Cápac Yupanqui 1400, Lima 11, Perú. E- Center for Genetic Engineering and Biotechnology; La Habana, Cuba. E-mail: mail: [email protected]; [email protected] [email protected]
Introduction: 85% of Research Ethics Committees exist in Peru and The “bottle-neck” of new product development in the last years has they are concentrated in Lima. Most are private and only 2 of them been safety and efficacy demonstration in the clinical setting, which is account for over 50% of approvals of clinical trials nationwide. Thus, the most expensive stage as well. Following the established regulatory the National Institute of Health assumes the challenge of developing a paradigm, this evaluation must follow the sequential phase I-IV national system of monitoring and control in research ethics, creating pathway, which is quite time-consuming. A new approach is required in the National Network of Bioethics and Research in Peru (RENABIP). order to optimize this process. Recently, innovations concerning clinical trials design and interpretation have been introduced. They Material and methods: Strategies for the implementation process of include adaptive designs where “bridges” between subsequent phases the RENABIP were raised to determine regional capabilities, develop (I – II or II - III) can be envisaged. Improvements in knowledge on the and disseminate policies, national standards, guidelines and technical biological mechanisms involved in disease and drug actions also permit tools, advocate and implement the Regional Coordinating Centers of a better rationale for trials justification and evaluation. Adaptive Institutional Ethics Committees Research, develop skills, alliances and designs permit the modification of one or more aspects in a prospective cooperation agreements and determination of extension mechanisms, way, based on analyses of data gathered from study subjects as long as communication, expansion and sustainability. they are obtained. These modifications should be previewed in the trial Results: In July 2012, the process of implementing the RENABIP began protocol. Examples of such trials, sponsored by the Center for Genetic in 12 regions of Peru, achieving to involve 277 authorities of Regional Engineering and Biotechnology where these techniques have been used Coordinating Centers of Research Ethics Committees; technical for several years (with the agreement of the corresponding ethics meetings and/or workshops were also performed, and coordination committees and the Cuban regulatory authority) will be shown. More with key stakeholders in each region for research management were than 300 subjects have been “saved” to be included in those trials, established. In March of 2013, the virtual platform was implemented including more than one third that would had received a placebo. A for education and training in national Bioethics. In April 2013, the more flexible and rational regulatory paradigm is proposed where an Research Ethics Course started, in order to train and strengthen the exploratory phase is conceived to gain knowledge on the products’ members of the Research Ethics Committees of the regions, and in this clinical performance in order to go into a confirmatory phase to attain way support the management of research regional health priorities. approval. Conclusions: Today we continue with the process of implementing the National Plan of strengthening and sustainability RENABIP; and it has been scheduled the monitoring and evaluation of the RENABIP.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S10
LATINFARMA 2013 Resúmenes/Abstracts
MR 001: CLINICAL TRIALS: PERSPECTIVE AND UPDATING CO 022: EFFICACY AND SAFETY OF RECOMBINANT STREPTOKINASE VERSUS HYDROCORTISONE ACETATE- Pascual López MA1, Hernández Rodriguez A1, Marrero Miragaya MA1, Orta Hernández SD2 BASED SUPPOSITORIES IN THE TREATMENT OF HEMORRHOIDAL DISEASE. RANDOMIZED, CONTROLLED 1Clinical Trial Coordinator National Centre (CENCEC), La Habana, Cuba. TRIAL (THERESA-4 STUDY) 2National Regulatory Agency (CECMED), La Habana, Cuba. 1 2 1 Hernández-Bernal F , Castellanos-Sierra G , Valenzuela-Silva CM , Catasús-Álvarez KM1, Martínez-Serrano O3, Lazo-Diago OC1, Causa- Introduction: The principles and practice of clinical trials presents a García JR4, Domínguez-Suárez JE5 and López-Saura PA1 for the detailed account of how to conduct the trials. It describes the design, THERESA-4 (Treatment of HEmorrhoids with REcombinant analysis, and interpretation of clinical trials in a non-technical activity. Streptokinase Application) Group of Investigators.
Objectives: This panel provides a general perspective on the historical 1Center for Genetic Engineering and Biotechnology, La Habana, Cuba. development, current status, and future strategy of the clinical trial in 2“Juan B. Zayas” Hospital, Santiago de Cuba. Cuba. 3“Ernesto Guevara” Hospital, Las Tunas, Cuba. 4“Celia Sánchez” Hospital, Manzanillo, Granma, Cuba. , Cuba Results and conclusions: It’s including 20th years of experience 5“Gustavo Aldereguía” Hospital, Cienfuegos, Cuba. planning, conducing and monitoring national and internationally clinical trials. The other hands, experience gained from national regulatory agency and your adequate system for clinical trial control Introduction: The aim of this study was compare the efficacy and safety indicates the challenges for many countries in our region for fully of two schedules of recombinant streptokinase (rSK) suppositories and a effective regulation implementation. Features examples derived from hydrocortisone acetate-based suppository (Anusol-HC®), for the the author's personal experience. treatment of acute hemorrhoidal disease. Material and methods: A multicenter (11 sites), randomized (1:1:1), open, parallel groups, active controlled trial was done. After inclusion, subjects with acute symptoms of hemorrhoids, who gave their written, informed consent to participate, were centrally randomized to receive, as outpatients, rSK (200000 IU, schedules A or B) or Anusol-HC® (25 mg hydrocortisone acetate) suppositories, which had different organoleptic characteristics. rSK was administered by the rectal route, three units, one every 8 hours, and then five units, one every 12 hours (schedule A) or six units, one every 8 hours (schedule B). Anusol-HC® suppositories were given every 8 hours up to a maximum of 24 administrations according to the product label. Evaluations were performed at 3, 5 and 10 days post- inclusion. The main end-point was the 5th-day response (disappearance of pain and bleeding, and ≥70% reduction of the lesion size). Time to response and need for thrombectomy were secondary efficacy variables. Adverse events were evaluated too. Results: Response rates were 156/170 (91.8%) and 155/170 (91.2%) with rSK schedules A and B, respectively, which were significantly larger (p<0.001) than with Anusol-HC® suppositories (46/170; 27.1%). Time for response were significantly shorter (p<0.001; log-rank test) in the rSK groups (median: 3 days) with respect to the active control (median: 10 days). Thrombectomy was necessary in 2/122 and 2/129 with baseline thrombosis in the rSK schedules A and B, respectively vs. 14/133 in the Anusol-HC® group (p=0.001). There were no adverse events attributable to the experimental treatment. Conclusion: rSK suppositories showed a significant advantage over the widely used over-the-counter Anusol-HC® for the treatment of acute hemorrhoidal illness, with an adequate safety profile.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S11
LATINFARMA 2013 Resúmenes/Abstracts
CO 023: TRIMETAZIDINE INHIBITS THE RENAL FIBROSIS the renal fibrosis. Fibrosis was quantified using the Image Pro Plus INDUCED BY CYCLOSPORIN A software (NIH). By Transmission electron microscope (TEM) the renal ultrastructure was analyzed. Transforming Growth Factor beta and De la Cruz Rodríguez L, Rey M, Honoré S, Oldano A, Araujo C. Collagen I were evidenced by immunohistochemistry. Facultad de Bioquímica Química y Farmacia. Universidad Nacional de Tucumán, Results: animals treated with 25 mg CyA/kg/day presented hydropic Balcarce 747. (4000) San Miguel de Tucumán, Argentina. E-mail: degeneration with nuclei displaced and in some cases are found in the [email protected] tubular lumen, observed by optical microscopy. Ultrastructure analyzed by TEM showed edematous mitochondria with loss of its internal structure. Interstitial fibrosis was confirmed by evidenced Introduction: Cyclosporin A (CyA) is an immunosuppressor used in immunohistochemistry Transforming Growth Factor Beta and Collagen transplanted patients. Adverse effects like as nephrotoxicity and I using specific antibodies. Pre-treatment with TMZ for 20 days and the hepatotoxicity, have been described. Our previous papers synergistic treatment TMZ+CyA, showed biochemical parameters demonstrated that Trimetazidine (TMZ) is able to reverse the CyA- within the reference values and preserved cytoarchitecture, with induced nephrotoxicity. Objectives: contribute to the knowledge of the negative immunohistochemistry to the markers studied. mechanisms of action of TMZ in renal fibrosis induced by CyA. Conclusions: Interstitial fibrosis induced by CyA was dose and time Material and methods: The experimental design was carried out for dependent. The production of inflammatory mediators, Transforming 120 days. Included four groups (n = 8) of male Wistar rats treated Growth Factor Beta and the synthesis of Collagen I, would be inhibited with: A control. B treated with CyA (25 mg/kg/day). C treated with by TMZ. TMZ (20 mg/kg/day). D treated TMZ for 20 days (20 mg/kg/day), them for 120 days with TMZ (20 mg/kg/day) and CyA (25 mg/kg/day). Urea and serum creatinine as well as the excretion of urinary gamma glutamyl transpeptidase were determined. Structural studies were performed with hematoxylin-eosin and Mallory staining to evidence
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S12
LATINFARMA 2013 Resúmenes/Abstracts
Taller de Métodos Alternativos (3Rs) en Farmacología, Toxicología y Enseñanza / Workshop on 3Rs Alternatives in Pharmacology, Toxicology and Teaching. Sesión: Farmacología y Toxicología / Session: Pharmacology and Toxicology
C 003: INTERNATIONAL VALIDATION AND REGULATORY CO 024: ALTERNATIVE METHODS IN THE SAFETY ACCEPTANCE OF ALTERNATIVE METHODS: PROGRESSES EVALUATION OF COSMETIC: EUROPEAN SITUATION AND PROSPECTS Vinardell MP. Eskes C. Dep. Fisiología, Facultad de Farmacia, Universitat de Barcelona, Av. Joan XXIII s/n ESTIV, Switzerland. 08028 Barcelona, Spain. E-mail: [email protected] The last years have been marked by the validation and acceptance of a number of regulatory in vitro alternative methods to animal testing adopted at international level such as by the OECD program on Test From July 11, 2013 onward, cosmetic products placed on the market of Guidelines. One of the contributing drivers is certainly the strong European Economic Area are obliged to comply with the new requests from the European Union, where the legislation on cosmetics European cosmetics regulations, of which some provisions will be prohibited the testing of finished cosmetic products and their enforced before the above date. These new cosmetic requirements are ingredients on animals as well as the marketing within the European released in the form of EU regulations in the 27 EU member states plus Union of cosmetics products tested or containing ingredients tested on Norway, Iceland and Liechtenstein, and implemented as national law, animals. In addition to cosmetics, the European Union Regulation on unlike the EU directives which need converting into each domestic new and existing Chemicals (REACH) also emphasizes the use of version. This Regulation will replace the old cosmetics directive of and alternative methods, requiring the use of animal testing only as a last the subsequent 67 amendments. The new regulation simplifies the resort, and establishes several rules where hazard identification might cosmetic requirements of European Economic Area, making itself a be carried out using alternative methods to animal testing. In order for single law, and eliminate ambiguities that may occur among the alternative methods to gain international regulatory acceptance, they member states during the enforcement process. generally need to undergo a process of independent scientific validation. In the last years, several in vitro test methods have been The European Cosmetic Regulation indicates that all cosmetic products validated and adopted at a regulatory level in the areas of ocular and in the European Union should be safe for the human health in the dermal hazard identification for either the full or the partial normal use conditions. In Europe the safety of cosmetics is based on replacement of the animal test. In particular the adoption of full the safety evaluation of each individual ingredient. Currently, the replacement in vitro methods is leading to new approaches of chemical safety of cosmetic products has to be assessed prior to release by a safety assessment with no animal data. These new approaches bring in ‘suitably qualified’ person. The new regulations specify that the turn a number of questions related to the application of alternative qualifications should be in toxicology and that the assessment should methods for specific purposes and their possible combination in test follow a particular protocol. strategies. The latest progress achieved in the formal validation, Cosmetics in general, do not induce severe problems to health, but this regulatory acceptance and application of alternative methods will be is not synonymous of innocuous. All the substances that should presented, as well as the new challenges that safety assessors and represent any serious health risk are listed in the annexes of the regulators may need to face regarding the regulatory application of Regulation, including forbidden products, with restrictions, colorants, alternative test methods. preservatives and UV filter. In these cases, the responsible of safe evaluation is the European Commission through the Directorate General for Health and Consumers (DG SANCO), the safety evaluation performed by the Scientific Committee on Cosmetic Safety (SCCS). This evaluation is based on the data of the dossiers submitted by industry. The SCCS publishes an opinion that appears in the open DG SANCO web. The European Directive on Cosmetic 2003/15/EC established since March 2009 a ban to use animals in the safety evaluation of cosmetic ingredients. In practice, the safety evaluations of the SCCS are based on old studies done with animals and prior to the ban and recently on in vitro studies. In this talk the percentage of in vitro methods evaluated by the SCCS since 2009 will be presented. One of the difficulties relative to the use of in vitro methods is the lack of validated ones. The most used in vitro methods presented in the dossiers are the studies of dermal absorption, mutagenicity and genotoxicity and in a less extents studies of eye irritation and dermal irritation.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S13
LATINFARMA 2013 Resúmenes/Abstracts
CO 025: PRINCIPLE OF REDUCTION AND THE VALIDITY AND CO 026: ALTERNATIVE METHODS AND THE SAFETY EFFICIENCY OF ANIMAL ASSAYS ASSESSMENT OF HEALTH PRODUCTS: EXPERIENCE OF NATIONAL INSTITUTE OF QUALITY CONTROL IN HEALTH, Rosenkranz A. BRAZIL Bioterio Central, FCEyN, Universidad de Buenos Aires, Argentina. E-mail: [email protected] Fernandes Delgado I, Chaves Leal E. National Institute of Quality Control in Health (INCQS) - Oswaldo Cruz Foundation (Fiocruz) – Av. Brasil, 4365 – Manguinhos - Rio de Janeiro - Brasil. According the International Guiding Principles animals should only be www.incqs.fiocruz.br - E-mail: [email protected]. used when necessary and the Principles of the Three Rs should be incorporated in the design and conduct of the activities and, when no alternative methods are available to replace the use of live animals, the The National Institute of Quality Control in Health (INCQS) is a minimum number of animals should be used to achieve the goals. The technical-scientific unit of the Oswaldo Cruz Foundation (Fiocruz) and most important international Journals require the authors to follow is the Brazilian Reference Laboratory which handles the quality control International Guidelines like the Guide for the Care and Use of of food, drugs, biological products, health-related and dialysis items, Laboratory Animals, NRC, USA, that request for justification of the hygienizing and disinfectant agents, diagnostic kits, cosmetics, blood number of animals and experimental group sizes. In order to assure and blood derivatives, environments and services. Its mission is to valid and reproducible experiments it is imperative to use animals contribute to the promotion and recovery of health conditions, to the with a defined dramatype. Factors such as: species, strains, sex, age, prevention of diseases, acting as the National Reference for scientific weight, cage, bedding , temperature, humidity, air velocity, noise, light, and technical issues regarding the quality control of products, odors, day of the week, circadian rhythms, nutrition, presence of environments and health services. Regarding safety assessment, our microorganisms, human/animal interaction, order of administration of staff has been dealing with toxicological assays and also works to substances and order of euthanasia may affect the response of the develop, adjust and implement new methodologies. In the field of animals and introduce bias or lower the precision of the results of the alternative methods, some new approaches have been investigated, experiments. Adequate reporting of the conditions of animal use are such as: (i.) alternatives to eye and skin irritation tests, including HET- important to enable replication, and also to allow readers to judge CAM, RBC and cytotoxicity assays, (ii.) alternatives to pyrogen test and scientific quality, but analyses of published studies with research (iii.) phototoxicity, as well as (iv.) in silico alternatives. Additionally, our animals have demonstrated numerous deficiencies in the reporting of staff has been working in strait collaboration with Brazilian Health details of research methods for animal studies and many papers Surveillance Agency (Anvisa) in order to consolidate activities of the omitted the number of animals used. An unspoken industry rule newly created Brazilian Center for Validation of Alternative Methods alleges that at least 50% of published studies from academic (BraCVAM). By means of this initiative, it is aimed to achieve inter- laboratories cannot be repeated in an industrial setting, Unavoidable laboratory validation of alternative methodologies, seeking the variability could be controlled using an experimental design with regulatory acceptance. randomized blocks. The range of applicability might be extended using factorial designs. The analysis should always be appropriate to the type of experimental design used. Several studies demonstrate that inappropriate statistical methods were used in more than 60% of papers. The editors of scientific journals should promote high-quality reporting.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S14
LATINFARMA 2013 Resúmenes/Abstracts
CO 027: PROPOSED METHODS AND ESPECIALLY STEM CELLS CO 028: BASIC ASPECTS OF THE TOXICOLOGICAL AS POTENTIAL REPLACEMENT METHODS TO STUDY EVALUATION OF NANOMATERIALS HUMAN PATHOLOGIES Vinardell MP, Nogueira DR, Mitjans M. Bercovier H. Departament de Fisiologia, Facultat de Farmàcia, Universitat de Barcelona, Av. Head of the National Committee for Animal Experimentation and Hebrew Joan XXIII s/n, 08028, Barcelona, Spain. E-mail: [email protected] University of Jerusalem, Israel.
Nowadays there are no established protocols to evaluate the safety of Ex vivo experiments, Phase 0, computational modeling, fMRI on Human nanomaterials, but this is an important concern due to the progressive and Stem Cells studies have been presented as potential replacement used of this kind of substances in many areas. Because of public and methods for animal experimentation. Many paradoxes are not often governmental urging to develop alternatives to in vivo testing, in vitro envisaged such as the following statement as an example: “instead of cell-based models may be of great relevance for testing of using living animals, certain experiments can be carried out on tissue nanomaterials. We especially aimed to create predictive in vitro samples in vitro. However the ex vivo preparations cannot regenerate, toxicological approaches for testing nanotechnology-based products so they must be acquired by killing animals. Legally, killing an animal to designed for topical applications. obtain tissue samples is not considered an animal experiment (therefore reducing artificially the number of animal The physicochemical and morphological characterization of experimentations!!!), even if the animal in question is a vertebrate. In nanomaterials is crucial for a correct evaluation together with the contrast, it is regarded as an animal experiment to anesthetize a study of a potential size change of the nanomaterial in contact with the vertebrate, make observations while the animal is under anesthesia cell culture medium, as has been described in some papers. and then to kill the animal by increasing the dose of anesthetic”. The In this context, we have studied novel formulations based on mixed replacement of in vivo experiments with in vitro methods does not cationic vesicles composed by the phosphocholine DMPC, cholesterol reduce significantly at first the number of research animals that are and three different cationic lysine-based surfactants that differ in the killed. On the contrary, the limited survival time of brain slices, for cationic charge position and in the alkyl chain length. example, restricts the amount of data that can be obtained from a single experiment. We will further discuss additional replacement methods The physicochemical properties (particle size, polydispersity index, and evaluate them in the light of new molecular tools and common morphology and zeta potential) and the amount of surfactant sense. incorporated in each cationic nanovesicle formulation were assessed. The cytotoxicity of these nanomaterials was evaluated by means of three in vitro endpoints (MTT, NRU and LDH) using skin representative cell lines (HaCaT keratinocytes and 3T3 fibroblasts). Moreover, the phototoxic effect of the formulations (UVA light, 2.5 J/cm2) and the modulation of the IL-1α cytokine production as inflammatory indicator were also studied. The cationic nanovesicles were roughly spherical shape with average diameter ranging from 110 to 170 nm, as determined by DLS. The nanovesicles size showed by TEM images was in general smaller. It was observed vesicles with diameter of ~ 150 nm (corroborating the DLS measurements), together with a population of vesicles with diameter ranging from 20 to 50 nm. The amount of surfactant incorporated into the nanovesicles ranged from 75 to 99%. After 24-h of cell exposure to the formulations, different cytotoxic responses were observed, depending on the surfactant, cell line and endpoint assayed. MTT was the most sensitive assay to detect the cytotoxicity, while NRU and LDH assays showed higher IC50 values. Formulations containing the surfactant with the longest alkyl chain showed the most significant cytotoxic effects. Moreover, no significant phototoxic activity was observed in HaCaT cells, while only minimal inflammatory response was induced in HaCaT as demonstrated by the IL-1α production. Taken together, our results demonstrated that the nanomaterials composition play a key role in the resulting toxicity, and also showed that the combination of different assays and skin cell models offers an in depth and comprehensive evaluation of the potential toxic effects of nanomaterials designed for topical delivery of biologically active substances.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S15
LATINFARMA 2013 Resúmenes/Abstracts
Taller de Métodos Alternativos (3Rs) en Farmacología, Toxicología y Enseñanza / Workshop on 3Rs Alternatives in Pharmacology, Toxicology and Teaching. Sesión: Educación / Session: Education
CO 029: BEST PRACTICE AND ALTERNATIVES TO ANIMAL CO 031: ALTERNATIVES TO THE USE OF ANIMALS IN EXPERIMENTS IN EDUCATION VETERINARY MEDICINE EDUCATION Jukes N. Torres M, Guerrero R, Serrano C, Arcila V.
InterNICHE, Leicester, England. Grupo de Investigación en Ciencias Animales, GRICA. Facultad de Medicina Veterinaria y Zootecnia. Universidad Cooperativa de Colombia, UCC, Sede Bucaramanga. E-mail: [email protected] The design of the curriculum and of training courses in biological science, medicine and veterinary medicine involves choices about the The training of biomedical students including veterinarians, involves tools employed to meet teaching objectives. Ensuring that the tools are the use of animals. These practices have been proven to cause high the most appropriate requires an awareness of developments in levels of stress that affect animal welfare and health. The traditional technology, educational practice and ethics. Harmful animal use, such teaching model raises a hard ethical dilemma; at the center of this as animal experimentation and the dissection of purpose-killed debate lays claims about animal rights to do not suffer pain and animals, continues to be employed in some practical classes and anguish. On the other hand there is the student training, which requires training courses. However, innovative and humane alternatives are the acquisition of high level skills for the future professional life. The now widely available and are increasingly being implemented to aim of this study was to develop a sensitization strategy for the enhance knowledge and skills acquisition and to replace harmful academic community addressing alternatives to the use of animals in animal use worldwide. This process of transition reflects a growing higher education. Reducing the use of animals in the classroom and commitment to best practice, a realization of the potential of biomedical research through the design of inanimate anatomical technology, and the demands of students, trainees and campaigners. models (IAM). A pilot study was conducted on the students attending to Alternatives include non-animal alternative tools such as multimedia a university medical practice. The skills acquisition was assessed in the software and virtual reality (VR), training models, mannequins and control and experimental group. The results suggest that the use of IAM simulators. They also include alternative approaches such as student might improve the students learning process and the development of self-experimentation, the use of ethically sourced animal cadavers, and technical abilities with a positive impact in the animal health. The clinical learning opportunities with patients. In this presentation, the entailment of IAM as part of the teaching-learning processes should be alternatives employed within pharmacology and other disciplines will considered for approval at the educative institutions curriculum be detailed, and selected products will be demonstrated. Teaching committee. Thus, in order to establish the academic guidelines, which objectives and the lessons of the hidden curriculum will be explored, are necessary for the implementation of IAM. From an economic point and published studies will provide further evidence of the pedagogical, of view, the use of IAM will benefit faculty expenses considering the ethical and economic advantages of alternatives. The positive impact of substantial reduction on animal maintenance, supplies and drugs costs. humane education on students, teachers, society, the professions and As socially acceptable alternative, the use of IAM produces a large the animals will be traced, and case studies will show that such tools positive impact on the relationships with the animal rights and approaches are often no longer considered ‘alternative’, but the organizations and Non-governmental organizations (NGOs). norm.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S16
LATINFARMA 2013 Resúmenes/Abstracts
CO 032: SUPER-SELECTIVE OPHTHALMIC ARTERY CO 033: USING VIDEOS AND PLASTINATED MURINE MODELS CATHETERIZATION IN THE PIG AS A TRAINING MODEL FOR TRAINING WITH POSSIBLE IMPLICATIONS FOR RETINOBLASTOMA Streber ML, Ramirez MA. TREATMENT INCMNSZ, Vasco de Quiroga No. 15, México City, México. E-mail: Asprea M, Schaiquevich P, Requejo F, Buitrago E, Chantada G. [email protected] DVM, SENASA, SENASICA, SAGARPA, Tecamac, México, México. Hospital de Pediatría JP Garrahan, Buenos Aires. Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Argentina. Our training program is based in Mexican Norm NOM-062-ZOO-1999, Introduction: Super-selective ophthalmic artery infusion was studied one of the species used as a requirement are small rodents. Most of in a porcine model and compared to periocular administration as an times, students have different animal experience and different levels of alternative route for administration in retinoblastoma. Ophthalmic manual skills. We refined this program using classroom presentations, artery infusion of topotecan results in significantly higher vitreous a training video in Spanish and also a plastinated murine model. We exposure compared to periocular administration. Systemic exposure used 30 adult nude mice, no longer needed as reproducers, they were was low after both routes of administration, confirming feasibility of euthanized by CO2, internal organs were removed, and cotton balls the method. were placed inside. The bodies including, head and skin or the skeleton were fixed by immersion in 10% buffered formalin. After several weeks Purpose: To develop a technique for local drug administration in a of fixation, bodies were washed with tap water and allowed to dry with porcine model with potential translation to retinoblastoma paper towels. Cotton balls were removed. Immediately, the bodies were chemotherapy treatment. placed in a glass jar over a lake of acetone. After two changes, the bodies were immersed in glycerin. The process was finalized when the Material and methods: Six domestic Landrace pigs were included. In skin was soft and translucid. Plastinated nude mice were used for four, the ophthalmic artery catheterization was performed in an learning handling and also different routes of administration (ocular, anesthesized animal under anticoagulation. A 5-French arterial sheath per os, IP, IM, SC), specially because the nu/nu strain is very expensive was placed in the femoral artery and a 5-F catheter was guided into the and sensitive. Also, the murine models could be used to learn blood common carotid artery to the maxillary artery. The ophthalmic artery sample taking and tissue sampling. Each plastinated mouse has a soft was super-selectively catheterized (OAI) using a microcatheter. Serial consistence, no bad odor, and could be re-used as many times as angiograms were performed. Super-selective OAI of topotecan (1 mg) student needs. Total length of course: 25 hr. Each wet lab: 4 h, toone eye and periocular injection (1 mg) to the fellow eye was composed of 15 students. Survey questions were tested before and performed after a wash-out period. Chemotherapy (topotecan) was after training. The learning curve using the video, plastinated models delivered in a pulsating fashion. The microcatheter was removed and and anesthetized animals, was reduced. The students felt comfortable systematic procurement of vitreous and plasma samples was started to have the opportunity to learn a lot in a short period of time and to immediately. Two other animals were only administered intra- have the experience before using live un-anesthetized animals. This arterially (IA) with the same dose of chemotherapy through the format has the potential to improve animal welfare, and promote high external carotid, and plasma and vitreous samples were obtained. All quality research, avoiding accidents like bites and harming animals. animals were sacrificed at the end of the experiment according to an approved method of euthanasia. Results: The ophthalmic artery of all six animals was successfully catheterized by means of the super-selective ophthalmic artery technique. Maximum total topotecan concentration in the vitreous (median, range) after OAI and IA was 131.8 ng/mL (112.9-138.7) and 5.4 ng/mL (4.7-6.1), respectively. Systemic exposure for topotecan was low after both modalities of administration with a median (range) value of 10.6 ng/h/mL (6.8-13.4). Conclusion: We were able to develop the super-selective ophthalmic artery catheterization in a porcine model. Topotecan was infused using this technique and vitreous drug levels were 24 times higher than those attained after IA infusion of the same dose of chemotherapy. Topotecan systemic exposure was low and comparable between drug administration techniques. These results show the selectivity of the infusion to attain the ocular structures with potential implications in retinoblastoma treatment.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S17
LATINFARMA 2013 Resúmenes/Abstracts
CO 034: DISSECTION OF THE VENTRAL NERVE CORD-DEEP placing what remained on top of a dissection table. The ventral ABDONIMAL FLEXOR MUSCLE SYSTEM OF THE nervous-abdominal flexor muscle system was isolated after removal of FRESHWATER LOBSTER OF THE Cherax GENUS: AN IN SITU the shell and abdominal cuticle. The caudal end of the muscle was MODEL FOR TEACHING PHARMACOLOGY attached to a myograph and the nerves were electrically stimulated using a varying voltage of 0.1 mV – 110 V; any muscular contractions Islas V, Martínez C, Alavez JS, Hernández A, Lazo RE. were recorded. The electrical stimulation was repeated two more times, once with the addition of a solution of 2% lidocaine, and the Facultad de Estudios Superiores “Zaragoza”, UNAM. Av. Guelatao No. 66, Col. other with the addition of 2% pilocarpine. Ejército de Oriente, Iztapalapa, C.P. 09230, México DF. Instituto de Ciencias Nucleares, UNAM, Circuito Exterior, Ciudad Universitaria Results: The central nervous cord and the deep flexor muscle were No. 3000, México D.F. E-mail: [email protected] easily isolated. All nerve-muscle dissections presented flexor-muscle contractions after stimulation of the ventral nerve with voltages ≥ 40 V. The contractions were inhibited after adding licodaine, and they were Introduction: The publication of norms regarding the use of favored in the presence of pilocarpine. laboratory animals has limited the implementation of practices towards the teaching of pharmacology, arising the need to develop Conclusions: The simple nervous and muscular structure of the Cherax alternative experimental models. In the present work, an in situ model genus lobster facilitated the dissection of the ventral nerve-deep of the ventral nerve cord-deep abdominal flexor muscle system as a abdominal flexor muscle system. By electrically stimulating the system, pharmacology-teaching tool was developed. positive muscular contractions were obtained starting with 40 V. The contractions were also studied under the presence of lidocaine and Material and methods: Five lobsters of the Cherax genus were pilocarpine. The above work gives a suitable alternative model for the dissected separately as follows: the lobsters were anesthetized by teaching of pharmacology. submerging them for 10 minutes in an ice-bath. Afterwards, the head, the cephalothorax, and other crustacean extremities were removed,
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S18
LATINFARMA 2013 Resúmenes/Abstracts
Taller de Farmacoepidemiología / Workshop on Pharmacoepidemiology
CO 036: DRUG USE IN PREGNANT WOMEN C 004: THE DISCREET FASCINATION OF THE DRUGS Viroga S, Ramos C, Artagaveytia P, Speranza N, Tamosiunas G. Pérez J. Department of Pharmacology and Therapeutics, School of Medicine, UdelaR, Ministerio de Salud Pública, La Habana, Cuba. E-mail: [email protected] Uruguay.
This paper is an analysis of the current situation of the Global Introduction: There are few local data on drug use during pregnancy Pharmaceutical Industry. The analysis includes the global in our country. The selection of drugs in pregnancy must be based on pharmaceutical market and its growing in the last ten years, the efficacy and safety, taking into account the pharmacokinetic and distribution of these markets around the world. The paper identifies pharmacodynamic changes that occur during pregnancy and the the top ten pharmaceutical industries and the top ten drugs selling last potential harm to the fetus. year. Objective: To study the drug consumption profile in pregnant women The analysis embraces the megamerger industries and the in a maternal referential hospital in Uruguay. specialization of the manufacturers. Development and research drugs, the control of the knowledge and scientific information, the functioning Methods: Descriptional study, survey conducted by students of the of the national and the international regulatory authorities, College of Midwives from July to November 2010. The variables international trade and intellectual property rights and the challenge considered were: medications used, frequency of use of medications, of the future in this area are other subjects for discussing. source of prescription, teratogenic risk and use of abuse substances. Results: 126 pregnant women (96.9%) used medications during their pregnancy. 364 drugs were used, including 64 active principles. The average use of drugs was 2.8 per woman. The most used drugs were iron, folic acid and dexamethasone. The 11.5% of the drugs were self prescribed (93% were NSAIDs). 37% of pregnant women consumed some abuse substance and 43% of those were consumed during the first trimester. Most used drugs corresponded to the B FDA category. Conclusions: Despite popular belief, there is a high percentage of pregnant women using drugs. Contrary to the idea that drugs should not be used in pregnant women, there are certain drugs approved for its use in this population. The high percentage use of abuse substances, especially during the first trimester, is a concerning situation. The sample included in our study is not representative of the general population, but it allowed a situational assessment, pharmaco- epidemiology important for our country. A future study with a larger number of patients will be needed. This study also resulted in the creation of research lines and allowed students to be involved in investigational activities.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S19
LATINFARMA 2013 Resúmenes/Abstracts
CO 037: MEDICAL PRACTICE CONFIRMS CLINICAL TRIAL CO 038: FREQUENCY OF USE OF THE MONOCLONAL RESULTS OF THE USE OF INTRALESIONAL HUMAN ANTIBODY RITUXIMAB ON THE NATIONAL CANCER RECOMBINANT EPIDERMAL GROWTH FACTOR IN INSTITUTE OF MEXICO: ONE YEAR EXPERIENCE ADVANCED DIABETIC FOOT ULCERS López-Gamboa M1,2, Aguilar-Ponce JL2, Espinoza-Zamora JR2, Davalos- López-Saura PA1, Yera-Alos IB1, Valenzuela-Silva C1, González-Díaz O1, Fiesco M2, Mena-Rodríguez FJ2, Castañeda-Hernández G1. del Río-Martín A1, Berlanga-Acosta J1, Fernández-Montequín JI2, 1Departamento de Farmacología, Centro de Estudios Avanzados del Instituto 1 1 1 Acevedo-Castro B , López-Mola E , Herrera-Martínez L. Politécnico Nacional, Av. Instituto Politécnico Nacional 2508, San Pedro Zacatenco, C.P. 07360, México D.F. 1Center for Genetic Engineering and Biotechnology, Havana, Cuba. 2Instituto Nacional de Cancerología; Av. San Fernando No. 22, Sol. Sección XVI, 2National Institute for Angiology and Vascular Surgery, Havana, Cuba. E-mail: [email protected] C.P. 14080, México D.F. E-mail: [email protected], Fax: (+52) 55 54743394.
Introduction: For the health care professionals and for the maker The intralesional injection of recombinant human epidermal growth decisions staff on the hospital is very important have a real panorama factor (rhEGF) has been recently approved and introduced in several about the use of the drugs in order to improve the patient attention. In countries for the treatment of advanced diabetic foot ulcers (DFU), Mexico for the oncology therapeutic segment, Rituximab the chimeric, based on the results of five exploratory and one confirmatory, phase III anti-CD20 monoclonal antibody is registered for: a) the treatment of clinical trials in 344 subjects. A significant stimulatory effect of this Non-Hodgking´s Lymphoma (CD20+); b) also combined with product on the healing process, given by granulation tissue chemotherapy for previously untreated patients with development and re-epithelization was shown in these trials, as well as relapsed/refractory of chronic lymphocytic leukemia. a reduction in lesion recurrences during follow-up, and a tendency to a reduction of the risk of amputations, with an acceptable safety profile. Methods: With the aim of determine the Rituximab frequency usage However, products not always perform the same way in current on the National Cancer Institute of Mexico we made a retrospective medical practice. The present review summarizes the clinical analysis of the rituximab dispensation data from march 2012 to march information available from the intralesional use of rhEGF for advanced 2013. Our collected data were: the pharmaceutical presentation and DFU and shows that in this case the postmarketing experiences in more vials quantity of Rituximab dispensed per patient; and from the clinical than 4000 subjects confirm the results of the clinical trials, with 75% record the data recorded included: clinical indication (diagnostic) probability of complete granulation response, 61% healing, and a 16% result of CD20 test, weigh, height, age, and Rituximab dosage absolute and 71% relative reduction of the risk of amputation. The prescribed. benefit includes ischemic patients. The safety profile in current practice Results: During the twelve-month period, a total of 2663 Rituximab was satisfactory. Serious adverse events are not attributable to the vials where dispensed from the Institute pharmacy, 1353 were 500 mg treatment but to the underlying conditions of the patients. No evidence vials, and 1308 were 100 mg vials, distributed on 304 patients. The list of cancer promotion by the growth factor has been found. The benefit- of primary diagnostics included 75 different pathologies. All patients risk ratio of the procedure is favorable. had immunohystochemical test, the 95% of the cases were positive to the CD 20 test, 4.7% of the patients had not report and 0.3% were negative to the CD20 test. Conclusion: Even when Rituximab was prescribed for a diverse range of clinical conditions, the use of CD20 test was a standard followed on the patients, this practice showed the specific use of Rituximab.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S20
LATINFARMA 2013 Resúmenes/Abstracts
C 005: PHARMACOKINETIC CHANGES INDUCED BY SPINAL CO 039: RATIONAL USE OF MEDICINES IN PRIMARY HEALTH CORD INJURY CARE: POLYPHARMACY IN PEOPLE AGED 60 YEARS AND OLDER Castañeda G. Ponce LN, Brizuela NY. Departamento de Farmacología. Centro de investigación y de Estudios Avanzados del Instituto Politécnico Nacional. Av. Instituto Politécnico Nacional 2508, 07360 Cátedra de Farmacología General. Facultad de Ciencias Médicas .Universidad México, D.F. Nacional de Córdoba. Argentina. E-mail: [email protected]
Spinal cord injury (SCI) is a life-threatening event that not only results in a sensory-motor loss below the site of lesion, but also causes Introduction: Pharmacotherapy in the elderly population is autonomic alterations including gastrointestinal and hemodynamic complicated by several factors that increase the risk of drugs. Rational changes. These changes are known to modify drug availability. use of medicines refers to the correct, proper and appropriate use of Significant changes in drug absorption, volume of distribution and medicines. More than 50% of all medicines are prescribed, dispensed clearance have been reported in patients after cord lesion and it has or sold inappropriately, and half of all patients fail to take medicines been suggested that these changes could have an impact on the efficacy correctly. This article aims to highlight the increasing impact of and safety of a variety of drugs in this population. Characterization of polypharmacy in the elderly patients. the physiopathological alterations underlying pharmacokinetic Methodology: The present study is prospective in nature, descriptive, changes that occur in patients with SCI has been complicated because cross sectional, carried out between February and May 2011, in a of the important variability induced by differences in injury primary care clinic at a senior center in the city of Cordoba, Argentina. characteristics, as well as in the individual conditions of each patient. Moreover, not all drugs exhibit altered disposition after SCI. Therefore, Results: In this sample, 74.21% used from 5 to 8 medicines daily; all of depending on which physiological mechanisms are involved in the them used to take each medication at least 3 times daily. In this sample, absorption, distribution and elimination of a given drug, SCI will or will 73.04% had increased risk of adverse drug reaction (ADRs) and 78% not change its pharmacokinetic parameters. There is evidence came from different physicians. A third (34%) of the patients was suggesting that the magnitude of the pharmacokinetic changes will treated predominately with cardiovascular diseases drugs. Metabolic depend on variables related to the injury itself: site of injury, intensity diseases (25%), digestive illness (14.5%), neurological and psychiatric and the time elapsed after lesion. However, at present we do not have disorders (14.5%) and the others (14.5%). A quarter (25%) of the enough information to propose a rational strategy for drug dosing in patients was treated with very little therapeutic value drugs. patients with spinal cord injury. Doses are selected on empirical bases, Conclusions: Polypharmacy, as well as inappropriate prescribing, for often resulting in therapeutic failure. Thus, systematic research is the elderly is a major problem and a challenge that contributes to required to fully elucidate this issue. Hence, our group has used animal costs, adverse drug events, confusion, compliance issues, and errors in models, where the lesion can be standardized, to characterize and management. A systematic approach to drug monitoring is an understand the impact of spinal cord injury on drug disposition. important aspect of appropriate prescribing.
Attention to prescribing of medications, consistent review of medication lists, and reevaluation of indications and outcomes of prescribing are essential to ensure that polypharmacy is minimized and safety for patients is maximized.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S21
LATINFARMA 2013 Resúmenes/Abstracts
CO 040: EDUCATIVE INTERVENTION ON ESSENTIAL CO 041: EFFECTIVENESS OF ANTIRETROVIRAL TREATMENT MEDICATIONS TO BE USED IN DISASTERS BY FAMILY IN COLOMBIA DOCTORS IN ARROYO NARANJO MUNICIPALITY, IN 2012 Machado-Alba JE1, Vidal X2. López Aguilera AF, Furones Mourelle JA, Bravo Palma PP. 1Grupo Investigación Farmacoepidemiología y Farmacovigilancia, Universidad Facultad de Medicina Julio Trigo López, La Habana, Cuba. E-mail: Tecnológica de Pereira, Pereira, Colombia. E-mail: [email protected]; [email protected] [email protected] 2Universitat Autònoma de Barcelona, Fundación Instituto Catalán de Farmacología, Barcelona, Spain. Introduction: The World Health Organization (WHO) has proposed a list of essential medications to be used in case of natural and Objective: To evaluate the effectiveness of antiretroviral therapies and anthropogenic disasters. Cuba in its list of essential medications has factors associated with HIV/AIDS control in a population of patients included almost all these medications as recommended by that treated by the Colombian Health Social Security System (SGSSS). organization. Methods: This was a descriptive study of 510 HIV/AIDS patients Objective: To improve the knowledge on essential medications to be treated with antiretroviral therapies in 19 cities in Colombia from June used in case of disasters on the part of family doctors in Arroyo 1992 – April 2011. Factors assessed from each patient's clinical history Naranjo municipality. were: viral load, CD4 count, antiretroviral treatment regimens, Method: A quasi experimental study on essential medications to be prescribed daily doses of medications, length of disease evolution, used in case of disasters was conducted before and after the educative duration of therapy, history of opportunistic diseases, and drug costs. intervention in Arroyo Naranjo municipality in 2012. The work Results: Patients were predominantly male (75.1% males versus universe was composed of 70 family doctors. The sample consisted of 24.9% women), with a mean age of 41.0 ± 11.4 years and an average 55 doctors. These doctors were chosen by non-probabilistic sampling length of disease progression of 72 months. All recommended by expert criteria. They were subjected to an initial inquire to find out treatment regimens were prescribed at the defined daily dose. the weak points on their knowledge about essential medications in Treatment was effective in 65.3% of patients (viral load < 50 copies case of disasters. The variables taken into consideration were the per mL). Non-adherence to treatment, treatment failure, the presence actual existence of medications, kinds of medications, pharmacological of anxiety or depression, and treatment in the city of Barranquilla were group, nonexistent medications, and substitutive medications. The lists associated with an increased risk of uncontrolled HIV infection. The of essential medications in case of emergencies of the WHO were used mean annual cost of drugs per patient was US $ 2 736. as a referential pattern. Absolute frequencies and percentages were used as summation measurement. Conclusions: Factors associated with uncontrolled HIV infection, especially regarding treatment adherence, must be identified to Results: At the beginning 87.4% of the family doctors’ knowledge on promote solutions for health care programs treating patients with the matter was evaluated as BAD, and only 5.4% as GOOD. Later on, in HIV/AIDS. the second evaluative period, 89.2% of the doctors reached the qualitative category of GOOD. All conceptual errors on different aspects found in the first evaluative period were improved. Conclusions: The educative intervention proved to be useful when trying to improve the family doctors’ knowledge concerning essential medications when facing disasters.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S22
LATINFARMA 2013 Resúmenes/Abstracts
CO 042: IMPACT OF AN ANTIBIOTIC POLICY ON CO 043: CLINICAL PHARMACIST PERFORMANCE IN ANTIMICROBIAL CONSUMPTION AT COMANDANTE MULTIPROFESSIONAL TEAM IN A TEACHING HOSPITAL MANUEL FAJARDO UNIVERSITY HOSPITAL, 2011 Amaral Pedroso L, Martins Macedo J, Moreira da Costa J, Moreira Reis Morejón M, Tirado J, Jiménez A, Mulen M. A, Santos Castro C, Andrade RA.
Hospital Universitario “Cmdte. Manuel Fajardo”, Zapata y D, Vedado, La Habana, Hospital Risoleta Tolentino Neves, Universidade Federal De Minas Gerais, Brasil. Cuba. E-mail: [email protected] E-mail: [email protected]; [email protected]
Introduction: At present, it is unanimous among scientists that the use Aim: Changes that comes from senescence causes an impact on the of antibiotics, specifically their misuse, is the most significant factor in metabolism of drugs in elderly patients. This makes them more the emergence and development of bacterial resistance. Today, over susceptible to intoxication and adverse drug reactions. Besides, elderly 50% of hospitalized patients receive antibiotics; it is considered that often shows a larger number of comorbidities, associated to a complex 25-50% is unnecessary. This has concerned all levels. That is why; the pharmacotherapy, which difficult the effectiveness and adherence. WHO issued a document in 2001: "Strategies to contain antimicrobial Seeking to suit pharmacotherapy and to prevent further complications, resistance," which states in its first page that the main cause of it is indispensable to develop practice of clinical pharmacy. Wishing to bacterial resistance is the inappropriate use of antimicrobials. contribute on elderly’s pharmacotherapy safety in a teaching hospital, Therefore, one of its recommendations calls for the creation of pharmacists linked to multiprofessional internship provides clinical antibiotic policies and monitoring their consumption in all health pharmacy service. institutions. Method: Patients are selected through active search or clinical Objectives: To determine how the patterns of antimicrobial suggestion. At first contact, previous clinical historic and subjective prescriptions vary with the application of an antibiotic policy. data are identified. Afterwards, a pharmacotherapy analysis is made and interventions along with medical staff, if needed. All medicines Results: There was a variation of consumption in the cephalosporin used are analyzed focusing effectiveness and safety. family, which was further used; cefuroxime was the highest consumed, three times more than ceftriaxone, whereas cefazolin was only used in Results: From March 2012 to February 2013, 193 patients were surgical prophylaxis, and cefepime was only used in the intensive care accompanied; their average age is 76 years old. During the held of the units. meropenem and piperazicillina/tazolbactam were only used on experiment, 349 pharmaceutics evolution were made (1.80 per serious case in the care units. patient), 225 considerations (1.16 per patient) and 573 interventions (2.97 per patient). From a total of evolutions, 19% had a catheter Conclusions: The patterns of prescription of antimicrobial drugs met enthrall record, 10.31% registered a renal clearance lower than favorably the recommended guidelines for the policy of antibiotics use, 30mL/min, 32.8% had renal clearance between 30 and 60mL/min and which could promote a more rational use of them. 9.75% reported moderate or intense ache. The most relevant intervention were orientation post-discharged (16.75%) and potential medicinal interaction (16.6%) warnings, as well as decrease of drug dose (9.77%). 49.74% of accompanied patients received pharmaceutics orientation postdischarged, 81.25% out of these were referenced to primary attention, through the pharmacotherapeutic summary, to continuity of care. Conclusion: During the follow up was noticed that pharmacotherapeutic segment contributed in an effective way to prevent, to detect and to solve related problems to drug, health problems and increase life quality.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S23
LATINFARMA 2013 Resúmenes/Abstracts
CO 044: LIPID-LOWERING THERAPY EFFECTIVENESS IN A CO 045: NSAID AND GASTROPROTECTIVE AGENTS SAMPLE OF COLOMBIAN PATIENTS PRESCRIPTION AT THE CLINICAL HOSPITAL “DR. MANUEL QUINTELA” Machado-Alba JE, Murillo MM, Machado ME. Cuñetti L, Catenaccio V, Ramos C, Viroga S, Artagaveytia P, Speranza N, Grupo Investigación Farmacoepidemiología y Farmacovigilancia, Universidad Tecnológica de Pereira, Pereira, Colombia. E-mail: [email protected]; Tamosiunas G. [email protected] Departamento de Farmacología y Terapéutica - Facultad de Medicina, Universidad de la República, Hospital de Clínicas Av. Italia s/n Montevideo, Uruguay. E-mail: [email protected] Objective: To determine the effectiveness of lipid-lowering therapy in a sample of patients affiliated with the Colombian Health System. Introduction: NSAID are one of the most used drugs worldwide. In Methods: The cross-sectional study was conducted between January 1, order to reach a rational use of this group of drugs we need to know it´s 2010 and June 30, 2011. Of a total of 8316 patients, a random sample use in our hospital in which we also have a List of Essential Medicines. of 600 people from ten cities was stratified according to dyslipidemia. Information on socio-demographic and anthropometric characteristics, Objective: Our aim is to determine NSAID prescription profile and the risk factors, pharmacological and laboratory variables were obtained use of gastro-protection strategies in our hospital. from medical records. Methods: Descriptive transversal study, analyzing clinical records of Results: There was a female predominance (56.2%) with a mean age all patients hospitalized during August 3rd, 2012 in the Clinical of 65.1 ± 11.5 years in the subjects, and 93.2% had hypertension, Hospital. Data collection was performed by medical students and staff 29.0% had diabetes mellitus, and 10.2% had a history of myocardial of our department. A preformed form was filled out, and a pilot study infarction. The patients were treated with lovastatin alone (84.1%), took place to unify criteria. NSAID prescription and of any medicine gemfibrozil (12.3%) at doses below those recommended and associated to a different gastrointestinal risk were evaluated. We atorvastatin (1.8%). In patients with a high cardiovascular risk, 38.6% classified either the patients or the NSAID in low or high risk to achieved goals for LDL-C levels (<100 mg/dL), while 49.4% of those develop NSAID gastroenteropathy. with a moderate risk reached the target level (<130 mg/dL). On average, there was a 4.9% reduction in LDL-C. Sex, age, personal Results: 239 clinical records were evaluated, 156 (65%) had at least history of cardiovascular disease and diabetes mellitus, use of one NSAID prescribed. 50% of NSAID were administered hydrochlorothiazide and poor therapy adherence were statistically intravenously. 20.5% were for antiplatelet therapy, 80% were associated with a lack of control of dyslipidemia. indicated for pain or/and fever. From all the patients who received NSAID 108 (69.2%) had at least one risk factor to develop NSAID Conclusions: Because a lack of control over LDL-C levels occurred in gastroenteropathy. 59 (55%) had omeprazol 19 (17%) had ranitidine men over 55 years, diabetic patients, or those with a history of and 30 (27.7%) didn’t have any gastroprotective treatment. From this cardiovascular disease, who received lower doses of lovastatin or were 30, 6 had one risk factor associated to a low risk NSAID; the rest (24 non-adherent to treatment, it is recommended that the dose be cases) had various risk factors and/or at least one high risk NSAID. increased based on clearly defined therapeutic objectives and that the From the 48 patient without risk to develop NSAID gastroenteropathy, presence of comorbidities be assessed, which will then be treated 22 (14.2%) almost half of them had gastroprotection associated. properly. Conclusions: We need to study the use of intravenous route of NSAID and to improve the selection of risk patients and the association of gastroprotective agents in the NSAID prescription. We still have more to do in order to use this group of medicines in a rational manner.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S24
LATINFARMA 2013 Resúmenes/Abstracts
Simposio de Farmacología del Dolor / Symposium on Pharmacology of Pain
C 006: BETWEEN HYPERTENSION AND PAIN CO 046: MANGIFERIN FOR THE MANAGEMENT OF PAIN: ADVANTAGES OF ITS TRANSCIENT AND LONG TERM Henrique Ferreira S. NEUROMODULATORY EFFECTS School of Medicine of Ribeirão Preto, Department of Pharmacology, Campus USP, Brazil. Garrido BB1, Castro M1, Rodeiro I2, Hernández I2, Pardo Z1, Menédez R1, Delgado R1
1Drug Research and Development Center, Ave 26, No. 1605 Boyeros y Puentes In the present communication Prof Sergio Henrique Ferreira describes Grandes, CP 10600, Plaza de la Revolución, La Habana, Cuba. his personal trajectory in the Department of Pharmacology from the 2Center of Marine Bioproducts, Loma y 37, CP 10300, Nuevo Vedado, La Habana, Ribeirão Preto Medical School. Cuba. The discovery of bradykinin, Prof Rocha e Silva just received a sample of that he had previously described when he incubated Jararaca Venom Introduction: Neuroimmune activation and nitroxidative stress are together with blood plasma. The synthetic bradykinin however was implicated in glutamatergic system dysfunction, which induces much weaker than the blood plasma product, thus suggesting the excytotoxic neural damage, desinhibition and central hyperexcitability presence in the Jararaca venom of a potentiating factor, named by us subjacent in chronic pain. Mangiferin (MG), a naturally occurring BPF, i.e. bradykinin potentiating factor. Thus, plasma contained an glucoxylxanthone isolated from the standard aqueous bark extract of enzyme that inactivates bradykinin and by coincidence it was the same Mangifera indica L. shows inhibition of NF-κB signaling pathway, enzyme that was responsible for the conversion of angiotensin I to neuroprotective effects, antioxidant activity and it is able to limit angiotensin II. Angiotensin II is the biological factor responsible for microglial activation. Besides, reversible mono-amine oxidase (MAO) hypertensive activity of this peptide. The smallest peptide of BPF, PCA- inhibitory activity is reported by xanthones, an effect that may Lys-Tryp-Ala –Pro, was used as basis for the industrial development of modulate catecholamine concentration in the synaptic cleft modulating the potent anti-hypertensive drugs, angiotensin converting enzyme spinal nociceptive processing through the PAG/RVM/DLPT descending inhibitors. modulatory network. This conference focuses on unifying the cumulus During the years of 64-67 working in London in the department of Prof of evidences around the MG effects on several animal models of pain, J.R. Vane, I participated in the discovery of the mechanism of action of hypothesizing about their mechanism of actions according to a aspirin-like-drugs. I proposed that its analgesic action was due to the pharmacological approach. prevention of the stimulation of primary sensory neurons by Results: The acute administration of MG (10-100 mg/kg, i.p.) mediators, particularly by prostaglandins. Recently we found that decreases licking/biting behaviors exclusivity in tonic phase of opiates have a peripheral analgesic effect by means of the stimulation formalin 5% test. Pre-treatment with naloxone, a non selective opioid of the Arginine/NO/GMPc pathway. This mechanism may stimulate the antagonist and yohimbine a selective α2 adrenergic antagonist partially development of new analgesics. reversed this effect. Intrathecal MG injection also reproduced the same behaviors. In addition, MG decreases visceral nociceptive behaviors in ovariectomized (OVX)-induced hyperalgesia in rats, which show monoamine levels decreased in brain. Preventive repeated systemic administration of MG before sciatic chronic constriction injury (CCI) in rats reduced mechanical hyperalgesia at 7 and 14 days and also decreased the signs of Wallerian degeneration of the sciatic nerve. As well as, MG improved the PC-12 cellular viability (70%) exposure to glutamate-mediated excytotoxic injury. Likewise, oral acute and chronic administration of MG in rats with chronic post-ischemia pain (CPIP), a complex regional pain syndrome type I model, decreased mechanical allodynia from 2h of MG administration and IL-1β concentration in spinal cord homogenates. A long term anti- hyperalgesic effects, even after discontinuation of the medication, were observed. Conclusions: MG may modulate pathological and persistent painful status, and its anti-hyperalgesic effect could be mediated, at least in part, in the spinal cord by opioid and noradrenergic transient mechanisms. Long term effects mediated by transcriptional changes could be implicated in peripheral and central pain mechanisms, especially central sensitization.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S25
LATINFARMA 2013 Resúmenes/Abstracts
CO 047: ANTINOCICEPTIVE ACTIVITY OF MANGIFERIN IN CO 048: ANTI-HYPERALGESIC EFFECT OF A FORMALIN PAIN NEUROPROTECTIVE COMPOUND IN ANIMAL MODELS OF PAIN Espinoza de los Monteros-Zuñiga Aa, Cervantes-Durán Cb, Lozada- García MCa, Izquierdo-Sánchez Ta, Godínez-Chaparro, Ba,c. Castro M, Garrido-Suárez B, Pardo-Ruiz Z, Alcantara Y, Iglesias L, Merino N, Valdés O, Delgado R. aDepto. Sistemas Biológicos, División de Ciencias Biológicas y de la Salud. Universidad Autónoma Metropolitana-Xochimilco (UAM-X), Center of Research and Drug Development, Ave 26, No. 1605 Boyeros y Puentes bDepto. Farmacobiología, Centro de Investigación y de Estudios Avanzados, Sede Grandes, CP 10600, Plaza de la Revolucion, La Habana, Cuba. E-mail: Sur. (CINVESTAV-Sur), México. [email protected] cInstituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla, Querétaro, 76230, México. E-mail: [email protected] Introduction: Mangiferin is a glucoxylxanthone present in the Introduction: Chronic pain has been estimated to affect 8% of aqueous extract of Mangifera indica L., the extract has shown multiple population. However it doesn´t exist an effective treatment for these pharmacological effects as antioxidant, anti-inflammatory and anti- pathologic phenomena, for this reason, new pharmacologic strategies nociceptive effects. The present study was undertaken to determine have emerged to release chronic pain. the possible antinociceptive activity of mangiferin in rats, as well as its possible mechanisms of action. Aim: In the present study we evaluate the antihyperalgesic effect of systemic administration of a novel neuroprotective compound (NP1) Material and methods: Nociceptive behavior was quantified as the in animal models of chronic pain with inflammatory and neuropathic numbers of flinches of the injected paw during 1-min per 5 min, up to components. 60 min after 1% formalin injection. Magniferin was given orally (1-30 mg/kg), locally (1-30 µg/paw in 50 µL) or intrathecally (1-30 µg/rat in Methods: Nociceptive responding, indicated by licking/biting the 10 µL) 30 min and 10 min before, respectively, 1% formalin injection affected hindlimb, was quantified during 45 min after formalin in the dorsum paw. Diclofenac was used as a positive control. Animals injection (5%) and mechanical allodynia was measured with von Frey were administered with vehicle or methiothepin (30 µg/paw), filaments in chronic constriction injury (CCI). In CCI model was also naloxone (5-50 µg/paw), naltrindole (0.1-1 µg/paw), 5-GNTI (0.1-1 determined nitric oxide concentration in sciatic nerve and in lumbar µg/paw), L-NAME (10-100 µg/paw), ODQ (5-50 µg/paw) or spinal cord, and was analysed qualitative changes in the histology of glibenclamide (10-100 µg/paw) were administrated 20 min before sciatic nerve. mangiferin (30 µg/paw) which was given 10 min before of 1% Results: NP1 (10-40 mg/kg, p.o.) was effective in attenuating only the formalin injection. acute phase (phase II) of the formalin licking/biting response, Results: The ipsilateral local peripheral (1-30 µg/paw), intrathecal (1- dependending the dosis. Benzodiazepine antagonist flumazenil (10 30 µg/rat) and oral (1-30 mg/kg) administration of mangiferin mg/kg i.p.) partially reversed this effect. Its oral administration during produced a dose-dependent reduction in formalin-induced 7 days in CCI model augmented the mechanical response thresholds nociception. The antinociceptive effect of this drug was similar to (g) respect with CCI-vehicle group and increased nitric oxide induced by diclofenac after oral and local peripheral administration. concentration in spinal cord, but not in sciatic nerve. Histologically, it The local peripheral antinociceptive effect in the formalin test was was found that NP1 has a neuroprotective action against Wallerian blocked by naloxone (50 μg/paw), naltrindole (1 μg/paw), 5-GNTI (1 degeneration in CCI model, which includes less macrophage µg/paw), L-NAME (100 μg/paw), (50 μg/paw) and glibenclamide (50 infiltration, number of digestion chambers and axonal degradation. μg/paw), but not by methiothepin (30 μg/paw). Conclusions: Because of this we can conclude that NP1 shows an Conclusions: These data suggest, that the antinociceptive effect antihyperalgesic effect in formalin test it could be related with his induced by mangiferin are mediated by the modulation of peripheral actions into GABAA/BDZ receptor, and it also has an antiallodynic and opioidergic system involving the activation of δ, κ, and probably μ, neuroprotective action in CCI model, which could be mediated by L- receptors, but not serotonergic receptors. Also suggests that mangiferin Arginine-NO-GMPc pathway. activates the NO-cyclic GMP-ATP-sensitive K+ channels pathway related to modulate local peripheral nociceptive effect in rats.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S26
LATINFARMA 2013 Resúmenes/Abstracts
C 007: PHENOTYPIC MODIFICATIONS OF PRIMARY C 008: THE RATIONALE OF ANALGESIS COMBINATIONS AFFERENT NEURONS INNERVATING OSTEOARTHRITIC Granizo E. JOINTS Universidad Central de Ecuador. Castro-Lopes JM, Adães S, Ferreira-Gomes J. No single analgesic agent is perfect and no single analgesic can treat all Department of Experimental Biology, Faculty of Medicine of the University of types of pain. Oral fixed drug combinations analgesics potentially have Porto and IBMC, Portugal. a number of advantages over monotherapy, but these benefits can only be attained through careful design that is not the case in some available preparations. Chronic pain associated with osteoarthritis (OA) is highly prevalent, but its mechanisms are not fully understood, and the pharmacological A combination is most effective when the individual agents act through control of OA-associated pain is far from optimal. In an attempt to different analgesic mechanisms and act synergistically. The fixed-dose further clarify the neuronal mechanisms underlying nociception in OA, combinations analgesics are of value only when they have bee we have performed a series of studies on primary afferent neurons developed according to rationale pharmacokinetic and innervating OA joints, using the experimental model of intra-articular pharmacodynamic criteria. injection of mono-sodium iodoacetate (MIA) in the knee joint of adult This overview highlights the therapeutic potential of combining rats, which causes a destruction of the articular cartilage. analgesic medications with different mechanisms of action like a By using the neuronal tracer Fluorogold (FG), we observed a decrease NSAIDs drugs or acetaminophen with an opioid or tramadol. of 37% in the number of neurons innervating OA joints as compared to control animals, although there was no reduction in the total number of neurons in the dorsal root ganglia (DRGs). However, there was a decrease in the number of small neurons and a small increase of medium-large neurons in OA animals. Given that neurogenesis was not found in the DRGs of OA animals, those observations indicated a phenomenon of neuronal hypertrophy. Regarding neurochemical markers for subpopulations of primary afferent neurons, there was an increase in the percentage of CGRP positive (peptidergic) neurons that innervate OA joints. Such increase occurred in small and large neurons. Since this peptide is usually not expressed in large neurons, our observation in OA animals points to a phenomenon of hypertrophy of medium-small neurons that normally express CGRP, or a phenotypic alteration of large neurons. No differences between OA and control animals were observed in what concerns labelling for IB4 or NF200 (labelling non-peptidergic or large non-nociceptive primary afferent neurons, respectively). The changes described above could suggest the existence of damages in neurons that innervate OA joints. Therefore, we studied the expression of ATF-3 and NPY in the DRGs, since its expression has been associated with peripheral neuronal damage. Both markers were expressed in DRG neurons three days after injection of MIA, a very early stage in the development of experimental OA, decreased at day 14 of development of OA, and there was a second wave of expression later. We have also observed expression of GAP-43, a marker of neuronal regeneration, in ATF-3 positive cells. Together, our results suggest that primary afferents that innervate MIA-induced OA joints are damaged, which may trigger the activation of neuronal regeneration mechanisms. Further studies are needed to clarify to which extent these phenomena contribute to pain associated with OA.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S27
LATINFARMA 2013 Resúmenes/Abstracts
C 009: CARDIOVASCULAR RISK OF NONSTEROIDAL ANTI- CO 051: OPIOIDS UPDATE IN 2013. PAIN FREE HOSPITALS, INFLAMMATORY DRUG FREQUENTLY USED IMPORTANCE OF ITS DEVELOPMENT IN CUBA Prozzi GR. Yera-Nadal JL.
Applied Pharmacology, Faculty of Medicine, National University of La Plata. Clínica del Dolor Hospital Hermanos Ameijeiras, La Habana, Cuba. E-mail: Health Institute, National University “Arturo Jauretche”. Argentina. E-mail: [email protected] [email protected]
Opioids are still important analgesics in the management of acute and Introduction: The non-steroidal anti-inflammatory drugs (NSAIDs) chronic pain. They can be very effective and also safe if used wisely, are an important part of treatment for many people with painful and with a thorough understanding of their pharmacology. Opioids often inflammatory conditions and are amongst the most commonly used cause adverse effects; respiratory depression and nausea are drugs worldwide. The extent to which an NSAID inhibits the respective important adverse effects when opioids are used to treat acute pain, cyclooxygenase isoforms (COX-1 and COX-2) may be related to whereas constipation, cognitive impairment, hormonal effects, cardiovascular risk (CVR). There is a growing body of evidence that addiction and tolerance are relevant concerns in chronic most NSAIDs are associated with an increased CVR, some more than administration. However, nothing like nonsteroidal anti-inflammatory others. drugs, there are not evidences of severe injury on vital organs as heart, liver and kidney by its long term use. In the present review it discussed The aim was to review: the cardiovascular toxicity of different NSAIDs, the use of opioids in acute and chronic pain, with focus in MOR epidemiology of use and recommendations of published guidelines. agonists as morphine, oxycodone, fentanyl, methadone, Results: In the VIGOR (2000) study was observed that rofecoxib was hydromorphone and buprenorphine, particularly in the news special associated with a fourfold increase in the incidence of myocardial routes and modes of administration. We also analyzed the importance infarction (MI) compared with naproxen. It was the first evidence of of nonopioid effects that are relevant for its analgesic profile. For CVR of a coxib. Six years later, a meta-analysis of randomised trials, example, racemic methadone and its ability by binding to N-methyl–D and a systematic review of the observational studies found that coxibs, aspartate (NMDA) receptor, that exhibit noncompetitive antagonism. diclofenac and possibly ibuprofen were associated with higher CVR As well as, tramadol and tapentadol, which also inhibit the reuptake of than naproxen. Those were the first evidences of CVR of traditional monoamines. Moreover, it will provide up to date information NSAIDs. In 2011, a network meta-analyses of randomised trials, and regarding the pharmacokinetic and pharmacogenetic differences the biggest systematic review of the observational studies reported among opioids. On the other hand we are considering about the similar results. The highest CVR were seen with coxibs and diclofenac importance of accepting pain as a vital sign and then develop pain free and the lower with naproxen. In 2013, Bainget´s meta-analyses hospitals in our country. This information can be used to improve the indicated that in high-dose, the CVR of diclofenac and possibly effective and safe use of available opioids in the management of pain ibuprofen are comparable to coxibs, whereas high-dose naproxen is and it also offers possibilities for improving opioid efficacy and associated with less vascular risk than other. For every 1000 patients reversing opioid tolerance. allocated to a year of treatment with a coxib regimen or high-dose diclofenac, about three would have a MI, of which one would be fatal. However, NSAIDs with a high CVR are still widely used. Diclofenac and etoricoxib together account for approximately one-third of all sales of NSAIDs in several countries. Conclusions: While the benefits of NSAIDs for the treatment of pain outweighs their risks, their use should be at the lowest effective dose for the shortest possible time. Where pharmacological treatment is required for patients at risk of cardiovascular complications paracetamol, naproxen or aspirin is recommended and coxibs or diclofenac should be avoided.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S28
LATINFARMA 2013 Resúmenes/Abstracts
Simposio sobre Epigenética / Symposium on Epigenetics
C 010: FLAVANOLS MODULATE THE TRANSCRIPTION OF C 011: EPIGENETIC DEREGULATION IN CANCER: GENES INVOLVED IN ATHEROSCLEROSIS WITH THERAPEUTIC APPLICATIONS HETEROGENIC EPIGENETIC CHANGES OF THEIR DNA Berdasco M. METHYLATION STATE Cancer Epigenetics and Biology Program (PEBC), Institut d' Investigació Weseler AR1, Milenkovic D2, Szarcvel Szic K3, Declerck K3, Heyninck K4, Biomedica de Bellvitge (IDIBELL), Barcelona, Spain. Haegeman G4, Haenen GRMM1, Bast A1, Fuks F5, Gerhauser C6, Vanden Berghe W3,4
1Maastricht University, The Netherlands. Initially, cancer was thought to be solely a consequence of genetic 2INRA Research Centre Clermont-Ferrand/Theix, France. changes in key tumor-suppressor genes and oncogenes that regulate 3University of Antwerp, Belgium. E-mail: [email protected] cell proliferation, DNA repair, cell differentiation, and other 4University of Gent, Belgium. homeostatic functions. However, recent research suggests that these 5 Free University of Brussels, Belgium alterations could also be due to epigenetic disruption. The study of 6DKFZ Heidelberg, Germany. epigenetic mechanisms in cancer, such as DNA methylation, histone modification, nucleosome positioning and micro-RNA expression, has provided extensive information about the mechanisms that contribute Epidemiological studies show that a flavanol-rich diet (cocoa, grape) is to the neoplastic phenotype through the regulation of expression of associated with a decreased risk of cardiovascular disease (CVD). In genes critical to transformation pathways. Regarding DNA methylation, how far biological effects occur in endothelial HUVEC cells exposed to the low level of CpG methylation in tumors compared with that in their flavanols in vitro or in humans upon flavanol supplementation is yet normal-tissue counterparts and the hypermethylation of the CpG unclear. In the Flaviola-consortium (www.flaviola.org), potential islands in the promoter regions of tumor-suppressor are accepted as biological processes modified by flavanols were evaluated at the being a common feature of human cancer. Due to the complexity of transcriptomic and epigenomic levelin HUVEC cells exposed to specific permutations and combinations, less is known about the patterns of flavanol metabolites or in leukocyte samples collected from diet histone modification disruption in human tumors. Results have shown intervention studies. In vitro experiments in HUVEC cells demonstrate that the CpG promoter hypermethylation event in tumor-suppressor that flavanols significantly decrease monocyte cell adhesion, genes in cancer cells is associated with a particular combination of concomitantly with changes in gene expression and DNA methylation in histone markers and the opposite of that observed in normal cells. cell adhesion pathways. Furthermore, in a randomized, double-blind, Aberrations in the epigenetic profiles, with respect to DNA methylation placebo controlled trial, healthy male smokers supplemented for 8 and histone modifications, could also be a consequence of genetic weeks with 200 mg/d oligomeric flavanols, unveiled pleiotropic disruption of the epigenetic machinery, such as disruption of the vascular health benefit by an integrative multi-biomarker approach histone methyltransferase NSD1 in neuroblastomas or mutations in the (PLoS One. 2011;6(12):e28460.).Gene expression analysis via cDNA histone deacetylase HDAC2 in colon cancer. The deregulation of miRNA microarrays (Agilent 4x44Kv2) further revealed significant changes in expression has also been linked to tumor progression. Changes in various cellular processes like chemotaxis, cell adhesion, cell miRNA expression in cancer can be achieved through various infiltration and cytoskeleton organization. Regarding DNA methylation mechanisms, including impairment of miRNA processing machinery, changes measured by Illumina 450K CpG array, heterogenic responses such as the recently identified mutations of TRBP2 (an essential were observed in gene clusters involved in detoxification, metabolism functional partner of the DICER1 complex) in sporadic and hereditary and cell adhesion. Although the intervention triggered significant carcinomas with microsatellite instability or by CpG hypermethylation changes in DNA methylation levels (>10%) of 0.2-1% of the methylome of miRNAs with tumor-suppressor properties. The possibility of (450.000 CGI) at the individual level, no common flavanol-specific DNA “resetting” the abnormal cancer epigenome by applying pharmacologic methylation response of specific target genes involved in CVD could be or genetic strategies will be also discussed. identified at the cohort level. Interestingly, strong interindividual variability in DNA methylation levels of detoxification and metabolisation genes can be linked to long-term smoking history, which may overrule diet specific effects of an 8 week diet intervention. Altogether, flavanols may elicit cardioprotective effects by decreasing cell adhesion pathways at the transcriptomic and epigenomic level. Furthermore, smoking history may be a confounding factor in epigenetic profiling studies of leucocytes from subjects involved in a flavanol diet intervention.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S29
LATINFARMA 2013 Resúmenes/Abstracts
C 012: EPIGENETIC REGULATION OF BREAST CANCER C 013: PROMISES & CHALLENGES OF MICRORNAS IN METASTASIS BY STEROIDAL LACTONE WITHAFERIN A MULTIPLE MYELOMA THERAPY
Szarcvel Szic K1, Scherf D2, Beck IM3, Bracke M3, De Meyer T4, Palagani A1, Stefan Naulaerts2, Ken Op de Beeck3, Vandesompele J4, Gerhauser C2, Vanden Berghe W.1 Mestdagh F4, Guy Van Camp3, Kris Laukens2,Vanden Berghe W.1
1Laboratory of Protein Chemistry, Proteomics and Epigenetic Signalling, 1Laboratory of Protein Chemistry, Proteomics and Epigenetic Signalling, Department of Biomedical Sciences, University of Antwerp (UA), 2Department of Mathematics and Computer Science, 3Center of Medical Genetics, Universiteitsplein 1, Campus DrieEiken, 2610, Wilrijk, Belgium. Department of Biomedical Sciences, University of Antwerp, Belgium. 2Cancer Chemoprevention, Epigenomics and Cancer Risk Factors, German Cancer 4Center for Medical Genetics, Ghent University, Belgium. Research Center (DKFZ), ImNeuenheimer Feld 280, 69120, Heidelberg, Germany.
3Laboratory for Experimental Cancer Research, Department of Radiation Therapy & Experimental Cancer Research, De Pintelaan 185, Building 1P7, Ghent Multiple myeloma (MM) is an incurable plasma cell malignancy and is University Hospital, B-9000, Gent, Belgium. the second most common hematological cancer. It is characterized by 4Department of Mathematical Modelling, Ghent University, Ghent, Belgium. complex, recurrent genetic and epigenetic abnormalities. Perturbed transcription of various noncoding miRNAs has been demonstrated in MM and their functional roles in MM pathogenesis and therapy Because a vast majority of cancer patients succumb metastatic disease response just starts to be unraveled. miRNAs are about 20 nucleotide, interfering with metastatic cascade remains one of the main challenges single strand, non-coding RNAs that may act as tumor suppressors or in cancer therapy. This dangerous, yet very inefficient process includes oncogenes and regulate gene expression by mRNA degradation or several discrete steps: local invasion, intravasation (or dissemination translational repression of hundreds of genes, often in a tissue-specific in lymph nodes or body cavities), circulation and survival, manner. As such, miRNA dysregulation can have profound cellular extravasation, growth at distinct sites and angiogenesis, all of which consequences. Whereas the loss of tumour-suppressive miRNAs occur in a context of tumour promoting microenvironment. It is now enhances the expression of target oncogenes, increased expression of becoming apparent that these cell-microenvironment interactions are oncogenic miRNAs (known as oncomirs) can repress target tumour highly susceptible to epigenetic regulation, both by internal and suppressor genes. This creates complex networks regulating a large external cues. variety of cellular processes, including differentiation, development, Here we show that several essential components of metastasis, apoptosis and cell cycle progression. Understanding the molecular including urokinase plasminogen activator (PLAU), ADAM8 biology of myeloma also requires linking the miRNome to genomic, metallopeptidase, and tumour promoting cytokine TNFSF12 are transcriptomic, epigenomic and proteomic features of malignant regulated epigenetically by DNA methylation in breast cancer as plasma cells. Integrative analysis based on computational target revealed by 450K IlluminaBeadChipArray and EpiTyper Mass Array. prediction, quantitative proteomics and miRNA/mRNA profiling Moreover, Withaferin A, a natural compound derived from Withania revealed various functional miRNA-target regulatory networks somnifera decreases breast cancer invasion by increasing methylation supported by expression data. We will discuss convergence of of these genes leading to lowered gene expression as revealed by qPCR. microRNA regulation and nuclear factor-κB (NF-κB) and glucocorticoid pathways in MM therapy response. As such, interfering with microRNAs in myeloma regulatory networks holds promise to overcome drug resistance, which may improve clinical outcome.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S30
LATINFARMA 2013 Resúmenes/Abstracts
C 015: EFFECT OF DNA DEMETHYLATION ON CYP1A1 GENE However, PAHs exposure affects not only CYP1A1 expression through EXPRESSION IN RAT CELLS AhR but also may affect other proteins involved in epigenetic regulation. In order to test this hypothesis, rat hepatocytes clone-9 cell Olguín-Reyes S, Camacho-Carranza R, Espinosa-Aguirre JJ. line (C9) was exposed to benzo[a]pyrene (BaP) and to the DNMTs inhibitor 5’-Aza-2’-deoxycitidine (5AzadC), with their respective Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, UNAM, México D.F. controls. CYP1A1 expression was determined by qPCR and western blot analysis. The concentration of DNMT3a was also determined. CYP1A1 gene expression was increased after BaP treatment and exacerbated when 5AzadC was co-administrated. DNMT3a protein Gene regulation involves transcription factors, responsive elements, level decrease in C9 culture after 5AzadC as expected. BaP treatment enhancers, insulators, DNA methylation, histone methylation, also produces decrease in DNMT3a protein, although not at the same acetylation, and deacetylation, among others. In a whole organism, level seen after 5AzadC treatment. We can conclude that the such components may depend on external factors such as mechanism behind the positive modulation of CYP1A1 by BaP involves environmental pollution. Polycyclic aromatic hydrocarbons (PAH) not only AhR but other proteins of the epigenetic machinery like found in environmental pollution, are susceptible of biotransformation DNMT. by CYP1A1, a phase I enzyme. In turn, CYP1A1 gene expression is induced by PAHs through the aromatic hydrocarbon receptor (AhR).
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S31
LATINFARMA 2013 Resúmenes/Abstracts
Taller de Nanofarmacología / Workshop of Nanopharmacology
CO 052: CRITICAL POINTS TO CONSIDER WHEN CO 053: SYNTHESIS, CHARACTERIZATION AND DRUG DEVELOPING PHARMACEUTICAL PRODUCTS BASED ON DELIVERY PROFILE OF MAGNETIC PLGA-PEG- MICROSPHERES CONTAINING PROTEINS PLGA/MAGHEMITE NANOCOMPOSITE
Saez V. Pereira ED1, Souza FG Jr1, Pinto JC2, Cerruti R1, Santana C.1
Macromolecular Chemistry Department, Center for Biomaterials (BIOMAT), 1Laboratório de Biopolímeros e Sensores – Instituto de Macromoléculas - University of Havana, Havana, Cuba. E-mail: [email protected] Universidade Federal do Rio de Janeiro, Brasil. E-mail: [email protected] 2Programa de Engenharia Química – COPPE - Universidade Federal do Rio de Janeiro, Brasil. Nowadays peptides and proteins are commonly used as the active principle of many pharmaceutical products. However the design of The kinetics and spatial controls of drug delivery offers many dosage forms with these biomolecules has some limitations related to advantages compared to conventional methods. These delivery the adverse events and the relatively short elimination half-life. systems often use biocompatible magnetic nanoparticles as maghemite Consequently novel protein administration systems have been to promote spatial control and synthetic biocompatible polymers as investigated to exploit the therapeutic potential of them while drug carriers to promote a kinetic control of this release. This study simultaneously avoiding the limitations. Biodegradable microspheres was focused study of the magnetic field influence on the release profile are one of the most widely explored because they could (i) reduce the of cotrimoxazole inserted in PLGA-PEG-PLGA/maghemite administration frequency of the product, (ii) maintain appropriate nanocomposites prepared by melt mixing. The synthesized samples protein levels in the blood for an adequate period of time, (iii) decrease were prepared and characterized by 1H-NMR, FTIR, XRD, and magnetic adverse events and hence (iv) improve the compliance of patients force. The drug release profile was monitored by UV analysis along 6 during the treatments. In the last decades numerous investigations hours with and without magnetic field. The release profile of the drug about the encapsulation of therapeutic proteins have been developed showed to be sustained and the presence of maghemite, in the but only a few products are already under clinical application. This is presence of a magnetic field, were able to perform a magnetic because the protein microencapsulation is a complex process governed constriction of the material, making the drug release faster than in the by multiple factors that should be optimized in order to program the absence of the magnetic field. This release behavior may be useful to properties desired for a specific protein-loaded microsphere perform a fine tuning of the system, allowing the easier adjustment of preparation. In addition, the properties of the encapsulated protein are the speed and amount of released drug, improving medical treatments often modified as a result of the encapsulation process, thus they and even the welfare of the patients. should be carefully evaluated in order to demonstrate the ability of the protein to exert its biological function. On the other hand, microspheres are typically manufactured by an aseptic process because terminal sterilization (heat sterilization and gamma irradiation) results in premature degradation of the particles. Due to the complexity in the development and manufacturing process for microsphere drug products an appropriate quality control strategy should be designed. This talk reviews through practical examples, the current state of microspheres containing therapeutic proteins from basic research to its clinical application and debate controversial aspects related to the development of pharmaceutical products based on these novel drug delivery systems. Regulatory topics associated with these products are also discussed.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S32
LATINFARMA 2013 Resúmenes/Abstracts
CO 054: AFFINITY MATURATION AND FINE FUNCTIONAL CO 055: NANOEMULSION PREPARATIONS FROM A PLANT MAPPING OF AN ANTIBODY FRAGMENT AGAINST A NOVEL LIPID EXTRACT WITH WIDE RANGE OF APPLICATIONS IN NEUTRALIZING EPITOPE ON HUMAN VASCULAR MEDICINE ENDOTHELIAL GROWTH FACTOR Turiño L1, González E2, Nogueira A3, López O.3 Lamdan Ha, Gavilondo JVa, Muñoz Ya, Pupo Ab, Huerta Va, Musacchio Aa, 1Centro de Estudios Avanzados de Cuba (CEAC). Carretera de San Antonio km a a b c d Pérez L , Ayala M , Rojas G , Balint RF , Larrick JW . 1½, La Lisa, La Habana, Cuba. E-mail: [email protected] 2Centro Nacional de Biopreparados (BIOCEN). Carretera a Beltrán km 1½, aCenter for Genetic Engineering and Biotechnology, La Habana 10600, Cuba. E- Bejucal, Mayabeque, Cuba. E-mail: [email protected] mail: [email protected] 3Centro de Investigación y Desarrollo de Medicamentos (CIDEM). Ave. 26 No. b Center of Molecular Immunology, La Habana 11600, Cuba. 1605, e/ Puentes Grandes y Boyeros, Plaza de la Revolución, La Habana, Cuba. E- c CytoDesign, Inc., Palo Alto, CA 94306, USA. mail: [email protected] dPanorama Research Inc., Sunnyvale, CA 94089, USA.
Introduction: The lipid extracts from vegetal origin have shown a very Vascular endothelial growth factor (VEGF) is a major mediator of effective activity on the different mechanisms related to Benign pathological angiogenesis. VEGF antagonists represent attractive Prostatic Hyperplasia. The oil obtained from the seeds of the Cuban candidates as therapeutic agents in the treatment of tumors and other pumpkin species Cucurbita pepo L., is an example of natural angiogenesis-dependent diseases. Despite the clinical success of components useful for men who suffer this common hypertrophy. The Bevacizumab, a humanized monoclonal antibody that blocks the administration of oily components by oral way as nanocapsules would interaction between VEGF and its receptors, the search for new be a variant of minimal invasion consumption and would also neutralizing antibodies targeting this molecule has continued until represent a strategy for favoring the absorption and bioavailability of now. We used a human VEGF variant containing three mutations in the the product. region recognized by Bevacizumab to direct antibody selection towards recognition of other epitopes. A total of seven phage-displayed Material and methods: In this work, the main objective was to obtain antibody fragments were obtained from a human phage display nanoemulsions by means of a high-energy method called High-speed library. All of them were able to recognize not only the selector Homogenization, using lipid extract from the seeds of Cucurbita pepo L. mutated antigen, but also native VEGF. One of these phage-displayed as a dispersed phase. The droplet size determination was performed antibody fragments, denominated 2H1, was shown to compete with by the diffraction method, Induced Grating. Through an experimental the VEGF receptor 2 for VEGF binding. Soluble 2H1 inhibited VEGF design, the influence of three speed levels (9500, 13500 and biological activity but exhibited a moderate binding affinity. We 20500/min) and three distance from the disperser to the bottom of the performed the affinity maturation of 2H1 antibody fragment. Two vessel, where the nanoemulsions were prepared (5, 10 and 15 mm) on phage-displayed libraries were constructed by diversification of the droplet diameter were evaluated. third complementarity-determining regions (CDRs) of the light (VL) and heavy (VH) chain variable domains of 2H1 using parsimonious Results: It was shown statistically that for the studied values related to mutagenesis. A competitive phage-selection strategy in the presence of the distance from the disperser to the bottom, any significant 2H1 as a competitor was used to eliminate low affinity binders. High difference was obtained, not being this the case the effect shown by the affinity variants were retrieved from both libraries. An optimized VL speed, since for the highest level of speed, a diameter 10 times lower variant was constructed by combining recurrent replacements found (11.64 nm) relative to the one achieved with the minimum operation among selected variants, resulting in an additional affinity increase. speed was reached. Further affinity improvements were achieved by combining this Conclusions: The result obtained in this investigation showed that by optimized VL with the best VH variants. The final variant, L3H6, subjecting the system to a high degree of shear, a significant reduction showed an overall affinity improvement of 18-fold over the parental of the droplet size in the oil phase is guaranteed, which has an impact antibody and exhibited an enhanced potency to block the binding of on absorption, due to the small size reached. VEGF to its receptor. Functional mapping studies of L3H6 using phage display and extensive mutagenesis of VEGF revealed a novel neutralizing epitope on human VEGF.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S33
LATINFARMA 2013 Resúmenes/Abstracts
CO 056: DEVELOPMENT AND CHARACTERIZATION OF C 017: LOW LEVEL LASER THERAPY (LLLT): THERAPEUTIC MANGIFERIN NANOCAPSULES EFFECTS, DOSES, INDICATIONS AND CONTRAINDICATIONS, SIDE EFFECTS Moura UJ, Barbosa MG, Genro C, Seibel D, Gomes P, Raffin PR. Fornaini C, Merigo E. Centro Universitário Franciscano. Rua dos Andradas, 1614, Santa Maria-RS, Brasil. Dental School, Faculty of Medicine and Surgery, University of Parma, Italy. E-mail: [email protected] Introduction: Manginferin (1,3,6,7-tetrahydroxi-xantona-C2-b-D- glucosilada) is a natural bioactive, more specifically a glycosylated xanthone isolated from Mangifera indica L. Mangiferin is the main Introduction: The first laser device was constructed in 1960 by component of mango extract that presents pharmacological activities Maiman and, some years after, this technology began to be used also in on different organs and tissues, promoting preventive and therapeutic medicine. Since 1967 Mester performed several studies reporting that effects against a considerable number of diseases. laser irradiation, at extremely low power (mJ), caused several changes in the target tissues determining at macroscopic level, for example, a However, one of the problems of mangiferin is its low solubility in better and faster healing of skin burns or ulcerative lesions. water and the poor chemical stability. In this way, nanoencapsulation can be a promising tool to improve mangiferin bioavailability and Material and methods: A literature metanalysis demonstrated that stability in order to develop new medicines. The objectives of this these effects, invisible to the naked eye, lead essentially to two types of study were developed and characterize a nanoencapsulated results: the so-called "biostimulation" or, according to newer formulation containing mangiferin and evaluate the physico-chemical definitions, “biomodulation” which, exploiting the action of the beam characteristics of this nanosystem. on the mitochondria, through the increase of ATP production and the proliferation and differentiation of fibroblasts, accelerates the healing Material and methods: The interfacial deposition of preformed of tissues decreasing, at the same time, the inflammatory reactions, polymer technique was used to produce nanocapsules. It was and the analgesic effect caused by the change of the electric potential at necessary to add small amounts of DMSO in order to solubilize membrane level (theory of the gate). mangiferin in the organic phase. Mangifrin was encapsulated at 0.025%. Particle size, polydispersity index and zeta potential were Results: Mechanisms of laser action on the tissues in LLLT protocols evaluated in ZetaSizer NanoSeries. pH was assessed directly into the are described in this work by showing several and different clinical colloidal suspensions. Drug content and drug release experiments cases with a medium-long term follow-up until the gain of clinical (dialysis) were analyzed in HPLC through a validated method. result. Laser parameters are analysed in order to give well-defined and reproducible protocols for the clinical practice. Results: Nanocapsules were successfully obtained using Eudragit S100 as polymer. Particle size was 96.37 nm, polydispersity index was Conclusion: These photochemical effects, caused by the action of laser 0.202 and zeta potential was -16.63 mV. pH was 3.42. The results on tissues and commonly known under the name of LLLT (Low Level showed no significant difference (p < 0.05) between nanocapsules Laser Therapy) have countless fields of application but must be with and without mangiferin. Encapsulation efficiency was obtained administered according to very precise rules and parameters to achieve by ultrafiltration/centrifugation and it was approximately 80.0%. maximum results. Drug release profiles showed that mangiferin was released from nanocapsules half of the amount than free mangiferin, demonstrating a controlled profile. Conclusions: Based on these results, we can conclude that mangiferin nanocapsules were developed with adequate characteristics for biological experiments.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S34
LATINFARMA 2013 Resúmenes/Abstracts
CO 057: COMBINATION EFFECT OF SONOPHORESIS AND CO 058: NANOPARTICLES AS DRUG CARRIERS: IONTOPHORESIS ON ANTIPYRINE TRANSDERMAL CHARACTERISTICS AND PERSPECTIVES PENETRATION Oropesa-Nuñez R1, Jáuregui-Haza U.2 Aoyagi T1, Watanabe S2, Ga K2, Yamamoto K.3 1Centro de Estudios Avanzados de Cuba (CEAC). Carretera San Antonio, Km 1 1National Institute for Materials Science, 1-1, Namiki, Tsukuba, Ibaraki 305-0044, 1/2, Valle Grande, La Lisa, La Habana, Cuba Japan. E-mail: [email protected] 2Instituto Superior de Tecnologías y Ciencias Aplicadas (InSTEC). Ave. Salvador 2Yutoku Pharmaceutical Ind. Co., Japan. Allende y Luaces, Plaza de la Revolución, La Habana, Cuba. E-mail: 3Kagoshima University, Japan. [email protected]
Introduction: Transdermal drug delivery is promising method to Nanoparticles can copy or modify biological processes because they administrate unstable drugs in digestive organs or avoids first pass propose solutions to the old problems associated with solubility, effect. To promote the drug penetration, sonophoresis and bioavailability, immunocompatibility and cytotoxicity of many iontophoresis are very effective as physical enhancing methods. The traditional drugs. Carbon nanotubes are an example of nanoparticles each enhancing effects have been widely studied and actually there are and nanotechnology due to their small diameters. They can be many reports. In this study, we investigated the combination effect of manipulated chemically and physically. Besides, they are mainly used in sonophoresis and iontophoresis of transdermal penetration of nanomedicine as carriers and as excipients to obtain different drug antipyrene as model drug. delivery systems. In this work, the state of the art of the research on nanoparticles as drug carriers for medical applications, with emphasis Material and method: We used Sonoion® was used to achieve the on their properties, determination of physico-chemical properties and objective. It is developed by Kagoshima Supersonic Laboratory Co., Ltd. carbon nanotubes applications is analyzed. It is demonstrated that drug The excised back and abdominal skin of hairless mouse was used to formulation and administration has been changed with the advances of estimate the enhanced condition of Sonoion® such as current, voltage nanotechnology. The application of nanoparticles in medicine includes and order of application (sono. to ionto. or ionto. to sono.) and so on. their use as carriers through the functionalization or drug The animal is established by Kyudo Co., in Kumamoto, Japan. The encapsulation. With the use of nanoformulations, an important amount excised skin was set in Franz-type cell and the Sonoion® was applied. of pharmaceuticals have improved their therapeutic action. The The temperature was kept in 37°C. biomedical applications of carbon nanotubes have open a way to a new field in therapy and medical diagnosis. The main part of these Results: The combination of sonophoresis and iontophoresis showed applications might consist on the implant of nanotubes or synergy effect on the antipyrine skin permeation. By Field-Emission functionalized nanotubes in patients. However, the use of carbon scanning electron microscopy (FE-SEM), the some small holes in nanotubes in medicine depends on the evaluation of their toxicity in stratum corneum was observed by sonophoresis apply. In terms of the humans. order of application, the higher effect was obtained by first sonophoresis application. Moreover, the long drug release was observed by only short time application of Sonoion®. Conclusion: The combination of sonophoresis andiontophoresis is very effective to enhance drug permeation and long-time drug release. Such effect would be based on the small holes formation and deposition of the drug molecules in stratum corneum.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S35
LATINFARMA 2013 Resúmenes/Abstracts
CO 059: NOVEL PEGYLATION TECHNOLOGIES FOR THE CO 060: PEGYLATION: AN EFFECTIVE TOOL FOR DEVELOPMENT OF NEXT GENERATION BIODRUGS BIOMASKING
Ikeda Y1, Katamachi J1, Kawasaki H1and Nagasaki Y.2 Ramón JA1, Saez V1, Peniche C1, Hardy E.2
1Department of Materials Science, Graduate School of Pure and Applied Sciences, 1Center for Biomaterials, University of Havana, P.O. Box 6130, Havana, Cuba. E- University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan mail: [email protected] 2 Master’s School of Medical Sciences, Graduate School of Comprehensive Human 2Institute for Science and Technology of Materials, University of Havana, Havana, Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8573, Cuba. Japan 3Satellite Laboratory, International Center for Materials Nanoarchitectonics (MANA), National Institute of Materials Science (NIMS), Tennodai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan. E-mail: [email protected] Nowadays, a large group of medical treatments are based on new substances. These were obtained due to strong development of science and technology in last few decades and include: (i) proteins and peptides used as replacement therapy and as inhibitors or regulators Introduction: PEGylation refers to the covalent attachment of of the immune system, (ii) materials used in drug delivery systems like poly(ethylene glycol) on the biomolecules. PEGylation is recognized as phospholipids and biodegradable polymers, and (iii) metals and their a promising method to increase the therapeutic efficacy of medicines in alloys, polymers, ceramics and composites of them used in various clinical settings. A variety of molecules have been modified with PEG devices such as prostheses, stents, heart valves, etc. and several PEGylated drugs have been approved in clinical settings. In this presentation, our recent developments of novel PEGylation Unfortunately the behaviour of these materials in the body is technologies on biomolecules will be shown. sometimes negative for the initial purpose. For example, proteins and peptides have low stability in vivo, a short half-life time and Material and methods: For the construction of PEGylated immunogenicity. Among the problems associated with other materials oligonucleotide by solid phase synthesis, a novel solid phase which was are: a) thrombus formation on artificial surfaces in contact with living pre-installed with PEG was prepared. In the case of protein PEGylation, tissues, b) damages to the tissues (e.g. vascular weakening produced a novel PEG derivative which possesses glutaraldehyde at one end has by the liposomes) and c) recognition and elimination by the been synthesized. reticuloendothelial system of micro/nano-devices used as DDS like Results: Solid phase synthesis of PEGylated oligonucleotide. A novel liposomes and biodegradable polymer microspheres. solid-phase synthesis method for poly(ethylene glycol) (PEG)- In general, all these phenomena are due to unwanted interactions that oligonucleotide conjugates was developed to increase the stability of occur at the interfaces between biodrugs or synthetic biomaterials and therapeutic oligonucleotides such as antisense oligonucleotides and biological medium. Consequently, any agent that mediates this siRNA. A prepared solid phase was pre-installed with PEG to provide interaction, and become to this in a more "natural" fashion, promotes oligonucleotides modified with PEG at the 3′ terminus. Compared with the acceptance by living organisms of these "foreign bodies". An ideal the conventional liquid-phase synthesis method, the developed solid- substance for this mediation, it might be call “biomasking”, is the phase method is simple and reproducible. PEGylation at the 3′- polyethylene glycol (PEG). terminus was confirmed to stabilize not only DNA but also RNA more than PEGylation at the 5′ terminus, which has been widely used thus This presentation is about advantages of PEGylation (conjugation to far. A novel chemistry for the PEGylated protein with a high activity. PEG) for biomasking. PEGylation is a well-established technology used Several PEGylated proteins have been approved as therapeutic drugs. to transform proteins, peptides, small molecules and oligonucleotides In many cases, PEGylated protein has been synthesized by the into more potent drugs than their corresponding unmodified native conjugation reaction between PEG possessing activated ester and molecules. Furthermore, PEGylated liposomes had received approval amine(s) in the protein. This reaction, however, often causes for improve the delivery of encapsulated drugs, such as the anticancer inactivation of PEGylated proteins. agent doxorubicin, and PEG-modified polymers (such as n- hexadecylcyanoacrylate and PLGA) are studied extensively to obtain Conclusions: In this report, we present a novel chemistry which enhanced particulate delivery systems. enables the PEGylation of proteins under the mild reaction condition. PEGylated protein prepared by the method developed exhibited much higher biological activity than the PEGylated protein prepared by the conventional method.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S36
LATINFARMA 2013 Resúmenes/Abstracts
CO 061: NANOSTRUCTURE: SURFACE MODIFICATIONS BY MR 002: DRUG REGULATORY AUTHORITY OF CUBA. YEAR 25 LASER BEAM Sánchez C, Debesa F, Yañez R and López, A. Guastaldi AC. Centro para el Control Estatal de Medicamentos, Equipos y Dispositivos Médicos Grupo de Biomateriais. Instituto de Química de Araraquara, UNESP, Brasil. E- (CECMED), La Habana, Cuba. E-mails: [email protected], mail: [email protected] [email protected], [email protected], [email protected]
This presentation is directed related to surface modifications by laser Introduction: The former “Centre for State Control of Drug Quality” beam comparing to various existing processes, such as: mechanical (CECMED) was created 25 years ago, with the main purpose of (machining and jetting with abrasives), chemistries (acid attack and centralize actions intended to develop of regulation and surveillance of passivation) and thermal processes (plasma-spray). The modification quality, safety and efficacy of medicines and in vitro diagnostics for of the surface obtained by the laser beam incidence in the surface of the human use in Cuba. This research was carried out for characterizing implant cause micro/nanomorphologic structure assembles the evolution and performing of implemented sanitary regulation and its equivalent characteristic without leaving vestige of contamination for perspectives. being a clean, reproducible process and to make possible a larger Material and methods: An observational and retrospective study was control of the variables of the process. Commercially pure titanium made, were consulted dispositions supporting CECMED´s work since implants with surfaces modified by laser beam with and without the legal point of view, and also reviewed regulations issued by this chemical deposition of apatite applied biomechanical and Centre since 1989 till 2013, which are available from public and non- topographical analysis in rabbits. The contemporaneous implantology edited sources. looks for advances on implants’ surfaces which allow a safer rehabilitation treatment in a lower period of time. Once the Results: Regulatory milestones and its renovation through the time implantation used is subjected to the action of complex mechanical were identified for each of the basic regulatory functions of CECMED, efforts and variations of the physical-chemical properties of the way in such as, regulatory system; marketing authorization; state inspections which is applied. Literature shows that the implant needs a and establishment licenses; market surveillance and pharmaco- micro/nanomorphologic superficial structure, not only to assure the vigilance, clinical trials, laboratory assays and lot release. Legal bases mechanic anchorage of the bone on its surface, but also to provide which back regulation up and current sanitary actions for violations bone-interaction, which can be understood as the direct connection were summarized. It was emphasized organization, scope to all phases between the new-formed bone and the surface of an implant, without of the life-cycle of drugs, diagnostics and medical devices, including the fibrous tissue interposition. However, it is difficult to conclude investigation, manufacturing, distribution and use. Also was precisely what causes the increase in bone response to a modified underlined the improvement achieved for regulation, transparency surface, particularly in the HA coated implants, as this process alters and participation of regulated in the construction of each regulatory the chemistry by the addition of HA, but simultaneously, it may alter piece. The success of recognition of satisfactory performance of Cuban the physical-chemical properties, micro and nanoroughness. Moreover, Regulatory Authority by the World and Pan American Health depending on the application process of HA, alteration may occur in the Organizations (WHO/PAHO) was enhanced, and its current role as surface area. The research considered here validates its development; Regional Reference Drug Regulatory Authority for The Americas area. thereafter it is characterized with great potential to generate and to transfer Brazilian technology, from a process of ample commercial use. Conclusions: The safeguard of the health of Cuban population has on It is treated, thus, of a clear possibility of application of an innovative CECMED an efficient keeper, which is upgrading permanently its chemical covering process of bioactive layers in the surfaces of procedures and sanitary actions of regulation and control, with implants, which will facilitate the access to a population socially less constant development and timely response to the necessities and attended, reverting, thus, with a notable social character. Finally, the challenges. physical chemical properties of the surface are responsible by osseointegration phenomenon and the nanoroughness or nano- morphologic will supply more or less area to occur osseointegration.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S37
LATINFARMA 2013 Resúmenes/Abstracts
Sesión para la Constitución de la Red Latinoamericana - Iberoamericana de Alternativas basadas en las 3Rs / Session for the Constitution of the Latin-American - Iberoamerican Network for 3 Rs Alternatives
CO 062: THE ROLE OF THE BRAZILIAN CENTER FOR CO 063: ALTERNATIVE METHODS AT THE END OF THE VALIDATION OF ALTERNATIVE METHODS (BraCVAM) IN WORLD THE PROCESS OF VALIDATION IN BRAZIL: LOOKING TO Asprea M. THE FUTURE Office of Laboratory Animal Care, Department of Laboratory Services, Hospital de Presgrave O, Moura W, Caldeira C, Delgado I. Pediatría JP Garrahan, Buenos Aires, Argentina. Instituto Nacional de Controle de Qualidade em Saúde (INCQS)/Fundação Oswaldo Cruz (FIOCRUZ), Brasil. E-mail: [email protected] Seeing at the new alternative methods technologies in the use of laboratory animals and with the wish of bring new contributions, we Introduction: Brazilian Law 11,794/2008 rules the animal use and have launched a Regional Network with the aim to get integrated to the created the Council for the Control of Animal Experimentation rest of the community. (CONCEA) which is responsible, among many other activities, for From Aacytal (Argentina Association for Science and Technology making alternative methods official in Brazil. The Brazilian Center for Laboratory Animals), along Aucytal (Uruguayan Association of Animal Validation of Alternative Methods (BraCVAM) was created in order to Science and Technology Laboratory) and Asochical (Chilean identify laboratories and the need of validation, as well as organize and Association for Laboratory Animal Science, we call to join us. make feasible the execution of validation process. The reality show us that in our region there is little done so far in Objectives: Show how BraCVAM expects to work in Brazil and its alternative technology, due to shortcomings in legislation and relation with similar organizations. regulation on animal testing laboratory. Results: BraCVAM will organize studies to be executed by the National The lack of government financial investment in promoting this Network on Alternative Methods (RENAMA) following OECD Guideline technology, preclude an important tool for achieving objectives. 34 and it will count on two Committees. The first will peer review the results during the validation and the second will evaluate and Another weakness is the user ignorance to these new trends and the recommend finished result to CONCEA. RENAMA received a financial difficulty to leave traditional forms of their normal duties. support from National Council of Technological and Scientific Development (CNPq) to help starting two lines: 1) introduction of The irregularity in the legislation is a threat. already validated methods and 2) development of a skin model. It will We believe to have sufficient strength to fulfill our mission and one of also be used for starting the process of laboratories accreditation in them is the support of the Association of Laboratory Animal Sciences in GLP. BraCVAM was already invited for participating as an observer at the region, which will facilitate the collection of information needed to the International Cooperation on Alternative Test Methods (ICATM) build a network between areas of biomedical research, science and to join the OECD Guideline Programme. education of life or biological product development, to generate a Conclusions: Creation of BraCVAM and RENAMA will lead Brazil to join database. countries that search for alternative methods either for experimental How are we working? and educational purposes. It makes possible to participate on international studies for validation of methods as well as keep mutual We have opened an Internet portal that will propagate the message. evaluation and acceptance with international 3Rs Centers. BraCVAM and RENAMA will contribute to join institutions that work on We are participating as speakers in events that help in spreading the alternative methods and it will be possible to develop its own theme, developing new alternative methods in ours institutions and validation strategy of new ingredients or products, especially those using other strategies that have been developed previously and join our ones derived from nature. In a similar way, BraCVAM hope to help the project. development of networks in Latin America and Caribbean.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S38
LATINFARMA 2013 Resúmenes/Abstracts
CO 064: CUBAN EXPERIENCE IN THE DEVELOPMENT OF 3RS CO 065: WHY AND FOR WHAT CREATING A IN THE FIELD OF TOXICOLOGY AND METABOLISM OF LATINAMERICAN-IBEROAMERICAN NETWORK FOR DRUGS ALTERNATIVES? Rodeiro I. Chovel ML.
Departamento de Farmacología, Centro de Bioproductos Marinos, Plaza de la Instituto Finlay, La Habana, Cuba. Revolución, La Habana, Cuba. E-mail: [email protected]
To the light of the new approaches and trends, as well as considering Since 1990, the alternative methods and the 3Rs principles have been the progress reached in the development, validation and the promoted in Cuba. National consensus where all parties concerned implementation of technologies and methods based on the principle of have been represented, including animal welfare, industry, academia 3Rs worldwide, it is absolutely necessary to create a framework able to and government for introducing alternatives methods in the integrate the groups working on alternatives in Latin-America. Thus, it pharmaco-toxicological evaluation of new pharmaceuticals have been will be possible to reinforce our strengths and to overcome our development. Educational programmes where 3Rs are promoted in weaknesses by means of the experience exchange and the scientific different specialties of our university have been introduced. During collaboration, courses and trainings, participation in proficiency and these years, different assays as useful tools for preclinical in vitro interlaboratory validation studies and platform of projects fully focused screening of both synthetic and natural drugs have been development on the development and implementation of Alternatives for and validated. At this work, Cuban experience on this way is revised. Pharmaceuticals and Biological products, as well as for Cosmetics, Food, Chemicals, etc. For that, it is needed to identify what each Group/National Network is able to contribute with in technical and scientific terms and the funding bodies interested in supporting this initiative in a continent with a low development in the field of 3Rs. Moreover, the collaboration with experienced institutions and organizations devoted to Alternatives from developed countries could provide significant benefits to reach our purposes. The definition of statements, a working structure (including a Board) and an Action Plan will be the priority of this Presentation in order to give the first step toward a near future with more development and implementation of Alternatives in Latin-America.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S39
LATINFARMA 2013 Resúmenes/Abstracts
MIÉRCOLES, OCTUBRE 23 / WEDNESDAY, OCTOBER 23rd SESIÓN PLENARIA / PLENARY SESSION
PL 005: PERSONALIZED CANCER VACCINES: WHO SHOULD PL 006: DRUG METABOLISM IN THE BRAIN AND HOW IT PICK THE TARGET? CAN ALTER DRUG RESPONSE Overwijk WW. Tyndale R.
Houston, TX, USA. Toronto, Canadá
T cells can mediate remarkable tumor regressions including complete The brain has a unique expression profile of drug and toxin cure in patients with metastatic cancer. Genetic alterations in an metabolizing cytochrome P450 enzymes (CYPs); multiple forms of CYPs individual’s cancer cells (the mutanome) encode unique peptides (m- have been identified in the brains of different species including rodents, peptides) that can be targets for T cells. The recent advances in next- dogs, monkeys and humans. These CYPs are genetically polymorphic, generation sequencing and computation prediction allow, for the first similar to their expression in the liver meaning some people have high time, the rapid and affordable identification of m-peptides in individual levels, while other people have no expression. These CYPs are uniquely patients. Despite excitement about this extended spectrum of potential expressed and regulated in a cell and brain-region specific manner and targets in personalized immunotherapy, there is no experience or can metabolize many centrally relevant compounds including centrally consensus on the path to their successful clinical application. A major acting drugs, neurotoxins and neurotransmitters. Drugs and toxins that question is which peptides to target therapeutically. One approach is to act on the central nervous system (CNS) may be metabolized in situ in select peptides based on mutation analysis and peptide binding the brain, and differences in in situ metabolism may contribute to prediction algorithms. Alternatively, we can let the immune system variation in an individual’s response to drugs and toxins. Studies in “pick” the target peptide by inducing a tumor microenvironment that artificial in vitro systems, with added cofactors, indicate that brain CYPs promotes T cell priming in vivo. We will present data on both have similar substrate specificity and in vitro kinetics to their hepatic approaches and discuss pros and cons of either approach. forms. We have shown that brain CYPs are metabolically active in situ using a radio-labeled suicide inhibitor, which takes advantage of the brain CYP metabolic activity of the animal, injected directly into the brain of a living rat. We have also subsequently demonstrated in vivo, using a similar brain inhibitor or induction approach, that enzymes within the brain can alter drug effect. This is illustrated using CYP2B inactivation of the anesthetic propofol within the rat brain and its resulting impact on sedation, CYP2B activation of a neurotoxic pesticide chlorpyrifos and its alteration of neurotoxicity. Likewise we have shown that brain CYP2D activation of codeine to morphine is important to the early time points for analgesia, and that brain CYP2D may importantly alter risk for Parkinson’s disease through its ability to inactivate neurotoxins such as MPTP. These results indicate that brain CYPs are actively able to metabolize CNS acting drugs and neurotoxins and can contribute significantly to local drug response. The induction of brain CYPs by nicotine and alcohol, and higher levels in the brains of smokers and alcoholics, suggests that in addition to pharmacogenetic variation, commonly used drugs could also alter responses to centrally- acting drugs and toxins. More broadly these studies indicate that brain CYPs are active in situ and have sufficient local enzymatic activity to meaningfully alter the pharmacology of centrally acting drugs and neurotoxins.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S40
LATINFARMA 2013 Resúmenes/Abstracts
SIMPOSIOS Y TALLERES / SYMPOSIA AND WORKSHOPS CONFERENCIAS Y COMUNICACIONES ORALES / CONFERENCES AND ORAL COMMUNICATIONS Taller Inmunofarmacología y Biotecnología. Sesión: Inmunofarmacología / Workshop on Immunopharmacology and Biotechnology. Session: Immunopharmacology
CO 066: CIGB-814, A PEPTIDE AS IMMUNOMODULATOR FOR CO 067: ENHANCEMENT OF THE INHIBITORY EFFECT OF AN THE TREATMENT OF RHEUMATOID ARTHRITIS IL-15 ANTAGONIST PEPTIDE BY ALANINE SCANNING
Domínguez MC1, Lorenzo N1, Barberá A1, Ancizar JA1, Torres AM2, Rodríguez Y1, Reyes O1, Gerónimo H1, Chico A2, Garay H1, Ojeda M1, Hernandez MV2, Hernandez I2, Gil R2, Altruda F3, Silengo L3, Padrón Arrieta C1, Estévez M2, Guillén G1 and Santos A1. GR1. 1Center for Genetic Engineering and Biotechnology, P.O. Box 6162, Havana City 1 Centro de Ingeniería Genética y Biotecnología, La Habana, Cuba. E-mail: 10600, Cuba. E-mail: [email protected] [email protected] 2Hermanos Ameijeiras Hospital, San Lazaro 701, Havana 10300, Cuba. 2 Servicio Nacional de Reumatología, La Habana, Cuba. 3 Universidad de Turín, Italia. Introduction: IL-15 is a proinflammatory cytokine that acts early in the inflammatory response and has been associated with several Induction of immune tolerance as therapeutic approach for autoimmune diseases including Rheumatoid Arthritis (RA), where it autoimmune diseases constitutes a current research focal point. In this had been proposed as a therapeutic target. We recently reported an IL- sense, we aimed to evaluate an Altered Peptides Ligand (APL) for 15 antagonist peptide corresponding to sequence 36–45 of IL-15 induction of peripheral tolerance in patients with Rheumatoid Arthritis (KVTAMKCFLL) named P8, which specifically binds to IL-15Rα and (RA). A novel T cell epitope from human heat-shock protein 60 inhibits IL-15 biological activity with a half maximal inhibitory (Hsp60), an autoantigen involved in the pathogenesis of RA, was concentration (IC50) of 130μM in CTLL-2 proliferation assay. identified by bioinformatics tools and an APL was design from this epitope (CIGB-814). Firstly, we investigated the ability of this peptide Material and methods: In order to improve binding of peptide P8 to for inducing regulatory T cells (Treg cells) in mice. CIGB-814 induced the receptor IL-15Rα, we used an Ala scan strategy to study an increase of the proportions of Treg cells in the draining lymph nodes contribution of each individual amino acid to the peptide’s antagonist of the injected site in mice. On other hand, this peptide increases the effect. To evaluate the effects of the peptides, CTLL-2 cells were proportions of the CD4+CD25highFoxP3+ Treg cells in ex vivo assays incubated with serial dilutions of peptides in presence of 300pg of IL- using PBMC isolated from RA patients. In addition, we evaluated the 15 during 72 hours. Proliferation was measured by MTT mitochondrial therapeutic effect of this APL in two animal models: adjuvant induced staining. Cells from patients with RA were incubated with 50 µg/mL of arthritis (AA) in Lewis rat and collagen induced arthritis (CIA) in peptide or 60 ng/mL of IL-15, or a combination of both. After 48h DBA/1 mice. Our approach was compared to metotrexate (MTX), the incubation, supernatants were collected and TNF-α concentration was gold standard treatment for RA, in CIA model. Clinical score, Treg, TNFα determined by ELISA. levels and histopathology were monitored. CIGB-814 efficiently Results: Here, we found that Phe and Cys are important for peptide inhibited the course of AA and CIA, with significant reduction of the binding to IL-15Rα. We also investigated other single site mutations clinical and histopathology score. The therapeutic effect induced by and replaced the second Lys in the sequence by the polar non-charged CIGB-814 is mediated by an increase of the proportions of Treg cells amino acid threonine. The resulting peptide [K6T]P8 exhibited a and a decrease of TNFα levels. These results indicate a therapeutic higher activity than P8 with an IC50 of 24 μM. CTLL-2 proliferation potentiality of this peptide and support further investigation of this assays showed that the dimeric form of [K6T] P8 had a higher candidate drugs for treatment of RA. Interference of the pathogenic T inhibitory activity (IC50 8 μM) than the monomeric form. We also found cell function in a specific manner using an APL derived from an that this peptide was more active than peptide P8 in the inhibition of autoantigen that can induce tolerance mediated by activation of Tregs TNFα secretion by synovial cells from RA patients. as shows here, represents an attractive therapeutic approach for autoimmune diseases. Conclusion The peptide [K6T]P8 described in this work is a new type of IL-15 antagonist and constitutes a potential therapeutic agent for RA.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S41
LATINFARMA 2013 Resúmenes/Abstracts
CO 068: THE LONG PENTRAXIN PTX3: A NON-REDUNDANT CO 069: LEVELS OF SOLUBLE IL-15, IL-6, TNFΑ AND IL-15RΑ COMPONENT OF THE HUMORAL INNATE IMMUNITY AND A IN SYNOVIAL FLUID AND MEMBRANE BOUND IL-15 ON PROMISING BIOMARKER IN INFLAMMATORY CONDITIONS SYNOVIAL CELLS FROM PATIENTS WITH RHEUMATOID ARTHRITIS AND OSTEOARTHRITIS Garlanda C1, Jaillon S1, Barbati E1, Bottazzi B1, Mantovani A.1 Machado-Díaz AC1, Arrieta-Aguero C1, Chico-Capote A2, Rodriguez- 1Humanitas Clinical and Research Center, via Manzoni 113, Rozzano, 20089, Italy. 1 1 1 1 E-mail: [email protected] Alvarez Y , García-del Barco Herrera D , Raices-Cruz I , Falcón-Cama V , 2Department of Translational Medicine, University of Milan, Milan, Italy. Chacón-Quintero Y1, Guillen-Nieto G1, Santos-Savio A1. 1Centro de Ingeniería Genética y Biotenología. La Habana, Cuba. E-mail: [email protected] Pentraxins are a family of evolutionarily conserved multifunctional 2 Hospital Hermanos Amejeiras. La Habana, Cuba. pattern-recognition proteins characterized by a cyclic multimeric structure. Based on the primary structure of the subunit, the pentraxins are divided into two groups: short pentraxins and long Introduction: Cytokines are a family of proteins involved in regulation pentraxins. C-reactive protein (CRP) and serum amyloid P-component of the immune system and the intercellular communication. Many (SAP) are the two short pentraxins. The prototype protein of the long autoimmune diseases such as Rheumatoid arthritis (RA) are related to pentraxin group is pentraxin 3 (PTX3). CRP and SAP are produced deregulation of cytokine expression. High levels of pro-inflammatory primarily in the liver in response to IL-6, while PTX3 is produced by a cytokines IL-15, IL-6 and TNF-α have been described in synovial fluid variety of tissues and cells and in particular by innate immunity cells in from RA patients. . response to pro-inflammatory signals and Toll-like receptor (TLR) engagement. Material and methods: In this study we quantified these cytokines levels in synovial fluid from 18 RA and 17 osteoarthritis (OA) patients, Through in vitro and in vivo studies performed with original tools from Rheumatology service at B. Ameijeiras hospital, who presented generated by this group (recombinant human and mouse PTX3, its inflammation and abundant synovial fluid in damaged joints. We also domains and mutated variants, original anti-PTX3 antibodies and PTX3 quantified levels of soluble IL-15Rα, a private receptor for IL-15, using gene targeted mice), it has been shown that PTX3 interacts with an ELISA designed by our group. We also studied expression of several ligands, including growth factors, extracellular matrix membrane-bound IL-15 on synovial cells by FACS and EM. components and selected pathogens, playing a role in complement activation and pathogen recognition by phagocytes, in tuning Results: Current study confirmed presence of soluble IL-15Rα in inflammation and in tissue remodelling. synovial fluids from RA and OA patients. Although we detected expression of membrane IL-15 on cells from synovial fluids of RA In addition, data obtained so far with ELISA assays on human plasma patients. Also we determined that IL-15 is present as a membrane or serum suggest that PTX3 may represent a useful marker of different bound ligand. Acidic treatment produced a slight decrease in the inflammatory conditions including cardiovascular pathology amount of membrane-bound IL-15. Indicating that, in addition to complementary to CRP: being directly produced by damaged tissues, transmembrane IL-15, a certain number of IL-15 molecules are bound its increase precedes CRP and rapidly reflects the vascular involvement to membrane IL-15Rα. Interestingly, we found a positive correlation by inflammatory process. The combination of PTX3 and classical between high levels of IL-6 and high levels of IL-15Rα in RA but not in biomarkers showed an incremental diagnostic and prognostic value in OA. several conditions, including sepsis, acute coronary syndromes and chronic heart failure. Conclusions: The presence of soluble IL-15Rα and membrane IL-15 suggested that soluble IL-15Rα could induce IL-6 through a reverse Thus, the prototypic long pentraxin PTX3 is a multifunctional soluble signaling pathway and then contributing to a proinflammatory medium pattern recognition receptor acting as a non-redundant component of in RA. the humoral arm of innate immunity and a novel promising biomarker to provide useful prognostic information for clinical outcomes in inflammatory conditions.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S42
LATINFARMA 2013 Resúmenes/Abstracts
CO 070: IMMUNOMODULATING AND ENHANCING CO 071: EARLY PHASE OF SYSTEMIC REACTION TO ORAL ACTIVITIES OF SOLUBLE GLUCANS FROM Sacharomyces ASPIRIN CHALLENGE IS RELATED TO AN INCREASE IN THE cerevisiae ASSESED BY MONOCYTE ACTIVATION TEST LEVELS OF IL-6 AND THE PERCENTAGE OF EFFECTORS MEMORY T-CELLS Pardo-Ruiz Z, Perdomo-Morales R, Pacios-Michelena A. Pérez-Novo CA1, Świerczyńska-Krępa M2,3, Niżankowska-Mogilnicka Centro de Investigación y Desarrollo de Medicamentos (CIDEM). Ave. 26 No. 2 2 2 1 2 1 1605. Plaza de la Revolución. La Habana, Cuba. E-mail: E , Sanak M , De Ruyck N , Holtappels G , Szczeklik A , Bachert C. [email protected] 1Upper Airways Research Laboratory, Dept. of Otorhinolaryngology, Ghent University Hospital, Belgium. 2Dept. of Medicine, Jagiellonian University School of Medicine, Cracow, Poland. Introduction: Beta-glucans are homopolymers of glucose that have 3 Out-patient Allergy ClinicMedex, Bielsko-Biała, Poland. shown immunomodulating effects depending on their structural characteristics and could be potential contaminants of some parenterals that are clarified through cellulose filters. The ability of Introduction: Systemic reactions have been suggested to be linked to glucans to develop an immune response or enhance the immune the hypersensitivity reactions occurring in aspirin exacerbated response induced by other pathogens is overlooked by the respiratory disease; however the mechanism has not been elucidated conventional pyrogen tests. Thus, the objective of this work was to yet. In this study we aim to study the T- cell response and release of determine the enhancing immune effect of glucans from the yeast inflammatory mediators at systemic level following oral aspirin Sacharomyses cerevisiae when they are incubated concomitantly with challenge and their possible link with clinical reactions in patients with LPS and to confirm the significance of Monocyte Activation Test (MAT) aspirin exacerbated respiratory disease (AERD). for detecting such activities. Methods: Patients with nasal polyposis and asthma with (n=20) and Material and methods: Soluble glucans were purified from S. without AERD (n=18) were orally challenged with aspirin in a double cerevisiae and were partially characterized. The content of hexoses was placebo controlled study. Peripheral blood mononuclear cells were determined by phenol-sulphuric colorimetric method and endotoxin isolated and serum samples were collected before and after placebo contamination was evaluated by the Limulus test. Both and aspirin oral challenges. Cells were analyzed for CD4, CD8, CD25, immunostimulating and enhancing effects were determined by CD127, CD45RA and CD45RO surface markers by Flow cytometry. employing MAT. As monocyte source was used human whole blood Serum levels of inflammatory mediators: cytokines, chemokines and that was incubated in polypropilene tubes with glucans, either alone or lipid mediators were assayed by using the Bioplex (Luminex) concomitantly with LPS. The releasing of Interleukin-6, -1β and Tumor technology and ELISA. Urinary LTE4, 9α, 11β-PGF2 were analysed by Necrosis Factor-α was determined in the supernatant by ELISA. ELISA. Results: Glucans induced the releasing of all proinflammatory Results: At baseline, AERD patients showed significant higher levels of + + + pos cytokines assayed, TNF-α was the most released cytokine, followed by sIL5Ra, uLTE4 and percentage of CD4 , CD4 CD25 CD127 and + - + IL-6 and IL-1β. In addition, the LPS induced-immunostimulating effect CD4 CD45RA CD45RO but decreased levels of TGF-β1 and number of was powerfully enhanced by glucans. CD4+CD25+CD127neg cells. Serum concentrations of IL-8 and sIL5R-α were significantly elevated in patients reacting to a dose of aspirin Conclusions: Glucans showed enhancing and immunomodulating lower than 250 mg (half of the cumulative dose of 500 mg) when effects that became evident through MAT. It was shown that MAT could compared to non-AERD subjects and patients reacting to the highest be an appropriate test to evaluate glucans activities. doses of aspirin administrated (500 mg). Oral aspirin challenge resulted in the release of IL-6, urinary LTE4 and in the increased of the number of CD4+CD45RA-CD45RO+ memory T-cells only in AERD patients but failed to reduce the levels of sCD40L as occurred in non- AERD subjects. The release of IL-6 was elevated in patients with bronchial and nasal reactions when compared to subjects showing only bronchial reactions. Conclusion: In conclusion, we demonstrated that early phase of systemic reaction after oral administration of aspirin is characterized by the release of IL-6 and the recruitment of effector memory T-cells. This points out to a novel mechanism that has been already discussed in allergy, asthma but not in AERD.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S43
LATINFARMA 2013 Resúmenes/Abstracts
Taller Inmunofarmacología y Biotecnología. Sesión: Desarrollo e Investigación sobre Vacunas / Workshop on Immunopharmacology and Biotechnology. Session: Development and Research on Vaccines
CO 073: CONJUGATE VACCINE CANDIDATE AGAINST CO 074: A Salmonella typhi POLYSACCHARIDE VI- Neisseria meningitidis DIPHTHERIA TOXOID (VI-DT) CONJUGATE VACCINE AGAINST TYPHOID FEVER Acevedo R1, González M2, Cedré B1, Valmaseda T1, Aranguren Y1, Fernández S1, Zayas C1, García L1, Cardoso F2, Garrido R2, Faez I2, Fernández S1, Soubal JP2, Valmaseda T1, Santana D2, Aranguren Y1, Rodríguez L2, Verez V2, Cardoso D.1 Ramírez U1, Merchán Y1, Romeu B1, Padrón MA1, García A1, Muñoz M1, Hechevarría JA2, Acevedo R1, Cardoso F2, Lastre M1, D Rey E2, Reyes L1, 1Finlay Institute, La Habana, Cuba. E-mail: [email protected] 1 1 1 1 1 1 2Centro de Química Biomolecular. La Habana, Cuba. Pérez O , Fariñas M , Borrero Y , Lescaille D , Blaín K , Cabrera R , Zayas C1, Mandiarote A1, Costa N1, Nuñez D1, Serrano D1, Oliva R1, Pérez JL1, Valdés Y2, García L1, Vérez V2, Cardoso D.1
Introduction: Meningoccocal disease is one of the most important 1Finlay Institute, Havana. Cuba. E-mail: [email protected] causes of meningitis. Estimates from WHO indicates that every year 2Biomolecular Chemistry Center (CQB), Havana. Cuba. occurred more than 1 million of invasive cases and 100 000 deaths.
The situation is more difficult in African countries from the “meningitis belt” where epidemics from serogroups A, W135 affect entire region. Introduction: Typhoid fever continues to be a major public health Conjugated polysaccharide vaccines are more immunogenic, induce problem according with estimates of World Health Organization. None long lasting immune response, memory and herd immunity compared of the available typhoid vaccines are licensed for children under 2 with plain polysaccharide vaccines. However, conjugated vaccines are years old, the age group who reaches the highest mortality. more expensive and less affordable to poor countries. Finlay Institute Conjugation of polysaccharides to an immunogenic protein revert the in collaboration with the Center of Biomolecular Chemistry (CQB) aims Tyme independent pattern of polysaccharides to a T-dependent to develop an affordable multivalent conjugated vaccine candidate pattern and induce immune response in infants. The aim of this work against N. meningitidis. was to obtain and evaluate a conjugate candidate vaccine as part of the project conducted by Finlay Institute and Biomolecular Chemistry Material and methods: Polysaccharides were conjugated to Center. diphtheria toxoid and evaluated as tetravalent formulation. A dose response study was carried out in Balb/c mice with the conjugate Material and methods: Vi polysaccharide (PsVi) of Salmonella typhi formulation and compared to commercial vaccines. was conjugated to diphtheria toxoid (Vi-DT) at different scales. Analytic assays were done to formulations at 10 μg/mL and 20 μg/mL. Results: Conjugates of serogroups A, C, Y, W135 of N. meningitidis Immunogenicity of conjugates was evaluated in Balb/c mice. were formulated and the dose response study demonstrated that high Additionally, some preliminary toxicological studies were done in antibodies level and bactericidal activity were induced, comparable Sprague Dawley (SD) rats. with the commercial vaccine Menveo. Results: All lots of conjugate formulations showed similar Conclusions: Evaluation of tetravalent conjugate formulation during characteristics. Vi-DT conjugates were immunogenic in Balb/c mice experimental stage was successful. The development of the multivalent and the immune response was dose dependent. Mice immunized with vaccine candidate is ongoing. Vi-DT conjugate exhibited high levels of IgG subclasses, IgG affinity maturation and Th1 cytokine profile (IL-12 and IFN-γ). Memory B cell and memory T cell responses after booster dose with a plain polysaccharide vaccine were induced. Conjugates were also immunogenic in SD rats and no toxicity evidence was observed in this model. Conclusions: These results demonstrated that Vi-DT conjugates are safe and immunogenic in animal models, encouraging us to continue the development of a conjugate vaccine against typhoid.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S44
LATINFARMA 2013 Resúmenes/Abstracts
CO 075: FORMULATION, CHARACTERIZATION AND CO 076: DEVELOPMENT OF NOVEL THERAPEUTIC RELEASING OF A LIVE-ATTENUATED 638 Vibrio cholerae HEPATITIS B VACCINE: NASVAC ORAL VACCINE Guillén G, Aguilar JC, Pentón E, Lobaina Y, Aguilar A, Muzio V. Tamayo Y, Martínez JC, Mandiarote A, García L, Martínez R, Ochoa R. Centro de Ingeneria Genetica y Biotecnologia, La Habana, Cuba. E-mail: Finlay Institute, La Habana, Cuba. [email protected] Introduction: Cholera remains as a global threat to public health in developing countries, where infrastructure lacks access to water and to Introduction: Despite the existence of effective prophylactic vaccines, a suitable sanitation. Vibrio cholerae is the infectious agent responsible hepatitis B virus (HBV) infections remain a major public health for cholera. Only Vibrio cholerae O1 and O139 serogroups are known to problem. About 370 million people are chronically infected worldwide. cause epidemics of cholera. Isolates of V. cholerae serogroup O1 are Chronic hepatitis B (CHB) infection also increases the risk of liver classified into two biotypes, El Tor and classical, on the basis of several diseases such as cirrhosis and hepatocellular carcinoma. phenotypic characteristics. Currently, the El Tor biotype is responsible for virtually all of the cholera cases throughout the world and classical Current antiviral therapies fail to control viral replication in the long biotype isolates have virtually disappeared worldwide. In addition, V. term in most patients. As HBV persistence has been associated with a cholerae O1 is classified into two main serotypes, Inaba and Ogawa, defect in the development of HBV-specific cellular immunity, based on agglutination test using polyvalent antiserum against therapeutic vaccination has been extensively studied in CHB. lipopolysaccharide (LPS) antigens. Vaccination against cholera continues to be a feasible strategy against this infection. A Live, orally HBsAg-based vaccines, including prophylactic vaccines and HBsAg- administered, attenuated vaccine strains of V. cholerae have many based formulations with novel adjuvants have been used with unclear theoretical advantages over killer vaccine. A new lyophilized live oral or negative results. The development of therapeutic vaccines against cholera vaccine candidate has been developed in Cuba by NCCI and CHB requires proofing the capacity of the formulation to subvert a Finlay Institute, containing genetically modified Vibrio cholerae strain tolerated immune response. 638 (biotype El Tor, serotype Ogawa) as active pharmaceutical Material and methods: NASVAC as a new generation vaccine include ingredient. The aim of this work was to formulate, characterize and the use of a novel immunization route (intranasal-IN) and a novel release six batches of this vaccine candidate. antigen (HBcAg) expressed in E. coli, used in a combined formulation Material and methods: The batches were formulated using the with HBsAg expressed in Pichia pastoris, both as VLPs and more than established methodology, with adequate controls in each step of the 95% purity. The formulation is a simple mixture of proteins in process. The assays for characterization and releasing were: phosphate buffer administered by the IN and SC routes. The description, residual moisture, viability (colony forming units), immunogenicity in Balb/c and transgenic mice was measured using identity, purity, PCR, immunogenicity and colonization. ELISA, LPA and IFN-g ELISPOT assays. The clinical trials with human volunteers where approved by the Research Ethics Board of the Results: The physicochemical, microbiological and biological assays Hospitals. allowed the characterization and releasing of the six batches of this vaccine candidate to asses content, purity, safety and activity of the live Results: The evaluation in mouse support the rationality of the oral 638 cholera vaccine candidate. therapeutic vaccine candidate targeting the stimulation of CD4(+) and CD8(+) T-cell responses and the induction of pro-inflammatory Conclusion: We concluded that the microbiological properties, cytokines capable of controlling viral replication. NASVAC proved to be colonizing capability, immunogenicity and non-toxigenicity of the final immunogenic in mouse models and then in phase I, II and III, product were suitable and technologically consistent. randomized, double blinded and placebo controlled clinical trials developed in healthy volunteers and CHB patients. Conclusion: Preclinical and clinical results with NASVAC evidenced immunogenicity, safety and efficacy of the vaccine candidate.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S45
LATINFARMA 2013 Resúmenes/Abstracts
CO 077: HEPTAVALENT CONJUGATE VACCINE AGAINST THE CO 078: ADVANCES IN THE CHARACTERIZATION OF A MOST PREVALENT SEROTYPES OF Streptococcus Bordetella pertussis DERIVED PROTEOLIPOSOME AS pneumoniae IN LATINOAMERICA: PRECLINICAL VACCINE CANDIDATE AGAINST WHOOPING COUGH EVALUATION Pérez JL, Fernández S, Herrera Y, Reyes G, Fernández Y, Fajardo EM, García-Rivera D1, Rodríguez L1, Valdés Y2, Martin Y3, Pérez A4, Soroa Mandiarote A, Landys M, Año G, Padrón MA, Acosta M, Cabreras R, Y1, Luque Y3, Serrano J5, Pedroso J6, Santana D2, Villar A7, Chang J5, Riverón L, Fariñas M, Díaz D, García L, Cardoso D, Campa C. Vérez V2. Instituto Finlay, La Habana, Cuba. E-mail: [email protected] 1Laboratory of Immunology, 2Head of Project, 3Laboratory Animal Breeding
Group, 4Group of Immunochemistry, 5Group of Glycoconjugation, 6Group of 7 Chemical Analysis, Glycotechnology Deparment, Center of Biomolecular Introduction: Bordetella pertussis, the whooping cough causative Chemistry, La Habana, Cuba. E-mail: [email protected] agent, has increased its incidence worldwide among adolescents and adults in spite of the high vaccine coverage. That is the reason why the development of new vaccine strategies which provide a long lasting Introduction: A new conjugate vaccine containing the seven serotypes effective immunity has been recommended. Finlay Institute studies the of S. pneumoniae more frequently associated with infection in Latina- properties of a B. pertussis derived proteoliposome (PLBp), purified American was designed for its introduction in Cuba and other from the outer surface of 165 wild type strain, as vaccine candidate. countries of the region. The candidate vaccine contains 2 µg of each capsular polysaccharide 1, 5, 14, 18C, 19F and 23F as well 4 µg for 6B - Results: Scanning electronic microscopy showed spherical structures all of the conjugated to tetanus toxoid- and aluminium phosphate as 50-140nm diameter which was confirmed by photonic correlation adjuvant. As results of many years of development, several batches spectroscopy. Western blot using monoclonal antibodies revealed the were produced with the aim of assessing their physicochemical presence of relevant antigens used in acellular vaccines. LAL assay properties and conducting preclinical evaluation. showed inferior endotoxine levels when compared with other proteoliposomes vaccine, while pirogenicity assay was negative to 75 Material and methods: The studies herein discussed include ng/mL. Histopathological studies performed after intranasal immunogenicity in New Zealand rabbits; prove of memory by a booster administration of 18323 WHO reference strain revealed remarkable with the unconjugated CPS after 4 months and opsonophagocytic differences in the lung tissue damage between PLBp immunized and activity of serum antibodies. DT immunized mice. In addition PLBp showed similar protective Results: The results proved that the vaccine elicited high titer of total capacity than Finlay Institute DPT vaccine in challenge models. The IgG with high avidity and specificity to the CPS after the two doses. administration of PLBp formulated with tetanic and diphtheric toxoid Antibodies were functional as shown by their opsonophagocytic titer (PLBp-dt) raised a high IgG response against B. pertussis in mice. over 1:8 for each serotype. On the other hand, safety was assessed by Conclusions: This PLBp has shown its properties as vaccine candidate several toxicological studies in rats, demonstrating that the vaccine and its potentiality to prevent whooping cough in adolescents and candidate doesn´t induce any sign of unexpected toxicity. adults in a PLBp-dt combined vaccine. Conclusions: The conjugated vaccine candidate is immunogenic and safe in laboratory animals, thus paving the way toward first Latin- American conjugate vaccine against S. pneumoniae.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S46
LATINFARMA 2013 Resúmenes/Abstracts
Taller sobre Estrés Oxidativo y Ozonoterapia / Workshop on Oxidative Stress and Ozonetherapy
C 019: OZONE´S THERAPEUTICAL TARGETS. BASIS OF THEIR CO 079: THE EFFECT OF OZONE ACTIVATED AUTOLOGOUS PLEIOTROPIC EFFECTS PLATELET-RICH PLASMA INJECTION ON PATTERN HAIR LOSS: A PRELIMINARY STUDY León Fernández OS1, Díaz Soto MT1, Dranguet Vaillant J.1 Martínez-Sánchez G, Ricci V. 1Pharmacy and Food Institute of the University of Havana, Cuba. Medical Center Beauty Benefit srl., San Biagio di Osimo (AN) Via Mons. Oscar Romero, 31. Osimo, Italy. Tel. +39 3483833064, E-mails: [email protected]; Ozone´s therapeutic effects have been demonstrated in different [email protected] diseases which are “seeminlgy” no connected between them. Ozone Oxidative Pre/Postconditioning mechanism showed that ozone administration in low doses and controlled number of treatments was Currently, autologous platelet-rich plasma (PRP) has attracted able to increase antioxidant endogenous defence systems therefore a attention in various medical fields, including, dentistry, plastic and condition in order to expect a therapeutical success with ozonetherapy orthopedic surgery and dermatology, for its ability to promote wound is that disease has a chronic oxidative stress as component of its healing. PRP has been tested during facelift and hair transplantation to etiology so cellular redox balance happen in a therapeutical target of reduce swelling and pain and to increase hair density. In addition, medical ozone. Superoxide dismutase activity is an enzyme which is activated autologous PRP has been reported to induce the proliferation involved in different diseases, mainly vascular disorders. At the same of dermal papilla cells. Incubation of PRP with O2/O3 increases the basal time, adenosine plays an important role in stress conditions. Both, concentration of grow factor. The effect of autologous PRP on superoxide dismutase and adenosine, are ubiquitous molecules, miniaturized hair and hair loss was study. PRP preparation activated 2+ achieve its effects through signal transductions and they are modified with Ca , O2/O3 and epinephrine was injected on the scalps of 6 male in specific way by ozonetherapy. Above mentioned ozone´s patients with pattern hair loss every 21 day to reach 6 treatments. therapeutical targets are shown through diseases as ischemic Wash test, micro and global photos were analyzed every month to syndrome, diabetes and disc hernia which demonstrate ozonetherapy follow the clinical evolution. One month after the first treatment the pleiotropic effects. wash test shown a clinical improvement in all patients. Three months after the first treatment, the patients presented clinical improvement in the mean number of hair thickness, 42.5 ± 21.7% (p<0.001), compared with baseline values. At 6 months, the patients presented clinical improvement in mean hair count, 27.4 ± 15.7% (p<0.001), mean hair thickness, 76.2 ± 35.1% (p<0.001), compared with baseline. Our data suggest that the interfollicular injection of O2/O3 activated autologous PRP preparation has a positive therapeutic effect on male pattern hair loss without remarkable major side-effects. Although few studies tested the effects of activated PRP on hair growth, this research provides support for possible clinical application of autologous O2/O3 activated PRP for promotion of hair growth.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S47
LATINFARMA 2013 Resúmenes/Abstracts
CO 080: OZONE OXIDATIVE POSTCONDITIONING CO 081: OZONE THERAPY AMELIORATES NERVOUS SYSTEM AMELIORATES JOINT DAMAGE AND DECREASES DISORDERS AND OXIDATIVE STRESS IN PATIENTS DURING PROINFLAMMATORY CYTOKINES LEVELS AND OXIDATIVE ETHANOL WITHDRAWAL—A PILOT STUDY STRESS IN PG/PS-INDUCED ARTHRITIS IN RATS Díaz M1, Fraga A1, Dranguet J1, Mallok A1, Viebahn-Hänsler R2, Dranguet J1, Fraga A1, Navarro A1, Díaz M1, Viebahn- Hänsler R2, Menéndez S3 and León O.1 Fahmy Z2, Mallok A1, Barberá A3, Delgado L1, Menéndez S4, León O.1 1Pharmacy and Food Institute, University of Havana, Havana 10 400, Cuba. 2 1Pharmacy and Food Institute, University of Havana, Havana 10 400, Cuba. E- Medical Society for the Use of Ozone in Prevention and Therapy, D-76473, mail: [email protected] Iffezheim, Germany. 3 2Medical Society for the Use of Ozone in Prevention and Therapy, D-76473, Centro ProDanza. Ave 51 No. 118005 (Ministerio de Cultura), Marianao. La Iffezheim, Germany. Habana, Cuba. E-mail: [email protected] 3Biomedical Research Department, Center for Genetic Engineering and Biotechnology, Havana, Cuba. 4 Centro ProDanza. Ave 51 No. 118005 (Ministerio de Cultura), Marianao. La Chronic oxidative stress and acetaldehyde accumulation are associated Habana, Cuba. with brain damage during Ethanol Withdrawal (EW). Ozone therapy is a regulator of cellular redox balance and it controls important functions of nervous system during EW at experimental level. The aim of this Rheumatoid Arthritis (RA) is the most prevalent chronic condition work was to develop a pilot study in order to evaluate the ozone´s present in 1% of the adult population. Many proinflammatory effects on EW signs and oxidative stress in 10 patients “Before” and mediators are increased in RA, including Reactive Oxygen Species such “After” ozone treatments. Ozone improved 70% of the signs from as nitric oxide NO, proinflammatory cytokines as tumor necrosis factor Clinical Institute Withdrawal Scale (CIWA-Ar), mainly those associated alpha (TNF-), interleukin-1beta (IL-1β) and other molecules. Ozone to Central Nervous System (CNS). Ozone´s efficacy was observed in oxidative postconditioning has regulatory effects on some pathological patients that required pharmacological treatment. Reduction of CIWA- targets associated with RA. Thus, the aim of this study was to Ar scores and the oxidative stress (p < 0.05) was demonstrated. In investigate the efficacy of ozone therapy in PG/PS-induced arthritis in summary, ozone improved CNS functions and reduced oxidative stress rats in point of joints inflammation and morphology. Moreover, in patients during EW. These results were according to experimental cytokines, nitric oxide and oxidative stress levels in spleen findings and suggest ozone´s regulator effects on important homogenates were evaluated. Ozone treatment ameliorated joint neurotransmitters of the CNS. damage, reduced TNF- concentrations as well as TNF- and IL- 1 β mRNA levels. Besides, cellular redox balance, nitric oxide and fructolysine levels were re-established after ozone oxidative postconditioning. It was concluded that pleiotropic ozone’s effects clarify its therapeutic efficacy in RA. Decreasing inflammation and joint injury, reduction of proinflammatory cytokines, TNF- and IL-1 β transcripts and re-establishment of cellular redox balance after ozone treatment were demonstrated.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S48
LATINFARMA 2013 Resúmenes/Abstracts
C 020: OZONE CONDITIONING EFFECT, NRF2 PATHWAY AND CO 082: EVALUATION OF INHIBITION CAPACITY TO LIPIDIC EPRE. AN IN VIVO STUDY DURING MAYOR AUTHO- PEROXIDATION AT BRAIN LEVEL OF FREE AND HEMOTHERAPY ESTERIFIED PHYTOSTEROLS
Re L,1, Martínez-Sánchez, G2, Bordicchia M3, Malcangi G1, Pocognoli A3, Hernández Ra, Canales Ab, Osegueda Ma, Sandoval G.b Morales-Segura M4, Rothchild J5 and Rojas A.6 aUnidad Profesional Interdisciplinaria de Ingeniería, Campus Guanajuato, 1Clinical Pharmacology & Toxicology Dept, Medinat SAS, Via Fazioli 22, 60021 Instituto Politécnico Nacional. Av. Mineral de Valenciana No. 200 Fracc. Industrial Camerano, Ancona, Italy. Tel. +39 071 731076 Fax. +39 071 731347, E-Mail: Puerto Interior Silao de la Victoria, Guanajuato. C.P. 36275. Tel. (55) 57 29 60 00 [email protected] Ext. 81380. E-mail. [email protected], [email protected] 2Medical Center Beauty Benefit - San Biagio di Osimo, Via Mons. Oscar Romero, bCentro de Investigación y Asistencia en Tecnología y Diseño del Estado de 31 60027 Osimo, Ancona, Italy. Tel. +39 3483833064, E.Mail: Jalisco, A.C. Av. Normalistas 800 Colinas de la Normal, C.P. 44270. Guadalajara, [email protected] Jal. México. Tel. y Fax:+52 33455200 3Department of Internal Medicine, University of Ancona, Politecnica delle Marche, 60131 Ancona, Italy. 4Dept. Pharmacology, Faculty of Medicine, University of Chile, Santiago de Chile, Chile. The phytosterols are plant sterols widely distributed in nature, 5Holistic Dentist Clinic, 175 Mercado Street Suite115, Durango, CO 81301, USA. structurally similar to cholesterol and similar functions. Phytosterols 6Biomedical Research Laboratories, Medicine Faculty, Catholic University of exhibit effects of interest, highlighting the anti-atherosclerotic, anti- Maule, Talca, Chile. cancer, anti-inflammatory, anti-oxidant and hypocholesterolemic, both total cholesterol and LDL-cholesterol.
Several authors suggest that oxidation of LDL-cholesterol is associated Despite the long experience in the field of medical ozone therapy, and with the development of neurodegenerative diseases, because the its positive clinical effects when used at appropriate concentrations, the human brain contains high levels of fatty acids, easily oxidized and low most intimate molecular mechanisms are still partially unknown. The levels of antioxidant enzymes. The main products of lipid oxidation, 4- aim of our ongoing study, of which the present represents only the first hydroxynonenal (4-HNE) and malondialdehyde (MDA) are cytotoxic step, was to verify some hypotheses to study on humans the compounds with the capacity of change the structure of apolipoprotein involvement of the EpRE (electrophile-responsive element) system. Six E3, linked to the transport and uptake of cholesterol in the brain. adult healthy subjects of both gender and Caucasian ethnicity were eligible to participate in the study. Mayor Auto-hemotherapy (MAH) This study evaluated the ability of inhibition of lipid peroxidation in the was performed, using a dose of ozone of 45 μg/kg of BW with ozone brain of free and esterified phytosterols, using male mice Balb/c, 4-7 concentrations of 35 μg/mL. Patients were treated with 3 MAHs, one months old, 25-35 g. Forming 4 groups of 6 individuals during the test every 2 days interval. Blood samples for biochemical analysis were three groups were fed diets high in saturated fat, adding 200 mg/kg obtained after a 12 h overnight fast, at: 1) Immediately before the first body mass of free phytosterols or modified phytosterols diets of two MAH, 2) From the bottle during the first MAH after bubbling blood with groups. The fourth group was fed throughout the test with standard ozone, 3) From the patients 30 min after the first MAH, 4) From the diet (Rodent Lab Chow 5001). The trial period was 12 weeks, at the end patients the day after the application of the third MAH. Periphery of which total cholesterol was determined in blood, also determined the lymphocytes were isolated to assay Nrf2 levels and erythrocytes lysate concentration of MDA in brain tissue. The concentration of MDA/mg of were obtained to measure oxidative stress mediators. Nrf2 binding protein in the group fed with high fat diet without free or esterified activity was increased (p<0.01) in human lymphocytes directly exposed phytosterols was highest in those groups, in contrast to those groups to O3 and also (p<0.005) in circulating lymphocytes after MAH. Nrf2 whose diet was added in free or esterified phytosterols had signal back to normal status during the time. The initial activation of concentrations of MDA/mg of protein below certain in the group fed a Nrf2 induced by ozone increase the level of antioxidants enzymes. standard diet, suggesting that free and esterified phytosterols inhibit These data provide new evidences on the mechanism responsible for lipid peroxidation at the cerebral level. the induction of antioxidant enzymes expression by ozonated MAH, and have a practical and clinical importance as an approach to the treatment of patients targeted to the restoration of redox homeostasis.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S49
LATINFARMA 2013 Resúmenes/Abstracts
CO 083: CHARACTERIZATION OF OXIDATIVE STRESS IN CO 084: EFFECT ANTIPROLIFERATIVE OF (-)-EPICATECHIN DIFFERENT CLINICAL CONDITIONS AND INTERVENTIONS, AND ITS RELATIONSHIP WITH REACTIVE OXYGEN SPECIES USING REDOX INDEXES WITH DIAGNOSTIC VALUE IN BREAST CANCER CELL LINES
Gil del Valle L1, León Fernández OS2, Pérez Avila J1, González Blanco I2, Perez AG, Olivares IM, Ceballos GM, Osorio Y, García JR. Milián Díaz LC3, Guevara García M4. Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina 1Institute “Pedro Kourí”, La Habana, Cuba. E-mail: [email protected] del Instituto Politécnico Nacional. Plan de San Luis y Diaz Mirón, Casco de Santo 2Institute of Pharmacy and Food-Havana University, La Habana, Cuba. Tomas, 11340 México Distrito Federal, México. Teléfono y fax: 57296300 Ext. 3LIORAD, La Habana, Cuba. 62820. E-mails: [email protected], [email protected] 4Vimang Clinic, LABIOFAM, La Habana, Cuba.
Introduction: Breast cancer is the neoplasia of increased morbidity The redox status imbalance could be related to diverse clinical entities. and mortality in women from world. New therapeutic strategies Recognized analytic methodologies quantifying both: oxidative against this neoplasia have focused on natural products such as biomolecular damage and antioxidant activity were used for the polyphenols. Whether well, (-)-epicatechin is the most common characterization of redox balance in human samples (urine, polyphenol with several benefic effects on health; few studies have lymphocytes, plasma and serum) in relation with progression markers been performed about of its antineoplasic proprieties. Currently, it is of diverse clinical conditions. Case and control studies of Human well documented that cancer cells have a metabolism increased, which immunodeficiency virus (HIV), Dengue, Diabetes mellitus (DM) type 1, induce higher production of reactive oxygen species (ROS). However, Human-T lymphotropic virus type-1 patients and apparently healthy cancerous cells are able to evade the damage by ROS, process that it individuals (18-84 years) were carried out. The evaluation was also has been related with the overexpression of uncoupling protein 2 applied in intervention designs. (UCP2). The results evidenced oxidative alterations and antioxidant capacity Aim: To determine whether antiproliferative effect of (-)-epicatechin is decreased significantly (p < 0.05) in patients compared to healthy related with a downregulation in UCP2 expression, an increase in ROS individuals related in age and gender. Studies of nutritional production and apoptosis induction. intervention and antioxidant supplementation with Vimang® in 40 and 81 HIV Cuban patients respectively showed significant beneficial Material and methods: (-)-epicatechin, breast cancer cells (MCF-7, changes (p < 0.05) in 56% and 43.9% of cases respectively. An MDA-MB-231) and endothelial cells (non-transformed cells) were observational study in 56 HIV Cuban patients was carried out involving used. Inhibitory concentration fifty (IC50) from (-)-epicatechin was two combinations of antiretroviral therapy. The study showed determined in breast cancer cells by (MTT) assays. ROS production evidences of oxidative modifications significant (p < 0.05) in 87% of the was analyzed by the values of biomarkers of oxidative damage cases, finding differences among combinations. An observational study (carbonyl groups and malondialdehyde); superoxide anion production TM involving 40 Cuban DM type 1 patients with change of neutral was determined by fluorescence microscopy by MitoSOX . protamine Hagedorn insulin from pig to human recombinant, showed a Glutathione peroxidase activity was analyzed and DNA fragmentation significant beneficial change (p < 0.05) in 81% of the cases after the assay was performed to determine the induction of apoptosis. change. The integral characterization could be useful for follow up and Results: Antiproliferative effect of (-)-epicatechin showed an IC50=350 individuals’ management of patients but also contribute to the μM, effect that was coordinated with a downregulation in UCP2 knowledge of the molecular mechanisms underlying in these illnesses. expression, increase in the values of biomarker of oxidative damage, high production of superoxide anion, decreasing in GSH-Px activity and a DNA fragmentation or induction of apoptosis. Interestingly, when (-)- epicatechin was used in combination with chemotherapeutics drugs we observed a better effect, suggesting the possibility to be used as adjuvant in cancer treatment. Conclusions: The data obtained in this work, suggest that the effect antiproliferative of (-)-epicatechin is mediated by an induction of apoptosis, an increase in the production of ROS, decreasing of antioxidant defenses and downregulation in UCP2 expression.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S50
LATINFARMA 2013 Resúmenes/Abstracts
CO 085: THE TREATMENT WITH CHP3R99-LALA CO 086: CONTRIBUTION OF OXIDATIVE STRESS AND MONOCLONAL ANTIBODY REDUCES OXIDATIVE STRESS INFLAMMATION TO THE HYPERTENSION INDUCED BY AND PROINFLAMMATORY CYTOKINE EXPRESSION IN INTERMITTENT HYPOXIA IN A RAT EXPERIMENTAL EXPERIMENTAL MODELS OF ATHEROSCLEROSIS MODEL OF OBSTRUCTIVE SLEEP APNEA
Delgado L1, Acosta E2, Fernández JR3, Pérez A4, Hernández Y1, Soto Y4, Iturriaga R, Del Rio R, Moya EA. Fernández-Sánchez E1, Vázquez AM.4 Laboratorio de Neurobiología. Facultad de Ciencias Biológicas, P. Universidad 1 Center of Studies for Research and Biological Evaluations (CEIEB), Pharmacy Católica de Chile. E-mail: [email protected] and Food Sciences College, University of Havana, Cuba. 2 Center of Advanced Studies (CEAC), Havana, Cuba. 3 Center for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba. 4 Department of Antibody Engineering, Center of Molecular Immunology (CIM), Introduction: The obstructive sleep apnea (OSA) syndrome, a growing Havana, Cuba. sleep-breathing disorder is recognized as an independent risk factor for systemic hypertension and other cardiovascular diseases. Among the disturbances produced by OSA, the chronic intermittent hypoxia (CIH) is considered the main factor for the hypertension. Oxidative The subendothelial retention of low-density lipoproteins (LDL) by stress, inflammation, and sympathetic overactivity have been proposed glycosaminoglycans (GAGs) represents a key event in atherosclerosis as potential mechanisms involved in the onset of the hypertension. In development. The retained LDL are more susceptible to reactive experimental models of OSA, CIH enhances the carotid body (CB) oxygen species (ROS)-mediated oxidation, contributing to oxidative chemosensory and ventilatory responses to hypoxia, impairs the stress (OS) and inflammation. Recently, our group demonstrated that baroreflex and heart rate variability, and produces hypertension. inhibition of LDL-GAG binding by the chimeric monoclonal antibody These alterations have been attributed to oxidative stress, since chP3R99-LALA prevents atherosclerotic lesions development in acute antioxidants treatment prevent the enhanced chemosensory and and chronic models of atherosclerosis. Taking into account these ventilatory hypoxic responses and the hypertension. findings, we hypothesized that in vivo inhibition of LDL-GAG binding by chP3R99-LALA mAb treatment reduces OS and proinflammatory Methods: We hypothesized that oxidative stress-induced upregulation cytokines gene expression. In the present work we evaluated the effect of pro-inflammatory cytokines TNF-α and IL-1β are involved in the CB of chP3R99-LALA treatment on aortic redox status and and cardiorespiratory alterations elicited by CIH. We determine the proinflammatory cytokines IL-1β and TNF-α expression. The redox effects of ibuprofen (40 mg/kg day) on TNF-α, IL-1β and 3- biomarkers (MDA, AOPP, SOD, CAT, GSH, NO3/NO2) were determined nitrotyrosine (3-NT) levels in the CB, chemosensory and ventilatory by spectrophotometric methods; meanwhile, cytokines gene expression hypoxic responses, and arterial blood pressure in male Sprague- was assayed by quantitative real time PCR. Our results demonstrated Dawley rats exposed to CIH (5%O2, 12 times/h for 8 h/day) for 21 that the treatment with this antibody prevents aortic OS, reducing days. biomolecules damages and preserving both enzymatic and non- enzymatic antioxidants. The endothelial function was positively Results: CIH increased TNF-α, IL-1β and 3-NT in the CB, enhanced modulated by a restoration of NO3/NO2 levels. Furthermore, the IL-1β chemosensory and ventilatory hypoxic responses, and produces and TNF-α gene expression was downregulated by the immunization hypertension. Ibuprofen prevents the TNF-α and IL-1β upregulation with chP3R99-LALA mAb. These results confirmed our early hypothesis and cardioventilatory alterations, but not the enhanced chemosensory and contribute to elucidate the mechanism of action of this anti-GAG hypoxic response and 3-NT accumulation. Ascorbic acid treatment antibody. prevented the increased CB cytokines and 3-NT expression, the chemosensory and ventilatory potentiation, and the hypertension. Conclusion: Present results indicate that the CIH-induced potentiation of CB chemosensory hypoxic responses depends on the oxidative stress, but not on the CB inflammation. Therefore, our results suggest a plausible role for pro-inflammatory cytokines in the control of breathing and arterial pressure during CIH acting by an independent CB pathway.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S51
LATINFARMA 2013 Resúmenes/Abstracts
CO 087: DETERMINATION OF STRUCTURAL ALERTS TO CO 088: CLUSIANONE, A NATURAL OCCURRING PREDICT CLASTOGENIC ACTIVITY OF PRO-OXIDANT NEMOROSONE’S REGIOSOMER, UNCOUPLED FLAVONOID COMPOUNDS: QUANTITATIVE STRUCTURE- MITOCHONDRIA AND INDUCED CELL DEATH ACTIVITY RELATIONSHIP STUDY Pardo-Andreu GL, Zuccolotto dos Reis FH, Nuñez-Figueredo Y, Cuesta- Molina E1,3, Guardado E1,2, Matos MJ2, Castro R1, Santana L2, Uriarte E.2 Rubio O, Uyemura SA, Leopoldino AM, Curti C, Alberici LC.
1Universidad de Camagüey “Ignacio Agramonte y Loynaz”, Camagüey, Cuba. E- 1Centro de Estudio para las Investigaciones y Evaluaciones Biológicas, Instituto mail: [email protected] de Farmacia y Alimentos, Universidad de La Habana, ave. 23 # 21425 e/214 and 2Universidad de Santiago de Compostela, Santiago de Compostela, España. 222, La Coronela, La Lisa,CP 13600, La Habana, Cuba. E-mail: 3Universidade do Estado do Amazonas, Amazonas, Brasil. [email protected]
Flavonoids have been reported to exert multiple biological effects that Clusianone is a member of the polycyclic polyprenylated include acting as pro-oxidants at very high doses. Structural alerts to acylphloroglucinol family of natural products with uncharted cytotoxic identify the clastogenic activity of a series of flavonoids with pro- activity. Its structural similarity with nemorosone prompts us to oxidant activity were determined. The methodology was based on a speculate that this molecule could affect mitochondrial function by quantitative structure–activity relationship (QSAR) study. Specifically, uncoupling respiration. Flow cytometric analyses demonstrated that it was developed a virtual screening methodology for a clastogenic clusianone induces cellular events in HepG2 cells belonging to the model using the topological substructural molecular design (TOPS- apoptosis process, such as mitochondrial potential collapse, and MODE) approach. It represents a useful platform for the automatic phosphatidyl serine externalization. In addition, clusianone induces a generation of structural alerts, based on the calculation of spectral rapid ATP depletion. This cellular response associated to mitochondrial moments of molecular bond matrices appropriately weighted, taking impairment was investigated in isolated rat liver mitochondria. We into account hydrophobic, electronic, and steric molecular features. provided for the first time evidences that, in addition to its toxicity on Therefore, it was possible to establish the structural criteria for HepG2 cells, clusianone is a protonophoric mitochondrial uncoupler maximal clastogenicity of pro-oxidant flavonoids: the presence of a 3- evidenced by: organelle membrane potential dissipation/state 4 hydroxyl group and a 4-carbonyl group in ring C, the maximal number respiration rate increase, inhibition of Ca2+ influx and promotion of of hydroxyl groups in ring B, the presence of methoxyl and phenyl loaded Ca2+ efflux, ATP depletion, mitochondrial NAD(P)H groups, the absence of a 2,3-double bond in ring C, and the presence of depletion/oxidation, ROS levels decrease, and swelling induced on 5,7-hydroxyl groups in ring A. The presented clastogenic model may be valinomycin-treated mitochondria incubated in hyposmotic potassium useful for screening new pro-oxidant compounds. This alert could help acetate medium. Its cytotoxic and uncoupling potency were appreciably in the design of new and efficient flavonoids, which could be used as lower than those for nemorosone, probably due to an intra-molecular bioactive compounds in nutraceuticals and functional food. hydrogen bonding with the juxtaposed carbonyl group in C15.
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LATINFARMA 2013 Resúmenes/Abstracts
CO 089: LEARNING OF CELLULAR REDOX BALANCE IN diseases as starting point in the rational inquiry of new drugs. Above PHARMACY AND FOOD INSTITUTE OF THE UNIVERSITY OF mentioned backgrounds were the basis for teaching of this scientific HAVANA, CUBA subject in Pharmacy and Food Institute of the Havana University. In this presentation are showed contents, learning figures, technique and León Fernández OS, Díaz Soto MT, González I, Hernández M, Dranguet methods which were used in cognitive process. Cellular Redox Balance J, Delgado L. is teached in all figures (Pharmacy bachelor and postgraduated studies): Bachelor, which in addition consider an Optative subject
Pharmacy and Food Institute of the University of Havana, Cuba. (Oxidative Stress in Human Health) located in the last year In Posgraduate there is a Diplomate of Oxidative Stress and different themes are introduced in Master of Sciences (Clinic Pharmacy, Chronic oxidative stress is associated to the majority of diseases Pharmacology, Pharmaceutical Chemistry, and Clinic Laboratory). therefore investigations of new antioxidant drugs which achieves their Likewise, different PhD theses have investigated the role of oxidative effects through direct or celular signaling mechanisms, are ever- stress, and its control, in vascular, endocrine, autoimmune and Central growing. On the other hand, knowledge of transient oxidative stress Nervous System disorders. (physiological) plays an important role in order to elucidate etiology
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LATINFARMA 2013 Resúmenes/Abstracts
Simposio de Productos Naturales / Symposium of Natural Products
CO 090: MECHANISMS INVOLVED IN THE ANTITUMOR- CO 091: PROTEOLYTIC FRACTION FROM Vasconcellea ANTIMETASTATIC ACTIVITIES OF PROTEOLYTIC cundinamarcensis LATEX STIMULATES MACROPHAGES FRACTION DERIVED FROM Vasconcellea cundinamarcensis ACTIVITY AGAINST INFLAMMATORY BREAST CANCER LATEX CELLS
Lemos FO1, Pires SF2, Andrade HM2, Salas CE3, Lopes MTP1. Braga AD1, Freitas KM1, Salas CE2, Lopes MTP.1
Departments of 1Pharmacology, 2Parasitology, 3Biochemistry and Immunology, Departments of 1Pharmacology and 2Biochemistry and Immunology, Institute of Instituto de Ciências Biológicas, UFMG – Belo Horizonte, Minas Gerais, Brazil. E- Biological Sciencies, Federal University of Minas Gerais, Belo Horizonte, Minas mail: [email protected] Gerais, Brazil. E-mail: [email protected]
Studies showed that CMS-2 proteolytic fraction, recovered by Previous studies demonstrated that aproteolytic fraction (P1G10) from Vasconcellea cundinamarcensis latex (Voucher 15063, La Serena V. cundinamarcensis latex has antitumor/antimetastatic activity on University, Chile) decrease the number of metastases of animals with different murine models. In 4T1 breast carcinoma model, P1G10 colon carcinoma and melanoma. It was observed that CMS-2 increased reduced tumor mass likely by reducing inflammation, angiogenesis and the amount of fragmented DNA in tumor cells by a caspase dependent by increasing activity on tumor associated-macrophages. Here, we pathway and further, decreasing the invasion and adhesion to different investigate if P1G10 is able to activate a cytotoxic action of ECM components. Here, we present results that partially characterize macrophages against tumor cells. Balb/c female mice received the mode of action of this protein mixture as antitumoral and thioglycollate (4%, i.p.) and after 4 days, peritoneal macrophages were antimetastatic agent. It was determined an IC50 ≈ 10 µg/mL (resazurin harvested by peritoneal lavage. Macrophages were seeded in 24 well metabolism) of CMS-2 on murine melanoma (B16-F10) and plates (3x105 cells/well) and treated with P1G10 (5-50 µg/mL) for 24 melanocytes (Melan-a) cells. However, in the presence of CMS-2 was or 48h. These cultures were washed and co-cultures made byplating not observed membrane lysis, measured by LDH activity. The cellular 4T1 cells (1.5 x 105 cell/well). In the macrophages treatment for 24h, migration, by Scratch assay test, showed that CMS-2, at 7.5 and 10 no significant changes on 4T1 cells number was observed, however for µg/mL, reduced the migratory capacity of both lineages. Besides this, 48h, P1G10 (25 and 50 µg/mL) promoted a reduction in cell number CMS-2 (10 µg/mL) promoted melanogenesis in B16-F10 and Melan-a (28.0 ± 2.4 and 15.8 ± 0.8 vs 40.8 ± 2.6 cells/fields, respectively, cells, measured by amount of melanin and tyrosinase activity, after 24 p<0.0001). P1G10 reduced VEGF levels, concentration-dependent (5- or 48h of exposition. DIGE (2-D Fluorescence Difference Gel 50 µg/mL), until 89% (26.72 ± 3.01 vs. 249.92 ± 14.42 ρg/mL control, Electrophoresis) was applied to identify differences in protein p<0.0001) and in single cultured macrophages, until 73% (49.02 ± 4.33 expression. Seventy spots were statistically different between Melan-a vs. 182.46 ± 4.11 ρg/mL control, p<0.0001). Regarding to TNF-α level, and B16-F10 cells, however, after the treatment with CMS-2, this P1G10 displays a dual effect. With a 24h exposure, P1G10 (5-50 number was reduced to 24. Important proteins which are µg/mL) reduced TNF-α (~37%) in macrophages (13.22 ± 1.24 ƞg/mL overexpressed in B16-F10, as calreticulin, glutathione S-transferase, control, p<0.01), but did not alter its level in co-cultures. The exposure elongation factor 1-beta, creatine kinase B, FK506 binding protein, to 25 or 50 µg/mL for 48 h increased at 12 or 20%, respectively, the protein disulfide-isomerase, heat shock protein, vimentin and TNF-α content in single cultured macrophages (8.59 ± 0.24 or 9.23 ± endoplasmin, had their expression levels similar to normal lineage 0.21 vs. 7.67 ± 0.39 ƞg/mL control, p< 0.001). In co-cultures were after CMS-2 exposition. The results indicate that the reduction of observed an increase by 31 or 123% (0.17 ± 0.01 or 0.29 ± 0.02 vs. 0.13 viability and cell migration, important to tumor expansion and ± 0.01 control, p< 0.0001) in the TNF-α levels/number of cells but do invasiveness, besides the activation of melanogenesis (differentiation not altering the absolute levels of this cytokine. The results suggest marker) can explain the antitumor and antimetastatic activity of CMS- that P1G10 is able to reduce the angiogenesis and enhance cytotoxic 2. This fraction isable to revert to normal standards some proteins activity of macrophages against tumor cells, which can contribute to related to tumorigenesis, which place themes possible targets of action. antitumor activity of fraction. Supported by CNPq, CAPES and FAPEMIG. Support by CNPq, Capes and Fapemig.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S54
LATINFARMA 2013 Resúmenes/Abstracts
CO 092: MECHANISTIC EFFECTS OF Ganoderma lucidum CO 093: RJLB-14 PEPTIDE: EXPERIMENTAL EVIDENCES AND (REISHI) ON INFLAMMATORY BREAST CANCER POTENTIAL IN CANCER TREATMENT PROGRESSION Díaz-García A1, Gali Medina RM1, Estepa Perez MA2, Ruiz-Fuentes JL3, Martínez-Montemayor MM, Rosario-Acevedo R, Suarez-Arroyo I, Rodríguez Sanchez H3, Morier Díaz L3, Fraga Castro JA.1 Loperena-Alvarez Y, Cubano LA. 1Laboratories of Biopharmaceuticals and Chemistry Productions (LABIOFAM), Universidad Central del Caribe, Escuela de Medicina, Bayamón, Puerto Rico. E- Havana, Cuba. E-mail: [email protected] mail: [email protected] 2Miguel Hernandez University, Spain. 3Microbiology Department, Tropical Medicine Institute “Pedro Kouri”, Havana, Cuba. Inflammatory Breast Cancer (IBC) is most lethal and rare form of breast cancer with a survival rate of less than five percent in five years. Cancer represents the most growing-not transmissible disease around The pathogenesis of the disease was initially defined as an the world. Therapeutic peptides offer advantages in the treatment of inflammatory reaction displaying erythema, edema, swelling of the cancer, by their size, wide distribution in the body and high specificity breast, pain and “peaud’orange”. However these symptoms are actually for tumor cells. RJLB-14 is a peptide, obtained by bio-guide assays associated with the formation of tumor emboli (tumor spheroids in procedures from scorpion Rhopalurus junceus and demonstrated vitro), which are non-adherent cell clusters that invade the dermal cytotoxicity and high selectivity in tumor cells from solid tissue. This lymphatic’s overlying the breast causing the inflammatory peptide was recently obtained by recombinant techniques so it was phenotype.Our published data shows that the medicinal mushroom, interesting evaluated through in vitro and in vivo experiments their Ganodermalucidum (Reishi), inhibits IBC progression via disintegration potential in cancer treatment. The effect of RJLB-14 on the viability in a of tumor spheroids, selective cancer cell viability inhibition, and panel of normal and tumor cell lines was observed by MTT apoptosis induction. Herein, SUM-149 IBC cells were treated with or colorimetric assay. Additionally, the effect of peptide on cell death was without Reishi for various timepoints, to delineate the mechanistic and assayed by fluorescence microscopy and RT-PCR. The antitumor effect potential autophagy cell death inducing effects of Reishi in vitro. was evaluated in a murine breast cancer model at different doses (1.25 Experiments in vivo were performed in severe combined mg/kg-5 mg/kg) for 10 days by intraperitoneal route. The tumor immunocompromised mice injected with IBC cells. Mice were treated growth was determined for each experimental group. without or with (28 mg/kg BW) Reishifor 13 wk. Our results show that Reishi downregulates the expression of common proteins In vitro studies showed that RJLB-14 induces a significant and overexpressed in IBC in vitro and in vivo, significantly reduces tumor differential toxicity against tumor cells while normal cells were not growth by 58%, and also induces autophagic cell death in IBC cells. Our sensitive. The peptide induces preferentially apoptotic cell death results provide evidence to highlight the therapeutic potential of Reishi evidenced by chromatin condensation, over-expression of apoptosis- to improve the quality of life of women afflicted with IBC, who suffer a related genes and down-expression of anti-apoptotic genes. disease for which no targeted therapy currently exists. Additionally, treatment with different doses of RJLB-14 showed a significant delay in tumor progression compared to control tumor This project was sponsored by Title V PPOHA US-Dept of Education #P031M105050 (UCC), NIH/RCMI #2G12RR003035 (UCC), NIH/INBRE group. The different doses showed a dose-response relationship for #5P20RR016470 (UPR/UCC), NIH/NCRR #U54RR026139 (UPR/UCC), and a both the tumor volume and the weight of the tumors of each research donation from the Commonwealth of Puerto Rico to UCC-Centro experimental group. Universitario de Medicina Integral y Complementaria (CUMIC)/ MMM. These experimental evidences promote future studies of this peptide in different in vivo models of cancer. Antitumoral properties of the recombinant peptide RJLB-14 make it an attractive and promising biological therapy for cancer treatment.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S55
LATINFARMA 2013 Resúmenes/Abstracts
CO 094: ANTI-CANCER ACTIVITY OF Thalassia testudinum EXTRACT CO 095: Xanthium strumarium L. SHOWS ANTIPROLIFERATIVE REGULATES ATF4, P53 AND HIF1 DEPENDENT GENE EXPRESSION ACTIVITY THROUGH INDUCING CELL CYCLE ARREST AT G2/M PROGRAMS RELATED TO CELL DEATH AND SURVIVAL, CELLULAR CHECKPOINT DEVELOPMENT AND GROWTH AND PROLIFERATION Pérez CL1, Piloto J2, Sánchez A3, Valdivia D2, González ML2, Francisco M2, Hernandez I1, Rodeiro I1, Menéndez R2, Fernández MD1,K. Szarcvel Szic3, K. Op Quiñones O2, Rodeiro I4. de Beeck4, S. Naulaerts5, K. Laukens5, G. Van Camp4,Delgado R2, Van den Berghe 1Departmento de Bioquímica, Instituto de Ciencias Básicas y Preclínicas (ICBP) “Victoria de 3 W. Girón”, 146 # 3102, Playa, La Hababa, Cuba. E-mail: [email protected] 2Centro de Investigación y Desarrollo de Medicamentos (CIDEM), Ave. 26 # 1605, Nuevo 1Center of Marine Bioproducts (CEBIMAR), Havana, Cuba. Vedado, La Habana, Cuba. E-mail: [email protected] 2Drug Research and Development Centre (CIDEM), Havana, Cuba. 3Laboratorio Genética Toxicológica, Facultad de Biología, Universidad de la Habana, Calle 25, 3PPES lab, Department of Biomedical Sciences, Antwerp University, Belgium. No. 455, e/ I y J, Vedado, La Habana, Cuba. 4Center of Medical Genetics, Department of Biomedical Sciences, University of Antwerp, 4Departamento Farmacología, Centro de Bioproductos Marinos (CEBIMAR). Belgium. 5 Biomedical Informatics Research Center Antwerpen (Biomina), Department of Mathematics and Computer Science, University of Antwerp, Middelheimlaan 1, 2020 Antwerp, Belgium.
Introduction: Xanthium strumarium L. (Family: Asteraceae) is widely distributed in America and Asia and commonly used in traditional medicine. Worldwide, Introduction: The aqueous ethanol extract of Thalassia testudinum leaves is different extracts of the plant has been reported to show hypoglycemic, diuretic, currently being developed in Cuba as a nutritional supplement due to its anti-inflammatory, antioxidant, antitumor and anticancer activities. The aim of promising pharmacological properties. Its phytochemical composition this study was to evaluate the effect of a hydroalcoholic extract of Xanthium demonstrates that this product is a rich source of natural antioxidants with strumarium L. in cell proliferation, mitosis and cell cycle progression. potential applications in pharmaceutical, cosmetic and food industries. Material and methods: The product was obtained by hydroalcoholic extraction Objectives: The present study evaluated the cytotoxic effects of Thalassia of the aerial parts of the plant Xanthium strumarium L. The antiproliferative testudinum extract on several human tumor cell lines. activity was assessed by the MTT assay in several cell types (CHO, F3II, CT-26, MDA-MB-231, MCF7, U937), in a range of concentration from 6.25 to 100 µg/mL. Methods: Cellular viability was measured by MTT and x Celligence assays. Cell cycle progression was assessed by cytofluorimetric analysis and immunohistochemistry was used to visualize the mitotic spindle. Results: The extract dose dependently decreases the cell viability of cervix (Hela), breast cancer (MDAMB-231 and MCF-7) and colon cancer (RKO and Results: The hydroalcoholic extract showed moderate to high in vitro SW480) cell lines at 24, 48 and 72 hours of exposition, whereas the colon cancer antiproliferative activity in normal and cancer cell. The lowest IC50 was observed cell lines revealed the highest sensitivity. Upon further investigation of in the colon cancer cell CT-26 (IC50 2.76 µg/mL). The cytofluorimetric analysis of transcriptional changes in response to Thalassia extract by illumina bead array shows that Xanthium strumarium L. extract induces a reduction of cells in S- and subsequent Ingenuity Pathway Analysis, various molecular and cellular phase of the cell cycle and increases the G2/M cell populations. A significant targets were identified related to cell death and survival, cellular development increment in dividing cells was induced with an increment in the proportion of and growth and proliferation. Furthermore, three transcriptional factors (ATF4, prometaphase-metaphase. Treated cells shows higher percentage of abnormal p53 and HIF-1A) were identified as upstream regulators of Thalassia testudinum spindles than control. Mechanistic data revealed that X strumarium extract extract responsive target genes. Furthermore, cellular exposure to tunicamycin inhibit the polymerisation of tubulin affecting of dynamic the microtubules as most closely resembles treatment with Thalassia testudinum extract, suggesting a integral part of the mitotic spindle in cellular proliferation. significant role for endoplasmic reticulum stress in the anti-cancer effects observed. Conclusions: The extract of Xanthium strumarium L. displays significant antiproliferative effects through cell cycle arrest. Conclusions: Altogether, these results reveal that T. testudinum extract and its phytochemical constituents should promise for development of new antitumor treatments via interference with angiogenesis, cell survival and apoptosis in cancer progression.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S56
LATINFARMA 2013 Resúmenes/Abstracts
CO 096: Xanthium strumarium L. A POTENTIAL ANTI- CO 097: ANTIPROLIFERATIVE ACTIONS OF THREE TUMOUR AGENT Hypericum SPECIES: EFFECTS OF LEAVE AND FLOWER EXTRACTS OF H. perforatum, H. montbretii AND H. Piloto J1, Sánchez A2, Valdivia D1, González ML1, Francisco M1, Quiñones O1, Pérez C3, Rodeiro I4. origanifolium 1 1 2 3 1Centro de Investigación y Desarrollo de Medicamentos (CIDEM). Ave 26 #1605 Öztürk Y , Güzey G *, Öztürk N , Potoglu-Erkara I . e/ Puentes grandes y Boyeros. La Habana. Cuba. E-mail: Anadolu University, Faculty of Pharmacy, Departments of 1Pharmacology and [email protected] 2Pharmacognosy, 3Eskisehir Osmangazi University, Faculty of Science and Art, 2Facultad de Biología, Universidad de la Habana, Calle 25 No. 455, e/ I y J, Department of Biology, Eskisehir, Turkey (*Present address: Hospital of Vedado, C. Habana, Cuba. Eskisehir Osmangazi University, Department of Pharmacy, Turkey). E-mail: 3 Instituto de Ciencias Básicas y Preclínicas (ICBP) “Victoria de Girón”, 146 # [email protected] 3102, Playa, La Hababa, Cuba. 4Departamento de Farmacología, Centro de Bioproductos Marinos (CEBIMAR). Being potential sources of pharmaceutical industry, Hypericum species Introduction: Xanthium strumarium L. (Family: Asteraceae ) a have been used in traditional medicine for various curative purposes medicinal plant widely distributed in North America, Brazil, China, including wound healing and neoplastic diseases. St.-John’s worth (H. Malaysia and hotter parts of India. The crude extract of Xanthium perforatum) has been previously reported to possess wound healing strumarium L, have been used in traditional Cuban medicine as an and antiproliferative activities in experimental studies In the present effective diuretic drug. Internationally some others activities has been study, we aimed to investigate the antiproliferative effects of reported, e.g. antifungal, anti-inflammatory, hypoglycemic, antioxidant, methanolic extracts of leaf and flowers of H. perforatum, H. montbretii diuretic effects, by in particular, anti-tumour, anti-cancer activity, so and H. origanifolium on A549 and HeLa cells (cancer cell lines) much attention is focused on the herb. In the present study, we comparing with NIH3T3 cells (normal cells) in culture media. evaluated the cytotoxicity effect of X. strumarium extract in cancer cell Antiproliferative effects were studied using neutral red, acridine lines using assay MTT and the anti-metastatic activity by using an in orange experiments and soft agar gel colony forming assay. Extracts, vivo mouse lung metastasis model in CT26 ( colon) cell line. whose preparation procedures and phytochemical compositions have been previously reported, were applied in media in a concentration Material and methods: The product was obtained by hydroalcoholic range of 1-250 µg/mL and incubated with cells up to 4 days. All extraction of the aerial parts of the plant Xanthium strumarium L. To extracts applied were found to have inhibitory effects in colony evaluate of extract cytotoxicity were used the cancer cell lines: MDA- formation assay, although they exhibited antiproliferative/cytotoxic MB-231 (breast), U937 (histiocytic lymphoma), MCF7 (breast), HeLa activities in different profiles of action and at different concentrations (cervix), A549 (lung), CT26 (colon), F3II (breast) and PC12 in other experiments performed for antiproliferative activities. (pheochromocytoma). The IC50 values, were determined from a dose- Findings obtained in the present study revealed that these three response curve by using 5 different concentrations (6.5, 12.5, 25, 50 y Hypericum species have potentials for antineoplastic activity, which 100 µg/mL). The anti-metastatic activity was evaluated using the lung deserve further future investigations. tissues with tumor nodules. The total numbers of superficially visible colonies per lung were counted using an ocular micrometer. Results: The extract showed moderate to high in vitro cytotoxic activity in the cancer cell lines. The lowest IC50 was observed in the colon cancer cell CT-26 (IC50 2.76 µg/mL). The formation of tumour nodules was significantly attenuated by the treatment of the extract (100 and 200 mg/kg, BW/day). Conclusions: These results suggest that Xanthium strumarium may have considerable potential for development as an anti-metastatic agent.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S57
LATINFARMA 2013 Resúmenes/Abstracts
CO 102: EXTRACTS AND FRACTIONS FROM Cryptostegia CO 103: EVALUATION OF THE PROTECTIVE EFFECT OF grandiflora L. EXHIBITED ANTI-INFLAMMATORY EFFECTS ETHANOL EXTRACT OF Dracontium SP. ON LETHAL AND IN VIVO AND INHIBITED NITRIC OXIDE AND PGE2 COAGULANT ACTIONS INDUCED BY VENOM OF Bothrops PRODUCTION IN LPS-STIMULATED RAW 264.7 MOUSE asper MACROPHAGES IN VITRO Franco L, Herazo H, Alarcón B, Castro J, Ocampo Y. Castro J, Ocampo Y, Franco L. Biological Evaluation of Promissory Substances Group. Faculty of Pharmaceutical Biological Evaluation of Promissory Substances Group. Faculty of Pharmaceutical Sciences. University of Cartagena. Cartagena, Colombia. E-mail: Sciences. University of Cartagena. Cartagena, Colombia. E-mail: [email protected] [email protected]
Introduction: In Colombia, Bothrops asper snakes are responsible for Introduction: Chronic inflammation is a complex physiological 70-90% of the ophidic accidents reported annually. Snake bites are process that can lead to severe diseases such as osteoarthritis, frequently attended by healers using medicinal plants; including rheumatoid arthritis, gout, asthma, diabetes and cancer; that represent several species native of the Colombian Caribbean belonging to an important cause of morbidity and mortality worldwide. Cryptostegia Dracontium genus. grandiflora leaves are widely used in Colombian folk medicine for their Material and methods: In this work we evaluated the neutralizing anti-inflammatory effects, but there are no studies that support its activity of the ethanol extract of Dracontium sp. roots (COL538421), popular use and the pharmacological mechanisms involved in this against lethal and coagulant effects of Bothrops asper venom in ICR activity are still unknown. mice. To assess lethal inhibition, the extract (0.5 and 1 mg/g), was Material and methods: Plant material were collected in Pueblo incubated with 2LD50 of venom and injected intraperitoneally. Nuevo-Bolivar, extracted by maceration with ethanol, and fractionated Mixtures of venom and extract (1/10-1/1000 µg/µg) were tested to by liquid-liquid partition. In vivo anti-inflammatory activity was evaluate coagulant activityand changes in its proteomic profile by SDS- evaluated using the 12-O-tetradecanoylphorbol-13-acetate induced ear PAGE. In addition, a phytochemistry screening was performed. edema in mice, determining myeloperoxidase (MPO) activity and Results: The venom of B. asper exhibited high toxicity (DL50 = 3.07 ± performing histopathologic analysis. In addition, we evaluated the 0.16 μg/g), while Dracontium extract did not show toxicity at tested effect of fractions from Cryptostegia grandiflora on nitric oxide (NO) doses. All animals survived to the effect of 2DL50 of venom after 48 h, and prostaglandin E2 (PGE2) production in LPS-stimulated RAW 264.7 with total recuperation at 20 h, for the highest dosage level. Post- macrophages. Finally we measured NO•-scavenging activity. mortem evaluation showed severe hemorrhage at macroscopic and Results: The total ethanol extract reduced significantly the edema microscopic level, which was significantly decreased by the extract. No (42.1 ± 0.9%) and MPO activity (39.1 ± 5.4%). In accordance, significant differences were observed in clotting times of plasma histological analysis revealed a reduction of edema and leukocyte incubated with extract and venom. Extract of Dracontium neither alter infiltration. In vitro studies of ether and dichloromethane fractions also the electrophoretic pattern of venom. Phytochemistry screening showed a reduction on the NO and PGE2 production, at non-toxic showed presence of cardiotonic glycosides, phenolic compounds, concentrations to RAW 264.7 macrophages. redactor sugars, tannins and steroids/triterpenoids, according with previous reports for species of this genus2. Conclusions: Our results demonstrated the anti-inflammatory activity of Cryptostegia grandiflora leaves, supporting their traditional Conclusions: Results of evaluation of ethanol extract of Dracontium application. This activity was shown to be related to inhibition of PGE2 give scientific support for its use in folk medicine; such activity is not and NO production, and MPO activity. These mechanisms could related to inhibition of procoagulant activity or alterations to the contribute, at least in part, to the anti-inflammatory effect observed for protein pattern of venom. Further studies are needed to isolate and this plant. identify the metabolites responsible for the activity and the mechanism of action.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S58
LATINFARMA 2013 Resúmenes/Abstracts
CO 104: ANTIOXIDANT ACTIVITY OF ETHANOL EXTRACT OF CO 105: PROTECTOR EFFECT OF THE PHYTO-THERAPEUTIC THE FRUIT OF THE SPECIES Syzygium samarangense (WAX Piper aduncum (MATICO) IN BREAST CANCER INDUCED IN APPLE) RATS Fonseca A, Camacho O, Yaruro G. Arroyo J, Ráez E, Chávez Asmat R, Donaires R, Cisneros B, Palomino R, Condorhuamán M, Buendia J. Grupo de Investigación Fitoquímica, Facultad de Química y Farmacia, Universidad del Atlántico, Km 7. Antigua via Puerto Colombia. Atlántico, Facultad de Medicina Universidad Nacional Mayor de San Marcos. Lima Peru. E- Colombia. mail: [email protected]
Through antioxidant activity research of many fruits have been found Objetive: to demonstrate the security and protective effect of one an interest on world population, because scientific evidence related to phytodrug in capsules with etanolic extract of Piper aduncum (matico) antioxidant properties of phenolic compounds such as flavonoids and in breast cancer in rats. anthocyanins against oxidative stress-related diseases. Antioxidant activity of the fruit of Syzygium samarangense species has been Material and methods: leaves of Piper aduncum, 60 rats stub investigated in Indonesia and Malaysia where it is native and has Holzman. Interventions: 6 groups of animals: 1) normal; 2) Phytodrug shown satisfactory results in human health. This species has a common 200 mg/kg; 3) inductor DMBA agent; 4) DMBA + phytodrug 5 mg/kg; growth in the north coast of Colombia. Was performed preliminary 5) DMBA + phytodrug 150 mg/kg; y 6) DMBA + phytodrug 30 mg/kg; phytochemical up which identified the presence of related compounds the breast cancer was induced with dimetil benz antracen 20 mg such as phenols and flavonoids. In relation to free radical scavenging (DMBA). Hepatic profile, mark SOD of oxudative stress (MDA), by ORAC method Syzygium samarangense fruit (0.9 μMol biochemical and hematological signs, pathoanatomical of the TROLOX®/mg) compared to other fruits as mango (0.0100), pineapple mammary gland, ethical norms were considered in the study with (0.0079), banana (0.0089), papaya (0.0045) and the α-tocopherol (0.1) animals of experimentation, the confidence level was 95%. used as reference substance, higher values are obtained. For Results: It was proved that 25% of protection again the development determinate anthocyanins by differential pH, colors differentiation is of breast cancer, it had a good antioxidant effect as observed as observed by adding buffer solutions being a positive indication of the increment of SOD. presence of antioxidants structures. Analysis to determine the possible flavonoids using shift reagents, the spectra obtained to respond Conclusions: the phytodrug had a light effect in reducing the tumor optimally performing bathochromic shifts reagents revealing the mass of breast cancer induced in rats, but it demonstrated antioxidant presence of flavonoids qualitatively. The compounds identified by activity. HPLC as gallic acid, (-)epicatechin gallate, quercetin, valid signal given the presence of potent antioxidants, being quantified to infer actual biological activity against diseases related to oxidative stress.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S59
LATINFARMA 2013 Resúmenes/Abstracts
Taller de Farmacoeconomía / Workshop on Pharmacoeconomy
C 021: CRITERIA FOR THE REGULATION OF THE PRICE OF MR 003: ECONOMIC IMPLICATIONS IN SAFETY AND DRUG MEDICINES USE. CUBAN EXPERIENCE Rovira J. Gálvez González AM, Lara Bastanzuri MC, Jiménez López G.
University of Barcelona, Spain. Escuela Nacional de Salud Pública, Dirección de Medicamentos y Tecnologías Médicas MINSAP, Centro Estatal para el Control de los Medicamentos y Equipos Médicos (CECMED), La Habana, Cuba. The pharmaceutical sector does seldom operate as a competitive and efficient market mechanism due to multiple well known factors: asymmetry of information, non-sensitiveness of the demand to prices, Considerations for the updating of drugs economic policies in barriers of entry on the supply side, and so on. This situation is Cuba especially true in the case of products under patent protection and other forms of market exclusivity, which confer suppliers a temporary legal monopoly. Introduction: Drugs and other pharmaceutical expenditure in represent a huge percentage of the total health budget. It is necessary Most countries therefore apply direct and indirect forms of price to use tools aimed to control and guarantee an efficient use of these control aimed at containing prices and ultimately pharmaceutical resources Drugs economics policies in Cuba are a continuous process expenditure. There are however many modalities of price control and of improvement. These processes are complex and have many goals, of criteria for setting the appropriate regulated price. The present not always exists consensus about the main goals. It is necessary to debate focuses on international/external reference pricing and value establish priorities, this are the basis for the rational use of drugs. based pricing. Methods: A consensus group with experts and decision makers in In order to assess the appropriateness of a pricing approach it is drugs area was developed in order to identify main goals of drugs necessary to define its objectives and feasibility. As the pharmaceutical policies in Cuba. market is an increasingly globalised and interdependent one, the analysis of a pricing approach must have a global perspective that Results: The consensus group sets main goals of drugs policies in Cuba takes into account not only how it will affect the market where it is as follows: to priorize drugs equitable access, to improve efficiency applied, but also the impact on other countries. approach and financial sustainability in the decision making, to support research and development in drugs area, to develop a Cuban From a global perspective a pricing approach for new medicines should national drug industry and to reach affordable drug s price for on one hand provide the appropriate incentives for potential research population. It was proposed another round of discussion in order to to address the research priorities of societies and it should also reflect deep in each topic identified. some form of agreement or consensus on how countries should contribute to the cost of innovation. An alternative option is to radically change the business model by delinking the incentives for innovation from the prices of medicines.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S60
LATINFARMA 2013 Resúmenes/Abstracts
CO 106: NATIONAL PROGRAMME CHILDREN’S CO 107: HEALTH TECHNOLOGY ASSESSMENT (HTA): A IMMUNIZATION IN CUBA. ECONOMICS AND HEALTH BROAD ECONOMIC PERSPECTIVE IMPACTS IN THIS COUNTRY 1962-2012 Rovira J. Collazo Herrera M1, Galindo M2. University of Barcelona, Spain. 1INHEM, MINSAP, La Habana, Cuba.
2National Programme Children’s Immunization, MINSAP, La Habana, Cuba. HTA includes a broad range of activities aimed at generating, gathering, synthesizing and communicating information on relevant The objective of this work is to carry out an estimate of the economic aspects of health technologies with the final purpose of assisting and social impacts in terms of health, obtained since Vaccination decision makers which have a responsibility in the market Programme was introduced than 50 years ago in the Cuban National authorization, pricing, reimbursement and utilization of the said Health System. The more relevant direct cost was estimated as technologies. Vaccination Programme annual costs. It was made a through analytical technique of cost benefits analysis to compare different national Economic evaluation, in a narrow sense, is often identified with a set of production vaccines comparing these ones with foreign vaccines analyses – cost-effectiveness (CEA), budget impact, etc. – which selecting by the World Health Organization (WHO), to calculate the net explicitly address the resource implications of using a certain savings obtained as a cost avoided in the substitution of imports. With technology. However, economic evaluation is not carried out the national production of vaccines, the country will save for this independently from other types of HTA: In fact, CEA are necessarily necessary resources concept around $ 109 960,3 thousand dollars for dependent on the results of clinical research. Moreover, all types of 50 years, as well as the economical repercussion $ 1031 916,0 3 HTA, as long as they have an impact on the use of a technology, do have thousand dollars, so that every infectious disease could be prevented, an economic impact. For instance, if a technology is not authorized due what would imply to have a relationship cost benefit of 9.4:1 in favour to safety concerns, it will not become an economic good and a source of of the national production of vaccines to comparing relationship cost health expenditure, and might lead to losses for those that have benefit 4.6:1 foreign vaccines. In conclusion, the implementation of developed it. On the other hand, a clinical trial, even if it is not aimed at National Vaccination Programme in Cuba introduced than 50 years ago generating information on the costs of the treatments compared, is a in the country, this programme has had a great social-economical resource consuming activity: decisions have therefore to be made on impact because of the results obtained in selected health indicators which clinical trials will be carried out and if so, how many individuals reported by official statistics, the eradication of a few preventable will be enrolled and for how long they will be followed. diseases by the use of vaccines, as well as the economical repercussion This presentation will present a broad economic approach to HTA and of lower Cuban vaccines expenses, compared these with the imported suggest the contribution that economic analysis – as opposed to the vaccines. This way, the Cuban economy has been favored with savings narrower set of economic evaluation techniques – can do to improve in hard currency. HTA and its positive impact on the health and wellbeing of society.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S61
LATINFARMA 2013 Resúmenes/Abstracts
CO 108: CONSUMPTION OF ANTINEOPLASTIC AND SUPPORT CO 109: EFFICIENCY OF TWO TREATMENT MODALITIES FOR DRUGS IN LAS TUNAS PROVINCE , FROM 2009 TO 2012 ANXIETY CAUSED BY NEUROSIS
Pérez JE1, Santos H2, Ávila Y3, Guevara G4, Velasco Y.5 Casas Gross S1, Álvarez Ramírez G, Gross Fernández M, Herrero Aguirre H. 1Hospital General Docente “Dr. Ernesto Guevara de la Serna”, Las Tunas, Cuba. E- mail: [email protected] Universidad de Ciencias Médicas de Santiago de Cuba Ave. de las Américas S/N 2Universidad de Ciencias Médicas de Las Tunas, 3Empresa Asesoría Informática entre Calle E y Calle I, Santiago de Cuba. E-mail: [email protected] DESOF, 4Hospital General Docente “Antonio Luaces Iraola”, 5Policlínico Manuel Fajardo, Las Tunas, Cuba.
Anxiety disorders are the most frequent causes of consultation in primary health care representing one of the greatest health problems Introduction: The human cost of patients with cancer is very well in the community. There are two alternative therapies to solve them: known. Everybody has had a friend or next of kin who has suffered acupuncture and drug therapy. Any health problem that has more of from this disease. Great economic resources have been allocated for than one alternative therapy is susceptible to economic evaluation, an the treatment of these patients. The Cuban government has given instrument that will allow us to decide what is the best solution, priority to their attention, but the expenses performance due to proposing as an objective to determine the effectiveness of cytostatic and support treatment is still needs a deeper level of acupuncture and drug treatment in patients with panic disorder. A investigation, mainly in local areas. study of pharmacoepidemiology that combines therapeutic phase IV Material and method: A descriptive, observational and retrospective clinical trial to determine the effectiveness of treatments and a study was carried out in “Dr. Ernesto Guevara” Hospital, with the pharmaco-economic study (cost-effectiveness) were done, to quantify objective of determining the behavior of the cytostatic and support the costs of the two treatment modalities. The therapeutic effects on drugs consumption for the treatment of cancer in Las Tunas province, health and resources were measured through indicators allowing from January, 2009 to December 2012, as well as to know the total cost further comparison of the results. For acupuncture treatment the of these drugs during the last year. The universe coincided with the following acupuncture points: DU-20, PC-6, C-7, P-6, R-3 and H-3 were sample which was made up by 1762 patients that received used and in the drug treatment the following psychotropic drugs were chemotherapy in this center from 2009 to 2012. 67 medicines were used: diazepam, trifluoperazine, amitriptyline and imipramine. The analyzed. results allowed us to confirm that both treatments were effective because they reached the cure of the disease, thus the benefits through Results: The demands of chemotherapy for breast, head, neck and lung acupuncture were obtained in less time than we really expected it was cancer as well as for non-Hodgkin's lymphoma, increased. The less expensive than the pharmacological one, so acupunctural bifosfonates consumption to treat bone metastasis was increase; too. treatment is more efficient than drug treatment. The bicalutamide, goserelin, nimotuzumab and docetaxel, are considered the most expensive drugs (52% of total consumption). Only the consumption of goserelin, bicalutamide and flutamide for the prostate cancer represented 37% of the expenses. The Nimotuzumab use by 4 patients represented 11% of costs. The cost of the anticancer drugs consumed by the patients during 2012 was of 1.394.355,00 pesos. Conclusion: The expenses of antitumoral and support drugs are high. They could be lowered by means of prevention and earlier diagnosis of cancer, so the use of expensive drugs for advanced stages of this disease could be avoided.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S62
LATINFARMA 2013 Resúmenes/Abstracts
CO 110: ASSESSING FEASIBILITY IN THE DEVELOPMENT AND CO 111: COST-EFFECTIVE OPTIONS IN THE MANAGEMENT MARKETING OF PHYTOMEDICINES: THE CASE OF A Lippia OF DIABETES IN A DEVELOPING COUNTRY alba (VERBENACEAE) ANTI-INFLAMMATORY GEL IN THE Wynter-Adams D1, Simon OR2 and Paul T.2 COSTA RICAN MARKET 1University of Technology, Jamaica. E-mail: [email protected] Segura S. 2University of the West Indies, Jamaica. Universidad de Costa Rica. Escuela de Medicina, Ciudad Universitaria Rodrigo Facio. Montes de Oca, San José, Costa Rica. E-mail: [email protected] As the prevalence of chronic non-communicable diseases, such as diabetes, continues to increase, developing countries like Jamaica need Introduction: The development of phytomedicines is a growing field to maximize strategies to reduce the economic impact of such diseases. in the pharmaceutical industry, especially in Latin American, where the An analysis of diabetic treatment options in Jamaican public clinics was use of traditional medicine and the confidence in pharmaceutical conducted in the Kingston Metropolitan Area, using an intent-to-treat products are deep-rooted beliefs. However, the production of model. The objective was to determine the most cost-effective phytomedicines involves not only the evaluation of the treatment strategy in the management of recently diagnosed type 2 pharmacological properties of phytochemicals, but also the diabetic patients. The study revealed that of the most frequently used examination of technical, legal and financial aspects of the final anti-diabetic drugs such as a sulphonylurea, metformin and an alpha product. To evaluate these aspects is often a major challenge to glucosidase inhibitor, monotherapy with a sulphonylurea produced the pharmaceutical professionals, who traditionally have no training in greatest fall in blood sugar (62.9%) within the first year after how to conduct marketing research. diagnosis, but was not cost-effective in attaining acceptable blood Material and methods: I describe a method to assess the feasibility of glucose levels (FBG < 7.8 mmol/L) after one year. The combination of a phytomedicine production based on marketing theory and taking into sulphonylurea and metformin was able to cost-effectively result in the consideration the marketing mix (product, price, place and attainment of acceptable blood glucose levels which may be associated promotion). This methodology is tested using an analysis of additional cost reductions based on decreased morbidity and mortality commercial viability of a topical gel of Lippia alba (Verbenaceae), associated with attainment of good glycemic control. which has anti-inflammatory properties. In relating the pathophysiology of diabetes with the mechanism of The development of the gel begins with the identification and action of these agents, there is medical and economic value in using this processing of the plant, the preparation of the pharmaceutical form, combination which results in the release of insulin with sensitization to the characteristics of the final product, and its registration. The price its effects along with improvements in lipid profile. From the results, was assessed after considering all production costs, registration, Jamaica and other developing countries may perhaps reduce the distribution, administrative and financial expenses, as well as economic impact of diabetes through early intervention in patients at advertising of the product. Promotion strategies were based on the high risk for developing diabetes, with education, early use of results of a market research for this product, conducted to evaluate metformin or with the judicious use of newer agents such as dipeptidyl potential competitors and to identify its competitive advantages. I also peptidase inhibitors which are expensive but carry additional benefits conducted a financial analysis considering 5-year projections under that may offset the cost of the drugs. three different scenarios to calculate the net present value and internal rate of return of the product. Results and conclusions: Overall, current market situation allows the production and marketing of this gel in Costa Rica. The protocol described here can be applied to the analysis of feasibility for the production of other phytomedicines in the region.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S63
LATINFARMA 2013 Resúmenes/Abstracts
CO 112: ANALYSIS FROM A CUBAN POINT OF VIEW CO 113: MEASURING THE PRICES OF MEDICINES FOR NATIONAL SYSTEM OF HEALTH IN CUBA Pérez Ojeda L, Pérez Cristiá R. De la Cruz Pérez CB, Jacobo Casanuevas OL, Pérez Cristiá R. Centro para el Control Estatal de la Calidad de los Medicamentos y Equipos Médicos, CECMED, La Habana, Cuba. Centro para el Control Estatal de la Calidad de los Medicamentos y Equipos Médicos, CECMED, La Habana, Cuba.
The international debate on Intellectual Property Rights and the way those directly affect scientific health research and drugs access has Introduction: Every day, there are more drugs that are available on reached a surprising level last years. An Intergovernmental Working the world market; however, in many countries there is no adequate Group was called to analyze this subject in the Pan-American Health access due to the high cost of these. When we talk about access to Organization context, which concluded its work during 2008 adopting essential drugs means that there is equitable and affordable the Global Strategy and Plan of Action on Public Health, Innovation and availability with a demonstration of its quality, safety and efficacy. It is Intellectual Property (GSPA). This strategy should provide a very important to include in the health regulation the monitoring of sustainable framework for research and development activities on the price of medicines. The absence of a standard model to evaluate the those diseases which disproportionately affect developing countries. price is an obstacle to ensure access for medicines, that’s why the State must devise strategies toward resources optimization, and in this way, That implies that all of WHO country members, including Cuba, may to take advantageous procurement, therefore, the objective of this adopt national measures to guarantee this strategy implementation. research is to design a system for the measuring of the medicine prices Firstly it has to be analyzed the elements defined by this strategy from which are imported for National System of Cuban Health (SNS). a national point of view. The objectives of the investigation presented are to analyze the elements of the Global Strategy and Plan of Action Material and methods: Two criteria are used to define the range of and Cuba situation regarding its implementation, as well as to identify price proposed and as variables: Name of active ingredient, strength, the priority actions according to WHO recommendations. For this; it pharmaceutical form, description in the medicines basic list (CBM), was made an observation, exploratory and, retrospective study by a presentation, category of the medicinal product, referenced prices in documentary analysis method using the Global Strategy and Plan of other markets, WHO, and local historical price. Action as basic document. The elements set out in this document were analyzed and besides national situation regarding this subject. There Results: Due to this system implementation, have been evaluated 67 were also consulted WHO and PAHO documentation available as well medicines, with a minimum and maximum price proposal. From this as experts and no governmental organizations publications linked with list (67), the 88% is included in the CBM and belong to the category II. IGWG process. Apart from that, it was also analyzed national The 61% is found in a suitable pricing range, the rest, is out of the information related to patent legislations, the work performed by the proposed range, so the importing company is advised to analyze the National Working Group created for that purpose and the reports of price offer by the supplier. The pharmaceutical form more frequently Cuba participation in the Intergovernmental Working Group. was solution for injection. This analysis reached as conclusion that Cuba’s strengths constitute Conclusions: The system allows monitoring of medicinal products advantages for the EGPA implementation. These advantages are: Cuban which are imported to the SNS, price proposed by suppliers, ensuring State political will; the scientific policies are established as state timely access of medicinal products with quality, safety and efficiency policies, a solid human resources training program emphasizing on at the lowest possible price. health professional formation; the integration of primary health care to secondary and tertiary health care services; having institutions devoted to biomedical research with acknowledged international prestige and directly linked to the national health programs, moreover the strength of its biopharmaceutical industry and national regulatory authorities. It was also identified the subjects are needed to start working immediately such as: the need of approving a new Government Decree on patents, the implementation of mechanisms to strengthen the link between the intellectual Property National Office and competent Health Authorities to vigil the public health interest in the patents granting process and finally to study the position to be adopted by the country regarding the creation of an open code systems and drugs chemiolibrary proposed by GSPA.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S64
LATINFARMA 2013 Resúmenes/Abstracts
Taller sobre Daño Cerebral y Neuroprotección: Un Enfoque Básico y Clínico / Workshop on Brain Injury and Neuroprotection: A Basic and Clinical Approach
C 022: THE GUANINE-BASED PURINERGIC SYSTEM AS A NEW CO 114: THE ROLE OF ASTROCYTES IN METABOLISM AND TARGET FOR NEUROPROTECTION AGAINST GLUTAMA- NEUROTOXICITY OF THE PYRROLIZIDINE ALKALOID TERGIC EXCYTOTOXICITY MONOCROTALINE, THEMAINTOXIN OF Crotalaria retusa Souza DO. Lima Costa S.
Departamento de Bioquímica, PPG em Bioquímica e PPG em Educação em Laboratório de Neuroquímica e Biologia Celular, Instituto de Ciências daSaúde, Ciências, ICBS, UFRGS. Rua Ramiro Barcelos, 2600 – Anexo. CEP: 90035-003, Universidade Federal da Bahia, Salvador, Brazil. Porto alegre, RS, Brazil. E-mail: [email protected]
The metabolic interactions and signaling between neurons and glial Glutamate is the main excitatory neurotransmitter in mammalian CNS, cells are necessary for the development and maintenance of brain essential for brain activities, as those involved in development, ageing, functions and structures and for neuroprotection, which includes memory, and adaptation to the environment. However, hyper protection from chemical attack. Astrocytes are essential for cerebral activation of the glutamatergic system may be potentially neurotoxic, detoxification and present an efficient and specific cytochrome P450 involved in the pathogenesis of various acute and chronic brain enzymatic system. Whilst Crotalaria (Fabaceae, Leguminosae) plants injuries. The main process responsible by maintaining the extracellular are used in popular medicine, they are considered toxic and can cause glutamate levels below toxic levels, thus favoring the physiological damage to livestock and human health problems. Studies in animals glutamatergic tonus, is the glutamate uptake exerted by transporters have shown cases of poisoning by plants from the genus Crotalaria, located in neural cell membranes, mainly in astrocytes. Our group has which induced damage to the central nervous system. This finding has given strong evidence that the guanine-based purinergic system is been attributed to the toxic effects of the pyrrolizidine alkaloid (PA) effectively neuroprotective against glutamate toxicity, in acute and monocrotaline (MCT). The involvement of P450 enzymatic systems in chronic animal models, both in vitro and in vivo studies. Our results MCT hepatic and pulmonary metabolism and toxicity has been indicate that nucleoside guanosine (Guo) exerts neuroprotection. In elucidated, but little is known about the pathway simplified in the vivo Guo i.c.v., i.p. or orally administered in rodents protects against bioactivation of these systems and the direct contribution of these brain injury caused by overstimulation of the glutamatergic system. In systems to brain toxicity. This review will present the main vitro studies, Guo protects cell death in brain slices caused by in vitro toxicological aspects of the Crotalaria genus that are established in the ischemia. Searching for mechanisms implicated in this neuroprotection, literature and recent findings describing the mechanisms involved in we demonstrated that: i) Guo stimulates the astrocytic glutamate the neurotoxic effects of MCT, which was extracted from Crotalaria uptake (in astrocyte cultures and brain slices), the main process retusa, and its interaction with neurons in isolated astrocytes. involved in endogenous neuronal protection; ii) brain induced-injuries decrease glutamate uptake by brain slices and this decrease is reversed by Guo only when it acts as anticonvulsant; iii) brain oxidative stress caused by glutamate toxicity in experimental brain injury models is reversed by Guo administration. Thus we propose that the stimulatory effect on glutamate uptake and/or its antioxidant activity are involved in the neuroprotective actions of Guo. These results encourage further studies aiming at the therapeutic use in humans of Guo in acute (hypoxia, ischemia, brain traumatism) and chronic (neurodegenerative diseases) brain injuries involving glutamate excytotoxicity.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S65
LATINFARMA 2013 Resúmenes/Abstracts
CO 115: RESVERATROL PREVENTS CA1 NEURONS AGAINST CO 116: ACTION OF FATTY ACIDS ON GABAA RECEPTORS: ISCHEMIC INJURY BY MODULATION OF BOTH GSK-3Β AND IMPLICATIONS FOR THEIR ANXIOLYTIC-LIKE EFFECTS IN CREB THROUGH PI3-K/AKT PATHWAYS AND THE WISTAR RATS INFLAMMATORY RESPONSE Rodríguez-Landa JF1, García-Ríos RI1, Cueto-Escobedo J1, Bernal- Simão F, Matté A, Simões Pires E, Pagnussat AS, Netto CA, Salbego CG. Morales B1, Contreras CM.1,2
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, 1 Laboratorio de Neurofarmacología, Instituto de Neuroetología, Universidad Porto Alegre, RS, Brazil. Veracruzana, Xalapa 91190, Veracruz, México. E-mail: [email protected] 2 Unidad Periférica Xalapa, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Xalapa 91190, Veracruz, México. E-mail: [email protected]; [email protected] Neurodegeneration is a prominent feature of cerebrovascular disorders, particularly stroke syndromes that are a major cause of morbidity and mortality in middle and later life. Despite the growth in Introduction: A mixture of eight fatty acids (FAT-M) identified in the number of publications related to the characterization of the human amniotic fluid (C12:0, lauric acid, 0.9 g%; C14:0, myristic acid, processes involved in cell death due to ischemic insult, there is not yet a clinically effective therapeutic protocol to reduce brain damage induced 6.9 g%; C16:0, palmitic acid, 35.3 g%; C16:1, palmitoleic acid, 16.4 by ischemia. No drugs tested in clinical trials showed efficacy in g%; C18:0, stearic acid, 8.5 g%; C18:1cis, oleic acid, 18.4 g%; reducing mortality and/or morbidity of ischemic stroke. Therefore, it is C18:1trans, elaidic acid, 3.5 g%; C18:2, linoleic acid, 10.1 g%) necessary to search new strategies to change this situation, which is produce anxiolytic-like effects comparable to diazepam in Wistar rats, one of the main challenges for biomedical research of this century. Our suggesting the possible involvement of GABAA receptors, a possibility research group has been dedicated to the investigation of the not yet explored. Therefore, the present study explored the neuroprotective substances in models in vitro and in vivo participation of GABAA receptors in the anxiolytic-like effects of the neurodegenerative lesions such as cerebral ischemia. In the course of FAT-M. our investigations, we have demonstrated a potent neuroprotective Material and methods: Male Wistar rats were subjected to the effect of resveratrol, a phytoalexin (3,5,4'-trihydroxystilbene) defensive burying test, elevated plus maze, and open field test. In belonging to the family of stilbenes family of stilbenes. Our data suggest different groups of rats, three GABAA receptor antagonists were that the effect of resveratrol may be mediated through activation of the administered 30 min before the FAT-M, including the competitive PI3-K/Akt signaling pathway, subsequently downregulating expression GABA binding antagonist bicuculline (1 mg/kg), GABAA benzo- of GSK-3β and CREB, thereby leading to prevention of neuronal death diazepine antagonist flumazenil (5 mg/kg), and noncompetitive GABAA after brain ischemia in rats. Also we found that resveratrol treatment chloride channel antagonist picrotoxin (1 mg/kg). remarkably reduced astroglial and microglial activation and it greatly attenuated the activation of NF-κB and JNK with decreased COX-2 and Results: The FAT-M exerted anxiolytic-like effects in the defensive iNOS production. In conclusion, we can suggest that the burying test and elevated plus maze, without affecting locomotor neuroprotection of resveratrol involves the modulation of survival cell activity in the open field test. Administration of the GABAA antagonists signaling pathway and decreasing the neuroinflammation. alone did not produce significant changes in the behavioral tests. Picrotoxin, but neither bicuculline nor flumazenil, blocked the anxiolytic-like effect produced by the FAT-M. Conclusion: The FAT-M exerted its anxiolytic-like actions through GABAA receptor chloride channels in Wistar rats.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S66
LATINFARMA 2013 Resúmenes/Abstracts
CO 117: A MIXTURE OF FATTY ACIDS PRODUCES C 023: PRECLINICAL STUDIES OF A NEW HYBRID MOLECULE ANXIOLYTIC-LIKE BEHAVIOR IN THE WISTAR RAT: WITH NEUROPROTECTIVE EFFECTS IN THE TREATMENT COMPARISON WITH DIAZEPAM OF CEREBRAL ISCHEMIA
García-Ríos RI1, Rodríguez-Landa JF1,Contreras CM.1,2 Nuñez Y1, Pardo G2, Ramírez J1, García L1, Delgado R1, Merino N1, Valdés O1, Ochoa E2, Verdecia Y2, Iglesias L1, Onofre D3, Salbego C3, 1Laboratorio de Neurofarmacología, Instituto de Neuroetología, Universidad Hansel G3, Nicoloso E3, Porto M1. Veracruzana y 2Unidad Periférica Xalapa del Instituto de Investigaciones Biomédicas, UNAM. Av. Dr. Luis Castelazo s/n Col. Industrial Las Ánimas, Xalapa 1Centro de Investigación y Desarrollo de Medicamentos, Ave 26, No. 1605 91190, Veracruz, México. E-mails: [email protected] (GRRI), Boyeros y Puentes Grandes, CP 10600, La Habana, Cuba, E-mail: [email protected] (RLJF), [email protected] (CCM) [email protected] 2Centro de Estudio para las Investigaciones y Evaluaciones Biológicas, Instituto de Farmacia y Alimentos, Universidad de La Habana, ave. 23 # 21425 e/214 y Introduction: Human amniotic fluid and an artificial mixture of eight 222, La Coronela, La Lisa, CP 13600, La Habana, Cuba. 3Laboratorio de Síntesis Orgánica de La Facultad de Química de La Universidad of their fatty acids produce anxiolytic-like effects in male and female de La Habana (Zapata s/n entre G y Carlitos Aguirre, Vedado Plaza de la Wistar rats. However, it is unknown the minimal effective dose of the Revolución, CP 10400, La Habana, Cuba. fatty acids mixture. Therefore, this study explored if the anxiolytic-like 4Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, effect of the artificial mixture fatty acid follows a dose dependent Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 anexo, response. Porto Alegre, RS 90035-003, Brazil. Material and methods: Adult male Wistar rats were evaluated in the defensive burying, open field and rotarod tests after the administration Introduction: Cerebral ischemia has a high incidence at present, their of several doses of a fatty acids mixture. The basal mixture (1 ml) frequency increases with increasing life expectancy and the drugs contained a similar amount of fatty acids than amniotic fluid: C12:0, available have low effectiveness. Clinical evidence has shown lauric acid, 0.9 µg%; C14:0, myristic acid, 6.9 µg%; C16:0, palmitic acid, therapeutic failure of neuroprotective drugs, often caused by the use of 35.3 µg%; C16:1, palmitoleic acid, 16.4 µg%; C18:0, stearic acid, 8.5 drugs that act on a single mediator of damage in a disease that involves µg%; C18:1cis, oleic acid, 18.4 µg%; C18:1trans, elaidic acid, 3.5 µg%; a complex variety of events. That is why the study of multiligands C18:2, linoleic acid, 10.1 µg%. Lower tested volumes (0.5 ml, 0.25 ml compounds that may affect several steps of the ischemic cascade, could and 0.125 ml) contained the same proportion of fatty acids than be an attractive therapeutic option for this disease. amniotic fluid, but a half, a quarter and an eighth of the amounts of fatty acids. Diazepam (2 mg/kg) was used as a reference anxiolytic Material and methods: In the present work we evaluated, a novel 1,5- drug. benzodiazepines with the presence of a 1,4 dihydropyridine moiety fused to the benzodiazepine ring (JM-20) in different experimental Results: Although results followed a dose dependent response, only 1 models associated with ischemic brain damage, including behavioral mL of the fatty acid mixture increased burying latency, reduced models to evaluate GABAergic activity, cellular models for evaluate cumulative burying even more effectively than diazepam, without cytotoxicity induced by glutamate, hydrogen peroxide and oxygen altering locomotor activity or motor coordination in open field and glucose deprivation. Also we evaluated the effect of JM-20 on different rotarod test. parameters associated with mitochondrial dysfunction and on Conclusion: The amount of fatty acids contained in amniotic fluid is the histological, behavioral and biochemical alterations in animal models necessary to produce anxiolytic-like effects in male Wistar rats, of stroke. confirming additionally their anxiolytic-like actions. Results: The main results obtained show that JM-20 has a neurosedative profile similar to diazepam, however the presence of the dihydropyridine moiety in their structure, could be inhibiting damage associated exacerbated calcium in flux. Moreover, JM-20 showed strong neuroprotective effect in animals and cell models associated with the cerebral ischemia and on different parameters of mitocondrial dysfunction responsible of the neuronal death.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S67
LATINFARMA 2013 Resúmenes/Abstracts
C 024: Achyrocline satureioides (LAM) D.C. (MARCELA): CO 118: CHARACTERIZATION OF A MODEL OF GLOBAL PROTECTIVE EFFECTS IN PRIMARY NEURONAL CULTURES STROCK INDUCED BY PERMANENT OCCLUSION OF THE AND AGAINST AN ISCHEMIC INJURY IN VIVO ARTERIES COMMON CAROTIDS
Rivera F, Echeverry C, Arredondo F, Abin-Carriquiry JA, Martínez M, Pavón N, Pentón G, Almaguer W, León R, Marín J, Cruz A, Lorigados L, Dajas F. Blanco L, Estupiñán B, Merceron D and Bergado J.
Departamento de Neuroquímica. Instituto de Investigaciones Biológicas Clemente International Center of Neurological Restouration. Ave. 25 No. 15805, entre 158 y Estable. Unidad Asociada a Facultad de Ciencias. Universidad de la República. 160. Cubanacán, Playa, La Habana. E-mail: [email protected] Avenida Italia 3318. Montevideo. Uruguay. E-mail: [email protected]
Introduction: The cerebral stroke constitutes one of the main causes Introduction: Achyrocline satureioides (AS) is a South American plant of death around the world. That is why the animal models of brain widely used in popular medicine. Experimental studies have stroke are widely used so much in the study of the path physiology of confirmed its antioxidant and anti-inflammatory effects mainly due to stroke as well as in the evaluation of therapeutic agents with possible its high content of polyphenols. In this work we evaluated the protective effect or regeneration. protective effects of an AS decoction (2%) in primary neuronal cultures against an oxidative injury and against an ischemic process in Objectives: to examine the presence of neural damage in different rats in vivo. brain areas induced by the occlusion of common carotids arteries; as well as to evaluate consequences of this to proceed on the memory- Methods: Dried flowers of AS were used for the preparation of the learning processes. decoction. Primary cerebellar granule neurons in culture (DIV 7) were treated for 24h with AS decoction and subsequently exposed to an Methods: The groups included an experimental group of 30 rats to oxidative insult with H2O2 160 uM for 24h. MTT assay was used to those that were occluded at both arteries common carotids, and a analyze cell survival after the treatment. For in vivo assays, Sprague control group. The expression of genes related to stroke was evaluated Dawley rats (250-350 g) were divided in 4 experimental groups for technical of RT-PCR 24 hours post lesion, the morphology of the (sham, ischemia, AS alone, and AS + ischemia) (n = 6/group). Animals brain areas, 7 days post lesion, was also evaluated as well as the were pre-treated with water or AS decoction for 7, 14 or 21 days processes of learning, 12 days post lesion. followed by 24h of permanent middle cerebral artery occlusion. Results: The morphological results evidenced that proceeding induces Consumption of food and AS decoction/water of the rats was the death of cellular populations and modify the expression the genes evaluated daily and weight gain was monitored weekly. To assess and cytokine level like GFAP and ho, IL-6, IL-17 and IFN-gamma, which functional deficits a behavioral test was performed, and cerebral can be used as a early marker of stroke process. Additionally, ischemic damage was evidenced by TTC tetrazolium salt. event also caused deterioration in the space memory. This Results: AS (5 ug/mL total polyphenols) pre-treatment in neuronal characterization will allow having an experimental model to develop cultures showed protective effects against H2O2 injury. AS pre- future studies as well as to evaluate any therapeutic strategies in events treatment prevented the functional deficit caused by ischemic injury involving ischemic events. in all groups. Furthermore, AS pre-treatment for 21 days significantly decreased the infarction volume. Conclusions: AS decoction (2%) pre-treatment showed protective effects against both oxidative injury in primary neuronal cultures, and in vivo ischemic brain injury. Its high polyphenolic content could explain such protective effects, mainly due to the antioxidant and anti- inflammatory properties described for these compounds.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S68
LATINFARMA 2013 Resúmenes/Abstracts
CO 119: ORGANO SELENO COMPOUNDS AS NEURO- CO 120: NEUROPROTECTION AND CLINICAL TRIAL IN PROTECTIVE AGENTS: EMPHASIS IN DIPHENYL AUTISTIC DISORDER DISELENIDE (PHSE)2 Robinson-Agramonte MA1, García EN1, Rodriguez Ravelo MA1, Whilby Rocha JBT, Leal MLR, Soares FA, Nogueira CW. Santiesteban M3, Bernardi C2, Nardin P2, Baronio D2,3, Castro-Grokoski K2,3, Gonçalves CA2, Gottfried C2,3. Departamento de Química and Departamento de Clínica de Grande Animais, CCNE and CCR, Universidade Federal de Santa Maria, 97105900, Santa Maria, RS, 1International Center for Neurological Restoration, Cuba. Brazil. E-mail: [email protected] 2Dept of Biochemistry, Federal University of Rio Grande do Sul, Brazil. 3Children´s Hospital Las Catolicas, Cuba. 4Clinical Hospital of Porto Alegre, Brazil. Selenium is an essential element for mammalian cell physiology. It is found in a limited number of proteins in the form of selenocysteine. The selenol group of selenocysteine is essential for the antioxidant Introduction: In recent years, the role of the bi-directional properties of selenoenzymes, such as glutathione peroxidase (GPx) and communication between the brain and the immune system in the thioredoxin reductase (TrxR). About 3 decades ago, ebselen [2-phenyl- etiology of major psychiatric disorders has become an important topic 1,2-benzisoselenazol-3(2H)-one] was reported to exhibit interesting for research in neuroscience. Studies have demonstrated that some pharmacological activities in models of human pathologies, including patients with major psychiatric disorders exhibit characteristic signs of brain ischemia. Some years later ebselen was used with borderline immune as a common pathophysiological mechanism that underlies efficacy in humans and its therapeutic properties was attributed to its the development and progression of these disorders. GPx-like activity. In view of the neuroprotective effect of ebselen, the Objective: the aim of this study was to provide evidence on the antioxidant and pharmacological properties of diphenyl diselenide immune factors associated with ASD (Autistic Spectrum Disorder) and (PhSe)2 have been studied. (PhSe)2 is the simplest of the diaryl contribute to elucidate the link between the immune changes and the diselenides and its GPx-like activity is about 2 times that of ebselen. behavioral alterations and/or clinical symptoms associated with the (PhSe)2 exhibits antioxidant and neuroprotective effects in different in disorder. vitro and in vivo models of neurotoxicity. For instance, (PhSe)2 counteracted the pro-oxidant effect of Fe(II) and quinolic acid. In a Method: The participants were 15 children, age 3 to 9 years of age, similar way to ebselen, it protected hippocampal slices from O2 and with ASD, according to Diagnostic and Statistical Manual of Mental glucose deprivation and rats from brain ischemia. As a rule, (PhSe)2 Disorders 4t Edition, (DMS-IV). The severity of the disease was exhibits a better efficacy than ebselen. (PhSe)2 is less toxic to rodents measured by the Childhood Autism Rating Scale (CARS). TNF-α and IL- than ebselen and did not caused toxicity to sheep and rabbits. In 10 cytokines and brain-derived neurotrophic factor (BDNF) was addition to its GPx-like properties, (PhSe)2 can be protective assessed in serum of ASD patients. via stimulation of nuclear translocation of Nrf-2, a transcription factor modulating antioxidant responses. The results obtained in the last 15 Results: No differences were observed to TNFα and IL-10 cytokines and BDNF in autistic disorders compared to age matched controls. At years with the prototypal (PhSe)2 indicate that new diselenides should be tested. Indeed, thousands of diselenides have been synthesize; the same time, a significant correlation was observed to TNFα and however, we still need to develop rational in silico and in vitro protocols CARS, this last as measure of severity and between CARS and age onset to select which of them should be tested in in vivo mammalian models. of the disease in autistic disorder. Conclusions: The present findings reinforce current hypothesis involving inflammatory and excytotoxic mechanisms contributing to the pathophysiology of autistic disorder and contribute to clarify contact points between clinical and biological events involving neuroprotection in autism.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S69
LATINFARMA 2013 Resúmenes/Abstracts
Simposio de Farmacogenética y Farmacogenómica / Symposium of Pharmacogenetic and Pharmacogenomic
C 025: GENETIC VARIATION IN SMOKING AND LUNG CANCER C 026: PHARMACOGENETICS: CLINICAL IMPLICATIONS FOR EATING DISORDERS AND SUICIDE Tyndale R. Llerena A, Naranjo ME; Peñas-Lledo E. Centre for Addiction and Mental Health, Departments of Psychiatry, Pharmacology and Toxicology, University of Toronto, Toronto, Canada. Clinical Research Centre, Extremadura University Hospital and Medical School, Badajoz, Spain. Ibero Latino American Network of Pharmacogenetics (www.ribef.com) Nicotine is the main active component in cigarette which mediates tobacco dependence. About 80% of nicotine is metabolically inactivated to cotinine; the hepatic CYP2A6 enzyme is responsible for Pharmacogenomics Clinical implications. A higher frequency of over 90% of this conversion. Both in vivo and in vitro studies CYP2D6 UMs has been found among individuals who committed demonstrate considerable interindividual variation in CYP2A6 activity suicide (Zackrisson et al., 2010). One explanation for this relationship that is attributed to variations in the CYP2A6 gene. Individuals with at could be treatment failure with antidepressant drugs metabolized by least 1 copy of the genetically inactive or reduced activity CYP2A6 CYP2D6 (Llerena et al., 2004) widely used to prevent suicide or to treat variant (allele) have decreased nicotine metabolism. mood disorders. A complementary explanation could be via the implication of the polymorphic CYP2D6 in the endogenous We have found that slow nicotine inactivators are 2 times less likely metabolism. CYP2D6 has been associated with behavioral and clinical to be dependent smokers (OR 0.52 95% CI 0.29-0.95). Slow risk factors such as personality and vulnerability to psychopathology metabolizers that do become smokers consume 7-10 cigarettes less (Llerena et al., 1993; 2007; Gonzalez et al., 2008; Peñas-Lledó et al., per day than normal metabolizers, and also inhale less deeply. There 2009, 2010). Consistently, we found a relationship between UMs and are large differences among ethnic populations in the frequency of severity of suicide and lifetime history of suicidal behavior among slow metabolizers which may contribute to the ethnic differences Eating Disordered patients (Peñas-LLedó et al., 2010, 2011, 2012a). observed in rates of smoking and tobacco-related diseases. In general Moreover it seems also been related to antidepressant discontinuation the frequencies of variant alleles with large impacts on function are as recently shown (Peñas-LLedó et al., 2012b). Therefore low in Caucasians, while some of the alleles are prevalent (up to 20%) Pharmacogenomics might be useful to prevent relevant side effects for example in Asian and African populations. Variation in CYP2A6 such is suicide. genotype and/or the CYP2A6 metabolite ratio biomarker is associated with differences in the ability to quit smoking both in the absence of pharmacotherapy, and with nicotine replacement therapies. We found the odds of quitting with nicotine patch were reduced by 30% with each increasing quartile of the ratio; faster metabolizers were less successful in quitting than slow metabolizers. CYP2A6 is also capable of activating tobacco-procarcinogens such as NNK. Thus individuals with slower CYP2A6 smoke less and activate less tobacco-smoke procarcinogens resulting in lowered risk for tobacco- and dietary-related cancers such as lung cancers, while those with high levels of CYP2A6 are at greater risk. We have also shown that having a variant in the α3-α5-β4 nicotinic receptor cluster, a target for both nicotine and nitrosamines, also alters smoking and lung cancer risk. When examining variation in CYP2A6 and the nicotinic receptor variant together we observe an increase in both smoking and lung cancer risk for those who are faster CYP2A6 metabolizers and have the at risk nicotinic receptor variant.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S70
LATINFARMA 2013 Resúmenes/Abstracts
CO 121: POPULATION PHARMACOKINETIC OF CO 122: ASSOCIATION OF POLYMORPHISMS OF THE CYCLOSPORINE IN THE EARLY PERIOD THE POST RENAL CYP2C9*2,*3 AND CYP2C19*2,*3, THE NUTRITIONAL TRANSPLANT IN PAEDIATRIC PATIENTS STATUS AND CONCOMITANT TREATMENT, WITH PHENYTOIN PHARMACOKINETICS AND TREATMENT Lares-Asseff I1, Zaruma Torres F1, Saltzman Girshevich S2, Urbina Álvarez J1, Guillé-Pérez G3, Sosa Macías M1, Loera Castañeda V1, Galaviz RESPONSE, IN PATIENTS WITH EPILEPSY Hernández C1, Toledo López A.3 Gutiérrez Álvarez O1, Lares-Assef I2, Ruano Calderón LA3, Sosa Macías 4 5 6 4 1Instituto Politécnico Nacional, CIIDIR-IPN Unidad Durango, México. M , Chairez Hernández I , Salas Pacheco JM , Galaviz Hernández C , 2Servicio de Nefrología y la Unidad de Trasplante Renal del Instituto Nacional de Loera Castañeda V. 4 Pediatría, (INP), México. 1IPN y 2Academia de Genómica Aplicada CIIDIR, Unidad Durango, México. 3Departamento de Farmacología Clínica del INP, México. 3Especialista en Neurología del Hospital General del Estado de Durango, México. 4Laboratorio de Farmacogenómica y Biomedicina Molecular 5Laboratorio Estadística, Procesos Estocásticos y Modelación Matemática IPN Introduction: Cyclosporine (CsA) is an immunosuppressive agent CIIDIR Durango used to prevent transplant rejection through selective modification of 6Instituto de Investigación Científica de la UJED, Durango, México. the function of T helper lymphocytes. CsA is a therapeutic agent with a narrow therapeutic index and large variability in pharmacokinetics. Introduction: Variability in drug response is regulated by several Objectives: To identify differences in the CsA concentrations at steady factors which alter the pharmacokinetics and pharmacodynamics of state between patients with acceptance or rejection of renal transplant drugs. (RT), and determine the population pharmacokinetic of the drug. Objective: To determine the association of polymorphisms Material and methods: We included 64 patients 3-18 years enrolled CYP2C9*2,*3 and CYP2C19*2,*3, the nutritional status and in RT program of INP, Mexico. Were extracted from one to three concomitant treatment, both pharmacokinetics and response to samples per week for each patient, to determine plasma treatment with phenytoin. concentrations of CsA, using polarized immunofluorescence (DX Abbott). Material and methods: Fifty patients diagnosed with epilepsy pertaining to the neurology service to the General Hospital of Durango, Results: RT rejection was experienced in 35 patients [13 (37.1%) Mexico were enrolled. Nutritional status was assessed through of body males and 22 (62.1%) females] while the remaining 29 accepted the mass index (BMI). DFH serum concentrations were determined in th RT [19 (65.5%) males and 10 (34.5%) females]. We monitored 1955 IMMULITE 1000. The polymorphisms were evaluated by real-time PCR concentrations of CsA in accepting [sub-therapeutic 599 (30%), with Taqman probes. therapeutic 178 (8.9%) and toxic 12 (0.6%)] and rejecting [sub- therapeutic 809 (40.5%), therapeutic 265 (13.3%) and toxic 86 Results: Serum concentrations: 27 patients on subtherapeutic range, (4.3%)] patients p=0.01. The following population pharmacokinetics 10 patients with concentrations in risk of toxicity, and 13 patients in parameters of patients accepting RT were: AUC = 2587.35 therapeutic range. Concomitant therapy: 36 patients with -1 (mcg/mL/h), K10-HL = 2.09 (h) = 0.973 K01-HL (h) alpha (h ) = polypharmacy and 14 with monotherapy. Men responded better to 0.7355; beta = 0.0720 (h-1), alpha-HL = 0.94 (h), beta-HL = 9.61 (h-1), treatment than women x2 = 3.92, p˂ 0.05 with 1 df. We found that from the equation Cp =Aeα.t + Beβ.t, describing a two-compartment increasing the BMI, concentration of phenytoin decrease significantly, model, describing a two compartment model. r=0.33, r 2 = 0.114 with p˂0.05. Allele frequencies were: CYP2C9*2 (0.12), CYP2C9*3 (0.04), CYP2C19*2 (0.09) and CYP2C19*3 (0.01); Conclusions: 1) There are significant differences between sub- wild type genotype and heterozygocity were found in 27 and 23 therapeutic, therapeutic and toxic CsA concentrations within and patients respectively. No polymorphism was associated with the between the studied groups; those patients rejecting RT showed control over convulsive seizures. Phenytoin adverse effects: 15 of 50 significantly higher toxic concentrations; 2) Dose should be patients, 11 of them showed polymorphisms CYP2C9 *2,*3, and individualized and based on pharmacokinetic parameters in this CYP2C19*2,*3. population. 3) The new dose of cyclosporine in this population should be calculated on an individual basis, based on the pharmacokinetic Conclusions: Artificial Neural Networks (ANN) showed that the most parameters of the population studied. important variable in the variability of the elimination rate constant (Kel) of phenytoin is mainly dependent of polymorphisms and haplotypes of CYP2C9*2,*3 and CYP2C19*2,*3, with 36.5% and 33.4% BMI, concomitant treatment 19.3% and the response to treatment with 10.7%. There is an association between Pharmacokinetics Pharmacogenetics with DFH, BMI is not appropriate for drug dosage.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S71
LATINFARMA 2013 Resúmenes/Abstracts
CO 123: PHARMACOGENOMIC AND PHARMACOKINETIC CO 124: DETERMINATION OF MUTATIONS WITH CLINICAL PARTICULARITIES OF THE MEXICAN POPULATION: IMPLICATION OF THE NAT2, ABCB1, CYP2C9 AND CYP4F2 NECESSITY OF LOCAL CLINICAL PHARMACOLOGY STUDIES ON DRUG RESPONDS IN PERUVIAN SETTLERS IN LATIN AMERICA Salazar-Granara A1, Castañeda-Castañeda B2, Barboza-Coelho E3. Castañeda G. 1Centro de Investigación de Medicina Tradicional y Farmacología (CIMTFAR), Departamento de Farmacología. Centro de investigación y de Estudios Avanzados Facultad de Medicina Humana de la Universidad de San Martín de Porres (FMH- del Instituto Politécnico Nacional. Av. Instituto Politécnico Nacional 2508, 07360 USMP), Perú. E-mail: [email protected] México, D.F. 2Instituto de Investigación, CIMTFAR, FMH-USMP, Perú. 3Laboratorio de Hipertensión Experimental, Hospital de Clínicas de Riberao Preto, Universidad de Sao Paulo, Brasil. Interethnic variability in the pharmacokinetics of several drugs has been documented. In some cases, doses should be adjusted depending Objective: To determinate the frequency of mutations with clinical on the ethnic group. However, most studies compare Caucasian with repercussion of the genes: NAT2, ABCB1, CYP2C9 y CIP4F2 in Peruvian either African American or Asian populations. Information on Latin settlers. American subjects is scarce. Our group has documented that, for some drugs, Mexican Mestizoes exhibit an increased variability compared to Methods: Peruvian settlers from: Loreto. Ucayali, Amazonas, Caucasians, likely due to genetic differences in the expression of Apurimac, San Martín, Ancash, Puno, Arequipa and Lima, after cytochrome P450 enzymes. Characterization of CYP3A5 genotypes has accepted voluntary and freely donned us their biological samples of shown that the proportion of subjects with functional and blood and saliva for the research. We used the DNA to detect the dysfunctional enzymes in Mexicans is different from that observed in mutations with the following molecular techniques: RFLP-PCR, PCR, other ethnic groups. As these differences may be relevant for the RT-PCR, and genetic sequencing. dosing of critical drugs, such as tacrolimus and cyclosporine, the necessity of pharmacogenetic and pharmacokinetic studies in Latin Results: In the NAT2 gen we found the following polymorphisms: American countries will likely allow an optimization of therapeutics in 282C>T, 341T>C, 481C>T, 590G>A, 803A>G y 857G>A. We detected the region. 45% of people with genotype fast acetylates, 23% of slow acetylates and 32% of unknown genotype acetylates. In the ABCB! Gene we found 67% a frequency of mutation to 1236 T>C, 30% for mutation to 2677 G>T/A and 63% for mutation to polymorphism C3435T. The CYP2C9 showing a frequency of 11% for mutation to CYP2C9*2 and 3% to CYP2C9*3. Finally, the CYP4F2*3 gene, showed a frequency of mutation of 11%. The Hardy-wiembrg test showed an allelic equilibrium. Conclusion: We had observed a clinic relationship between Isoniazid and the mutations of NAT2 gene. Relationship of antineoplastic drug resistance and the ABCB1 gene implicated on the gene mutations and the mutations of CYP2C9 and CYP4F2 implicated in the responds to drugs as Warfarin and opioids a non-opioids analgesics. We determinate the first Peruvian frequency of mutations with clinic implication.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S72
LATINFARMA 2013 Resúmenes/Abstracts
CO 125: DISTRIBUTION OF CYP2C19 POLYMORPHISMS IN CO 126: ASSOCIATION OF CYP1A1*2C WITH HEPATIC EIGHT AMERINDIAN GROUPS FROM NORTHWEST MEXICO FUNCTION AND HYPERLIPIDEMIA IN A MEXICAN TEPEHUANO INDIGENOUS GROUP Sosa-Macías M1, Lazalde-Ramos BP2, Galaviz-Hernández C1, Bailón- Soto C1, Lares-Asseff I1, LLerena A3. Galaviz-Hernández C1, Bailón-Soto C1, Lazalde-Ramos BP2, Salas- Pacheco JM3, Llerena A4, Sosa-Macías M. 1 1Centro Interdisciplinario de Investigación para el Desarrollo Integral Regional del IPN Unidad Durango, CIIDIR-IPN, Sigma 119 Fracc. 20 de noviembre II. C.P. 1Centro Interdisciplinario de Investigación para el Desarrollo Integral Regional 34220, Durango, México. E-mail: [email protected] Tel +52 618 8142091, Fax +52 del IPN Unidad Durango, CIIDIR-IPN, Sigma 119 Fracc. 20 de noviembre II. C.P. 618 8144540. 34220, Durango, México. E-mail [email protected]. Tel +52 2Laboratorio de Medicina Molecular, Unidad Académica de Medicina Humana y 618 8142091, Fax +52 618 8144540. Ciencias de la Salud, Universidad Autónoma de Zacatecas, Zacatecas, México. 2Laboratorio de Medicina Molecular, Unidad Académica de Medicina Humana y 3CICAB Clinical Research Centre, Extremadura University Hospital and Medical Ciencias de la Salud, Universidad Autónoma de Zacatecas, Zacatecas, México. School, Badajoz, Spain. E-mail: [email protected]. 3Instituto de Investigación Científica de la UJED, Durango, México. 4CICAB Clinical Research Centre, Extremadura University Hospital and Medical School, Badajoz, Spain. Introduction: The CYP2C19*2,*3 and *17 mutant alleles are associated with the functional polymorphism of CYP2C19. These have been widely studied in several ethnic groups; however they are less known Introduction: The CYP1A1*2C allele influences both the hepatic in Native Mexican groups. function and the metabolism of cholesterol and other fatty acids; the last two related to cardiovascular risk. This polymorphism has been Objective: To determine the frequency of CYP2C19 polymorphisms in previously evaluated in two Mexican indigenous populations. eight indigenous groups from Mexico. Objective: Determine the frequency of CYP1A1*2C and its association Methods: Genotyping of CYP2C19*2,*3 and *17 variants was carried with hepatic function and triglyceride levels in a Mexican Tepehuano out in 487 volunteers by real-time PCR. indigenous group. Results: The CYP2C19*2 allele was more frequent in the Guarijío group Methods: Complete lipid profile and genotyping of CYP1A1*2C by RT- (0.43) than in the rest of groups (p≤0.011), with frequencies of 0.22 in PCR was done in 120 Tepehuano volunteers. Tarahumaras, 0.13 in Tepehuanos, 0.08 in Mayos, 0.062 in Coras, 0.051 in Mexicaneros, 0.045 in Huicholes, and 0.026 in Seris. The Results: Lipid profile did not revealed differences between sex on this CYP2C19*2/*2 genotype, which has therapeutic consequences, population. The frequency of *2C allele was 0.35, meanwhile that for presented a wide frequency range (0.8%-20%). CYP2C19*3 was not *2C/*2C genotype was ~0.11. After adjusting for age, sex, BMI, tobacco found. The CYP2C19*17 allele was detected in Coras, Tepehuanos, and alcohol consumption, the regression analysis revealed a significant Tarahumaras and Mayos in a range of 0.012-0.068. association between *2C allele and normal triglycerides [OR 4.37; 95%CI 1.24-17.98, p=0.017]; a significant association was also found Conclusion: Our data show the presence of inter-ethnic differences in with alanine aminotransferase (ALT) levels [OR 4.67; CI 95% 1.19- the CYP2C19*2 and *17 variant frequencies in the Amerindian groups, 18.34, p=0.034]. which is in agreement with previous studies in other Amerindian populations. Determination of CYP2C19 alleles is important in Conclusion: The observed frequency of CYP1A1*2C allele is lower than indigenous populations regard to the clinical use of drugs metabolized that previously reported in Teenek (0.66) and Mayos (0.55) Mexican by CYP2C19. Amerindian groups. The strong association found between CYP1A1*2C allele with normotriglyceridemia and normal ALT levels, suggests a Acknowledgements: This study was supported by CONACYT-Mexico Project 2009- potential protective role of this allele for development of cardiac and 01-113063. liver disease in Tepehuano indigenous group.
Acknowledgements: This study was supported by SIP IPN Project 20131835.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S73
LATINFARMA 2013 Resúmenes/Abstracts
CO 127: METABOLIC PHENOTYPES OF DEBRISOQUINE AND CO 129: POLYMORPHISMS OF THE BIOTRANSFORMATION GENOTYPIC OF CYP2D6 IN THE NICARAGUAN POPULATION AND ELIMINATION SYSTEMS OF THE MEDICINES: ON OVERVIEW TO STUDIES PERFORMED IN CUBA Ramírez Roa R. Rodeiro I1, Velázquez Y2, Dorado P 3, Martinez I4, Alvarez M4; Herrera Sección de Farmacología. Facultad de Ciencias Médicas. Universidad Nacional 5 4 2 2 1 4 Autónoma de Nicaragua- León, Nicaragua. J , Hernandez C , Garrido B , Rodriguez JC , Hernandez I , Perez B , Delgado R2, Llerena A.3
1Departamento de Farmacología, Centro de Bioproductos Marinos, Loma 37, Introducción: Las reacciones de oxidación, reducción o hidrólisis Nuevo Vedado, Plaza de la Revolución, La Habana, Cuba. E-mail: convierten a los medicamentos en metabolitos más hidrosolubles y, [email protected] 2 por tanto, más fáciles de eliminar. Estas reacciones se catalizan por las Centro de Investigación y Desarrollo de Medicamentos, Ave 26, No. 1605 Boyeros y Puentes Grandes, La Habana, Cuba. oxigenasas de función mixta, cuyo sistema más importante es el 3Centro de Investigaciones Clínicas, CICAB, Universidad de Extremadura, citocromo P-450 (CYP). El polimorfismo genético de este sistema es Badajoz, España. uno de los mayores determinantes de la variabilidad interindividual e 4Facultad de Ciencias Médicas, Universidad de la Habana, MINSAP, La Habana, interétnica de la farmacocinética y de la respuesta a los medicamentos. Cuba. De tal forma, pacientes que reciben dosis seguras y eficaces para la 5Universidad de la Habana, Zapata y G, Vedado, La Habana, Cuba. mayoría de lapoblación pueden producir respuestas anormales, como la presentación de efectos secundarios en metabolizadores lentos (ML) o fracasos terapéuticos enmetabolizadores rápidos (MR) o Polymorphic cytochrome P450 isoenzymes (CYPs) 2C9, 2C19 and 2D6 ultrarrápidos (UR). Existen más de 100 isoenzimas del del sistema P- metabolize many drugs. This polymorphism gives rise to 450. Las más relevantes para el metabolismo de los medicamentos interindividual and interethnic variability in the metabolism and incluyen CYP1A2, CYP2C9, CYP2C19, CYP2D6 Y, CYP3A4.El CYP2D6 disposition of therapeutic agents and may cause differences in their presenta una alta variabilidad fenotípica debida al polimorfismo clinical response. On the other hands, besides, it is postulated that genético. Esta variabilidad parece depender de la diferente tasa de ABCB1 polymorphisms contribute to variability in P-gp function. presentación de los alelos del CYP2D6. Entre los alelos más Single-nucleotide polymorphisms (SNPs) in MDR1 gene are associated importantes con ausencia total de actividad metabólica se encuentran with phenotypic variation in P-gp expression levels of tissue. The CYP2D6*3, CYP2D6*4, CYP2D6*5, CYP2D6*6; los CYP2D6*10 y wobble C3435T polymorphism at exon 26 has been associated with CYP2D6*17 muestran disminución de la actividad enzimática. La different expression levels and activity. Differences in allele frequency frecuencia de individuos portadores de determinadas variantes of the C3435T polymorphism have been demonstrated between ethnic genéticas presenta diferencias dependiendo de la raza y la procedencia groups. geografía, lo que podría explicar la variabilidad interétnica de la eficacia a distintos medicamentos observada entre distintos grupos Frequencies for the major CYP2C9, CYP2C19 and CYP2D6 mutated étnicos. alleles and genotypes were evaluated in 140 Cuban unrelated healthy volunteers (73 males and 67 females). Genotyping was performed on Objetivos: Determinar el polimorfismo metabólico de la hidroxilación peripheral leukocytes DNA by PCR-RFLP method. Genotype de la debrisoquina (marcador de la capacidad metabólica de CYP2D6) frequencies were in Hardy–Weinberg equilibrium. Results showed: en la población nicaragüense determinando la frecuencia de fenotipos 101 subjects (72.1%) expressed CYP2C9*1/*1, 22 (15.7%) expressed metabólicosy, la frecuencia de alelos CP2D6. CYP2C9*1/*2 genotypic and 3 (2.1%) presented the mutated allele CYP2C9*2/*2 (poor metabolisers). The rest were heterozygous for Pacientes y método: La capacidad metabólica del CYP2D6 se CYP2C9*1/*3 (8.6%), no CYP2C9*3/*3 was found. For CYP2C19, 137 determinó a partir del cálculo del índice metabólico (IM) en orina volunteers expressed the CYP2C19*1 (75% homozygous and 22.3% colectada 8 horas después de ingerido 10 mg oral de sulfato de heterozygous), two subjects were homozygous for CYP2C19*2/*2 debrisoquina en 133 voluntarios sanos. El genotipo CYP2D6 fue (2.1%) (poor metabolisers), no CYP2C19*3 was detected. Genotypes analizado por técnicas de PCR y PCR-RFPL para los CYP2D6 more represented for CYP2D6 were: *1/*1 (59.3%), CYP2D6*1/*10 *3,*4,*5,*6,*10,*17 y duplicación de alelos en 98 individuos. (20.7%) and CYP2D6*1/*17 (10.7%). CYP2D6 *10/*10 and Resultados: La frecuencia de metabolizadores lentos fue de 6%. CYP2D6*17/*17 were found in three volunteers (1.4 and 2.1% Proporción comparable a las observadas en españoles y cubanos. La respectively, poor metabolisers). Frequency of apparition of CYP2D6*3 frecuencia de UR fue de cero. En el 4,1% se determinó la presencia de was low, one subject expressed *1/*3 and other *3/*10. Frequencies of CYP2D6 con ausencia total de actividad metabólica. El CYP2D6*17 no the variant C3435T were evaluated in 140 Cuban unrelated healthy fue detectado, sin embargo el CYP2D6*10 se identificó en el 3,1%. En el volunteers (73 males and 67 females). Results showed: 65 subjects 2% se determinó la presencia de alelos de duplicación/multiplicación (46.4%) expressed CC, 58 (41.4%) expressed CT variant and 17 CYP2D6*1xN o 2xN. El alelo CYP2D6*4 con ausencia total de actividad (12.1%) presented the TT variant. Results fit to Cuban population metabólica es el más frecuente y se cuantificó en el 14,4% de los origins. individuos. Frequencies of the allelic variants of these systems in Cubans were Conclusión: No se identificaron UR y la frecuencia de metabolizadores similar to those of Spanish and Africans; a high frequency of lentos en la población nicaragüense es similar a las encontradas en CYP2D6*17 highly present in Africans but not in Caucasians. For otras poblaciones como la española y la cubana. El alelo no funcional CYP2C9 and CYP2C19, the allelic distribution was similar to más frecuente es CYP2D6*4. No se detectaron alelos CYP2D6*17. Caucasians, especially CYP2C9*3 were not found in the frequencies reported in Spanish or Africans. Results fit to Cuban population origins. The study of interactions and of genetic factors affecting pharmacokinetics and pharmacodynamics is expected to improve drug safety and will enable individualized drug therapy.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S74
LATINFARMA 2013 Resúmenes/Abstracts
CO 130: FROM PHARMACOGENETICS TO PERSONALIZED CO 131: PHARMACOGENETICS LEARNING IN MEDICAL MEDICINE: A CUBAN REGULATORY PERSPECTIVE STUDENTS USING ICTs AND PBL METHODOLOGY: AN ACTION RESEARCH STUDY IN A PUBLIC UNIVERSITY. LIMA- Remirez D. PERÚ National Centre for State Quality Control of Drugs (CECMED), Ave. 17 and 200 , Siboney, Playa, Havana, Cuba. E-mail: [email protected] Placencia M, Núñez M, Humberto G, Tenorio L, Simon S, Silva J. Facultad de Medicina de San Fernando, Universidad Nacional Mayor de San Marcos. E-mail: [email protected] The science of pharmacogenomics has advanced significantly in the last five years, but it is still in infancy and is mostly used on research basis. The Pharmacogenomics helps identify interindividual Introduction: Nowadays the understanding of pharmacogenetics is variabilities in drug response (both toxicity and effectiveness). This vital to achieve a personalized prescription and prevent treatment information will make it possible to individualize therapy with the failure but to conceptualize and analyze their basis and methodology, intent of maximizing effectiveness and minimizing risk. The aims of laboratories and latest equipment are required; that our School can't this work are to present the bases of pharmacogenetic, the advantage afford. To address this problem, we innovated this learning applying: and challenges of this specialty, the main enzymes characterized for "problem-based learning" (PBL) and "Information and communication the genetic polymorphism and the world and Cuban regulatory technologies" (ICTs) to achieve high levels of academic performance. perspective about this subject. We will show the main biomarkers for pharmacogenetics studies and a general guidance for submission of Material and methods: Action research study, which examined the this type of research. The hope for the future is that through implementation of PBL-ITC in the education of pharmacogenetics in personalized medicine, doctors and patients will be able to make third-year students at the Major National University of San Marcos, better-informed choices about treatment. This treatment will avoid the School of Medicine in 2011 (n=134) and 2013 (n=8). In 2011 we adverse drug reaction to the medication and will improve the diagnosis developed a Learning Guide with case-problems, bibliographic diseases as well as the prevention and treatment of diseases. resources, tasks and a matrix of skills assessment in PBL using Bloom scale with a score of 1-10 points. Prior to the class, we shared in our virtual classroom the Learning Guide and two cases about "CYP2C9/VKORC1 Genotypes and Warfarin Dosing". The tasks were delivered via internet for grading. The on-campus class sought to consolidate previous knowledge and link new knowledge through analysis and development of cases. In 2013 we developed a pilot with 8 students to implement this methodology in the field of HIV. After the course, there was a virtual competition where, by PBL methodology, the students solved 3 cases of pharmacogenetics applied to HIV. Results: 130 students (96.3%) achieved higher levels of learning: 13 students the level of analysis, 95 students the level of synthesis, 10 students the level of assessment and 12 students the level of creating Information. In total we obtained an average of 8.1 ± 0.162. Conclusions: The innovations of the lecture of pharmacogenetics with ABP and ICTs have a significant effect on achieving a higher level of learning, which implies the need to continue and expand this methodology in other fields.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S75
LATINFARMA 2013 Resúmenes/Abstracts
CO 132: PHARMACOEPIDEMIOLOGY AND PHARMACO- PL 013: THE ROLE OF ENVIRONMENT AND EPIGENETIC IN GENETICS OF SCHIZOPHRENY HYPERTENSION Fariñas H, Cáceres M, Moyano P, Sánchez T, de la Rubia A, Llerena A. Lopez-Jaramillo P.
Universidad de Extremadura. Badajoz. España. Clinica de Síndrome Metabólico, Prediabetes y Diabetes, Fundación Oftalmológica de Santander-FOSCAL, Torre Milton Salazar, Primer Piso, Calle 155 A No 23-09, Urbanizacion El Bosque, Floridablanca, Santander, Colombia. Email: [email protected], [email protected] Los antipsicóticos atípicos han cambiado las perspectivas evolutivas y de pronóstico de los pacientes con esquizofrenia. Los antipsicóticos de nueva generación son más eficaces que los de primera generación en la prevención de recaídas, ya que presentan un menor número de High blood pressure (BP) is the main cause of cardiovascular diseases reacciones adversas y mejoran la adherencia al tratamiento. Sin (CVD) and deaths globally. The importance of BP as a modifiable risk embargo, existe una gran controversia sobre la relación coste-eficacia factor for CVD is well recognized and many effective and inexpensive de estos nuevos fármacos en relación a su alto coste, así como los BP-lowering treatments are commonly available. However, the efectos adversos metabólicos. awareness, treatment and control of hypertension are low in all countries, despite hypertension being easily detectable. This suggests En estudios anteriores de nuestro grupo observamos una tendencia a the need for a clearer understanding of the factors that are decisive the la disminución del uso de fármacos antipsicóticos típicos y un aumento increase of BP. In the present review we discuss the importance of the de los atípicos. Además, la pauta mayormente utilizada es la de environment in the development of hypertension and the role playing politerapia, la cual se asocia a estancias mayores. by epigenetic mechanism. The increase in the incidence of hypertension in low and middle income countries may be associated with rapidly Se analizó la influencia de las diferentes pautas de tratamiento changing environmental conditions and could be the result of the (mono/politerapia, antipsicóticos típicos/atípicos) en los costes discrepancy between the nutritional environmental during fetal and directos del tratamiento hospitalario de la esquizofrenia (estancias, early life and the adult environment. This discrepancy causes a fármacos, pruebas diagnósticas) durante el periodo 2001-2009 en la mismatch between the fetal programming of the subject and the adult provincia de Badajoz, Extremadura. Asimismo se evaluó la influencia circumstances created by the imposition of new life styles. The conflict de los polimorfismos genéticos CYP2D6 en las pautas de tratamiento y between the earlier programming and the later presence of abdominal en los costes del tratamiento hospitalario de la esquizofrenia. obesity may have produced a higher sensitivity of this population to La estancia promedio aumentó de 20 a 32 días en el periodo evaluado. develop a state of low- degree inflammation, insulin resistance and, Los pacientes en politerapia tuvieron una estancia promedio 8 días consequently, an epidemic of hypertension, diabetes and CVD. mayor que los pacientes en monoterapia. Los pacientes tratados con Interactions between Angiotensin II and leptin/adiponectin imbalance antipsicóticos atípicos estuvieron ingresados 7 días más que los seem to play a key role in the metabolic alterations present in tratados con antipsicóticos típicos. Consecuentemente, la menor abdominal obesity and in the increased risk of developing estancia promedio en los pacientes en monoterapia condujo a un coste hypertension. Our proposal is that visceral adipocytes of people inferior en los pacientes con esta pauta de tratamiento en relación con experiencing the rapid environmental changes are overexpressing or los que estuvieron en politerapia de antipsicóticos. De igual forma, la silencing, by an epigenetic mechanism, the genes that regulate the mayor estancia promedio en los pacientes tratados con antipsicóticos synthesis of angiotensin II, leptin and adiponectin. The relative roles atípicos y el alto precio de estos fármacos, produjo un muy superior played by genetic and environmental factors and the interaction coste en el tratamiento hospitalario en comparación con los tratados between the two are still subjects of great debate and merit further con antipsicóticos típicos. research. Los antipsicóticos presentan una gran variabilidad interindividual en la respuesta. Diversas razones pueden ocasionar esta variabilidad, una de ellas son los cambios en los niveles plasmáticos de estos fármacos debido a la existencia de polimorfismos genéticos en su metabolismo. En el trabajo se discute la relevancia de los polimorfismos metabólicos (principalmente CYP2D6) para la variabilidad y costes del tratamiento de la esquizofrenia.
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LATINFARMA 2013 Resúmenes/Abstracts
JUEVES, OCTUBRE 24 / THURSDAY, OCTOBER 24th SESIÓN PLENARIA / PLENARY SESSION
PL 007: SEPSIS, INFLAMMATION AND CELL RESPONSE Etiopatogenia: No hay una causa definida (por lo que se habla de origen multifactorial). Entre los posibles desencadenantes: Salomao R. - Estrés físico o emocional. Respuesta anómala del eje hipotálamo- Laboratório de Imunologia Universidade Federal de São Paulo/Escola Paulista de hipófisis-suprarrenal. Medicina. Rua Pedro de Toledo, 781 - 15º andar - Vila Clementino. São Paulo, Brasil. E-mail: [email protected] - Alteración umbral del dolor (neurotrasmisores) - Agentes dietarios (conservantes, saborizantes) Since the definition of systemic inflammatory response - Alteraciones del sueño (fase IV no REM) syndrome/sepsis was originally proposed, a large amount of new information has been generated showing a much more complex - Trastornos inmunológicos (¿Virus?) scenario of inflammatory and counter inflammatory responses during - Alteraciones mitocondriales (cadena respirat) sepsis. Moreover, some fundamental mechanisms of sensing and destroying invading microorganisms have been uncovered, which - Anticuerpos (Ig) que agreden canales de K+ (relacionado con vías de include the discovery of TLR4 as the lipopolysaccharide (LPS) gene, hipersensibilidad) implications of innate immune cells as drivers of the adaptive response to infection, and the modulation of multiple accessory molecules that - Alteraciones en canales de calcio. stimulate or inhibit monocyte/macrophage and lymphocyte Patologías Vinculantes: Suelen aparecer: dolor crónico del cuello o la interactions. The complexity of the infection/injury-induced immune espalda, síndrome de fatiga crónica, colon irritable, depresión, response could be better appreciated with the application of genomics hipotiroidismo, enfermedad de Lyme, trastornos del sueño. and proteomics studies, and LPS was a useful tool in many of these studies. In this review, we discuss aspects of bacterial recognition and Clínica: El síntoma principal es el dolor intenso, profundo, punzante y induced cellular activation during sepsis. Because of the relevance of urente. Existen puntos de sensibilidad situados en el tejido blando de endotoxin (LPS) research in the field, we focus on LPS and host la parte posterior de cuello, hombros, tórax, región lumbar, cadera, interactions as a clue to understand microorganisms sensing and cell codos y rodillas. El dolor se irradia desde estas áreas. Las signaling, then we discuss how this response is modulated in septic articulaciones no se afectan, a pesar que pareciera el dolor originarse patients. en ellas. Suele haber dolor y rigidez desde la mañana. Algunos pacientes mejoran durante el día y empeoran de noche. Otros
presentan dolor todo el día. El dolor puede empeorar con la actividad, PL 008: OLD REMEDIES FOR NEW AILMENTS - PRESENT el frío, la humedad, la ansiedad y el estrés. TIME OF THE PHYTOMEDICINES (Enlarge abstract) Criterios Diagnósticos: Por lo menos 3 meses de dolor generalizado, además de dolor y sensibilidad en por lo menos 11 de las 18 áreas, Alonso J. señaladas (ver esquema superior). Los exámenes de orina y sangre Presidente de la Asociación Argentina de Fitoterapia; Buenos Aires, Argentina. suelen ser normales. No obstante pueden ser de utilidad para descartar otras patologías con síntomas similares. Ciertos trastornos diferentes a la fibromialgia, como el Síndrome de Fatiga Crónica, se pueden Algunas preguntas que nos hacemos los profesionales de la salud son presentar de forma simultánea. De hecho, los trastornos interactúan las siguientes: con frecuencia y pueden ser parte de una sola enfermedad general. Si la expectativa de vida es mayor que hace 50 años atrás. ¿Por qué Tratamiento Psicológico: El abordaje psicológico no debe faltar en enfermamos con más facilidad? Los nuevos fármacos ¿mejoraron ningún paciente. La terapia cognitiva conductista es una parte realmente nuestra calidad de vida? Las normas sobre calidad y control importante del tratamiento. Esta terapia le ayuda al paciente a de alimentos ¿se cumplen a ciencia cierta? ¿Vivimos realmente en paz y aprender a: armonía? ¿Hay enfermedades que tienen un común denominador ?. • Manejar pensamientos negativos. En los últimos 20 años han resurgido con mucha fuerza una • Llevar un diario de su dolor y síntomas determinada cantidad de enfermedades que en tiempos no tan lejanos tenían un débil impacto estadístico. Entre estas enfermedades nos • Reconocer qué empeora los síntomas. vamos a referir fundamentalmentalmente a tres: Fibromialgia, Sdre. de Fatiga Crónica y Sdre. de Colon Irritable. Trabajaremos en la hipótesis • Buscar actividades agradables. sobre la posibilidad de existencia de un común denominador entre • Establecer los propios límites de actividad. cada una de ellas. Tratamiento del dolor: Los analgésicos demostraron ser más eficaces FIBROMIALGIA que los AINE en el tratamiento del dolor en la fibromialgia. El tramadol Es un síndrome caracterizado por dolor prolongado en puntos y el paracetamol o ibuprofeno forman parte del esquema analgésico determinados del cuerpo, con una mayor sensibilidad en las convencional. Los corticoides están contraindicados por su acción articulaciones, los músculos, los tendones y otros tejidos blandos. miopática y por reducción del umbral del dolor. En el tratamiento Afecta mayormente a tejidos blandos del cuerpo, y a diferencia de la farmacológico, los antidepresivos tricíclicos -en especial amitriptilina- artritis, no produce dolor ni inflamación de las articulaciones. asociados a un relajante muscular de acción central, como la ciclobenzaprina, han sido los fármacos que han obtenido algunos
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LATINFARMA 2013 Resúmenes/Abstracts
resultados auspiciosos en el tratamiento de la fibromialgia. Se como el aspartamo, las infecciones dentales crónicas ocultas en analizarán en esta conferencia los efectos terapéuticos y colaterales de endodoncias y en los huesos maxilares, etc. duloxetina, pregabalina, milnaciprán, entre otros, de muy vasto empleo. Causas infecciosas: Son varios los agentes que se ha intentado vincular, destacando: Virus de Epstein-Barr, Candida albicans, Cytomegalovirus, Tratamiento Fitoterápico y Orthomolecular: Los factores dietarios Toxoplasma gondii (Toxoplasmosis), Herpesvirus tipo 6 y 7, pueden constituir un factor incidental. Por ej. el glutamato monosódico Parvovirus B19, Chlamydia, Mycoplasma, Hepatitis B y C, Borrelia como saborizante incorporado a infinidad de alimentos. Por otra parte burgdorferi (Enfermedad de Lyme - generada por picaduras de se han observado descensos significativos en las concentraciones garrapata), Brucelosis humana (enfermedad de Bang) y Sífilis venérea. plasmáticas de los aminoácidos: taurina, alanina, tirosina, valina, methionina, fenilalanina, y treonina en pacientes con fibromialgia. En la Prevalencia: Afecta a alrededor de un 0,5% de la población mundial. El conferencia se darán las bases científicas sobre la aplicación e grupo más afectado es el de las mujeres (9 mujeres por cada hombre). incorporación de capsaicina, coenzima Q-10, S-adenosil-Metionina, L- Aunque no se considera una enfermedad grave o mortal, es probable Carnitina, Hipérico, Adaptógenos, algunos trabajos con Homeopatía y que exista un número elevado de decesos debidos a ella, ya que las técnicas corporales como el Qi gong, Meditación, Tai Chi Chuan y causas de la muerte de estos enfermos suelen estar ligadas a fallo Balneoterapia. cardíaco, cáncer o suicidio, por lo que es difícil reconocerlas en su origen. SDRE. DE FATIGA CRÓNICA Tratamiento Convencional: Carece de un tratamiento único También conocido como encefalopatía o encefalomielitis miálgica es consensuado. Se manejan antidepresivos, pero con resultados muy una enfermedad neurológica grave y aparece en la lista americana de dispares y contradictorios. No se puede trabajar con ATB, sin saber enfermedades infecciosas nuevas, recurrentes y resistentes a los siquiera si hay algún germen responsable (especialmente si se trata de medicamentos. Puede afectar de manera progresiva al sistema virus). La Psicoterapia es fundamental. inmunitario, el neurológico el cardiovascular y el endócrino. En España es causa de invalidez laboral. Tratamiento Fitoterápico: Se darán a conocer los trabajos científicos relacionados con drogas inmunomoduladoras tales como Cuadro Clínico: Fatiga severa, febrícula o fiebre, sueño no reparador, Eleutherococo o Ginseng siberiano (genera inhibición del virus de intolerancia a la luz, sonido y cambios de temperatura, dolor muscular Epstein Barr), Equinácea (tiene actividad antiviral amplia), Pau d’arc y en las articulaciones, hipersensibilidad (incluyendo factores (Tabebuia avellanedae - es activo frente a hongos), Panax ginseng ambientales), sensación de estado gripal permanente, faringitis (adaptógeno para el manejo del estrés, energizante), Hongos crónica, pérdida sustancial de concentración y memoria, Medicinales (shiitake, maitake, etc), Cúrcuma (efecto AINE, desorientación especial, intolerancia al estrés emocional y a la Hepatoprotector), Hipérico (en el manejo del humor depresivo) y actividad física conceptos inherentes a la dieta. Muchas veces se presenta como un Síndrome de Intolerancia Química COLON IRRITABLE Múltiple ya que al individuo le afectan: vapores químicos y tóxicos como gasolina, detergentes, colorantes, desodorantes y perfumes. Se trata de una alteración funcional de la motilidad del tubo digestivo, También le afectan las luces brillantes, la presencia de computadoras con especial participación del colon. En su incidencia, afecta (pantallas), televisores, los campos electromagnéticos, medicamentos principalmente a mujeres (60-70%), mayores a 20-30 años de edad, (especialmente los que afectan el sistema nervioso central). disminuyendo la incidencia después de los 60 años. A nivel mundial afecta a 5 de cada 1.000 personas, representando en algunos países Etiopatogenia: Se desconoce al momento la causa de la enfermedad. En hasta el 25% de las consultas digestivas. Octubre de 2009 un norteamericano comunicó la posibilidad de que un retrovirus denominado XMRV fuera el agente desencadenante. Clínica: Malestar abdominal, dyspepsia, dolor postprandial, alivia defecación, espasmos – flatulencias, náuseas, vómitos, alteración del Científicos ingleses desestimaron esta teoría al no hallar el virus en sus ritmo evacuatorio, mayor tendencia a la constipación, palpitaciones, pacientes, no obstante EE.UU replicó que los ingleses no contaban con lumbalgia, dismenorrea, alteraciones emocionales. los reactivos adecuados para su detección. Hace veinte años se la llamó "la gripe del yuppie", pues se pensó que afectaba especialmente a Factores incidentes: Las dietas pobre en fibras suelen ser un factor muy jóvenes profesionales urbanos que sufrían de agotamiento por estrés. importante. También el abuso de laxantes y antibióticos, el estrés Posteriormente se pensó que se trataba de una infección crónica del emocional, alteraciones hormonales, sedentarismo, etc. virus de Epstein-Barr, causante de la llamada mononucleosis infecciosa Esfera emocional: Predominan las tendencias obsesivo-compulsivas, o "enfermedad del beso”. Más tarde se propuso un sobrecrecimiento agresividad, tendencia a la depresión e incluso histeria (ocasional). intestinal del hongo Candida albicans fruto del estilo de vida estresante, exceso de hidratos de carbono de absorción rápida en las Tratamiento: Se analizará cómo incide la merma en serotonina en comidas, o por el exceso de consumo de antibióticos y corticoides intestino, la dieta, los tratamientos con anticolinérgicos, y antidepresivos. El tratamiento fitoterápico abarcará el empleo del Agentes Incidentales: Pesticidas, agroquímicos, insecticidas aceite esencial de Mentha x piperita (yerba buena), el empleo oral de organofosforados, disolventes y monóxido de carbono serían los infusiones o cápsulas de psyllum o ispagul (Plantago ovata) y el uso de agentes tóxico-ambientales más señalados. También cabe mencionar al probióticos. mercurio (aguas, amalgamas dentales y vacunas), la radiación electromagnética ambiental, en especial a partir del desarrollo de la telefonía móvil y las antenas de repetición; los edulcorantes artificiales
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LATINFARMA 2013 Resúmenes/Abstracts
SIMPOSIOS Y TALLERES / SYMPOSIA AND WORKSHOPS CONFERENCIAS Y COMUNICACIONES ORALES / CONFERENCES AND ORAL COMMUNICATIONS Taller Inmunofarmacología y Biotecnología. Sesión: Vacunas de Tuberculosis / Workshop on Immunopharmacology and Biotechnology. Session: Tuberculosis vaccines
C 027: ANCIENT DNA STUDIES BRING NEW LIGHT ON THE C 028: DEVELOPMENT OF EXPERIMENTAL STRATEGIES FOR EPIDEMIOLOGY OF TUBERCULOSIS THE PROPHYLAXIS AND TREATMENT OF TUBERCULOSIS
Bercovier H. Acosta A1, Kadir R2, Ahmad F2, Puig A1, Borrero R1, Garcia MA1, Rodriguez L1, Camacho F1, Reyes F1, Aguilar A1, Otero O1, Rubio P1, Department of Microbiology and Molecular Genetics, The Faculty of Medicine, Marron R1, Tirado Y1, Reyes F1, Alvarez N1, Infante JF1, Fernandez S1, Hebrew University of Jerusalem, Israel. Zayas C1, Lanio ME3, Acevedo R1, Mohd Nor N2, Perez Quiñoy JL1, Sarmiento ME.1 Tuberculosis (TB) was highly active much before the Industrial 1Instituto Finlay, La Habana, Cuba. E-mail: [email protected] Revolution as proven by the documented presence of Mycobacterium 2Universiti Sains Malaysia, Malaysia. 3 tuberculosis in a North American Bison, 20.000 years ago, in Egyptian Faculty of Biology , University of Havana, Cuba. mommies, in human skeletons dating from the Middle-Age and up to the 17th Century in Western Europe. By the study of ancient DNA, we can retrace in Western Europe the emergence of TB that seems to reach Tuberculosis remains as one of the main causes of morbidity and its peak in the 18th Century and has declined since, especially in the mortality due to infectious diseases. The current situation of the 20th Century. In the late Middle age, the end of the epidemics of Leprosy disease is characterized by an elevated morbidity and mortality, the could already indicate the importance of the diffusion of TB in the low sensitivity of the diagnostic methods, the relative low therapeutic population; TB indeed may have conferred cross protection as it has coverage, the growing appearance of multidrug resistant strains and been shown for BCG. Study of ancient DNA in skeletons originating the low efficacy of BCG in the prevention of adult pulmonary from well characterized cemeteries showed that close to 25% of the tuberculosis and the transmission of the disease. Taking into population was infected by M. tuberculosis at the end of the Middle Age. consideration these antecedents, the development of new prophylactic, In addition, the social impact of TB was such that from the13th to the diagnostic and therapeutic strategies are of the maximal priority 18th Century French and English Queens and Kings inherited the divine internationally. Here we present our results in two main areas: The royal touch that cured Scrofula (TB lymphadenitis). In the 17th Century, study of role of specific antibodies in the protection against in the British registries, 20% of the recorded deaths were due to mycobacteria, where different formulations of antibodies were Consumption or Phthisis. In the 18th Century, in the city of Bristol evaluated in models of tuberculosis in mice. The administration of between 1790 and 1796 close to 50% of the recorded death were due monoclonal IgA antibodies against Hspx antigen of M. tuberculosis by Tuberculosis. This percentage drops to 25% at the beginning of the 19th the mucosal route demonstrated a protective effect. M. tuberculosis Century (the peak of the Industrial Revolution) and to 14% at the end preincubated with the same antibody decreased its infective capacity. of the19th Century. TB mortality decreased by half in adults in England In order to explore the potential for protection of human antibodies in between 1851 and 1890 indicating the beginning of the end of the the same model, human IgG formulations administered by the epidemics. It seems that the burst of the epidemics of TB was linked in intranasal route protects mice from infection. The same effect was Europe more with the development of commercial exchanges on a large obtained when M. tuberculosis was administered to mice after pre- scale and the development of cities and workshops rather than with the incubation with the human antibody formulation. Secretory human IgA Industrial Revolution. The food alimentary situation and the movement purified from colostrums showed similar behavior than the previous of population seem to have been additive factors for that burst. This formulations when evaluated in the same animal model. In another scenario could help us to predict what may happen in developing strategy, using the phage display technology, ligands specific for M. countries and what must be done to prevent a new burst of tuberculosis infected cells where developed. The results obtained with Tuberculosis. the different antibody formulations demonstrated the protective capacity of the specific antibody response against M. tuberculosis and support the application of these findings to the development of new vaccines and therapeutic tools against tuberculosis. Another area of interest is the evaluation of proteoliposomes and liposomes obtained from non pathogenic mycobacteria which where immunogenic and protective in mice.
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LATINFARMA 2013 Resúmenes/Abstracts
CO 134: IMMUNOLOGICAL EVALUATION OF A M. tuberculosis and the history of use of proteoliposomes in vaccine PROTEOLIPOSOME DERIVATE FROM Mycobacterium bovis formulations, we developed an immunological evaluation of PLBCG as BCG AS A POTENTIAL VACCINE CANDIDATE AGAINST a potential vaccine candidate against tuberculosis. TUBERCULOSIS Material and methods: PLBCG was obtained using sodium deoxycholate. The PL was characterized and evaluated its antigenicity Alvarez N, Serpa D, Tirado Y, Fernández S, Puig A, Barroso A, Cabrera and immunogenicity. R, Valdés Y, Izquierdo L, Sarmiento ME, Norazmi MN, Pérez JL, Acosta A. Results: The antigenicity of the PL was demonstrated in humans with long-standing exposure to the bacillus (with positive or negative Basic Research Sub-direction. Vice-presidency of Research-Development. Finlay Institute. Havana, Cuba. E-mail: [email protected] response to the tuberculin test) and in patients with active pulmonary tuberculosis. Additionally, it was demonstrated the humoral and cellular immunogenicity of PLBCG in mice, being this response potentiated by aluminum hydroxide. Also was observed the induction Introduction: Despite efforts to eradicate tuberculosis (TB) of cross-reactive responses against antigens of M. tuberculosis and M. worldwide, it remains a serious health problem. Bacillus Calmettte- smegmatis. Guérin (BCG), the only available vaccine against tuberculosis, has a questionable efficacy against pulmonary TB and only gives consistent Conclusions: PLBCG is antigenic in humans exposed to M. tuberculosis protection against severe forms of the disease in childhood. The and immunogenic in Balb/c mice, eliciting cross-reactive response research spectrum of new vaccine candidates against TB includes against M. tuberculosis. The evaluation of the protective capability in subunit vaccines, desoxirribonucleic acid (DNA) vaccines, recombinant challenge experiment in mice with M. tuberculosis showed that BCG, modified live M. smegmatis and attenuated M. tuberculosis, among immunization with PL-Al alone or as a booster to BCG induced others. Considering the antigenic similarities between M. bovis BCG and appropriate protection against challenge with M. tuberculosis.
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LATINFARMA 2013 Resúmenes/Abstracts
Taller Inmunofarmacología y Biotecnología. Sesión: Preclínica y Control de Calidad de Vacunas / Workshop on Immunopharmacology and Biotechnology. Session: Preclinical Studies and Quality Control of Vaccines
CO 136: 3RS FOR VACCINES: OPPORTUNITIES AND HURDLES CO 138: DEVELOPMENT OF ALTERNATIVE METHODS FOR QUALITY CONTROL ON IMMUNOBIOLOGICAL PRODUCTS: Hendriksen C. EXPERIENCE OF NATIONAL INSTITUTE OF QUALITY Institute for Translational Vaccinology (Intravacc), Bilthoven, The Netherlands & CONTROL IN HEALTH, BRAZIL Utrecht University, Faculty of Veterinary Medicine, Utrecht, The Netherlands. E- mail: [email protected] Chaves Leal E, Fernandes Delgado I.
National Institute of Quality Control in Health (INCQS) - Oswaldo Cruz Foundation (Fiocruz) – Av. Brasil, 4365 – Manguinhos - Rio de Janeiro - Brazil. A new directive for the protection of animals used for scientific www.incqs.fiocruz.br - E-mail: [email protected] purposes was adopted by the European Parliament and Council of Ministers on September 22, 2010. This directive (Directive 2010/63/EU) came info force in national legislation of all 28 EU The National Institute of Quality Control in Health (INCQS) is the Member States byJanuary 1, 2013. By doing so, Europe got one of the Brazilian Reference Laboratory which handles the quality control of most stringent regulations on laboratory animal use in the world. I will food, drugs, biological products, health-related and dialysis items, explain what it is that makes the European directive so unique. higienizing and desinfectant agents, diagnostic kits, cosmetics, blood The new directive reflects the current policy in Europe to replace, and blood derivatives, environments and services. As pre-qualified by reduce and refine (the 3Rs) the use of laboratory animals; for reasons World Health Organization (WHO), our institute is responsible for the of animal welfare, but also because it is strongly believed that analyses and approval for release and distribution of all batches of implementing 3Rs will result in more meaningful and less costly vaccines and sera produced and consumed in Brazil, including bacterial research and testing. and viral vaccines (e.g. diphtheria, tetanus, pertussis - DTP, Haemophilus influenzae - HiB, BCG, pneumococcal, meningococcal, To illustrate the ‘3Rs-friendly’ policy in Europe I will focus on some yellow fever, measles, mumps, rubella, hepatitis, influenza, ongoing activities. One of these is the European Partnership on poliomyelitis, rotavirus, rabies, varicella, among others) and hyper- Alternative Approaches to Animal Testing (EPAA). This is a immune sera (e.g. rabies, diphtheria, tetanus and anti-venom sera). partnership between the European Commission and the European Depending on the nature of the product, each batch is submitted to a industry with the aim to initiate, foster and coordinate 3R activities in battery of assays recommended by Pharmacopoeia. This evaluation the area of regulatory testing. I will provide some in-depth information includes potency testing, identity assay, thermo stability, bacterial and about EPAA’s aims and long range activities. One of EPAA’s main topics fungal sterility assays, residual humidity contents, pyrogen and analysis is vaccines, also the area I’m most familiar with. Currently, several 3R of vaccine/serum production and respective quality control protocols vaccine projects are on-going; on DTaP vaccines, on Rabies vaccines stated by manufactures, among others. INCQS also works to develop, and on Clostridial vaccines. The overall theme of these three projects is adjust and implement new methodologies. In the field of alternative to introduce a new strategy of testing in vaccine lot release; the methods, some new approaches have been investigated, such as: (i.) consistency approach. I will explore the principle of consistency alternatives to diphtheria and tetanus sera potency assays (i.e. toxin testing, discuss the conditions that have to be met; the analytical and in binding inhibition assay, or ToBI), (ii.) alternatives to rabies vaccines vitro models that can be used instead and show how to use the and sera potency evaluation, (iii.) new in vitro systems for hepatitis consistency testing in daily practice. vaccine quality control, and (iv.) alternatives to in vivo pyrogen assay. Additionally, our staff has been working in strait collaboration with Implementing new ideas about animal welfare and 3Rs is not always Brazilian Health Surveillance Agency (Anvisa) in order to consolidate an easy going process. There are many obstacles and hurdles that activities of the newly created Brazilian Center for Validation of might slow it down or even bring it to a halt, such as a lack of Alternative Methods (BraCVAM). By means of this initiative, it is aimed harmonization in test guidelines or tradition in the laboratories. to achieve inter-laboratory validation of alternative methodologies, Currently, we are performing a study on governance aspects of the 3R seeking the regulatory acceptance. acceptance and use in the regulatory framework. I will discuss some of the outcomes of the study. It speaks for itself that the implementation of 3Rs in regulatory testing is in line with the new European Directive. As a bonus however, it is also the best way forward to a system of vaccine quality control which is both humane and scientific sound.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S81
LATINFARMA 2013 Resúmenes/Abstracts
CO 139: EVALUATION OF WHOLE PERTUSSIS VACCINES BY CO 140: EXPERIENCE ON THE DEVELOPMENT OF COMBINING RELEVANT IMMUNOLOGICAL AND BIOMODELS FOR Haemophilus influenzae TYP B BIOLOGICAL ASSAYS AS STRATEGY FOR DETERMINING INFECTION THE ROLE OF TOTAL AND SPECIFIC ANTIBODIES FOR Infante Bourzac JF, Sifontes Rodríguez S. PROTECTION Finlay Institute, P.O. Box 16017, La Lisa, La Habana, Cuba. Chovel ML, Gutiérrez N, Lara M, Mahy T, Herrera L, Valle O, Núñez JF, Mandiarote A.
Finlay Institute, P.O. Box 16017, La Lisa, La Habana, Cuba. E-mail: The epidemiological situation of diseases caused by Haemophilus [email protected] influenzae type b is increasingly dramatic, being considered a global human health problem. There are several animal models to reproduce
different aspects of the clinical forms of Haemophilus influenzae Introduction: Although Mouse Protection Test (MPT) this test has infection, among them: inbred mice, rats and Guinea pigs. The aim of been deeply criticized, it still remains being the “golden standard” for the present work was integrating models established in our Institute to Pertussis Potency in vaccines. Pertussis Serology Potency Test (PSPT) answer several questions regarding the experimental infection by seems to be the most suitable alternative to MPT and a correlation Haemophilus influenzae and exploring their potential usefulness. between both methods has been described. Nonetheless, some issues C57/BL6, CBA/j and Balb/c inbred mice strains; infant (5-7 days old) related to the relevance of the antibodies for protection remain rather Sprague Dawley rats; adult (400-450 grams body weight) Duncan unclear. The present Paper aims to evaluate the relevance of Hartley Guinea pigs and the Eagan strain of Haemophilus influenzae antibodies for protection during PSPT, by combining immunological were used. Infant rats were inoculated by nasal or intraperitoneal and biological tests. routes and mice and Guinea pigs were treated with virulence enhancement substances for Haemophilus influenzae infection. The Material and methods: Several whole cell Pertussis vaccine batches disease was successfully reproduced in the three laboratory animal were tested in parallel by MPT and PSPT. Sera were tested for total and species assayed. However, infant rats were better for studies of specific antibodies (PT, FHA, PRN and FIMB 2 and 3) by whole-cell and bacteremia; inbred mice, for efficacy tests using death rate as endpoint; specific antigen ELISAs, respectively. The complement activating, and Guinea pigs, to study the pathogenesis of the disease. As novel neutralizing and bactericidal capacities were evaluated, as well as the results we demonstrated the efficacy of trypsin as virulence subclasses. The functionality of antibodies produced during PSPT was enhancement agent and the development of Haemophilus influenzae evaluated by using an in vitro opsonophagocytosis assay. All batches infection in Guinea pigs. This system of biomodels could be a valuable were also characterized by a 2D-electrophoresis procedure and by tool for understanding pathogenic aspects of Haemophilus influenzae antigen ELISA using monoclonal antibodies. infection and studying new products against them. Results: MPT and PSPT correlated and were able to discriminate potent and the sub-potent vaccines batches in an equivalent way. Specific antibody responses, neutralizing, complement activating and bactericidal titres showed poor correlations regarding MPT and PSPT titres, but a strong correlation against the opsonophagocytosis assay was obtained. 2-D electrophoresis and antigen ELISAs provided relevant information on the antigen profile of our vaccines with interesting links to the PSPT results. Conclusions: Relevant information obtained from the combination of immunological and biological assays was provided about the relationship between the total antibodies raised by wP component in vaccines and protection, thus supporting the possibility of replacing MPT by PSPT in a near future.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S82
LATINFARMA 2013 Resúmenes/Abstracts
CO 141: REPEATED DOSE TOXICITY STUDY OF THE CO 142: DEVELOPMENT AND VALIDATION OF METHOD FOR MENINGOCOCCAL SEROGROUP AW135 OUTER MEMBRANE QUANTIFICATION MULTIVALENT POLYSACCHARIDES VESICLE VACCINE IN SPRAGUE DAWLEY RATS VACCINES BY CAPILLARY ZONE ELECTROPHORESIS
Oliva R1, Fariñas M1, Infante JF1, Arencibia DF1, Días D1, Naess L2, Merchán Y, Cuello M, Abreu J, Delgado I, Landys M, Mandiarote A. Norheim G2, Tunheim G2, Hernández T1, Pérez V1, Valmaceda T1, Finlay Institute. Quality Control Division. Ave 27 No. 19805. La Coronela. La Lisa. Aranguren Y1, Rosenqvist E2, Pérez Y3, Oryarzabal A3, León AC4, La Habana, Cuba. E-mail: [email protected] Cardoso DT1, García LG1.
1Finlay Institute, P.O. Box 16017, La Lisa, Havana, Cuba. E-mail: [email protected]; [email protected] Introduction: Meningococcal polysaccharides are medically important 2 Norwegian Institute Public Health, Oslo, Norway. antigens and are the active components of vaccine against Neisseria 3National Center for Scientific Research - Natural Product Center, Havana, Cuba. 4National Center for Laboratory Animal Production, Havana, Cuba meningitidis serogroups A, C, and W135. In these polysaccharides vaccines, two components (the polysaccharide C and W135) contain sialic acid in their structure, which difficult its determination by traditional colorimetric methods, so in order to control quality of this Introduction: The outer membrane vesicles vaccine from A and W135 vaccine, was development a capillary zone electrophoresis method. meningococcal serogroups, are the result of scientific collaboration The capillary zone electrophoresis (CZE) has proved to be a sensitive between Finlay Institute and Norwegian Institute of Public Health. tool for quantification of multivalent meningococcal polysaccharides Objective: In order to study the toxicological potential of this vaccine, vaccines. The objective of this work was to develop and validated this we conducted a repeated dose toxicity study. analytical method, in order to show evidences that the test is sufficiently reliable to produce the intended result within the Material and methods: 130 Sprague Dawley rats were used predefined intervals. inoculated by intramuscular route. It was administered 0.2 mL volume of the vaccine in each dose. These were observed daily in search of Material and methods: For this purpose, the following parameters local and systemic symptoms of toxicity during 12 weeks as water and assessed system suitability, accuracy, precision, specificity, linearity food consumption, corporal weight and haematological, biochemical and range. We assembled the method to allowing the quantification and immunological studies. Also was made pathological studies for specific and accurate, using CZE in Capillary Ion Analyzer (Agilent possible adverse effects after immunization with the experimental corp.), with DAD at 200 nm. It employed a fused silica capillary vaccine. uncoated 50 µm (d.i.) and length of 40 cm. The data were gathered and processed with Chemstation software (Agilent Corp.). Results: No toxicity symptoms were observed during the study in the animals, nor differences of the experimental groups in body weight, Results: We obtained the best separation and resolution with BGE- water and food consumption. Pathological changes in toxicological Borate 20 mM – Phosphate 80mM for each polysaccharide. The value, analyzes macroscopic or microscopic, at the inoculation site validated method showed good accuracy, repeatability, linearity and were not observed whilst macrophage of type granulomatous specificity. processes were described. The relative weights of solid organs were Conclusions: The method rated satisfactory to use in the laboratory within historical averages and reported for the species in both sexes taking into account all the parameters validation evaluated, meet the and ages. The animals showed no haematological and biochemical requirements for an electrophoretic method for quantification the alterations in any of the experimental groups. Moreover, the model polysaccharides in vaccines. used demonstrated relevance to have a good response of antibody titers to both serogroups. Conclusion: Under the study conditions and according to established criteria, the vaccine candidate showed no toxicity evidence, in the repeated doses protocol.
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LATINFARMA 2013 Resúmenes/Abstracts
Taller de Farmacología Básica / Workshop on Basic Pharmacology
C 029: NEW PROMISING CANDIDATES FOR DIABETES TYPE CO 143: TRANSIENT MIDDLE CEREBRAL ARTERY 2 TREATMENTS OBTAINED FROM NATURAL SOURCES: OCCLUSION-INDUCED CHANGES ON VASCULAR INHIBITORY EFFECTS ON PTP1B, DPPIV AND GLUCOSE PROPERTIES ARE ABOLISHED BY URIC ACID UPTAKE IN VITRO ASSAYS Onett Yi, Jiménez-Altayó F, Vila E. Marrero Faz E1, Sánchez Calero E1, Young L2 and Departament de Farmacologia, Terapèutica i Toxicologia, Facultat de Medicina, 2 Harvey A. Universitat Autònoma de Barcelona, Barcelona, Spain.
1 Grupo de Desarrollo Biofarmacéutico, Centro Nacional de Sanidad Agropecuaria (CENSA), Mayabeque, Cuba. E-mail: [email protected] Introduction: Oxidative stress is involved in alterations of 2Strathclyde Institute for Biomedical Sciences, Strahclyde University, Scotland, cerebrovascular properties after an episode of ischemia/reperfusion. United Kingdom. The endogenous antioxidant uric acid (UA) protects the rat brain in a model of thromboembolic and transient focal ischemic injury. Nevertheless, the mechanisms whereby UA exerts its beneficial effects The present study is aimed to determine the underlying mechanism of are known. We hypothesized that UA could influence the vessel the antidiabetic efficacy of seven medicinal Cuban plants: Allophylus properties changes due to ischemia/reperfusion. cominia (L.) Sw., Ocimum tenuiflorum, Persea americana, Sechium edule green and white varieties, Momordica charantia and Jatropha Material and methods: Male Sprague-Dawley rats (270-320g) were aethiopica, some of them reported in Cuban ethnomedicine. The anaesthetized with isoflurane (3-2.5%) in O2:N2O (30:70) and aqueous extracts from these plants and their fractions were evaluated subjected to right middle cerebral artery (MCA) occlusion (90 min) and on type 2 diabetes therapeutic targets: protein tyrosine phosphatase 1B reperfusion (24 h). In sham-operated animals occlusion was less than (PTP1B) and dipeptidyl peptidase-IV (DPPIV) enzymatic activities and 1 min. Rats were divided into: sham-vehicle (n=7), ischemic-vehicle glucose uptake, in order to identify the candidate plants that can be (IV, n=18), sham-UA (n=4) and ischemic-UA (IUA, n=9). UA (16 mg/kg used more effectively in treating diabetes. All in vitro assays were in 3 ml Locke’s buffer, i.v.) or vehicle were infused (20 min) at 30 min performed on 96 micro well plates. In PTP1B enzymatic assay (6, 8- reperfusion. Mean arterial blood pressure (MBP), rectal temperature difluoro-4-methylumbelliferyl phosphate) (DiFMUP) was used as and cortical cerebral blood flow was permanently monitored. substrate and as standard inhibitor [Bis(4-Trifluoromethylsulfona- Afterwards (24 h), rats were killed under isoflurane (4%) and the midophenyl)-1,4-diisopropylbenzine] (TFMS); in DPPIV enzymatic ipsilateral MCA was removed and set up in a pressure myograph. assay [Gly-Pro-7-amido-4-methylcoumarin hydrobromide] (Gly-pro- Values are means ± S.E.M., compared by two-way ANOVA or Student’s AMC) was used as substrate and as standard inhibitor [(3N-[(2S, 3S)-2- t-Test. amino-3-methyl-pentanoyl]-1,3-thiazolidine) hemifumarate] (P32/98); Results and conclusions: UA reduced infarct volume (IV: 129.6 ± 23.5 in both assays, the enzymatic activity inhibition was calculated with the mm3, n=18; IUA: 48.9 ± 16.6 mm3, n=9, p<0.01), neurological score (IV: fluorescence values using an excitation wavelength of 360 nm and an 3.4 ± 0.4, n=18; IUA: 2.0 ± 0.3, n=9, p<0.05) and brain oedema (IV: 7.7 ± emission wavelength of 460 nm. Glucose uptake studies were 1.1, n=16; IUA: 2.9 ± 1.4, n=7, p<0.05). Ischemia/reperfusion increased performed on fully differentiated 3T3-L1 adipocytes using 2-deoxy-D- MCA wall thickness (p<0.01), cross-sectional area (p<0.05) and [3H] glucose and insulin as a positive control, the radioactivity wall/lumen ratio (p<0.05) while decreased wall stress (p<0.05) and incorporated into the cells was measured with a microplate stiffness (β value SV: 7.8 ± 0.1, n=5; β value IV: 6.8 ± 0.2, n=17, scintillation counter. The results revealed that only aqueous extracts p<0.001). UA prevented all MCA changes by ischemia/reperfusion. from A cominia, O tenuiflorum and P americana inhibited the enzymatic These results show that UA administered early after the onset of activity of PTP1B in an extract concentration dependent manner, reperfusion prevents MCA structural and mechanical alterations by resulting more active the more polar fractions from A cominia and P ischemia/reperfusion. We suggest that UA might exert beneficial americana extracts and fraction 2 from O tenuiflorum extract. All the actions on ischemic damage through prevention of cerebrovascular extracts and fractions showed only a slight inhibition of enzymatic remodelling. These results reinforce the involvement of the vascular activity of DPPIV, at higher concentrations, A cominia aqueous extract response in brain damage. also inhibited the enzymatic activity of this protease in an extract concentration dependent manner, only fraction 1 from P americana aqueous extract showed a moderate inhibitory effect. A cominia, O tenuiflorum and P americana extracts exhibited a moderate enhance of glucose uptake in 3T3-L1 adipocytes, resulting more active fractions 6 and 10 from A cominia extract and fraction 10 from P americana extract. The present research demonstrated that aqueous extracts from A cominia, P americana and O tenuiflorum and some of its fractions (AcF6, AcF10 and PaF10), are promising candidates for the development of antidiabetic phytopharmaceuticals and for drug discovery issues as well. Further research will be necessary in order to explore new molecular targets related with this metabolic disorder, such as: biomarkers of carbohydrates and lipids metabolism as well as to identify the secondary metabolites responsible of antidiabetic activity.
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LATINFARMA 2013 Resúmenes/Abstracts
CO 144: LACTOFERRIN IN ACTINOMYCETOMA GRAINS CO 145: SURFACEN DOWN-REGULATED THE Staphylococcus aureus-INDUCED TNF-Α AND IL-6 IN MONOCYTES AND NOT Castrillón RL1, Palma RA1, Padilla DC2, Vega ME3, Arenas GR3. AFFECT OXIDATIVE BURST IN VITRO 1Laboratorio de Inmunología. Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana Unidad Xochimilco. México DF. Lugones Y1, Sousa S2, Colo-Brunialti MK2, Blanco O1 and Salomão R.2 2Laboratorio de Micología. Centro Dermatológico "Dr. Ladislao de la Pascua", 1 México. Centro Nacional de Sanidad Agropecuaria CENSA, San José de las Lajas, Mayabeque, Cuba. E-mails: [email protected], [email protected] 3Servicio de Dermatología y Micología. Hospital General “Manuel Gea González”, 2 México Division of Infectious Diseases, Escola Paulista de Medicina, Federal University of Sao Paulo, Brazil.
Introduction: Mycetoma consisting of inflammatory lesions and Surfacen® is a clinical surfactant preparation of porcine origin. In the fistulas involving disfiguring skin tissue, subcutaneous and bone. It present study we have evaluated the behavior of Surfacen in the occurs most frequently on foot and is caused by actinomycetes modulation of oxidative burst in monocytes and neutrophils in whole (actinomycetoma) or true fungi (eumycetoma). In Mexico the most blood and pro-inflammatory cytokines productions in monocytes common are actinomycetomas by 97.9% compared to a 2.1% isolation from blood. The data indicated that Staphylococcus aureus- eumicetomas. Actinomycetoma grain is formed by bacteria and induced reactive oxygen species production was not affected by the polysaccharide autoproduced that amalgamates the microbial cells. concentrations of Surfacen used on whole blood monocytes or These grains are surrounded mainly by polymorphonuclear neutrophils that release their contents including hydrolytic enzymes neutrophil. Pre-incubation of PBMC cells with Surfacen at 125 and and lactoferrin (LF) once they are activated. This molecule has been 500 µg/mL showed a dose-dependent suppression of TNF-α release at shown to have antimicrobial and immunomodulatory activity which 4 hours of exposition of stimuli. Also a dose-dependent suppression of has not described its role in this pathology. The aim of this study was IL-6 release was seen at 4 hours (p ≤ 0.05) while at 24 hours dose- to indentify the presence of LF in actinomycetoma human grains. dependent was not observed. In summary, the present study provides experimental evidence in favor of an anti-inflammatory role of Material and methods: We evaluate eight skin biopsies from patients Surfacen in human monocytes and neutrophils in vitro. These results diagnosed with actinomycetoma and provided by two dermatological may explain, at least in part, the beneficial therapeutic effects of centers. Two samples by these biopsies were used to Haematoxilin- natural porcine surfactant in NRDS and ARDS. Eosin stain and labeling for LF by imunohistochemistry technique. Commercial kits (R&D) were used, the primary antibody was polyclonal IgG anti-human lactoferrin made in goat. The appearance of a brown color in samples is due to the reaction with diaminobenzidine enzyme present in the conjugate (secondary antibody) and determines the presence of lactoferrin in situ when the primary antibody reacts with lactoferrin. Results: Lactoferrin was observed directly attaches to the grains. In the case of actinomycetoma by A. madurae, we found 66.6% at high concentration in the skin biopsies and 33.3% at low concentration. In contrast Actinomycetoma by N. brasiliensis was found at high concentration in 60% of these samples and moderate and lower concentration (20% in each case). Conclusion: Lactoferrin was released into the actinomycetoma grain by neutrophils during the inflammatory process as innate immune resistance mechanism of this disease: The main cytotoxic mechansims associated with LF are iron abducts limiting microbial growth and generating pores directly.
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LATINFARMA 2013 Resúmenes/Abstracts
CO 146: REPETITIVE EXPOSURE OF NORADRENALINE CO 147: MUSCARINIC RECEPTOR SUBTYPE AND CALCIUM INDUCES FACILITATION OF THE RAT TESTICULAR SIGNALLING INVOLVED IN THE CONTRACTIONS INDUCED CAPSULE CONTRACTION THROUGH THE INTERACTION BY ACETYLCHOLINE OR CARBACHOL IN RAT TESTICULAR BETWEEN α1D- AND β-ADRENERGIC RECEPTORS CAPSULE Silva Júnior ED, Souza BP, Rodrigues JQD, Caricati-Neto A, Jurkiewicz Silva Júnior ED, Souza BP, Rodrigues JQD, Caricati-Neto A, Jurkiewicz NH, Jurkiewicz A. NH, Jurkiewicz A.
Federal University of São Paulo. Department of Pharmacology, 04044-020, São Federal University of São Paulo. Department of Pharmacology, 04044-020, São Paulo-SP, Brazil. Paulo-SP, Brazil. E-mail: [email protected] E-mail: [email protected]
Introduction: Noradrenaline is able to promote a sensitization of rat Introduction: The rat testicular capsule (TC) is able to contract in testicular capsule contraction which occurs through successive curves response to cholinergic agonists. However, the muscarinic for this agonist. Therefore, the aim of our study was to evaluate if the acetylcholine receptors (mAChRs) and the calcium (Ca2+) signalling adrenergic receptors (ARs) are involved in this phenomenon. related to the contractions induced by cholinergic drugs are poorly known. Material and methods: The testicular capsule from male Wistar rats, 3-4 months-old, was used in functional experiments. Repetitive Material and methods: The TC from male Wistar rats, 3-4 months-old, cumulative-concentration curves and single concentration exposure was used in functional experiments. In order to characterize the for noradrenaline were performed to obtain the facilitation of RTC mAChRs and cellular signaling by Ca2+ involved in rat TC contraction, contractions. Agonists of α1- (phenylephrine) or β-ARs (isoproterenol) the potency (pD2) of agonists (acetylcholine or carbachol) and 2+ and antagonists of α1-AR subtypes (5-methyl-urapidil, chlorethyl- antagonists (pA2) of mAChR, and effects of Ca cellular transport clonidine and BMY7378), α2-(yohimbine) or β-ARs (propranolol) were blockers were evaluated. also used to check the AR involved in this phenomenon. Results: The potency of acetylcholine (pD2 6.0) were ten-fold higher Results: Repetitive cumulative-concentration curves for noradrenaline than carbachol (pD2 5.0). Contractions induced by acetylcholine or (10-8 – 3.10-3 M) were able to increase the maximum contractile carbachol were antagonized by mAChRs antagonists. The order of response (Emax) without changing the apparent affinity (pD2) for this potency obtained for muscarinic antagonists (pA2) was atropine (8.8 to agonist. Moreover, single concentration exposure for noradrenaline 8.6) > 4-DAMP (8.05 to 8.03) > AF-DX116 (7.5 to 7.2) > pirenzepine -4 (10 M, for 2-3 min) also produced a gradual increase of RTC (6.1 to 6.2), corresponding to a typical profile of M3 mAChR (the slopes contraction. The sensitization of RTC contraction induced by repeated of the Schild plots did not differ from one unit). Contractions induced exposure to single concentration of noradrenaline (10-4 M) was only by acetylcholine or carbachol were inhibited by blockers of Ca2+ influx -5 -7 prevented by the α1D-AR antagonist BMY7378 10 M. The repetitive through voltage-dependent calcium channels (nifedipine 3.10 M and -8 -3 2+ -3 2+ cumulative curves for phenylephrine 10 - 3.10 M (α1-AR agonist) Ni 3.10 M), Ca reuptake by sarco-endoplasmic reticulum were unable to promote this effect, but the in vitro pre-treatment with (cyclopiazonic acid 3.10-5M) and mitochondria (FCCP 10-6M). However, isoproterenol (10-5 M, for 3 minutes) (β-AR agonist) caused an increase the protein kinase C (PKC) inhibitor chelerythrine (10-7 to 10-6M) only of maximum response for phenylephrine which was abolished by affected the acetylcholine-induced contractions. BMY7378 10-5M. Isoproterenol (10-9 – 3.10-3M) elicited relaxation was not altered after repetitive exposures for noradrenaline (10-4 M, for 2-3 Conclusion: The rat TC contractions induced by acetylcholine or min), indicating that the desensitization of β-ARs is not involved in the carbachol are mediated mainly by M3 mAChR followed by the increase 2+ tissue sensitization to noradrenaline. of cytosolic Ca concentration regulated by voltage-dependent calcium channels, sarco-endoplasmic reticulum and mitochondria. Conclusion: The facilitation of contractions induced by repetitive Furthermore, the differential effects of PKC inhibitor chelerythrine in stimulation with noradrenaline could be due to activation of β-ARs that the acetylcholine and carbachol-induced contractions could explain the lead to an increase of α1D-ARs function. higher potency of acetylcholine compared with carbachol.
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LATINFARMA 2013 Resúmenes/Abstracts
CO 148: LOWER DENSITY OF L-TYPE AND HIGHER DENSITY C 030: DIFFERENTIAL REGULATION BY P1 AND P2 OF P/Q-TYPE CALCIUM CHANNELS IN CHROMAFFIN CELLS PURINOCEPTORS OF ATRIAL CONTRACTION IN NORMO- OF HYPERTENSIVE, COMPARED WITH NORMOTENSIVE TENSIVE AND SPONTANEOUSLY HYPERTENSIVE RATS RATS Jurkiewicz A, Dantas da Silva Júnior E, de Magalhães Galvão K, Miranda-Ferreira R, De Pascual R, Galvão KM, Lameu C, Ulrich H, Miranda-Ferreira R, Caricati-Neto A, Jurkiewicz NH and Quintella Smaili SS, Caricati-Neto A, Jurkiewicz A, Garcıa AG, Gandıa L. Dantas Rodrigues J.
Department of Pharmacology, Universidade Federal de São Paulo, Brazil. Department of Pharmacology, Universidade Federal de São Paulo, Brazil. E-mail: [email protected]
Introduction: Enhanced activity of the sympatho-adrenal axis and augmented circulating catecholamines has been implicated in the Introduction: It is known that ATP and UTP exert a biphasic effect in development of hypertension. Previous studies of our lab have been the normotensive rat atrium consisting in an initial negative inotropic shown that the release of catecholamine from stimulated adrenal effect (NIE) that is followed by a subsequent positive inotropic effect medulla chromaffin cells is higher and longer in spontaneously (PIE). We have comparatively studied here those responses in hypertensive rats (SHRs), compared with normotensive Wistar rats normotensive Wistar rats (NWRs) and spontaneously hypertensive (NWRs). Those differences were associated to higher cytoplasmatic rats (SHRs). and mitochondrial calcium levels in chromaffin cells of SHR. However, Methods: Left atria (LA) of NWR and SHR animals (4-6 months) were we didn´t know if these higher calcium levels were due differences in isolated and mounted in isolated organ bath and submitted to the function of voltage-dependent calcium channels (VDCC) subtypes. transmural electrical stimulation (2 Hz, 5 ms and 8-12 V) to study the Because of that, we decided to study the contribution of L-, N-, or P/Q effect of ATP (10-3,5 M) and UTP (10-3,5 M) on atria inotropism in the VDCC subtypes on calcium influx of chromaffin cells from SHR and absence or presence of the purinoceptors antagonists or calcium NWR. blockers. The results were analyzed by unpaired t test and one-way Methods: Using cell culture we developed voltage-clamped studies ANOVA. using 10mM Ba2+ as charge carrier (IBa) in chromaffin cells from NWR Results: The NIE responses were lower and the PIE responses were and SHR. Upon these currents we used selective blockers to study the higher in SHR, in comparison with NWRs. P1 purinoceptor antagonist participation of each VDCC subtype. We did similar experiments in DPCPX partially blocked the NIE responses to both ATP and UTP and adrenal gland slices stimulating calcium entry by K+ depolarization. mildly enhanced the PIE responses in both NWRs and SHRs. After that we block the calcium channels using the same selective Furthermore, blockers of P2 purinoceptors Suramin and PPADS caused VDCC blockers. Because VDCC are modulated by purinergic signaling, a pronounced blocked of the PIE responses in both atrial types. The PIE we also quantified the purinergic receptors using PCR experiments. responses to ATP were inhibited more efficiently by nifedipine. In Results: We found that compared with NWR cells, SHR chromaffin contrast those responses were depressed by ryanodine and CCCP to a cells exhibited the following differences: (1) 30% diminution of the IBa lesser extent in SHR, compared with NWR atria. Higher responses in fraction carried by L-channels; (2) a doubling of the IBa fraction SHR rats suggest the existence of an augmented sarcoplasmic carried by P/Q channels; (3) more visible current modulation by ATP reticulum Ca2+ store and faster mitochondrial Ca2+ cycling in SHR, with that could be linked to a 10-fold higher mRNA levels for purinergic respect to NWR atria. receptors of the P2Y2 subtype; and (3) a higher contribution of PQ- Conclusion: These data add evidence to the hypothesis of a channels to the transients of the cytosolic calcium concentrations dysfunction of purinergic neurotransmission together with an ([Ca2+]c) generated by K+, compared with L-channels. enhanced sympathetic activity, as contributing factors in the Conclusions: These results may contribute to the better understanding pathogenesis of hypertension. of the higher calcium levels and greater secretory response of SHR compared with NWR chromaffin cells, found in three previous reports from our laboratories.
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LATINFARMA 2013 Resúmenes/Abstracts
CO 149: EFFECT OF PHOSPHATIDYLETHANOLAMINE ON THE CO 150: COUPLING BETWEEN THE ENDOPLASMIC ACTIVITY OF PEPTIDES StII1-30 AND StII11-30, DERIVED RETICULUM AND MITOCHONDRIA, IN CONTROLLING FROM THE PORE-FORMING TOXIN STICHOLYSIN II CATECHOLAMINE RELEASE FROM RAT EMBRYO CHROMAFFIN CELLS, COMPARED WITH ITS MOTHER Mesa Galloso H, Delgado Magnero KH, Ros Quincoces UL, Pedrera Puentes L, Valiente Flores PA, Alvarez CA. Musial DC1,4, Padín JF1,2, Fernández-Morales JC1,2, Miranda-Ferreira R4, Arranz-Tagarro JA1,2, Jurkiewicz A4 and Garcia AG1,2,3 Center for Protein Studies, Faculty of Biology, Havana University, CP 10400, Cuba. E-mail: [email protected], [email protected] 1Instituto Teófilo Hernando and 2Departamento de Farmacología, Facultad de Medicina, Universidad Autónoma de Madrid, Spain; 3Instituto de Investigación Sanitaria, Servicio de Farmacología Clínica, Hospital Universitario de la princesa, Madrid, Spain; 4Departamento de Farmacologia, Universidade Federal de São Sticholysin II (St II) is the most hemolytic isoform of the pore-forming Paulo, Brazil. E-mail: [email protected] or [email protected] proteins produced by the sea anemone Stichodactyla helianthus. StII has been shown to promote cell lysis via pore-formation. This toxin has important applications in biomedicine in the design of immunotoxins Introduction: In adult mammals, innervated chromaffin cells of the selective aimed to cause death of malign cells and the design of method adrenal medulla release catecholamines upon action potentials driven of cytosol molecular delivery. The N-terminal amino acid sequence of membrane. This secretory response also plays a relevant role in StII seems to be responsible for its pore-formation ability. In fact, the adaptation to stress during fetal and perinatal life. At these earlier peptide StII1-30 qualitatively reproduces the activity of StII. Two stages of development, immature chromaffin cells are not yet peptides that mimic the first thirty residues of StII (StII1-30 and StII11- innervated and thus hypoxia is the main mediator triggering the surge
30) have been synthesized to study the functional role of this region. of catecholamine to secure survival of the embryo. Close contacts with Here, we have assessed the effect of including phosphatidylethanol- the endoplasmic reticulum (ER) are determinant of mitochondrial Ca2+ amine (PE) in phosphatidylcholine (PC)-sphingomyelin (SM) lipidic responses. Whether this tight crosstalk has functional consequences model systems on binding and permeabilizing activity of StII1-30 and for the control of the quantal catecholamine release (QRC) responses its truncated peptide StII11-30. The results suggest that the inclusion of occurring during fetal life in response to stress, is unknown. Here, we PE a typical negative curvature inductor in membrane into PC-SM have explored this question in rat embryo chromaffin cells (ECCs) lipidic systems, promotes binding of StII1-30 membranes in contrast to stimulated with angiotensin II (AngII), known to cause the release of StII11-30, which indicates that the hydrophobic segment 1-10 has a catecholamine during adult life by releasing Ca2+ from the ER. relevant role on membrane insertion. However, PE inhibits the pore- formation activity of StII1-30, evincing that the presence of negative Material and methods: The study of secretion of catecholamines was curvature disfavors this process. On the other hand, we performed made using the amperometry techniques with isolated chromaffin cells coarse-grained computer simulations along 10 us using the MARTINI of the adrenal gland of female rats at 18 days of gestation. After force field to study the difference in the membrane binding and isolating the cells, they were incubated with nutrient medium and possible pore formation in dipalmitoilphosphatidyl choline (DPPC) incubated at 37°C and used after 1 day of culture. Carbon electrodes membranes by both peptides. The higher van der Waals interaction were used to register the release of cathecolamines these cells were + energies of StII1-30 compared to StII11-30 stands out the importance stimulated with K (30 mM) and AngII (1 µM). of the hydrophobic N-terminal sequence (residues 1–10) in the Results: Compared with their mother rat chromaffin cells (MCCs), mechanism of pore formation which explains the higher membrane ECCs responded with QCR response that was 30% that obtained in insertion and activity of StII1-30. These results shed light about the MCCs. However, while protonophoreFCCP augmented by 6-fold the observed differences between StII1-30 and StII11-30 in the membrane AngII-elicited QRC in ECCs, the response of MCCs was unaffected. The binding and activity in model and natural membranes. QRC responses triggered by high K+ were enhanced to a much lesser extent by FCCP, both in ECCs and MCCs. Conclusion: Data constitute a functional proof for the existence of a very tight coupling between ER and mitochondria during fetal life, as compared to adulthood.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S88
LATINFARMA 2013 Resúmenes/Abstracts
CO 151: ALTERATION FUNCTION OF P1 RECEPTOR COULD CO 152: IN VITRO ANTIPROLIFERATIVE EFFECT OF INDOLE CONTRIBUTE TO THE HIGH ACTIVITY OF ACE PHYTOALEXINS (ANGIOTENSIN-CONVERTING ENZYME) AND TO DEVELOP Mojzis J1, Varinska L1, Mirossay L1, Perjesi P3, Mojzisova G.2 THE HYPERTENSION IN STREPTOZOTOCIN-INDUCED DIABETIC RATS 1Department of Pharmacology, 2Department of Experimental Medicine, Faculty of Medicine, P.J. Šafárik University, Košice, Slovakia. Musial DC, Miranda-Ferreira R, Caricati-Neto A, Jurkiewicz A, Lima- 3Department of Medical Chemistry, Medical School, University of Pecs, Hungary. Landman MTR and Jurkiewicz NH.
Departamento de Farmacologia, Universidade Federal de São Paulo, Brasil. E- mail: [email protected], [email protected] – Phone +5511-5576-4443. Backround: This study was aimed at investigating the cytotoxic activity of camalexin and its five synthetic derivatives in cancer and non-cancer cells. Introduction: Diabetes is a pathology characterized by hyperglycemia Material and methods: Effects of these compounds were tested by but patients can also develop cardiovascular dysfunctions. Recent employing MTT cytotoxicity assay, cell cycle analysis, DNA studies showed the importance of purinergic neurotransmission in the fragmentation and quantitative real-time PCR. control of cardiac function. These studies have demonstrated that alterations in this neurotransmission are related to the development of Results: In cancer cells the benzocamalexin (BC) displayed the most several pathological conditions, such as hypertension. Because P1 potent activity with an IC50 value of 23.3-30.1 μmol/L. On the other receptors are related to the purinergic alteration observed in diabetic hand, minimal toxicity (IC50 100.0 μmol/L) in non-cancer cells was animals and this P1 receptor is involved in renin release from observed. Flow cytometric analysis revealed a BC-induced increase in juxtaglomerular cells, these alterations could also contribute to a the fraction of cells with sub-G0/G1 DNA content which is considered dysfunction in renin-angiotensin-aldosteron system. Here we present a to be a marker of apoptotic cell death. Apoptosis was also confirmed by study about purinergic neurotransmission in isolated atria, the blood DNA fragmentation assay. Moreover, quantitative real-time PCR pressure levels and the activity of ACE measured in streptozotocin- showed that BC downregulated the expression of antiapoptotic genes induced diabetic rats. Bcl-2 and Bcl-xL and upregulated the expression of proapoptotic Bax. Material and methods: Diabetes was induced in Wistar rats by I.P of BC also induced arrest of the cell cycle in the G2/M phase which was streptozotocin at dose of 60 mg/kg. The diabetic rats were sacrificed associated with downregulation of α-tubulin, α1-tubulin, β5-tubulin after 30 days of injection. Control rats received the injection of saline expression. These findings suggest the inhibitory effect of BC on solution. The left atria (LA) was removed and mounted in isolated microtubules. Moreover, BC downregulated the expression of organ bath to study the contractions induced by electrical field microtubule-related protein indicating the effect of this compound on stimulation (2 Hz; 5 ms, 20-40 V) in the presence of purinergic microtubule assembly. agonists. We also analyzed the blood pressure by noninvasive indirect Conclusion: The present study demonstrates antiproliferative effects method in the rat's tail and ACE activity which was measured by of benzocamalexin. We suggest that the blockade of cell cycle fluorescence. progression and initiation of apoptosis may play an important role in Results: The negative inotropic effect (mediated by P1 receptor) in LA the antiproliferative activity of BC in human cancer cells and this decreased about 25% in D30. Concentration-response curves for compound might have a potential to enter pre-clinical trials as a new adenosine showed a decrease of pD2 in D30 (3.4 ± 0.08; n=6), anticancer drug. compared to CG (3.70 ± 0.08; n=5). In D30 it was found an increase of blood pressure of 146 ± 1.7 mmHg of control for 160 ± 3.13 mmHg in D30 and activity of ACE increase 82% compared to control. Conclusion: Our data demonstrated changes in the purinergic neurotransmission of left atria, blood pressure and ACE activity in diabetic rats. These alterations might be related to the development of secondary pathological conditions, such as hypertension.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S89
LATINFARMA 2013 Resúmenes/Abstracts
CO 153: UNCOMPLETE INDIVIDUAL PROFILES (SPARSE CO 154: IN VITRO EVALUATION OF THE ANTI- DATA) IN NONCLINICAL RESEARCH. COMBINING PROLIFERATIVE EFFECT OF A SERIES OF SYNTHETIC COMPARTMENTAL ANALYSIS, IMAGING THECNIQUES AND COMPOUNDS ON HUMAN PROSTATE CANCER CELLS POPULATION PHARMACOKINETIC Roa J1, Carmona P1, Ocampo Y1, Pájaro I1, Trilleras J2, Gaitán R.3 Hernández I, Aldana L, León M, Ayra F. 1Biological Evaluation of Promissory Substances Group. Faculty of Centro de Isótopos, Carretera La Rada km 3.5, San José de las Lajas, Mayabeque, Pharmaceutical Sciences. University of Cartagena. Colombia. E-mail: Cuba. E-mail: [email protected] [email protected] 2Heterocyclic Compounds Research Group. Faculty of Sciences. University of Atlántico. Colombia. 3Natural Products Group. Faculty of Pharmaceutical Sciences. University of Population pharmacokinetic is applied to simulated data representing Cartagena. Colombia. two main experimental sampling schedules. Data were drawn from real experiments using blood sampling only or in combination with imaging procedures to build a compartmental model of tumor uptake Introduction: Prostate cancer is a leading cause of cancer death of radiolabeled drug. among men worldwide. Recent trends indicate a rise of incidence in Introduction: In pharmacokinetic evaluation small rodents are used in developing countries like Colombia. Current treatments are not safe or a large extend. Traditional pharmacokinetic evaluations by the two effective; therefore development of new therapies is still needed. The steps approach can be replaced by the sparse data design which may aim of this work was to identify cytotoxic molecules within a series of also represent a complicated situation to evaluate satisfactorily from 42 structurally diverse synthetic compounds: naphthoquinone the statistical point of view. In this presentation different situations of derivatives (NQ), pyrido[2,3-d]pyrimidine, and fused pyrazolo[3,4- sparse data sampling are analyzed based on practical consideration. b]pyrazines. Population was selected in order to estimate pharmacokinetic Material and methods: Compounds were synthesized and parameters in simulated data from real experimental results using characterized according to the methods we previously reported. PC3 blood sampling and imaging procedures. prostate cancer cells, which are androgen independent, highly Material and methods: Two situations of incomplete individual tumorigenic and metastaticin vivo, were cultured with test compounds profiles were evaluated, overlapping and no overlapping time point at concentrations ranging from zero (control) to 30 μM for 48 h. Cell distribution. Data were simulated following a two compartment model. viability was evaluated using methyl-tetrazolium bromide (MTT) or In all cases three to five blood samples were considered per time point. resazurinassays. Doxorubicin-HClwas employed as positive control. A combination of compartmental analysis with tumor uptake obtained Results: None of the pyrido[2,3-d]pyrimidine and pyrazolo[3,4- by gammagraphy of radiolabeled drugs is also evaluated. All b]pyrazines affect cell viability even at the highest concentration, pharmacokinetic profiles were analyzed by means of the population suggesting that substituents diminish their bioactivity. However, PC3 approach using the MONOLIX software version 4.2. cells were sensitive to the effect of ten NQ derivatives. Compounds 2, 6, Results: All sampling schedules yield the same results when computed 8, 17, 21, 22-24, showed potent cytotoxicity in a concentration- using the MONOLIX software and the SAEM algorithm. Population and dependent manner, with LC50<10 µM, maximum reference value to individual pharmacokinetic parameters were accurately estimated with select promissory compounds, and similar effect to that of doxorubicin three or five determination per sampling point. According with the (LC50 = 8.44 ± 0.05µM). Derivatives 8, 22 and 23 were the most active used methodology and software tool it can be an expected result, but of the series (LC50<1 µM). Preliminary SAR analysis indicates that 1,2- demonstrating the method performance in such situations, allow us to and 1,4-NQ fused with furan ring are important groups for toxicity, select a more flexible design using a very small number of animals in with 1,2-NQ having better activity. preclinical research. The combination with imaging procedures also Conclusion: This is the first work concerning the potential of tested NQ allows us to construct a completely structured compartmental analysis. derivatives to inhibit prostate cancer cell proliferation. Our results The same sampling approach can be considered in phase I or II clinical indicated that compounds 8, 22, and 23 might be considered as lead trials. molecules to develop new therapies.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S90
LATINFARMA 2013 Resúmenes/Abstracts
CO 155: SIMVASTATIN EFFECT ON THE EXPRESSION OF allowing the recruitment of inflammatory cells. Benznidazole is part of ENDOTHELIAL CELL ADHESION MOLECULES AND the current treatment of Chagas disease, acting as trypanocidal drug, INFECTION INDUCED BY Trypanosoma cruzi but may have serious side effects and has no proven effectiveness in the chronic phase. Therefore, improve the effectiveness of this drug, by Campos-Estrada C1, López-Muñoz R1, Kemmerling U2, Morello A 1, modifying the CCC physiopathology, such as inflammation, is a very Maya JD.1 interesting strategy. Thus, simvastatin has been studied due to their pleiotropic role in modulating the inflammatory response, among 1 2 Department of Clinical and Molecular Pharmacology, Department of Anatomy other effects. In this work, inparasitesisolated and EA.hy926 cells were and Developmental Biology, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile. E-mail: [email protected] determined theIC50from both drugs by MTT assay. Consequently the expression of E-CAMs induced by T. cruzi in EA.hy926 cells was determined. Furthermore, the effect of simvastatin and benznidazole on parasite load and the expression of V-CAM 1, I-CAM 1 and E-selectin Chagas disease affects 10 million Latin America people. In 2008 more by flow cytometry and immunocytofluorescence were evaluated. than 10000 people died from this cause. This disease is caused by the flagellate protozoan Trypanosoma cruzi. Parasite infects the cells of the In endothelial cells infected with T. cruzi, the increase on the expression immune system triggering an inflammatory response to control of E-CAMs was statistically significant respect control group. parasite replication. If the inflammatory response persists, it leads to Simvastatin was able to decrease the expression of cell adhesion the chronic phase of the disease, in the form of Chronic Chagas molecules without affecting the cell viability and also reduced parasite Cardiomyopathy (CCC) which is developed in 30% of infected patients. load. In conclusion, given the key role of inflammation in the During the infection, vascular endothelium is activated increasing the pathogenesis of Chagas disease simvastatin may contribute tothe expression of cell adhesion molecules on the endothelium (E-CAMs) treatment of Chagas disease.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S91
LATINFARMA 2013 Resúmenes/Abstracts
Simposio de Productos Naturales / Symposium of Natural Products
C 031: INHIBITION OF CYTOCHROME P450 BY NATURAL CO 156: THE AQUEOUS EXTRACT OF Montanoa frutescens PRODUCTS AS AN ANTIMUTAGENESIS MECHANISM PRODUCES ANTI-STRESS-LIKE EFFECTS IN MALE WISTAR RATS IN THE FORCED SWIM TEST Espinosa-Aguirre JJ. Flores-Aguilar LA1, Carro-Juárez M2, Rosas-Sánchez GU1, Rovirosa- Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de 3 3 3 México (UNAM), D.F., Mexico. E-mail: [email protected] Hernández MJ , García-Orduña F , Rodríguez-Landa JF.
1 Facultad de Química Farmacéutica Biológica, Programa Institucional de Tutoría para la Investigación, Universidad Veracruzana, Xalapa, Veracruz, México. Email: CYP enzymes are involved in the metabolism of xenobiotics as well as [email protected] 2 some endogenous compounds. Its activities lead to the production of Laboratorio de Comportamiento Reproductivo, Escuela de Medicina Veterinaria y Zootecnia, Universidad Autónoma de Tlaxcala, Tlaxcala, Tlaxcala, México. Email: mutagenic and carcinogenic entities that can react with important [email protected] macromolecules like proteins and nucleic acids. In theory, Inhibition of 3Instituto de Neuroetología, Universidad Veracruzana Xalapa, Veracruz, México. CYP catalysis could lead to inhibition of the mutagenic and carcinogenic E-mail: [email protected] processes considering the inhibitory compounds as beneficial chemoprotective agents. Using in vitro biochemical methods we have tested the CYP inhibitory capacity of several plant derived compounds Introduction: Montanoa tomentosa, Montanoa grandiflora, and like bergamotin, dehydrobergamotin and naringin from grapefruit, Montanoa frutescens extracts have been used in traditional Mexican quercetin and chiro-inositol from Heteroteca inuloides, mangiferin from medicine as remedies for reproductive, emotional, and mood disorders Mangifera indica and thalassiolin b from Thalassia testidinum. Results in women. M. frutescens extract produces anxiolytic-like effects in rats obtained showed the CYP inhibitory activity of these compounds, being through GABAA receptors, but unknown is whether this plant also bergamotin and thalassiolin b of the molecules with high inhibitory produces anti-despair-like effects similar to other GABAergic potential. Results from the Ames Assay in which we tested the compounds. The objective of this study was to evaluate the effect of M. antimutagenic properties of these compounds against known frutescens extracts on despair-like behavior in male Wistar rats and mutagens, shows that the inhibition of CYP activity can be traduced in compare their effects with fluoxetine. an antimutagenic effect in this Assay. These effects were also confirmed in rat hepatic cells in culture, where effects on activity/expression of Material and methods: One group received vehicle (control), two CYP1A1 were tested. The possible use of these antimutagenic groups received M. frutescens extract (25 and 50 mg/kg, p.o., substances as chemoprotective agents is discussed in the light of the respectively), and one group received fluoxetine (1 mg/kg, i.p.) as a existence of endogenous CYP substrates. reference antidepressant drug. The treatments were administered for 28 days, and their effects were evaluated in the forced swim and open field tests on days 0, 7, 14, 21 and 28 of treatment and 24 and 48 h post-treatment. The data were analyzed by two-way analysis of variance and the Student-Newman-Keuls post hoc test. Results: In the forced swim test, M. frutescens (50 mg/kg) significantly decreased total immobility time beginning on day 1 of treatment compared with the control group and baseline session. Fluoxetine reduced immobility beginning on day 14. The effect of M. frutescens disappeared 48 h after treatment, whereas the effects of fluoxetine remained 48 h after treatment. In the open field test, a reduction of locomotor activity was observed beginning on day 7 until the end of the experiments, independent of treatment. M. frutescens and fluoxetine keep grooming behavior in the open field test. Conclusion: M. frutescens extract exerted a protective effect against stress induced in the forced swim test but did not have antidepressant- like effects, thus supporting the anxiolytic-like effect identified in previous studies at the experimental level.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S92
LATINFARMA 2013 Resúmenes/Abstracts
CO 157: Montanoa grandiflora EXTRACT PRODUCES ANTI- CO 158: EVALUATION OF ANXIOLYTIC ACTIVITY OF STRESS-LIKE BUT NOT ANTI-DESPAIR-LIKE EFFECTS IN AQUEOUS EXTRACTS OF Plantago major L. AND Mentha WISTAR RATS: COMPARISON WITH FLUOXETINE viridis L.: PLANTS USED IN THE TRADITIONAL MEDICINE OF COLOMBIAN CARIBBEAN COAST Rosas-Sánchez GU1, Carro-Juárez M2, Flores-Aguilar LA1, Rovirosa- Hernández MJ3, García-Orduña F3, Rodríguez-Landa JF.3 Caro D, Rivera D, Franco L, Salas R
1Facultad de Química Farmacéutica Biológica, Programa de Tutoría para la Biological Evaluation of Promissory Substances Group. Faculty of Pharmaceutical Investigación, Universidad Veracruzana, Xalapa, Veracruz, México. Email: Sciences. University of Cartagena. Cartagena, Colombia. E-mail: [email protected] [email protected] 2Laboratorio de Comportamiento Reproductivo, Escuela de Medicina y Zootecnia, Universidad Autónoma de Tlaxcala, Tlaxcala, Tlaxcala, México. Email: [email protected] 3Instituto de Neuroetología, Universidad Veracruzana, Xalapa, Veracruz, México. Introduction: Generalized anxiety is a mental disorder that has a high E-mail: [email protected] prevalence in Colombia, affecting 19.3% of the population between 18- 65 years of age. Currently, the benzodiazepines are the choice pharmacologic treatment to handling anxiety; but they have several Introduction: Montanoa grandiflora, Montanoa tomentosa, and problems limiting widespread applicability, like dependency and Montanoa frutescens extracts have been used for centuries in withdrawal syndrome. Plantago major L. and Mentha viridis (L.) L. are traditional Mexican medicine as remedies to ameliorate mood and used in Colombian Caribbean folk medicine as an alternative treatment emotional alterations, among others. At the experimental level, the of this pathology, nevertheless there are not pharmacological studies extracts of M. frutescens and M. grandiflora produce anxiolytic-like of their anxiolytic properties. Therefore, in this study we investigated effects through actions on GABAA receptors. Interestingly, some the effect of aqueous extracts obtained from these plants using GABAergic compounds produce anti-despair-like effects in rats. We elevated plus maze (EPM) model. investigated whether M. grandiflora extract exerts anti-despair-like Material and methods: Ten Wistar rats weighing between 200-230 g effects in male Wistar rats compared with fluoxetine as a reference were treated with vehicle, extracts (1000 mg/kg, p.o.) or diazepam (1 anti-despair drug. mg/kg, i.p.), 30 min prior of placing them in the EPM device. A digital Material and methods: We included four groups: one group received camera was used to take a video of the animals’ behavior for a period vehicle (control), two groups received M. grandiflora extract (25 and of fifteen minutes to quantify the number of entries and the time spent 50 mg/kg, p.o., respectively), and one group received fluoxetine (1 in the arms. mg/kg, p.o.). The treatments were administered for 28 days, and the Results: Menthaviridis increased the number of entries and the effects were evaluated on day 0, 1, 7, 14, 21, and 28 of treatment and percentage of time spent in open arms from 9.08% to 35.62%, 24 and 48 h post-treatment in the forced swim and open field tests. compared to the control group. It also induced a slight reduction in the The data were analyzed by two-way analysis of variance. spent in closed arms. On the other hand Plantago major did not Results: M. grandiflora (50 mg/kg) decreased immobility from day 1 produce any effect on animal’s behavior. to 28 of treatment compared with the control group (p < 0.05), but this Conclusions: The results of this study demonstrated that aqueous effect disappeared 48 h post-treatment. Fluoxetine reduced immobility extracts obtained of Mentha viridis exerts an anxiolytic effect on male beginning on day 14 of treatment, and this effect endured until 48 h rats, providing a scientific evidence of the popular use. Further post-treatment. In the open field test, a reduction of locomotion was research should focus on the identification of the active constituents observed beginning on day 7, independent of treatment. Grooming was from this plant that might be useful to treat anxiety. reduced (p < 0.05) in the control group beginning on day 7, but not changes in grooming were detected in M. grandiflora (50 mg/kg) and fluoxetine groups. Conclusions: M. grandiflora extracts produced a protective effect against stress in rats in the forced swim test rather than an anti- despair-like effect. These data support the traditional use of M. grandiflora to ameliorate emotional alterations with a stress component.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S93
LATINFARMA 2013 Resúmenes/Abstracts
CO 159: Montanoa grandiflora EXTRACT PRODUCES CO 160: ANXIOLYTIC-LIKE EFFECT OF Montanoa frutescens ANXIOLYTIC-LIKE EFFECTS SIMILAR TO DIAZEPAM IN EXTRACT IN THE METESTRUS-DIESTRUS PHASE OF THE CYCLING FEMALE WISTAR RATS OVARIAN CYCLE IN WISTAR RATS
Vicente-Serna J1, Carro-Juárez M2, Rodríguez-Blanco A1, Rovirosa- Rodríguez-Blanco LA1, Carro-Juárez M2, Vicente-Serna J1, Rovirosa- Hernández MJ3, García-Orduña F3, Rodríguez-Landa JF.3 Hernández MJ3, García-Orduña F3, Rodríguez-Landa JF.3
1Facultad de Química Farmacéutica Biológica, Programa Institucional de Tutoría 1Facultad de Química Farmacéutica Biológica, Programa Institucional de Tutoría para la Investigación, Universidad Veracruzana, Xalapa, Veracruz, México. E-mail: para la Investigación, Universidad Veracruzana, Xalapa Veracruz, México. E-mail: [email protected] [email protected] 2Laboratorio de Comportamiento Reproductivo, Escuela de Medicina Veterinaria 2Laboratorio de Comportamiento Reproductivo, Escuela de Medicina Veterinaria y Zootecnia, Universidad Autónoma de Tlaxcala, Tlaxcala, Tlaxcala, México. E- y Zootecnia, Universidad Autónoma de Tlaxcala, Tlaxcala, Tlaxcala, México. E- mail: [email protected] mail: [email protected] 3Instituto de Neuroetología, Universidad Veracruzana Xalapa, Veracruz, México. 3Instituto de Neuroetología, Universidad Veracruzana, Xalapa Veracruz, México. E-mail: [email protected] E-mail: [email protected]
Introduction: Cihuapatli is the Nahuatl name for some plants grouped Introduction: Montanoa frutescens extract has been used for centuries in the genus Montanoa, in which Montanoa grandiflora is included. The in traditional Mexican medicine as a remedy for several illnesses in crude extracts from these plants have been used for centuries in women, including changes in mood and anxiety. The extract of this traditional Mexican medicine as remedies for reproductive plant produces anxiolytic-like effects through an action on GABAA impairments, anxiety, and depressive states. However, the effects of M. receptors in male Wistar rats, but the effect of M. frutescens extract on grandiflora on experimental anxiety remain unexplored. The aim of the anxiety-like behavior in female Wistar rats during ovarian cycle phases present study was to explore the effect of M. grandiflora extract on (proestrus-estrus and metaestrus-diestrus) remain to be explored. The anxiety-like behavior during different phases of the ovarian cycle in present study evaluated the potential anxiolytic-like effect of M. female Wistar rats. frutescens extract in cycling Wistar rats compared with the clinically effective anxiolytic drug diazepam. Material and methods: We included one group treated with vehicle (control), two groups treated with M. grandiflora extract (25 and 50 Material and methods: Female Wistar rats were assigned to four mg/kg, p.o.), and one group treated with diazepam (2 mg/kg, i.p.) as a independent groups: one group received vehicle (control), two groups reference anxiolytic drug. The effects were evaluated in the elevated received different doses of M. frutescens (25 and 50 mg/kg, p.o.), and plus maze and open field test. The phases of the ovarian cycle were one group received diazepam (2 mg/kg, i.p.) as a reference anxiolytic determined by microscopic analysis of vaginal smears to assign each drug. Sixty minutes after the single administration of vehicle, M. rat to proestrus-estrus and metestrus-diestrus subgroups. Each group frutescens extract, or diazepam, the rats were evaluated in the elevated had eight to 10 rats. The data were analyzed using two-way analysis of plus maze and subsequently in the open field test. The ovarian cycle variance with independent groups and Student-Newman-Keuls post phases were determined by microscopic analysis of vaginal smears, hoc test. and the rats were separated into subgroups (i.e., proestrus-estrus and metaestrus-diestrus). The data were analyzed by two-way analysis of Results: In the elevated plus maze, the rats treated with M. grandiflora variance with independent groups and the Student-Newman-Keuls (50 mg/kg) in the metestrus-diestrus phase exhibited an increase in post hoc test. the time spent in the open arms compared with the control group, similar to the effects of diazepam, without affecting crossings, rearing, Results: M. frutescens (25 and 50 mg/kg) increased the time spent in grooming, or resting time. In the proestrus-estrus phase, the plant the open arms of the elevated plus maze during the metaestrus- extract did not significantly affect locomotor activity, whereas diestrus phase, similar to the effects of diazepam, without affecting diazepam produced hypoactivity. locomotor activity. Diazepam but not M. frutescens extract produced locomotor hypoactivity during the proestrus-estrus phase. Conclusions: M. grandiflora produced anxiolytic-like effects during physiological states characterized by low hormonal levels, similar to Conclusion: M. frutescens extract possesses anxiolytic-like effects diazepam, without affecting locomotion. The present results support similar to diazepam during the metaestrus-diestrus phase, supporting the hypothesis that this plant possesses a potential anxiolytic effect as the traditional use of M. frutescens extract to alleviate anxiety in reported in traditional Mexican medicine. women.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S94
LATINFARMA 2013 Resúmenes/Abstracts
CO 161: HEPATOPROTECTIVE EFFECT OF SOLIDS LIPIDS CO 162: PHARMACOLOGY OF ANTIASTHMATIC NATURAL NANOPARTICLES WITH VANILLIN AGAINST CCL4-INDUCED PRODUCTS FROM MEXICAN MEDICINAL PLANTS ACUTE LIVER INJURY IN MICE Navarrete A, Rodríguez F, González M, Tapia G, Alfaro A. Castan L1, Del Toro García G2, Fernández A3, Ortiz Beatón E1, Reiners Facultad de Química. Departamento de Farmacia. Universidad Nacional 4 4 5 A , Salas H , Dbrok J. Autónoma de México. Ciudad Universitaria Coyoacán 04510, México D.F., México. E-mail: [email protected] 1Biomedical Engineering department, Electrical Engineering Faculty, University of Oriente, Santiago de Cuba, Cuba. Patricio Lumumba s/n Santiago de Cuba, Cuba. CP 90500. E-mail: [email protected] 2Foods and Pharmacy Institute, Havana University, Havana Cuba. Calle 222 Introduction: In this work several medicinal plants used in the #2317, e/ 23 y 31 La Coronela, La Lisa, La Habana, Cuba. Mexican traditional medicine as antiasthmatic remedies were studied 3Computer Science Department, Faculty of Mathematics and Computer Science, University of Oriente, Santiago de Cuba, Cuba. Patricio Lumumba s/n Santiago de by bioguided fractionation to isolate and identify the active compounds Cuba, Cuba. CP 90500 with the ability to show relaxant effect on guinea pig trachea. 4Center of Toxicology, Santiago de Cuba. Autopista Nacional Km 1 1/2. Apdo Postal 4033. Santiago de Cuba. CUBA Material and methods: The relaxant effect and the inhibition of 5Children’s north Hospital of Santiago de Cuba. Avenida de las Américas s/n. calcium chloride-induced contractions of extracts and pure compounds Santiago de Cuba, Cuba. were evaluated on guinea pig trachea model. The PDE inhibitory activity was evaluated using a cyclic nucleotide phosphodiesterase (PDE) colorimetric assay kit. Introduction: Vanillin is an aromatic aldehyde with antioxidant, anti- Results: The flavones gnaphaliin A and B were identified as tracheal inflammatory and antitumor properties. Biological activity of vanillin smooth muscle relaxant active principles from Gnaphalium liebmannii in animal models has been limited because it low oral bioavailability. (Asteraceae). The main relaxant mechanism of action of these flavones Nowadays, nanotecnology provides drug delivery systems as is the inhibition of PDEs with a preference to inhibit the degradation of alternative to improve bioavailability and pharmacological action of cGMP. The docking study suggested that these flavones bind with high drugs, either naturals or synthetics. Among these drug delivery system, specificity to the same binding site of sildenafil at PDE type 5. The solids lipids nanoparticles are attractive because their easy production. content of gnaphaliins varies widely with the particular Gnaphalium The aim of this work is to encapsulate vanillin in solid lipids species. On the other hand the alkaloid berberine (as carbonate) was nanoparticles to improve its hepatoprotective and antioxidant effects identified as one of the active relaxant principles in Argemone in mice after carbon tetrachloride induced liver acute damage. ochroleuca (Papaveraceae). The relaxant effect of berberine on tracheal Material and methods: Solid lipids nanoparticles containing vanillin muscle is due to its antagonistic effect on muscarinic acetylcholine (NSL-V) were obtained by solvent-injection technique using Stearic receptors. Thymol has been identified as active principle in other acid, Tween 80 and ethanol like solvent. Particles were characterized Mexican medicinal plants and aqueous extracts of Bougainvillea glabra by determination of entrapment efficiency and vanillin release. To potentiates the relaxant effect of salbutamol and ipratropium. The evaluate pharmacological activity, 3 groups of 8 Balb c mice were essential oil of Agastache mexicana subsp. mexicana, composed by treated orally with a single dose of carbon tetrachloride (1 mg/kg), and Estragole (80.281%) and D-limonene (17.555%), inhibits the one hour later NSL-V, vanillin in solution and empty solid lipids carbachol and histamine-induced contraction of guinea pig trachea and nanoparticles were administered. After 24 hours, the treatment was inhibits the calcium influx. repeated. Control group was treated with vehicle alone. Animals were Conclusion: The Mexican medicinal plants, used as antiasthmatic sacrificed and liver and blood samples were collected. To evaluate liver traditional remedies, contain active compounds that act as tracheal damage, determination of AST, ALT and histological analysis were smooth muscle relaxants through several conventional pharmaco- performed. Activity of SOD, Catalase, MDA levels and oxidized proteins logical mechanisms. were evaluated in liver homogenates.
Results: Solid lipids nanoparticles with good entrapment efficiency were obtained. Levels of AST and ALT were reduced in a significant manner with NSL-V treatment. Liver histology also showed a significant less injury in this group. Activity of SOD, Catalase, MDA levels and oxidized proteins were significantly reduced in the group treated with NSL-V, with values close to controls treated only with vehicle and without liver injury. Conclusion: These results show that solid lipids nanoparticles may improve pharmacological activity of vanillin, acting like suitable vehicle.
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LATINFARMA 2013 Resúmenes/Abstracts
CO 163: ANTIBACTERIAL ACTIVITY OF MEDICINAL PLANTS CO 164: Rosmarinus officinalis L. SECONDARY METABOLITES OF THE COLOMBIAN NORTHERN COAST CHARACTERIZATION IN PLANTS GROWN IN CUBA AND MEXICO Barrios L1, Orjuela V1, Caro D1, Castro J1, Díaz F2, Franco L.1 Fung Boix Y1, Molina Torres J2, Ramírez Chávez E2, Gómez Luna L1, 1Biological Evaluation of Promissory Substances Group. 2Laboratory of 1 3 Phytochemical and Pharmacological Research Faculty of Pharmaceutical Ferrer Dubois A , Verçosa de Medeiros Rapôso N . Sciences.University of Cartagena. E-mail: [email protected] 1National Center of Applied Electromagnetism. Univ. de Oriente. Ave. The Americas s/n. Santiago of Cuba City. Cuba. CP 90400. GP 4078. E-mail: [email protected] 2 Introduction: The increased incidence of infectious diseases CINVESTAV, UNIDAD IRAPUATO. Km9.6 Libramiento Norte, CP: 36821. Irapuato, Guanajuato. México. E-mail: [email protected], encourages the search for new antibacterial agents, being medicinal [email protected] plants an invaluable source. A variety of plants are used in Colombian 3Universidad Estadual del Amazonas, Escuela Superior de Tecnologia (EST), traditional medicine for the treatment of infectious diseases. Engenieria Florestal Laboratório de Cultivo de Teiidos Vegetal (Brasil). Ave. Therefore, obtain scientific information on the efficacy of these plants Darcy Vargas 1620, Parque Dez, Manaus, Amazonas, código postal 69050-020. represent a priority goal to our research groups.In this work, we Brasil. E-mail: [email protected] investigated the in vitro antibacterial activity of ten plants used in the folk medicine of the Colombian Northern Coast. Introduction: Rosemary belongs to the family Lamiaceae, has Material and methods: Total ethanol extracts of bark and/or leaf antioxidant properties and is currently widely used in natural from Mammea americana L., Anacardium occidentale L., Capparis medicine, pharmacy and as nutraceutical. In Mexico even as an odoratissima Jacq., Cecropia peltata L., Ambrosia cumanensis Kunth., introduced species it is used as a medicinal plant in several states of Chenopodium ambrosioides L., Murraya exotica L., Maclura tinctoria L., the country. In Cuba the species was introduced by the Spaniards and Croton malambo H. Karst, and Bauhinia guianensis Aubl., were is often grown in gardens of rural and urban areas. Propagation of this evaluated against ATCC strains of Staphylococcus aureus, species in Cuba is difficult by seeds or by vegetative techniques so this Staphylococcus epidermidis, Klebsiella pneumoniae, Pseudomonas limits its availability and is now removed from the National Form aeruginosa, Escherichia coli and Enterococcus faecalis, determining the Phytopharmaceuticals. Different research papers have argued that minimum inhibitory concentration (MIC) for extracts (1000 depending on the geographical location and natural conditions where µg/mL)that completely inhibited bacterial growth. it is grown results in changes in the concentration and type of bioactive Results: A. occidentale and M.americana were the most active of the molecules present. The magnetically treated water has been widely tested extracts, with MIC values between 132 and 4.125 µg/mL against used in irrigation, because it stimulates the growth and development of all the bacterial strains. Despite C. malambo and B. guianensis were plants. The aim of this work was to characterize volatile and bioactive active in a lesser extent (MIC=1056-528 µg/mL), their traditional use compounds in Rosmarinus officinalis L. cultured with magnetically is justified by our results. The remainder plants did not inhibited the treated water in Santiago de Cuba, Cuba and Guanajuato in Mexico. bacterial growth at tested concentrations. Material and methods: The methanolic extracts were analyzed in a Conclusions: We found scientific evidence that supports the medicinal GC/EIMSD (Agilent Technologies 7890 A, 5975C) using a capillary use of A. occidentale, M. americana, C. malambo, and B. guianensis. column UI DB1MS Agilent Technologies (60 x 0.25 x 0.25). Obtained Further studies are needed to isolate and identify the metabolites spectra were compared with the mass spectra databases, NIST 2011 responsible for the antibacterial activity. (National Institute of Standards and Technology, Standard Reference Data Program). Results: The composition of the extracts of Mexican and Cuban species which was treated with static magnetic field had similar compounds among which are found the α-pinene, camphene, β-pinene, β myrcene, camphor and terpinene. In control extracts less bioactive compounds were found in relation to treated extracts. Even when the total amount of volatiles was not significantly different in both, treated and control plants, the mass production in magnetic treated water plant was higher, so the potential of the technique got to be explored.
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LATINFARMA 2013 Resúmenes/Abstracts
CO 165: HUMAN CELLS PHOTOPROTECTION BY FRACTIONS CO 166: NEW INDICATION OF SURFACEN A PORCINE OBTAINED FROM Phyllanthus orbicularis Kunth NATURAL SURFACTANT IN THE TREATMENT OF THE ACUTE RESPIRATORY DISTRESS SYNDROME Vernhes M1, González-Pumariega M2, Ribeiro C3, Cabrera I4, Menck CFM3, Sánchez-Lamar A.2 Fernández Limia O1, Hidalgo AO2, Díaz E1, Faure R1., Barrese Y3, Uranga R3, Ávila Y3, Grupo de médicos y coordinadores regionales 1Centro de Aplicaciones Tecnológicas y Desarrollo Nuclear. Calle 30. #502, e/ 5ta 2 y 7ma. Miramar, Playa, La Habana, Cuba. E-mail: [email protected] participantes en el estudio . 2 Facultad de Biología de la Universidad de la Habana. Calle 25 e/ I y J. Vedado, La 1National Centre of animal and plants health (CENSA), Mayabeque, Cuba. E-mail: Habana, Cuba [email protected] 3 Departamento de Microbiología, Instituto de Ciencias Biomédicas, Universidad 2Ministry of Public Health of Cuba de Sao Paulo, Av. Prof Lineu Prestes, 1374, Sao Paulo, Brasil. 3National Coordinating Centre of Clinical Trials, La Habana, Cuba. 4Laboratorio de Farmacología, Hospital Salvador Allende. La Habana, Cuba.
In order to evaluate the efficacy and safety of SURFACEN in low, Numerous studies have implicated ultraviolet radiation (UVR) in repeated dose on arterial blood oxygenation in adult patients with severe skin diseases. Particularly, ultraviolet B radiation in sunlight is a ARDS also a change in mortality, days with endotracheal intubation, major risk factor for the development of photoaging and days with mechanical ventilation, time in the ICU and the presence of photocarcinogenesis. The main DNA lesions induced by UVR, adverse events. An Clinical Trial phase III, controlled, open, cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts (6- randomized, with two treatments groups was done: Treatment group 4PPs), are considered the principal causes of these cutaneous illnesses. with conventional oxygenation and mechanical ventilation + DNA photolesions are removed by nucleotide excision repair (NER) SURFACEN (100 mg) instilled by an endotracheal probe every 8 hours system. If UV photoproducts are not repaired properly may led to cell during three days and a Control group without the surfactant. A total of mutations and carcinogenic transformation. 45 patients were included in the trial. An increase in the PaO2/FiO2 in Currently, searching of phytocompounds as photoprotectors the 74% of the SURFACEN treated patients vs 26.1% in the Control constitutes an approach to protect human health against UVB harmful group (P<0.05). Other variables as mortality, days with intratracheal effects. Phyllanthus orbicularis K is a Cuban endemic plant using in folk intubation, days of mechanical ventilation and days in the ICU were not medicine. The aqueous extract of this plant has demonstrated modify by the treatment with the surfactant. The treatment proved to protective effect against several genotoxic agents, including UVR. be safe because 21 of the reported adverse events, the 92.7% were not Phytocompounds present in the extract have been related with the related with the product and 80% were of low or moderated intensity. beneficial properties. The use of low repeated dose of SURFACEN improve the arterial oxygenation although an improve in mortality or other outcomes were The present investigation was addressed to evaluate fractions obtained not observed that it is why the routine use of surfactant in adults with from P. orbicularis K, in the protection of human cells against UVB light. ARDS in not justified. DNA repair proficient and deficient fibroblasts (MRC5-SV and XP4PA) were used as experimental models. The damaging effects of UV were evaluated through clonogenic cell survival, while DNA repair was determined by the removal of CPD and host cellular reactivation assay. The results showed that, aqueous and dicloromethanolic fractions of P. orbicularis protect human cells against UVB light-induced damage. Both fractions increase the cell survival and the ability to repair DNA photodamage. This investigation deepened on the photoprotective capacity of P. orbicularis specie, also the photochemopreventive potential of this plant has been studied.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S97
LATINFARMA 2013 Resúmenes/Abstracts
Simposio Actualización Terapéutica en Oncoterapética / Symposium of Therapeutic Updating on Cancer
C 032: CHEMO-IMMUNOTHERAPY FOR CANCER: A likelihood of clinical success. Finally, delineating the impact of RATIONAL SCIENTIFIC AND THERAPEUTIC established cancer drugs and standard cancer treatment modalities on the immune system and on tumor immuno biology itself will be critical Soriano García JL. for the most effective integration of immune-based cancer therapy into state-of-the art multimodality cancer care. Clinical Oncology Service. Ameijeiras´Hospital, La Habana, Cuba.
Cancer therapy is designed to specifically integrate distinct treatment CO 167: RADIO-IMMUNOTHERAPY FOR MALIGNANCIES modalities in the most effective way to achieve the highest cure rate. Batista Albuerne N. Surgery and radiation therapies are used for loco regional disease control, whereas systemic therapies are used to treat micrometastatic Clinical Oncology Service. Ameijeiras´Hospital, La Habana, Cuba. or widespread metastatic cancers and hematologic malignancies. While systemic therapies have historically been given after local measures have been undertaken to remove the primary tumor, they are More recently, attention has turned to the development of RIT agents increasingly used prior to definitive local treatment both to achieve for the treatment of B-cell non-Hodgkin lymphomas, which are systemic disease control earlier and to evaluate the responsiveness of inherently radiosensitive and express antigens not typically found in the tumor to treatment. Regardless of the timing in relation to local normal tissue. During the next several years, the development of RIT therapy, these systemic treatments—chemotherapy, endocrine agents for B-cell non-Hodgkin lymphoma continued, which led to the therapy, small molecular targeted therapies and monoclonal FDA approval of 90Y ibritumomabtiuxetan in 200210 and iodine-131 antibodies–are designed to decrease the likelihood of relapse due to (131I) to situmomabin 2003. In general, solid tumors are much less micrometastatic disease. Cancer chemotherapy drugs have long been radiosensitive than B-cell lymphomas, requiring higher delivered doses considered immune suppressive. However, more recent data indicate for significant clinical efficacy. In colorectal cancer, several promising that some cytotoxic drugs effectively treat cancer in part by facilitating targets have been identified, including CEA, TAG-72, Ep-CAM, and A33. an immune response to the tumor when given at the standard dose and Overall, the results have been somewhat disappointing, with few schedule. These drugs induce a form of tumor cell death that is objective responses. However, in the setting of minimal residual immunologically active, thereby inducing an adaptive immune disease, some studies have demonstrated favorable progression-free response specific for the tumor. In addition, cancer chemotherapy survival (PFS) and OS compared with historic outcomes. In breast drugs can promote tumor immunity through ancillary and largely cancer, several active targets have been identified including CEA, TAG- unappreciated immunologic effects on both the malignant and normal 72, MUC-1, and L6. Modest responses have been seen, with greater host cells present within the tumor microenvironment. These more responses in the setting of high-dose RIT followed by autologous stem subtle immunomodulatory effects are dependent on the drug itself, its cell rescue. Interferon alfa may have the ability to upregulate dose, and its schedule in relation to an immune-based intervention. A expression of key RIT targets in patients with BC. Murine antibodies detailed understanding of the cellular and molecular basis of result in a high expression of HAMAs, limiting repeat dosing strategies. interactions between chemotherapy drugs and the immune system is A number of rational RIT targets have been described for prostate essential for devising the optimal strategy for integrating new immune- cancer, including TAG-72, L6, MUC-1, and PSMA. By contrast to most based therapies into the standard of care for various cancers, resulting solid tumor types, patients with PC have exhibited some reasonable in the greatest long-term clinical benefit for cancer patients. Current responses to RIT, particularly in the combined modality setting when data suggest that combining chemotherapy in standard and novel ways delivered with taxane chemotherapy. Patients with PC who also have with immune-based interventions will have great potential for skeletal metastases experienced significant pain relief, even with RIT optimizing the clinical outcomes of cancer patients. A new era of alone. The most promising agent currently in active clinical trials is effectively harnessing the immune system to treat and prevent cancer 177Lu-J591, which targets PSMA.RIT for ovarian cancer appears to be a has begun. These early successes have ledto heightened interest and potentially promising option, particularly in patients who have been activity in developing new strategies for tipping the balance of the host- optimally debulked following surgery and chemotherapy but who still tumor interaction toward definitive tumor rejection. It is clear that are at high risk for microscopic intraperitoneal disease. Alpha-emitting strategically integrating immune-based therapies with standard cancer radionuclides hold particular promise in non bulky disease, given the treatment modalities, in particular chemotherapy drugs, has the higher linear energy transfer and shorter path length compared with potential to reengineer the overall host milieu and the local tumor beta particles. Therefore, the accrual of ongoing clinical trials of these microenvironment to disrupt pathways of immune tolerance and novel agents should be encouraged. Significant advancements have suppression (to understand the differences in immunobiology between been made in the development of RIT during the last 60 years. Progress the distinct histologies and biologic subtypes of cancer will be critical in chimerization and humanization of monoclonal antibodies, the use of for identifying the optimal antigen and/or immunologic pathway to antibody fragments, pre-targeting methods, improved dosimetric target for a particular cancer or to dissect mechanisms of intrinsic and models, and novel radionuclides — including alpha-emitters — have adaptive therapeutic resistance to immune-based treatments will be opened the field beyond simply B-cell non-Hodgkin lymphomas. critical for ensuring clinical success). In designing combination Several new RIT agents are under active clinical investigation for many immunotherapy regimens, clinical investigators should consider how solid tumor types. Many of these are entering phase II and III clinical chemotherapy impacts the immune system in order to guide the dose trials, and physicians and their patients with cancer should be and schedule for integrating chemotherapy and immunotherapy. In encouraged to consider participating in these important endeavors. particular, systematically defining the optimal drug dose and timing in relation to immune-based therapy in early-phase clinical studies is imperative for the design of phase II and III clinical trials with a higher
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LATINFARMA 2013 Resúmenes/Abstracts
C 033: IMMUNOTHERAPY FOR NON HODGKIN’S CO 168: IMMUNOTHERAPY COMBINATIONS LYMPHOMAS. ADVANCES IN THE USE OF MONOCLONAL Crombet T. ANTIBODIES Center of Molecular Immunology, La Habana, Cuba. Gracia Medina E.
Medical Oncology Department. National Institute of Oncology and Radiobiology, La Habana, Cuba. E-mail: [email protected] There is dissociation between the accumulation of scientific knowledge on the immune system and the rather limited results of
immunotherapy in the clinical setting. The development of therapeutic Immunotherapy has been used systematically for the treatment of non combinations by the efficient use of monoclonal antibodies and Hodgkin’s Lymphomas (NHL). Modifier of immune response, therapeutic vaccines for the treatment of malignant tumors has been monoclonal antibodies (MAb) and therapeutics cancer vaccines have claimed to be the way to make major advances. According the NCI shown different grade of outcomes in the management of this register of clinical trials, there are more than 5000 trials evaluating heterogeneous disease. immunotherapy combinations (vaccines or monoclonal antibodies with any other agent).Registered antibodies (rituximab, trastuzumab, Over the last ten years, the introduction of monoclonal antibodies bevacizumab, cetuximab) have been perceived mainly as molecularly (MAbs) and specifically the anti-CD20 monoclonal antibody Rituximab targeting drugs and not as agents capable to mobilize adaptive cellular has radically changed treatment of B-cell NHL. The use of Rituximab in response. Consequently, they have been combined with the the treatment of such lymphomas has increased significantly the recommended chemo or radiotherapy for each approved medical response rates, the progression free survival and overall survival in condition. Regarding classical active immunotherapy, the most both indolent and aggressive B-cell NHL. Based in the results achieved appealing strategy has been to combine drugs devoted to reverse with this drug new strategies of treatment have been developed using tumor induced immunosuppression and cancer vaccines. Several MAbs against different epitopes of the CD20 molecule and against compounds that controls the regulatory T cells, the MDSC or that other molecules expressed in the surface of lymphoma cell such as reverse the intrinsic T cell inhibition, including antibodies against CD19, CD22, CD37 and CD30. Moreover, the new drugs such as CTLA-4 and PD1 are under clinical evaluation. The Centre of Molecular conjugated antibodies, which are design to carry cytotoxic inside to the Immunology (CIM) in Havana has been carrying out a basic and clinical target cell; bivalents MAb, and MAb against molecules that regulate the research program in cancer immunotherapy since 1990’s. The immune response are showing encourages results and they are rapidly simultaneous presence of monoclonal antibodies and therapeutic moving into efficacy studies. In this review we present the advances in vaccines projects creates the platform for combinations.CIM product the use of MAb for the treatment of NHL. pipeline concentrates around three main targets: the EGFR system, the tumor cell gangliosides, and the reversion of the tumor-induced immune suppression. So far, CIM has conducted several trials of combining cancer vaccines or antibodies and vaccines in the clinical setting. The latest results of the CIM immunotherapy combination program will be presented. Beside the big scientific dilemma, combination trials have clinical trial methodology challenges. Trial designs should be perfected to choose the best patient population, endpoints and treatment schedules. CIM experience on clinical trial designs for combinations will also be discussed.
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LATINFARMA 2013 Resúmenes/Abstracts
CO 169: REVIEW OF TARGETED THERAPIES IN HER2 CO 170: CHEMO-IMMUNOTHERAPY FOR GASTRO- POSITIVE BREAST CANCER INTESTINAL MALIGNANCIES Falla R. Lima Pérez M.
Roche Centroamérica & Caribe. E-mail: [email protected] Clinical Oncology Service. Ameijeiras´Hospital, La Habana, Cuba.
In this presentation I will review the data regarding the discovery of Immunotherapy is an emerging modality for the treatment of the gen that codifies the overexpression of the Her2 receptor in breast gastrointestinal (GI) cancers. Although monoclonal antibody (mAb) cancer, and the clinical implications of this finding. therapy comprises a significant proportion of immunotherapies for GI cancers, early clinical trials have demonstrated the safety and The results of the early trials of Trastuzumab in metastatic breast feasibility of vaccine-based strategies to induce positive immunologic cancer her2 positive and what it meant for this population of poor endpoints in patients with GI cancers. Colorectal cancer could be the prognostic patients and the data of the early trials of trastuzumab in prototypic cancer for which successful immunotherapy of other GI early breast cancer, in the adjuvant and neoadjuvant setting. malignancies is based. To date, three mAb regimens have been It will be presented a new route of administration for Trastuzumab successfully used. These successes may result in combination antibody with its clinical information and safety data. therapies and the potential for further novel therapies for this disease. For esophageal, gastroesophageal, and gastric cancers, many mAb I will present the newest information about two new drugs that targets therapies have been tested, with some promising data. In advanced the her2 positive population of breast cancer patients, which are esophageal cancer, nimotuzumab in combination with radiotherapy Pertuzumab and TDM-1, reviewing its mechanism of action and the and cisplatin/5 Fu-radiotherapy was well tolerated and significantly clinical data available. improves response rate. The approval of trastuzumabin 2010 marked the first immunotherapy approved for any of the upper GI tumors.
Pancreatic cancer continues to be a fatal disease; despite the application of novel immunotherapies. The use of mAb therapy has not yielded significant improvements in the outcome of unresectable pancreatic cancer. However, in ASCO 2013 was presented a Phase IIb/IIIa clinical trial using nimotuzumab plus gemcitabine versus gemcitabine alone. This combination was safe and well tolerated, the 1- year survival rate is significant improved, especially in patients ≥ 62 years old. We believe that advances in immunology, increased knowledge of the tumor microenvironment, and prior successes will drive clinicians and researchers a like to achieve practical and effective immunotherapeutic strategies.
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LATINFARMA 2013 Resúmenes/Abstracts
CO 171: TARGETED THERAPIES AGAINST SOFT-TISSUE CO 172: FAMILY HAPLOIDENTICAL STEM CELL SARCOMAS (OR THE DEVIL IN THE DETAILS) TRANSPLANTATION OUTCOME IS NOT INFERIOR TO STANDARD MATCHED RELATED AND UNRELATED DONOR Cubedo R. TRANSPLANTATION: AN INTENTION-TO-TREAT ANALYSIS OF 611 PATIENTS WITH ACUTE LEUKEMIAS Grupo Español de Investigación en Sarcomas. Oncología Médica. Hospital Ciceri F. Universitario Puerta de Hierro Majadahonda. Madrid. España Hematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milano, Italy Sarcomas represent a wide cancer-class neatly different from other malignant tumors: rarity, overwhelming range and lack of really useful medical treatments in most cases being its landmarks. Introduction: Allogeneic transplantation of haemopoietic stem cells (HCT) from an HLA-matched related (MRD) or unrelated donor (MUD) World Health Organization Classification recognizes over 150 sarcoma is a curative option for patients (pts) affected by high-risk acute subtypes, most of them assigned to a hypothetical origin in a given leukemias. Recently, protocols of HCT from family haploidentical mesenchimal tissue. Sarcoma oncologists have found little help in a donors based on unmanipulated graft have potentially extended to classification system that, being more academic than real-world, was 100% of candidate patients the access to HCT as the best chance of not very helpful with the development and selection of useful cure. We offered a haploidentical HCT to adult pts lacking a matched treatments. donor in the appropriate time according to clinical indications (www.leukemianet.org, www.ebmt.org) as part of tratment algorithm The essential distinction between bone and soft-tissue sarcomas gave for primary disease. rise to focused and consistent research around adjuvant treatments that shacked up osteosarcoma prognosis from last century 80s Methods: The intention-to-treat (ITT) analysis of HCT in all onwards. Nevertheless, widespread optimism generated after such consecutive pts referred to our Institution between January 2004 and progress soon crashed into the soft-tissue sarcoma wall. Many experts June 2012. Overall survival analysis at lowest follow-up of 12 months felt that failure pivoted on our deep ignorance about sarcomagenesis from HCT. intrinsic molecular mechanisms. A whole new fundamental knowledge should back up a novel classification, this time a useful one for Results: 611 pts were candidated to HCT (median age 49 y, range 10- researchers and patients alike, nor for the taxonomist. 76; male 394), 120 pts (20%) received a transplant from a MRD; 187 pts (30%) activated a MUD search; 118 pts (19% of total pts, 63% of First light did not shone until 21st century first years, with the crucial MUD searches) received a MUD transplant; 12 pts (2%) received a discovery of cKIT role in the genesis of Gastro-Intestinal Stromal umbilical cord blood unit. In ITT analysis, 80% of candidate pts Tumours (GIST) and the subsequent development of Imatinib, a received HCT. Overall, 237 pts received a haplo-HCT (49%). The treatment as revolutionary as that of osteosarcoma, a quarter century median time from indication to HCT was 87 days. The median time before. from indication to activation was 12 days and the median time from activation to HCT was 114 days (range 22-824). Overall survival (OS) GIST unique history has opened a brand-new era in sarcoma analysis in ITT for the entire population was 43% at 2 years. Notably, understanding. Nowadays, molecular pathways related to 2y-OS in pts in CR at time of HCT according to donor source (MRD vs sarcomagenesis are known by the dozens. More and more molecules MUD vs haplo-HCT) was comparable (p=ns). are proposed as sarcoma targeted-therapies leeward of this new knowledge. But such an unexpected abundance give also rise to new Conclusion: Unmanipulated graft transplantation from family dilemmas, not so different from old ones; problems related to clinical haploidentical offers an option of cure not inferior to standard matched trial design, rational selection of molecules worth investigating, donor transplantation when planned as part of the treatment plan. regulatory issues within the rare-diseases context and, last but not least, financial weakness in former buoyant economies, now facing crisis. This revision conference will deal with such issues from a comprehensive point of view, bearing in mind published evidence, in order to pick objective facts out from mere wish.
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LATINFARMA 2013 Resúmenes/Abstracts
CO 173: LOSS OF MISMATCHED HLA AT LEUKEMIA RELAPSE Results: A total of 83 relapses occurred, 72 and 11 after related and AFTER HEMATOPOIETIC STEM CELL TRANSPLANTATION unrelated HSCT. We documented 21 relapses with genomic loss of the IS SIGNIFICANTLY ASSOCIATED WITH CLINICAL AND mismatched HLA (25% of relapses). HLA loss occurred predominantly IMMUNO-GENETIC HALLMARKS OF DONOR-VERSUS-HOST in patients with AML (n=19), and in all 21 cases after mismatched family donor HSCT. Accordingly, the presence of more than 4 HLA ALLOREACTIVITY mismatches between donor and recipient represented a significant risk Ciceri F. factor for HLA loss (HR: 4.17, 95% CI: 0.88-19.82, p=0.07). None of the disease-related factors tested correlated significantly with HLA loss. Hematology and BMT Unit, San Raffaele Scientific Institute, Milano, Italy. HLA loss occurred more frequently in pts with clinical Graft-vs.-Host Disease (GvHD), either acute (p=0.02) or chronic (p=0.007). Interestingly, HLA loss relapses occurred later than their “classical” Introduction: Genomic loss of mismatched HLA is a frequent counterparts (median time to relapse 307 vs. 116 days, range 56-784 mechanism by which leukemic cells can evade donor T cell-mediated vs. 10-579, p<0.0001), suggesting a long phase of immune equilibrium immune control and determine a clinical relapse after allogeneic between donor immune system and residual leukemia before mutant Hematopoietic Stem Cell Transplantation (HSCT), but the actual variants emergence. HLA loss relapses shared risk factors with incidence and risk factors for these relapses are unknown (Vago L et al, extramedullary relapses, suggesting a common drive leading to two N Engl J Med 2009). immune escape mechanisms. Methods: We retrospectively evaluated 230 consecutive HSCT from Conclusion: Loss of the mismatched HLA is a frequent mechanism of partially HLA mismatched donors performed in our center over the relapse after mismatched family donor HSCT, and is associated with last decade (family mismatched: 170; volunteer unrelated: 60). All donor-versus-host alloreactivity, as demonstrated by its correlation patients (pts) were affected by myeloid malignancies (AML: 179; MDS: with the number of donor-recipient HLA mismatches and with the 27; Others: 24) occurrence of GvHD.
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LATINFARMA 2013 Resúmenes/Abstracts
Taller sobre Daño Cerebral y Neuroprotección: Un Enfoque Básico y Clínico / Workshop on Brain Injury and Neuroprotection: A Basic and Clinical Approach
C 034: EPIDERMAL GROWTH FACTOR AND GROWTH CO 174: THERAPEUTIC EFFECT OF THE COMBINED USE OF HORMONE-RELEASING PEPTIDE-6: COM-BINED GROWTH HORMONE RELEASING PEPTIDE-6 AND THERAPEUTIC APPROACH FOR NEURODEGENERATIVE EPIDERMAL GROWTH FACTOR IN A PROXIMAL DISEASES NEUROPATHY MODEL
García del Barco D1, Subirós Martínez N1, Perez-Saad H1, Coro RM2, García del Barco D1, Pérez-Saad H1, Subirós N1, Rodríguez V2, Marín J3, Suárez Alba J1, Berlanga J.1 Falcón V1, Martín J1, Berlanga J.1
1 Center for Genetic Engineering and Biotechnology. La Habana, Cuba. E-mail: 1Centro de Ingeniería Genética y Biotecnología, La Habana, Cuba. E-mail: [email protected] [email protected] 2 National Center for Medical Information (INFOMED). La Habana, Cuba. 2Center of Cuban Neuroscience, La Habana, Cuba 3Institute of Pharmacy and Food Science, La Habana, Cuba.
Introduction: Considering the multiple pathophysiological mecha- nisms involved in neurodegenerative diseases (amyotrophic lateral Introduction: Amyotrophic lateral sclerosis (ALS) is a disease of the sclerosis, multiple sclerosis, stroke and others), we sustain the central nervous system characterized by loss of spinal motor neurons, convenience of a combined therapy to induce brain protection. Such for which no effective treatment exists. Epidermal growth factor (EGF) strategy could allow a concerted blockade of key points of the complex and growth hormone releasing peptide-6 (GHRP-6) have been pathophysiology characteristic of neurodegenerative diseases. considered as good candidates for the treatment of this disease, due to their well documented effects in eliciting pleiotropic and cell survival Material and methods: We have developed a therapeutic approach mechanisms. The aim of the present work was to evaluate the separate based on the co-administration of EGF+GHRP6 which is in agreement and combined effects of both peptides in an experimental animal with the principle that successful protection of the central nervous model of proximal neuropathy induced by 1,2 diacetylbenzene (1,2 system compels the protection of all the cells thereof. DAB) in mice. Results: Some of the pathophysiological phenomena produced during Material and methods: The evaluations were conducted by means of brain damage are targeted by the cytoprotective effects of both EGF behavioral tests (trapeze, tail suspension, gait pattern, and open field) and GHRP6. The most relevant of these effects act on oxidative stress- and by recording the complex muscle action potential (CMAP) in three induced damage, on mitochondrial dysfunction and on glutamate- different hind limb segments: proximal S1, medial S2, and distal S3. induced excytotoxicity. All this properties can explain the salutary therapeutic effects of EGF+GHRP6 co-administration observed in Results: Intraperitoneal daily administration of 1,2 DAB produced different experimental models of amyotrophic lateral sclerosis, significant reduction in body weight, muscle strength, extensor reflex, multiple sclerosis and stroke during preclinical evaluations. spontaneous activity, and changes in gait pattern parameters. In parallel, 1,2 DAB produced significant prolongation of onset latency Conclusions: The combined therapy of EGF and GHRP6 simultaneously and decrease in amplitude of CMAP and in the integrated complex targets different patho-physiological key points involving not only action potential index. Daily administration of the separate compounds neurons, but also glial cells and vascular endothelium. In the biology of did not accelerate the recovery of the affected parameters, except for brain damage, neuroprotection is a limited concept, so it is necessary to the gait pattern. The combined treatment produced significant think of a more complete praxis involving brain-protection. The results improvement in behavioral parameters, as well as in of this work could be considered as an example of therapeutic electrophysiological recovery, particularly in the proximal segment of alternative holistically directed to brain-protection. CMAP. Conclusions: The results confirm the proximal character of 1,2 DAB neuropathy, and suggest that combined therapy with EGF and GHRP-6 might be a good therapeutic strategy for the treatment of ALS.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S103
LATINFARMA 2013 Resúmenes/Abstracts
CO 175: REDUCING ALZHEIMER’S DISEASE Β-AMYLOID BY CO 176: NEW EVIDENCES FROM NASAL NEUROEPO IN MANIPULATING IL-12/IL-23 SIGNALING ALZHEIMER NON-TRANSGENIC ANIMAL MODEL
Lopategui Cabezas I1,Prokop S2, vom Berg J3, Kälin R2, Werner A2, García Rodríguez JC1, Rodríguez Cruz Y3, Hariri Mustafa M2, Mair F3, Becher B3, Heppner FL2. Desrumaux C1,2,3, Keller E2, Naert G2, García-Barceló MC3, Tangui M.2
1Universidad de Ciencias Médicas de La Habana. ICBP Victoria de Girón, La 1Coordinator of Life Science and Nanosecurity. Scientific Advisor’s Office. State Habana, Cuba. E-mail: [email protected] Council. Havana, Cuba. E-mail: [email protected] 2Charite-Universitätsmedizin Berlin, Department of Neuropathology, Berlin, 2University of Montpellier 2, Montpellier, France. E-mail: tangui.maurice@univ- Germany montp2.fr 3University of Zürich, Institute of Experimental Immunology, Zürich, Switzerland 3Histology Department, Preclinical and Basic Science Institute; Havana Medical University, Havana Cuba.
Introduction: Alzheimer's disease (AD) is characterized by the presence of amyloid deposits in the patient’s brain. AD pathology Erythropoietin (EPO) promotes neurogenesis and neuroprotection. We displays an inflammatory component characterized by the release of here compared the protection induced by two EPO formulations in a pro-inflammatory cytokines particularly in response to β-amyloid. rodent model of Alzheimer’s disease (AD): rHu-EPO and a low sialic form, Neuro-EPO. We used the intracerebroventricular administration Aim: The aim of this work is to assess the impact of manipulating IL-12 of aggregated Aβ25- 35 peptide, a non-transgenic AD model. rHu-EPO and IL-23 signalling pathways in cerebral amyloidosis. was tested at 125–500 μg/kg intraperitoneally and Neuro-EPO at 62– Methods: CD45, CD11b and IL-12/IL-23p40 were studied by flow 250 μg/kg intranasally (IN). Behavioral procedures included cytometry in cells isolated from brains of APPPS1 transgenic mice, spontaneous alternation, passive avoidance, water-maze and object biomodels of AD. Morphometric analysis of Aß plaques was performed recognition, to address spatial and non-spatial, short- and long-term in p40, p19, p35 (IL-12/IL-23 cytokines subunits) deficient APPPS1 memories. Biochemical markers of Aβ25-35 toxicity in the mouse mice and also in animals treated with anti-p40 antibody and controls. hippocampus were examined and cell loss in the CA1 layer was determined. rHu-EPO and Neuro-EPO led to a significant prevention of Results: We observed the production of IL-12/IL-23p40 by microglia. A25-3β5-induced learning deficits. Both EPO formulations prevented Genetic ablation of p40, p35 and p19 subunits lead a substantial the induction of lipid peroxidation in the hippocampus, showing an reduction of cerebral amyloid load in mice APPPS1 of 120 and 250 antioxidant activity. rHu-EPO (250 μg/kg) or Neuro-EPO (125 μg/kg) days. Peripheral administration of anti-p40 antibody treatment results prevented the A2β5-35- induced increase in Bax level, TNFα and IL-1β in a significant reduction of cerebral β-amyloidosis on these AD production and decrease in Akt activation. A significant prevention of models. the Aβ25-35-induced cell loss in Conclusions: Our results suggest that the manipulation of IL-12/IL-23 CA1 was also observed. EPO is neuroprotective in the Aβ25-35 AD signalling modulates cerebral amyloidosis and poses a novel potential model, confirming its potential as an endogenous neuroprotection pharmacological target to combat AD. system that could be boosted for therapeutic efficacy. We here identified a new IN formulation of EPO showing high neuroprotective activity. Considering its efficacy, ease and safety, IN Neuro-EPO is a new promising therapeutic agent in AD.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S104
LATINFARMA 2013 Resúmenes/Abstracts
CO 177: BEHAVIOUR OF IMMUNOLOGIC HUMORAL C 035: EXPERIMENTAL HYPOTHYROIDISM DURING MARKERS IN NOT INFECTIOUS NEUROLOGIC ENTITIES LACTATION ALTERS NEUROENERGETIC IN RAT CEREBELLUM León-Toirac EJ1, Ponce-de-León O2, Cubas I3, Montesino S4, La-Rosa D5, Chávez E1, Agüero MV1, Olano R.3 de Assis AM1, Müller AP1, Longoni A1, Farina M3, Perry MLS1,2, Souza DO.1,2 1Neurology and Neurosurgery Institute. Calle 29 esquina a D. Plaza de la Revolución, Havana, Cuba. E-mail: [email protected] Phone number: 1Programa de Pós graduação em Bioquímica, Instituto de Ciências Biológicas da 834-55-44. Saúde, Universidade Federal do Rio grande do Sul, Porto Alegre, RS 90035-003, 2Molecular Immunology Center. Havana, Cuba. Brazil. 3 Endocrinology National Institute. Havana, Cuba. 2Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto 4Pediatric Hospital Marfán. Havana, Cuba. Alegre, RS 90035-003, Brazil. 5Gastroenterology National Institute. Havana, Cuba. 3Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade
Federal de Santa Catarina, 88040-900, Florianópolis, SC, Brazil. In spite of current scientist - technician development on the field of neuroimmunology, the access to the humoral immune mediators inside Thyroid hormone deficiency during perinatal development results in the nervous central system keeps on being across the lumbar puncture, significant alterations in neurological functions. The relationship procedure that implies risks and contraindications. At the same time, between such events and brain metabolism is not completely not infectious neurologic entities show a fluctuant etiopathogenic understood. The aim of this study was to investigate the effects of pattern that goes from hypersensitivity to autoimmunity. This could be hypothyroidism on leucine, mannose, glucose, and lactate metabolism confirmed by serologic inflammatory mediators produced by immune in rat cerebellar slices. Experimental hypothyroidism was induced by system. To value the utility of the profile of humoral immune markers exposing mothers and pups to propylthiouracil (PTU) until weaning - for the principal neurological not infectious entities it was performed a postnatal day 21. Metabolic analyses were performed in postnatal day descriptive and transversal work in 353 adult patients attended in the 10 (PND10) and 21 (PND21) animals. A matching group of animals immunology service of the Neurology Institute, for 2 years, by received the same oral treatment also after weaning until adulthood evaluating clinical and humoral immune profile processed with postnatal day 60 (PND60) with T3 supplement during lactation (P1- turbidimetric and fluorescent immunoassays. Humoral immune P21). In PND21 animals, PTU treatment significantly increased the rate markers digression happened in less than one third of the patients of leucine oxidation to CO2, although glucose and lactate oxidations evaluated (x: 80.87 SD: 29.86), with predominance in inflammatory were not affected. PTU treatment also increased the oxidation of and vascular neurological entities. In about the half of cases with leucine to CO2 at PND60 (adult animals). PND10 hypothyroidism inflammatory and cerebrovascular diseases there were increased animals showed a decrease in conversion of mannose to glycolipids autoreactivity serologic markers (p≤0.001). The clinical-laboratory and glycoprotein compared to control group. However, PTU treatment dissociation found in this study faces us again to the dilemma of increased the conversion of mannose to glycolipids and glycoprotein in humoral immune biomarkers reliability for evaluation of neurological PND21 animals. The replacement of T3 normalized mannose and not infectious entities. The need of more robust investigation designs leucine metabolism in adult rats. These results indicate that deficits in and more sensitive diagnostic means of laboratory keep on being thyroid hormones during lactation could delay or alter brain imperative in this context. development and metabolism.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S105
LATINFARMA 2013 Resúmenes/Abstracts
CO 178: PARTICIPATION OF THE MEDIAL AMYGDALA- CO 179: EFFECTS OF BACLOFEN AND VIGABATRIN ON HIPPOCAMPUS CIRCUIT ON THE DETECTION OF AN ALARM GABAERGIC TRANSMISSION IN THE RAT NUCLEUS PHEROMONE ASSOCIATED TO AN AVERSIVE STIMULUS ACCUMBENS DURING COCAINE WITHDRAWAL
Molina-Jiménez T1, Gutiérrez-García AG1,2, Contreras CM.1,3 Pastrana A, Espinosa K, Redondo C, Mercado J.
1Laboratorio de Neurofarmacología del Instituto de Neuroetología, Universidad School of Medicine, University of Cartagena. Cartagena, Colombia. E-mail: Veracruzana. Xalapa, Veracruz. México. [email protected] 2Facultad de Psicología, Universidad Veracruzana. Xalapa, Veracruz. México. 3Unidad Periférica Xalapa, Instituto de Investigaciones Biomédicas, UNAM. Xalapa, Veracruz. México. E-mails: [email protected], [email protected], [email protected] Psychostimulant drugs like cocaine by their reinforcing and hedonic properties can lead to addiction in our society. Cessation of cocaine use in the addicted people produces a withdrawal syndrome which can lead to craving and later relapse in its consumption. The available Introduction: Medial amygdala nucleus is implicated in the pharmacological approaches have not demonstrated an improve in this modulation of unconditioned fear behavior elicited by predator or co- situation. This study researched in a model of cocaine withdrawal in specifics odors. Herein, 2-heptanone is an alarm pheromone that rats as GABA levels in the nucleus accumbens were affected and as increases anxiety-like behaviors and also increases the neuronal firing these levels in the withdrawal period were modified by the (±)baclofen rate in basal amygdale nucleus. However, the involvement of medial and vigabatrin. A 28-day study was designed. It consisted of six groups amygdaline-hippocampal circuit in processing fear memories related which received in this time: The first group, saline. The second one, to odors is partially known. The aim of this study was to explore the cocaine. The third group received cocaine during seven days and possible time-dependent neuronal firing rate changes of medial withdrawal with saline for 21 days. A fourth group received cocaine for amygdalina-hippocampus circuit after simultaneous 2-heptanone seven days and later withdrawal during 21 days. The fifth one received odors and electric footshocks exposure. cocaine for seven days, withdrawal during 18 days and (±)baclofen for Material and methods: Adult male Wistar rats from control group (n three days. And the sixth group received cocaine for seven days, = 10) were introduced into a clean plaxiglass cage and twenty four withdrawal during 18 days and vigabatrin for three days. The obtained later, single-unit extracellular recordings from the hippocampus (CA1- results showed statistically significant alteration in the GABA levels in CA3) neurons identified by their connection to medial amygdala were the following way: The second and fifth group had a decrease and the obtained. Other two groups of rats were introduced into a similar-cage third, fourth and sixth group showed an increase in the levels of GABA. previously impregnated with 2-heptanone, and simultaneously These results could be explained due to correlation of dopaminergic received a short-series of unavoidable electrical footshocks. Twenty and GABAergic mechanisms in the nucleus accumbens through D2 and four (n = 11) and forty eight (n = 11) hours later we obtained single GABAB receptors respectively. The changes observed in the GABAergic unit recordings. activity could be useful in the development of new pharmacological strategies in addiction. These results pose the possibility of the use of Results: The hippocampal neuronal firing rate was higher the in 2- (±)baclofen or vigabatrin in cocaine addicted people depending on if heptanone+shocks groups [F(2, 2304) = 33.75, p < 0.001] than the they are active consumers or if they are in the withdrawal period. other experimental groups, 48 h after exposure to the combined These findings improve our neurochemistry comprehension of the stimulation, but not after 24 h. The peri-stimulus histogram analysis disease named addiction. illustrated an increased firing rate after medial amygdala electrical stimulation [F (2,256)= 42.85, p < 0.001] 48 h after stimulation. First order interval distribution histogram analysis showed that hippocampal neurons from both groups previously exposed to aversive stimulation reduced its first order intervals of firing. Conclusion: 48 h after a single exposition to 2-heptanone and footshocks seemingly produces a facilitation of medial amygdala- hippocampus circuit, probably reflecting a first step in the formation of a fear memory.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S106
LATINFARMA 2013 Resúmenes/Abstracts
CO 180: A NEW ANTICONVULSANT COMPOUND PREVENTS CO 181: NEW NEUROPROTECTOR THERAPIES FOR THE OXIDATIVE DAMAGE INDUCED BY PENTYLENE- MULTIPLE SCLEROSIS AND STROKE TETRAZOLE AND EXERTS ANTIDEPRESSANT-LIKE EFFECTS Pentón-Rol G1, Marín-Prida J2, Llópiz Arzuaga A1, Cervantes-Llanos M1, IN MICE Pavón-Fuentes N3, Falcón-Cama V1, Fernández-Massó JR1, Nazabal- Pastore Va,b, Wasowski Ca, Bruno-Blanch L.b, Marder M.a Gálvez M1, Cruz-Ramírez A1, Pardo -Andreu G2, Pentón-Arias E1.
1 aInstituto de Química y Fisicoquímica Biológicas, Facultad de Farmacia y Center for Genetic Engineering and Biotechnology (CIGB). Ave 31 e/ 158 y 190, Cubanacan, Playa, Havana City PO Box 6162, Havana 10600, Cuba. E-mail: [email protected] Bioquímica, UBA. Argentina. 2Center for Research and Biological Evaluations (CEIEB), Institute of Pharmacy and Food, bFacultad de Ciencias Exactas. Dpto de Cs. Biologicas. UNLP. Argentina. E-mail: University of Havana, Ave 23 e/ 214 y 222 PO Box 430, Havana, Cuba [email protected] 3International Center for Neurological Restoration (CIREN) Ave 25 No 15805, Havana, Cuba.
Epilepsy is recognized as one of the most common and serious Introduction: Neurological disorders, such as multiple sclerosis and neurological disorder affecting 1-2% of the world’s population. Among stroke have been increasing worldwide; therefore, new therapeutic various factors supposed to play role in epilepsy, oxidative stress and strategies focused on neuroprotection and neuroregeneration are reactive species (ROS) in seizure disorders have recently emerged. The required. We studied molecular mechanisms involved in the effect of C- most important effect of free radicals is lipid peroxidation (LP), which Phycocyanin (C-Pc) on multiple sclerosis (MS) and stroke. causes disruption of cell membrane thereby leading to their destruction. An increased of free radicals also decreased glutathione Methods and Results: In the first experimental block, we (GSH) concentration in the epileptic focus. We have synthesized N- demonstrated that C-Pc induced regulatory T cells in mononuclear butyl-1,2,3-oxathiazolidine-4-one-2,2-dioxide (NBOD), a bioisoster of cells from MS patients and in the Experimental Autoimmune trimethadione (a classical anticonvulsant), which showed Encephalomyelitis (EAE) model, confirming the authenticity of the anticonvulsant properties in maximal electroshock seizure (MES) and Tolerance Dominant paradigm in autoimmune diseases. On the other hand, ultra-structural analyses using Transmission Electron pentylenetetrazole (scPTZ) tests in mice, with ED50 of 0.06 mg/kg and 18 mg/kg, respectively. Many reports have suggested that ROS Microscopy demonstrated that C-Pc was able to remyelinate axons and generation may underlie the convulsant and neurotoxic effects of PTZ. the gene expression profile of Microarray studies identified common NBOD countered the effects of PTZ and protected brain from oxidative and specific processes modulated by C-Pc and beta IFN, suggesting the damage by decreasing LP and restoring GSH content. need of a combined Multiple Sclerosis therapy with two components targeting the main steps of the MS pathogenic mechanism, one related Additionally, major depression is common in patients with epilepsy to immune dysfunction and the other directed towards and correlates with a poor quality of life so a treatment with neurodegenerative changes. antidepressants is required. The continuous search for new, safer, and more effective drugs with both anticonvulsant and antidepressant In the second experimental block, we showed a neuroprotective effect activity is therefore imperative and is a challenge in medicinal of C-Pc and its tetrapyrrolic ring of Phycocyanobilin (PCB) on cerebral chemistry. The antidepressant activity of NBOD was also evaluated. A mitochondria exposed to neurotoxic agents, where it prevents cellular significant effect in the forced swimming and tail suspension tests (FST death and pro-apoptotic mitochondrial events. Moreover, an in vivo and TST), the most widely used models for assessing antidepressant neuroprotective effect was demonstrated in a global activity in rodents, was observed. ischemia/reperfusion (I/R) in Gerbils, retina focal I/R and a chronic brain hypo-perfusion model in rats. According to their molecular targets antiepileptic drugs have been categorized in three groups: those that block voltage gated ion channels Conclusion: Our results support C-Pc, its derivatives and combinations (Na and Ca), those that enhance GABAergic inhibition or reduce as strong therapeutic candidates for the treatment of MS and stroke. glutamatergic excitation. Preliminary studies on the mechanism of action of NBOD suggested that its anticonvulsant effect is not mediated via the GABAA receptor and that Na channels would be involved in its antidepressant activity.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S107
LATINFARMA 2013 Resúmenes/Abstracts
Simposio: Perspectivas de las Drogas Huérfanas en Latinoamérica: Desde la Investigación a la Accesibilidad / Symposium: Perspectives of Orphan Drugs in Latin America: From the Research to the Accesibility
C 036: IMPACT OF RARE DISEASES IN THE HEALTH POLICIES C 037: ORPHAN DRUGS: DEFINITIONS, RESEARCH & IN COUNTRIES UNDER DEVELOPMENT. EXPERIENCES AT DEVELOPMENT, MASTER PLANS, ACCESIBILITY AND LATIN-AMERICA AND CARIBBEAN (LA&C) BIOETHICAL ASPECTS Llera VA. Roldán E.
ICORD/GEISER, Argentina. GEISER Foundation, Buenos Aires – Argentina. E-mail: [email protected]
The inclusion of the Rare Diseases as a nosology within Public Health Orphan drugs are those in which cost of discovery and production was an initiative from the affected citizens living in USA during the overpass the recovery of Investments, hence there are only few 70´s. Ten years after, in such country and in collaboration with public available usually at a very high cost and not in all the countries. institutions, the first specific law was approved in 1983 (The Orphan Therefore new formulas require to be managed in order to cover Drug Act). The law defined the rare conditions and its treatments: the unmet medical needs and comply assistance to the population with orphan drugs. After thirty years from this first step, the concept was equality. These formulas includes the understanding of the magnitude reinforced in the developed world, and the R&D expansion and of the problem, the achievement of specific health and research investment was six fold increased from basal, especially in the policies, the organization of regional nets of information and research biotechnological area. Afterward LA&C was visualized handed by within master plans, and political decisions well harmonized with the GEISER Foundation, starting at 2002. Following 8 years of lobbying common interest of the region. We hereby illustrate the current national laws were incorporated at the official agenda of many LA&C scenario in Latin-American and Caribbean countries with some countries. This new scenario in the region validates open debates that examples and propose actions. Typically, researchers’ interested in facilitate approaching and links in the region. The GEISER Foundation orphan drugs are challenged by the lacks of information, poor proposal is the translation of the technological management within the development of diagnostic techniques, difficulties to contact patients, region in search of a rationale and a strong unified position, which in lack of financial support and/or academic programs, and with turn may provide accessible medical solutions for the people affected frequency minimal peer impact, discouraging the individual initiatives. by the rare diseases. Nevertheless, the field of orphan drugs is now envisioned as one of the main sources of discovery in the fields of biology and medicine, and one of the most productive in knowledge, goods, and human education. Therefore the current conditions should be quickly transformed and insert the capabilities of the local production within global master plans built under consensus. Many academic centers in Latin-America and Caribbean are highly prestigious world-wide and their human resources and knowledge will be welcome to the research and development of orphan products. Some differential bioethics aspects and transparency of interest will also be discussed as the affected people should be considered within the vulnerable population from several points of view.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S108
LATINFARMA 2013 Resúmenes/Abstracts
C 038: ECONOMIC EVALUATION AND ORPHAN DRUGS C 039: INTERNATIONAL COOPERATION AND ACTIONS FOR ORPHAN DRUGS. INCLUDING LATIN-AMERICA AND Gálvez González AM. CARIBBEAN WITHIN THE INTERNATIONAL LANDSCAPE Escuela Nacional de Salud Pública de Cuba, La Habana, Cuba. Llera VA.
ICORD/GEISER, Argentina. Introduction: Orphan drugs financing decisions are related with different criterion. Literature reports various papers explaining the importance of economical assessment on orphan drugs designed to In the field of rare disorders the quality of epidemiological data and treat rare diseases. knowledge of the regional situation is what permits the addition of Objective: The main goal of this paper is to highlight the importance of efforts for the development of strategies in the search of solutions. Due economic evaluation of orphan drugs for the decision making and its to the “rare” nature of the medical conditions the isolated plans has fail complexity in different context. or resulted costly. There are around 7 thousands of different rare diseases that demands medical research and may account for 6% of the Method: A review of literature was done employing Big 6 model for population. In order to expedite efficient solutions, as much as possible, the information competences management. Consults to experts in the international research community if jointly working in this sense. pharmacoeconomy, family doctors and decision makers in drugs area The possibilities of introducing LA&C countries are now approaching. were done. Therefore we will develop the conditions and chances required to fulfill this joint commitment. Results: The economic analysis of orphan drugs is a public health problem. Presently, it is a theme exposed in different space of discussion. Other economical items are important too, for example, to guarantee the equitative access to orphan drugs, the importance of enhance the knowledge in professionals about this subject, costs analysis , burden of rare diseases, financing and budgetary impact of orphan drugs. Finally international cooperation is identified as a key to develop future studies.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S109
LATINFARMA 2013 Resúmenes/Abstracts
Simposio de Farmacogenética y Farmacogenómica / Symposium of Pharmacogenetic and Pharmacogenomic
C 040: USE OF GENETICALLY MODIFIED MOUSE MODELS TO CO 182: IMMUNOGENETICS AND BIOINFORMATICS IN THE STUDY MECHANISMS OF CHEMICALLY-INDUCED LIVER PHARMACOGENETIC PROFILE OF VACCINES AND CANCER RISK BIOTECHNOLOGICAL PHARMACEUTICALS Grant DM. Serrano-Barrera OR.
Department of Pharmacology and Toxicology, University of Toronto, Toronto, Hospital General Docente Ernesto Guevara, Las Tunas, Cuba. Ave. Carlos J. Finlay, Canada. s/n. E-mails: [email protected], [email protected]
Liver cancer is the 5th most common malignancy and the 3rd most Pharmacogenetic studies have focused so far mainly on drugs from the common cause of cancer-related death, reflecting a very poor 5-year more traditional pharmaceutical industry, while recombinant proteins survival rate of less than 20%. Major liver cancer risk factors include and vaccines have received less much attention. For the latter, the hepatitis B/C infection, liver cirrhosis and obesity, which produce a immune system is sometimes involved or could be even critical, as it is tumor growth promoting, pro-inflammatory pathological state. for abacavir, a model drug in pharmacogenetics. Bioinformatics could However, liver cancer risk has also been linked to exposure to certain be of aid in the prediction and assessment of potential immune- genotoxic environmental chemicals, of which the most widely used mediated reactions by pharmaceuticals, as well as for the comparison liver-selective carcinogens in experimental rodent studies are the of responses between animal models and humans in order to select the aromatic amine 4-aminobiphenyl (ABP) and the nitrosamine best epitopes or assessed adverse events. A number of computational diethylnitrosamine (DEN). Studies in our laboratory are aimed at simulations was used to model the immune responses against two utilizing genetically modified mice to investigate the contributions of exogenous proteins: recombinant streptokinase, UniProt entry Q53284, carcinogen bioactivation, DNA damage, oxidative stress, cellular and hepatitis B surface antigen, GenBank entry X02763.1. The primary damage and inflammatory responses to the carcinogenicity of ABP and data and tools used were their primary sequences, algorithms to DEN. We compared the tumorigenicity of ABP in postnatally exposed identify B epitopes and tools to determine T-cell epitopes against class I male and female wild-type and arylamine N-acetyltransferase (NAT)- and II HLA molecules (HLA-A*0201, HLA-DRB1*0301 and HLA- deficient mice, and we observed that male NAT-deficient mice were DRB1*0701) and murine haplotypes H2-Kd and H2-Kk. Peptides with significantly protected against eventual tumor growth and female mice the highest scores were selected in each case. ABCPred algorithm were tumor-resistant regardless of strain. However, these differences showed a better capacity to predict B epitopes, while programs to in tumor incidence did not correlate with differences in measures of model T cell response had much higher matching results. There was an acute ABP-induced DNA damage or mutations, suggesting that the sex overlap among peptides identified by the immunoinformatic tools. and strain differences in tumor incidence are driven by events that are Region 100-150 from streptokinase contains a peptide which ranked independent of the genotoxicity of ABP. ABP and DEN produced no first with the two algorithms used to model T cell response. The acute hepatotoxicity at tumor-inducing doses in either sex or strain, epitopes generated by H2-Kk haplotype had a better similarity with and only DEN produced a modest acute elevation in the pro- those presented by selected HLA molecules, both for streptokinase and inflammatory cytokine IL-6. We are currently conducting studies to hepatitis B surface antigen. No evidence was found to support the compare the time course of chronic hepatotoxic, oxidative stress controversial relationship between hepatitis B vaccination and multiple inducing, pro-inflammatory and proliferative effects of postnatal ABP sclerosis. The identification of immunodominant epitopes, which could and DEN exposure. Using CYP1A2-deficient mice, we have also recently be delineated with the use of computational methods even before discovered that at the tumorigenic doses of ABP that are commonly inoculation in a laboratory animal, could be the base of modifications of used in rodent studies, the cytochrome P450 isoform CYP2E1 is likely the sequence that reduce or increase the immunogenicity, if needed. to be quantitatively more important than CYP1A2 in the bioactivation of ABP to its N-hydroxylated metabolite. Overall, we hope that our studies will shed light on the mechanisms that influence risk for liver tumor growth following chemical exposure, and lead to the identification of treatment or prevention measures for this disease in human at-risk populations.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S110
LATINFARMA 2013 Resúmenes/Abstracts
CO 183: PROTEIN-PROTEIN INTERACTIONS AND GENE CO 184: APPLICATION OF DNA MICROARRAYS TECHNOLOGY EXPRESSION STUDIES IDENTIFY MOLECULAR MECHA- FOR STUDY IN HUMAN BLOOD SAMPLES THE SPECIFIC NISMS DRIVING THE CYTOTOXIC EFFECT OF CIGB-552 GENE EXPRESSION PROFILE FOR GENDER
Fernández Massó JR1, Oliva Arguellez B2, Delgado-Roche L3, Tejeda Y1, Guillén I, Palenzuela D, Dueñas S, Fernández JR, Miranda J, Bringas R Palenzuela Gardon D1, Guillén Perez I1, Vázquez Blomquist D1, Novoa and Novoa LI. Perez L1, Vallespi M2. Center for Genetic Engineering and Biotechnology. 31 Avenue, between 158 and 1Department of Genomic, Center for Genetic Engineering and Biotechnology, 192, Cubanacán, Playa. Havana, Cuba. E-mail: [email protected] Cubanacan, P.O. Box 6162, 10600 Havana, Cuba. E-mail: [email protected] 2Pharmaceutical Department, Laboratory of Cancer Biology, Center for Genetic Engineering and Biotechnology, Cubanacan, P.O. Box 6162, 10600 Havana, Cuba Introduction: Human peripheral blood is a promising material for 3Center of Studies for Research and Biological Evaluations, Pharmacy and Food biomedical research. This tissue is increasingly considered a valuable Sciences College, University of Havana, 19250 Havana, Cuba. source of RNA for gene expression profiling (GEP) because blood GEPs may be used to determine whether toxicological or disease-related events have occurred in inaccessible target tissues. However, various Introduction: The CIGB-552 shows cytotoxic effect on different kinds of biological and technological factors result in a large degree of tumoral cell lines. Using yeast two hybrid studies and microarrays we variation in blood gene expression profiles. For example there is an identified several mechanism involved in the cytotoxic activity of CIGB- interindividual sample variation associated with donor sex. Sex and the 552. expression of genes related to this can be considered an environmental factor that can change the outcome of treatment. Peripheral blood is a Results: Y2H identified Commd1 as a target of CIGB-552. Validation source of cells to investigate the individual response to treatment, was conducted by IP and RNA interference studies. Microarray studies predict diseases (cancer, metabolic diseases and autoimmune detected a change in the expression profile of classes of genes conditions). associated with cell cycle arrest. Analyses by flow cytometry of the tumor cells treated with CIGB-552, showed the absence of the G2/M Methodology: Our study was based on gene expression analysis of 13 peak and the accumulations of the cells in S phase. Furthermore, cells healthy subjects, 5 women and 8 men. The blood mononuclear cells undergoing apoptosis after a 24-h treatment were observed by a were concentrated, and total RNA was isolated for analysis of gene significant increase in the sub-G1 peak. Here we show that CIGB-552 expression using the Affymetrix Gene Chip technology. DNA induces a cell cycle arrest, followed by cell death. Finally, the studies microarrays technology is an efficient tool for the quantification of identified a second set of genes that provide evidence of an altered gene expression profile in the cell. This technology is a key tool for redox balance. To confirm these several Oxidative Stress Variables understanding the biology of systems, and discovering new therapeutic were measured. We found that CIGB-552 decreases the antioxidant targets for the treatment and diagnosis of diseases. The results were capacity and induces the peroxidation of proteins and lipids in the obtained by using a scanner fluorescent, and the numerical data were tumor cells. analyzed using the software's BRB Array Tools and Tree-View. Conclusions: Altogether, this study provides new insights into the Results: The results by applying a supervised cluster of expression, mechanism of action of the peptide CIGB-552, which could be relevant showed a group of 37 genes that differentiate groups of individuals by in the design of future anticancer therapies. gender. These genes were analyzed according to their biological function and chromosomal location, with most of them located on the sex chromosomes X and Y. Conclusions: These results provide new insights into the genetic makeup that distinguishes both sexes and that might be associated with disease condition, or normal physiological stages of human aging.
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LATINFARMA 2013 Resúmenes/Abstracts
CO 185: EARLY SAT1 AND FAS GENE EXPRESSION IN CO 186: EXPLORATION OF A SET OF THE ANTITUMOR SUBJECTS TREATED WITH HEBERPAG FORMULATION PEPTIDE CIGB-300-REGULATED GENES IN AML CELL LINES
Bello C1, Vazquez D1, Tejeda Y1, Taylor CY1, Izquierdo Y3, Palenzuela D1, Vázquez-Blomquist D1, Miranda J2, Perera Y3, Taylor C1, Villarreal A1, Bello IJ.2 Novoa LI1, Palenzuela D1, Perea S3.
1Genomic, 2Clinical Assay, 3Pharmaceutical Divisions. Center for Genetic 1Genomic and Immunodiagnostic Division, 2Bioinformatic Department, Engineering and Biotechnology (CIGB). Ave 31 e/ 158 y 190, Playa, 10600 3Pharmaceutical Division. Center for Genetic Engineering and Biotechnology, 31 Havana, Cuba. E-mail: [email protected] entre 158 y 190, Cubanacán, Playa, Cuba. E-mail: [email protected]
Introduction: Interferons (IFNs) are pleiotropic proteins of the family Introduction: CIGB-300 is a peptide-based drug, in investigation for of cytokines. Its antiproliferative function has been taken into account oncologic application. It targets the phosphoaceptor site of CK2 for several clinical therapies against malignant diseases. New substrates in vitro and in vivo. The effects of this peptide has been formulation (HeberPag) based in the alpha-gamma IFNs combination studied in human cell lines derived from different type of cancers and a has been designed and produced at the Center for Genetic Engineering wide range of experiments have been carried out in order to and Biotechnology. HeberPag had been successfully used in the understand its mechanism of action; some of them as Pull Down, SSH treatment of non-melanoma skin carcinoma. The objective of the or Proteomic have generated a large data to take into account. CIGB300 present work is to obtain more evidences into the mode of action of has already entered in Clinical Trial phase, being well tolerated in HeberPag, through mRNA differential expression in a set of samples women with cervical malignancies. Recently, an exploratory clinical from subjects treated with this formulation. Protocol in acute leukemia has started. The investigation of the mechanisms involved in the action of CIGB-300 in leukemia is then of Methods: For this purpose we selected the stat1 and fas gen, activated importance. by IFNs and related with signal transcription and apoptosis events respectively. A total of 13 samples was used, six from healthy subjects Material and methods: We used quantitative PCR (qPCR), with and seven from Mycosis Fungoides patients. The samples were taken SYBRGreen chemistry and rotor type equipment, to measure the at different times after HeberPag administration. The mRNA of blood relative expression changes [respect to an untreated control] of a set of samples was obtained with high quality by Paxgen kit, Superscript II genes in two myeloid leukemia-derived cell lines after a time-serial (Invitrogene) was used for reverse transcription and gene treatment with CIGB-300. Appropriate controls were also used. Change amplifications were carried out by real time PCR (qPCR) using factors were obtained by the statistical software REST-MCS. Additional SYBRgreen (ABgen). The Ct and efficiency values obtained by qPCR and statistical analysis by SAM and data exploring methods were also Linreg(PCR) software respectively, were used to calculate the factor carried out. change respect to the control (t 0h) in the RestRG software. Results: We obtained a differential gene expression along the time- Results: All individuals include in the study had the maximum gene serial with CIGB-300 compared to experimental controls. It points to expression level in the first hours after HeberPag administrations. the possible role of some specific genes into the peptide mechanism in these AML models. Conclusions: This result suggests the early actions of this product over important genes in antiproliferative pathways. Conclusions: This is a first step into the understanding of the mode of action of CIGB-300 in leukemia cell lines.
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LATINFARMA 2013 Resúmenes/Abstracts
CO 187: OAS-1 AS PHARMACODYNAMIC BIOMARKER OF been successful in clinical treatment of advanced, recurrent, resistant to ACTION OF CIGB-128 IN MYFIC AND SOFÍA CLINIC TRIALS previous treatments basal and squamous cell skin carcinomas. Other applications of CIGB-128 have been used in patients with mycosis Izquierdo Y1, Vázquez D2, Tejeda Y2, Bello C2, Taylor C2, García I, García fungoide, a non-Hodgkin type of cancer that is characterized by a Y, Valenzuela C, Novoa L, Palenzuela D2, Bello I3. proliferation of T cells and the occurrence of cutaneous lesions that can include several tumors. In the present work a sample of 12 patients 1División de Farmacéuticos, 2División de Farmacogenómica, 3Sudirección de Ensayos Clínicos (EC), Centro de Ingeniería Genética y Biotecnología (CIGB), La suffering from mycosis fungoide (study MYFIC) and with healthy Habana, Cuba. E-mail: [email protected] volunteers (study SOFIA) was analyzed, aimed at determining the blood levels of the gene encoding for the 2´5´oligoadenilate synthetase (OAS- 1) enzyme using real time PCR, as a biomarker of the IFN responses. Interferons are cytokines having antiviral, antiproliferative and The top levels of expression are around 12 and 24 hours in both studies, with superior values to those reported for IFNs at literature. immunomodulatory effects. Nowadays, their uses are focused to cancer This result evidences the potentiation of the effect of the combination and autoimmune-disease treatments. The Center for Biological CIGB-128. Also, we evaluate levels of expression of cytokines that are Investigations developed a formulation that consists on the related with adverse events of IFNs (IL-6 and TNF-alfa). combination of IFNs α and γ, called CIGB-128. This formulation has
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LATINFARMA 2013 Resúmenes/Abstracts
VIERNES, OCTUBRE 25 / FRIDAY, OCTOBER 25th SESIÓN PLENARIA / PLENARY SESSION
PL 009: CEIBA: PHARMACOGENETICS IN IBEROAMERICANS PL 010: PHARMACOLOGICAL MANAGEMENT OF AND ITS CLINICAL IMPLICATIONS NEUROPATHIC PAIN Llerena A. Granizo E.
Clinical Research Centre, Extremadura University Hospital and Medical School, Universidad Central de Ecuador. Badajoz, Spain.
Patients with neuropathic pain are challenging to manage and Hispanic populations are diverse according to their genetic evidence-based clinical recommendations for pharmacologic composition resulting from the inter-ethnic crosses between management are needed. In the last years the scientific information on Amerindians, Europeans and Africans. The frequency of CYP2D6 PMs pharmacological treatment of neuropathic pain has increase and UMs in Spain is 7-10% and 4.9%, respectively (Llerena et al., 2009). considerably. The CEIBA-RIBEF Network Consortium aimed to evaluate the most relevant CYPs genetic polymorphism in different Ibero-American In the present review we take into account some groups of drugs populations (from Spain, South-, Central-Caribe and North-America in a classified by their site and mechanism of action: peripheral receptors; population of almost 6500 Healthy Volunteers included in the CEIBA b) peripherals nerve fibers, c) spinal pain modulators, d central consortium. Differences have been found, the frequency of CYP2D6 PMs descendent modulators (re-up take amines inhibitors) and opioids, ranged from 6%-3.9% in Nicaraguans-Cuban-Mestizos. The genetic tramadol. polymorphism of the most studied cytochrome P450, CYP2D6, is among We will review the recommended first line treatment include certain the major determinants of the interindividual and interethnic antidepressants, gabapentinoids, and topic lidocaine. Opioid analgesics variability of pharmacokinetics and drug response. Two CYP2D6 and tramadol are recommended as generally second-line treatments phenotypes have been described: "poor metabolizers" (PM), and that can be considered for first –line use in select clinical "extensive metabolizers" (EM) including a group of Ultra-rapid circumstances. Metabolizers (UMs). CYP2D6, antidepressants discontinuation and suicide. A higher frequency of UMs has been found among individuals We consider useful to give some concepts of the guidelines and who committed suicide (Zackrisson et al, 2010). One explanation for recommendations from “Consenso Latinoamericano para el Manejo del this relationship could be treatment failure with antidepressant drugs Dolor Neuropático” metabolized by CYP2D6 (Llerena et al., 2004) widely used to prevent suicide or to treat mood disorders. A complementary explanation could be via the implication of the polymorphic CYP2D6 in the endogenous metabolism. CYP2D6 has been associated with behavioral and clinical risk factors such as personality and vulnerability to psychopathology (Llerena et al., 1993; 2007; Gonzalez et al., 2008; Peñas-Lledó et al., 2009, 2010). Consistently, we found a relationship between UMs and severity of suicide and lifetime history of suicidal behavior among Eating Disordered patients (Peñas-LLedó et al., 2010, 2011, 2012a). Moreover it seems also been related to antidepressant discontinuation as recently shown in Mexican depressive patients (Peñas-LLedó et al 2012b). The pharmacogenetics of CYP2D6 may be a useful tool to predict unexpected side-effects, interactions, or therapeutic failures of many relevant drugs and may explain the interethnic differences observed not only in the response to psychotropic drugs, but also in the vulnerability to psychopathology including suicide.
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LATINFARMA 2013 Resúmenes/Abstracts
SIMPOSIOS Y TALLERES / SYMPOSIA AND WORKSHOPS CONFERENCIAS Y COMUNICACIONES ORALES / CONFERENCES AND ORAL COMMUNICATIONS Taller Inmunofarmacología y Biotecnología. Sesión: Biotecnología / Workshop on Immunopharmacology and Biotechnology. Session: Biotechnology
C 041: THE USE OF ENZYMES FOR POLYMER CONJUGATION increased selectivity towards the Glu inserted in the most flexible loops. Pasut G. This new era of enzymatic polymer conjugation is at the beginning and Department of Pharmaceutical and Pharmacological Sciences, University of it might possess greater potentials of development and feasibility for Padova, F. Marzolo 5, 35131, Padova, Italy. E-mail: [email protected] even more advanced protein conjugates.
Biocatalysis represents a promising area of research in organic chemistry. The specificity and selectivity of enzymes can dramatically improve the yields of synthesis, especially for those involving very complex structures. In the field of polymer conjugation, enzymes have C 042: SIMULATION OF PLASMID RECOVERY PROCESS FOR A also been considered as tools for site-specific conjugation at the level DNA VACCINE of amino acids not usually addressed with chemical methods. Different enzymatic protocols have been developed and proposed for polymer Limonta M1, Lendero N2, Vidic U2, Zumalacárregui L.3 conjugation to protein. The most advanced is GlycoPEGylation that, 1Center for Genetic Engineering and Biotechnology, Ave 31 e/ 158 y 190, PoBox applied to coagulation factor IX, yielded a conjugate presently in 6162, ZIP 10600, Habana, Cuba. E-mail: [email protected] clinical trials [1]. In this case the method is based on two enzymes to 2Bia Separations, Mirce 21, SI-5270 Ajdovscina, Slovenia. mimic O-glycosylationor N-glycosylation and consequently it has the 3Higher Polytechnic Institute José Antonio Echeverría, Cuba. advantage to couple PEG at the site of naturally occurring glycosylation. Although innovative, this approach involves two enzymes and therefore its feasibility at industrial scale might be The pIDKE2 plasmid is the main component of the CIGB's candidate limited. Another approach exploits the enzyme Sortase A to couple a vaccine against Hepatitis C virus (HVC), which is being used in HCV polymer at the C-terminus of proteins [2]. Also in this case there are chronically-infected individuals during clinical trials phase 1 and 2. some limitations such as the requirement of a specific C-terminal The designed downstream process of pIDKE2 plasmid produces up to consensus amino acid sequence as substrate for the enzyme. 179 g/year. In order to conduct further improvements, modeling of the A promising alternative is the transglutaminase (TGase) enzymes that downstream process was performed. A methodology based on process catalyze the transfer of a primary amine (amino donor) to the gamma- analysis tools, such as experimental design and modeling was carboxamide group of a glutamine (acyl donor) [3]. Interestingly, these established to identify factors with the highest influence on production enzymes recognize other substrate than ε-amino group of a lysine as cost and the amount of annual plasmid. Taking into account that the pIDKE2 downstream process designed is in its initial stages of amino donor, such as for example a PEG-NH2. My lab focused in microbial TGase (mTGase) from Streptomyces mobaraense, already development, CIM technology was evaluated as a new manufacturing approved as food additive. Beside the fact that this approach can target process on lab scale. Purity and recovery of CIM technology was better an amino acid that otherwise cannot be modified by chemical method than porous particle matrix, thus it was modeling in SuperPro another advantage of mTGase is its selectively. Among the several Designer. glutamines present in a protein only those inserted in very flexible The use of this Software as a computer tools is important in order to loops can be a substrate, therefore very homogeneous conjugates can consider the economic impact of some process parameters such as be obtained. Furthermore, mTGase preserves a good level of activity in recovery, purity and lifetime of matrices on the downstream process. a wide range of pH and ionic strength values and also in the presence This methodology was found very convenient to identify where cost of organic co-solvents (up to 50% v/v). We exploited this feature to reduction can be achieved at early stage of the development project develop tailor-made reaction conditions for specific proteins with the before the final stage of clinical trials was reached. The use of CIM C4 aim to stabilize the protein or to reduce the number of glutamines HLD, a monolith based media, instead of traditional beads based media substrate of mTGase, thus obtaining mono-PEGylated forms. at laboratory scale gives the necessary information to design a new The potential of mTGase-mediated PEGylation has been compared in process which could be increase productivity and equipment our lab to another known approach of site selective conjugation: N- requirements. terminal PEGylation. The methods were applied to hGH by using a 20kDa PEG, and the results were comparable in terms of yield, and pharmacokinetic/pharmacodynamic. Relevant was the efficacy of the conjugates able to produce a weight growth with a single weekly injection in hypophysectomized rats that was comparable to that obtained with 6 weekly injections of free hGH. The present and future development of TGase as tool for PEGylation is the development of a immobilized mTGase on resin beads, which will offer the relevant advantage of a fast removal of the enzymes and the possibility of a fast screening of several reactions conditions. Furthermore, we discovered that immobilized mTGase present an
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LATINFARMA 2013 Resúmenes/Abstracts
CO 188: PRODUCTION OF SCFV ANTIBODY FRAGMENT IN CO 189: COMPARISON OF DIFFERENT CULTURE CONDITIONS RECOMBINANT Pichia pastoris UNDER DIFFERENT OF GENETICALLY –MODIFIED Pichia pastoris TO PRODUCE CONCENTRATIONS OF COBALT SULFATE SCFV ANTIBODY FRAGMENT ANTI-LDL (-)
Weinacker DF1,2, Zepeda AB1,2, Figueroa CA1,2, Pessoa A2, Farías JG.1 Zepeda AB1,2, Figueroa CA1,2, Abdalla DSP3, Maranhão AQ4, Pessoa A2, Farías JG.1 1Departmento de Ingeniería Química, Facultad de Ingeniería, Ciencias y Administración, Universidad de La Frontera, Casilla 54-D, Temuco, Chile. 1Departamento de Ingeniería Química, Facultad de Ingeniería, Ciencias y 2Departamento de Tecnologia Bioquímico-Farmacêutica, Faculdade de Ciências Administración. Universidad de La Frontera. Casilla 54-D, Temuco, Chile. Farmacêuticas, Universidade de São Paulo, São Paulo, Brasil. E-mail: 2Departamento de Tecnologia Bioquímico-Farmacêutica, Faculdade de Ciências [email protected] Farmacêuticas, Universidade de São Paulo, São Paulo, Brasil.3Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, 4 Pichia pastoris is being used successfully for the production of various Universidade de São Paulo, São Paulo, Brasil. Departamento de Biología Celular, Instituto de Ciências Biológicas. Universidade de Brasilia, Brasil. recombinant heterologous proteins. This can be achieved influencing different parameters that control protein productivity. Oxygen availability has an impact on the physiology of recombinant yeasts. In eukaryotic cells, hypoxia strongly affects the core metabolism by The antibody production process largely depends of the yield causing energy deprivation. Since the protein expression machinery is a possessing the recombinant cell in shaker or bioreactor. The growth of multistep metabolic process that requires ATP, a shift to fermentative the yeast Pichia pastoris in the culture medium can be affected by metabolism could also impact on the protein synthesis and/or various factors such as the concentration of methanol, which one is the secretion processes. It is possible to mimic the effects of hypoxia in main carbon source for the cells, but at the same time can be diverse organisms by exposure to metals such as cobalt. Cobalt can metabolized to produce ethanol and to inhibit the production of induce a hypoxia-like gene response in the bakers’ yeast S. cerevisiae monoclonal antibodies. Temperature also affects important cellular that lack both HIF-1a. In this case, hypoxia and cobalt overlap in processes such as the central carbon metabolism, response to stress regulating genes involved in respiration and fatty acid biosynthesis. and protein folding. For this reason, the aim of this study is to The mechanism for this hypoxia-like effect of cobalt is not well determine the most optimal growing condition for P. pastoris understood. The main objective was to obtain a better performance in recombinant produces a high concentration of scFv antibody fragment the recombinant protein production. For that we tasted different anti-LDL(-). To conduct the study, we evaluated three critical factors for temperature (14°C, 22°C, 30°C) and methanol concentration (1%, 2%, concentrations of Cobalt sulfate [CoSO4] (Control = 0 mM; Sample 1 = 1.0 mM; Sample 2 = 2.0 mM), using a recombinant P. pastoris strain 3%). The heterologous protein was quantified by the Bradford method secreting an antibody scFv fragment. Cell viability and Hydrogen at the end of cultivation, and was analyzed Person's Coefficient Peroxide were measured in a flow cytometer. For lipid oxidation it was Correlation between biomass and quantification of the scFv fragment used the TBARS technique. In accordance to our results, the condition anti-LDL(-). The results showed different concentrations of the of chemical hypoxia induced with cobalt sulfate may increase the rate frafment in each condition, where the culture to 22°C with 2% (v/v) of cell division in this yeast. There were no increased levels of oxidative methanol, and the culture to 14°C with 1% (v/v) methanol showed a stress caused by the presence of hydrogen peroxide and lipid oxidation concentration higher than 20 mg/L, while the culture to 30°C and 14°C and there is a 5% of increase in the production of scFv anti LDL (-) in with 3% (v/v) methanol do not exceed 15 mg/L. Notably, the culture to the sample with a concentration of 1 mM cobalt sulfate. 14°C with 3% (v/v) methanol production presents a lower value not exceeding 5 mg/L. As for Pearson correlation analysis, it determined that no linear correlation exists between the biomass and the quantification of the fragment in each of the cultures analyzed. In conclusion, low temperatures and low concentrations of inductor favor the production of antibody fragments, but also the amount of biomass produced, it would be important to know the metabolic state in which the yeast is in each condition.
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LATINFARMA 2013 Resúmenes/Abstracts
CO 190: EFFECTS OF TEMPERATURE AND CONCENTRATION endogenous proteins and requires a simple purification of heterologous OF METHANOL ON THE EXPRESSION OF OXIDATIVE proteins. The use of methanol as inductor for production of proteins DAMAGE BIOMARKER IN MEMBRANES OF Pichia pastoris has been related with an increase of oxidative stress in yeast and it RECOMBINANT would to affect the production of proteins. The main objective of this work is to evaluate the effects of temperature and methanol in cell Figueroa CA1,2, Zepeda AB1,2, Ulloa P1, Abdalla DSP3, Maranhão AQ4, membrane damage and mitochondrial membrane potential of P. Pessoa A2, Farías JG.1 pastoris, We analyzed five different cultures conditions: 14°C – 1% (v/v) Methanol (M); 14°C – 3% M; 22°C – 2% M; 30°C–1% M and 30°C – 1Departamento de Ingeniería Química, Facultad de Ingeniería, Ciencias y 3% M. The oxidative cell membrane damage was evaluated by measure Administración. Universidad de La Frontera. Casilla 54-D, Temuco, Chile. of lipid peroxidation by determination of Thiobarbituric Acid Reactive 2Departamento de Tecnologia Bioquímico-Farmacêutica, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, Brasil.3Departamento de Substances (TBARS) and mitochondrial membrane potential was Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, evaluated by flow cytometry using JC-1 fluorescent dye. Recombinant P. Universidade de São Paulo, São Paulo, Brasil. 4Departamento de Biología Celular, pastoris grown at 30°C and 1% (v/v) Methanol increased the formation Instituto de Ciências Biológicas. Universidade de Brasilia, Brasil. of lipid peroxidation and decreased the relation between formation of aggregates and monomers of JC-1 dye. Our results shown that
Recombinant Pichia pastoris at 30°C and 1% of methanol presented Recombinant Pichia pastoris is a methylotrophic yeast used as an high level of oxidative stress and dysfunction of mitochondrial efficient expression system for production of heterologous proteins. P. membrane potential. pastoris easily grows to high cell densities produces low levels of
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LATINFARMA 2013 Resúmenes/Abstracts
Taller Inmunofarmacología y Biotecnología. Sesión: Vacunas / Workshop on Immunopharmacology and Biotechnology. Session: Vaccines
C 043: CONTROVERSIAL POINTS ABOUT VA-MENGOC-BC CO 191: AN ADVERSE EVENTS FOLLOWING IMMUNIZATION’S (AEFI) INVESTIGATION Ochoa Azze R. Lammer M1, Argüelles C2, Lovera T2, Rodriguez A1 , Slimovich R2 , Finlay Institute, Ave 27 No. 19805, Zip Code 11600, PO Box 16017, Havana, Cuba. 1 E-mail: [email protected] Brero ML. 1 2 Centro Nacional de Control de Calidad de Biológicos. Instituto Nacional de Producción de Biológicos A.N.L.I.S “Dr. Carlos G. Malbrán”. Av. Vélez Sarsfield Introduction: VA-MENGOC-BC is a bivalent vaccine against 563, CP 1281, Ciudad Autónoma de Buenos Aires. E-mail: [email protected] serogroups B and C Neisseria meningitidis. However, some researchers have declared that effective B meningococcal vaccines have not been developed yet. Others state that this vaccine does not provide As part of the monitoring of AEFI of the Health Ministry (HM) found protection in children under 4 years-old, as well as against that, some newborns presented necrosis at inoculation’s site after few heterologous strains. Also, there have been worries about the days post-vaccination. They had been vaccinated with Lyophilized-BCG possibility of hyporesponsiveness to C polysaccharide, if boosters are vaccine reconstituted with hypertonic Sodium Chloride solution (NaCl) necessary and regarding the influence of vaccination over the carrier 20% instead of diluent supplied by the manufacturer (NaCl 0.9%). state. The potency is performed through colony counts by the method Methods: All results of clinical trials and postlicensure studies were recommended by the WHO and European Pharmacopoeia. analyzed to clarify the immune response elicited by VA-MENGOC-BC, Our Institution is responsible for the quality control of vaccines and its influence on the meningococcal disease morbidity. supplied by the HM, as we proceeded to evaluate the possible causes of Results: VA-MENGOC-BC was licensed after successful clinical trials AEFI. that demonstrated high immunogenicity and efficacy. It induces a T- In order to know if the NaCl could be the reason of tissullar damage, helper 1 pattern with proper bactericidal and opsonophagocytic the lot of BCG-Vaccine (ESAVI) and another lot of Reference vaccine, activity. Protective response against different Neisseria meningitidis were tested simultaneously using diluent supplied by the serogroup B strains has been detected, even in infants. This vaccine manufacturer and NaCl 20%. Different assays were performed on both also induces strong immune response against serogroup C, which vaccines: Estimation of viable units on Lowenstein-Jensen medium and support the adjuvant capacity of the proteoliposome. The induction of XTT assay, examination of clumping degree by Ziehl-Nielsen, test for immunologic hyporesponsiveness has not been demonstrated. After bacterial concentration by measuring the optical density, Guinea pig vaccination campaigns there was a rapid fall in the incidence rates of skin reactivity and Necrotic Dose 50% NaCl solution. meningococcal disease in several countries. The incidence rates of this disease in Cuba remains under 0.1 x 100,000 inhabitants during last We found for both vaccines reconstituted with NaCl solution 20%: years, that is why there are not epidemiological reasons to add suffered a greater loss than 70% of relative viability and tissue boosters in Cuba, however other studies suggest that boosters could be necrosis at inoculation’s site in guinea pigs was produced. necessary. The B:4:P1.19,15 and NG:NT:P1.NST phenotypes were the Furthermore, there was no difference between the two suspensions on most found before and after vaccination respectively. clustering degree of the mycobacteria examined thought microscope after stained, as well as the values of optical densities. Conclusions: 1) VA-MENGOC-BC induces an evident protective immune response against both serogroup B and serogroup C strains in Moreover, the 50% dose necrotic corresponded to a solution of 7.07% infants, children and adults, 2) The immune response elicited by this NaCl vaccine is not completely limited to vaccine strains, 3) Immunologic hyporesponsiveness has not been proven, 4) The use of boosters Based on the results we can be inferred that the NaCl solution 20% should be additionally studied, 5) VA-MENGOC-BC modifies the carrier would be responsible for tissue necrosis and decreased the viability of state. the vaccine. Under the used conditions, the children exhibited a higher local lesions at the inoculation’s site that normally can be expected by vaccination with BCG, so we advice they should be revaccinated.
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LATINFARMA 2013 Resúmenes/Abstracts
CO 192: POTENTIAL OF THE SINGLE INSERTION MUTANT CO 193: NEW VACCINE STRATEGIES AGAINST Nesisseria TATC FOR THE PRODUCTION OF THE Mycobacterium meningitidis serogroup X tuberculosis APA ANTIGEN IN Streptomyces lividans Zayas C1, Acevedo R1, Fernández S1, Cedré B1, Valmaseda T1, Camacho Rodríguez C1, Vallín C1, Anné J2, Van Melleart L2, Pimienta E.1 F, Merchan Y, González H1, Mandiarote A1, González D1, Rosenqvist E2, Norheim G2, Bolgiano B3, García L1, Cardoso D1. 1Laboratory of Biotechnology, Center of Studies for Research and Biological Evaluations, Pharmacy and Food Sciences College, University of Havana, Havana, 1Finlay Institute, La Lisa, La Habana, Cuba. E-mail: [email protected] Cuba. E-mail: [email protected] 2Norwegian Institute of Public Health. Oslo, Norway. 2Laboratory of Molecular Bacteriology, Rega Institute for Biomedical Research, 3NIBSC, UK. Katholieke Universiteit Leuven, Leuven, Belgium.
Introduction: Most meningococcal disease in Africa is caused by The alanine-proline-rich antigen (Apa, Rv1860) is a dominant antigen serogroups A and W-135 of N. meningitidis. Recently, new cases of present during Mycobacterium tuberculosis infection. This antigen is a meningitis caused by N. meningitidis serogroup X have been reported cell-surface glycoprotein, whose mannose residues are involved in the in countries from “meningitis belt”. No vaccines have been developed interaction with the human pulmonary surfactant protein A. Recently, against this serogroup. The aim of this work is to show the different the intranasal subunit vaccination with Escherichia coli-derived Apa R&D strategies under evaluation in Finlay Institute against the (unglycosylated) imparted significant protection in the lungs and pathogen. spleen of mice against M. tuberculosis challenge. In 2004, Lara et al. reported the secretion of Apa into the culture medium of Streptomyces Material and methods: Experimental lots of OMVx were obtained by lividans with its glycosylated N-terminal and C-terminal domains, like deoxycholate extraction method from N. meningitidis serogroup X BuFa the native protein. Later, Vallin et al. (2006) reported an increment of 2/97 strain. Physico-chemical characterization was carried out to at least 16 times in the secretory production of Apa when it was fused determine the size, morphology and the main antigens in vesicles. In to the Streptomyces coelicolor agarase signal peptide, which has been addition, capsular polysaccharide X (PsX) was obtained by phenol free used as a reporter exclusively for Tat-mediated protein secretion. In process and characterized by HPLC, HPAEC-PAD and other analytical this study we evaluated if the secretion of the Apa protein is mediated techniques. OMVx were adsorbed to aluminum hydroxide (OMVx/AL) by the Tat pathway in S. lividans. For that purpose, tatB or tatC and were administered alone or in combination with PsX. Antigen insertion single mutants were transformed with the Streptomyces specific IgG responses induced by these formulations to plasmid pRGAPA and grown at 28 °C for 96 hours. Recombinant Apa polysaccharides or OMVx were evaluated by ELISA, and serum was detected via Western blotting using a polyclonal anti-Apa antibody. bactericidal assay (SBA). tatC pRGAPA showed growth rates similar to the wild type, while the Results: OMVx size was between 90-120 nm and OpcA, PorA and growth of tatB pRGAPA was remarkably slower than the wild type. RmpM protein were identified. Lots from PsX were obtained by high Surprisingly, tatC pRGAPA secreted three times higher levels scale process (100 L). PsX size was estimated in 500 g/mol/L and Kd in compared to the wild strain, according to densitometry analysis. In the 0.5. OMVx/AL induced high specific anti-OMVx antibodies response in case of tatB pRGAPA, the levels of Apa were similar to the wild type. sera with bactericidal activity. OMVx with PsX also contributes to Considering that the secretion of Apa was not blocked in tatB and increase SBA in the group of mice immunized with this formulation as tatC, we conclude that the secretion of the Apa protein is not mediated well as the induction of anti PsX antibodies. by the Tat pathway in S. lividans. From a biotechnological point of view, S. lividans tatC pRGAPA could be an attractive host for the secretory Conclusion: Development of novel vaccine candidates against production of the M. tuberculosis Apa protein. serogroup X is under evaluation. Combination of OMVx with the PsX as well as the formulation of multivalent ACYW135 and X plain polysaccharide vaccines could represent a viable solution to meningococcal disease in Africa.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S119
LATINFARMA 2013 Resúmenes/Abstracts
CO 194: STABILITY AND PRECLINICAL STUDIES OF THE (1- 6 months). The trials conducted in this study were organoleptic TETANUS DIPHTHERIA VACCINE IN ADULTS AND characteristics, pH, concentration of Aluminum Hydroxide Gel, ADOLESCENTS thiomersal concentration, sterility, identity, potency test, nonspecific safety; all these assay methods comply with WHO and USP XXIII. To Hernández León D, González Diaz P, González Díaz D, Obaya M, Pérez assess the toxic potential of this product a study of single-dose toxicity E, Mandiarote A, Feria J, Landys. M, Sánchez Fraga R. was conducted. The experimental design includes the intramuscular inoculation of Sprague Dawley rats of each vaccine formulation and Finlay Institute. Quality Control Vice-Presidency. La Habana, Cuba. E-mail: placebo, and they were subjected to histopathological study. This [email protected] design complies with the standards of the European agency. Introduction: Tetanus diphtheria vaccine consists of a preparation of diphtheria and tetanus toxoid previously detoxified and purified Results and conclusions: It was established 24 months as the expiry obtained from the Corynebacterium diphtheriae strains and date of the product taking into account that it is concluded up to 36 Clostridium tetani. Both adsorbed onto aluminum hydroxide and months of shelf life with satisfactory results and that there is evidence ° thiomersal as a preservative. A concentration of 1.5 Lf of diphtheria of its stability at 30 C up to 6 months, in the preclinical studies in toxoid and 5 Lf of tetanus toxoid was formulated what differs from the Sprague Dawley rats of both sexes, granulomatous macrophagic vaccine for children use. processes were established in groups at the level of the muscle, this type of injuries are not observed in the controls, presence of Objectives: to Reduce the concentrations of tetanus toxoid; assess hyperplasic type lesions were found at the level of the regional stability and preclinical Sprague Dawley rat. lymphatic ganglion, which intensity ranged from discreet and moderate in vaccinated individuals as well as in placebo. Material and methods: Lots were formulated for stability study and preclinical trial. The sampling times of 2-8°C (0 - 36 months) and 30°C
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S120
LATINFARMA 2013 Resúmenes/Abstracts
Simposio de Farmacología Básica / Symposium of Basic Pharmacology
C 044: NOVEL MODEL FOR “CALCIUM PARADOX” IN CO 197: ISOLATION, IDENTIFICATION AND TOXICOKINETICS SYMPATHETIC TRANSMISSION OF SMOOTH MUSCLES: OF AN ANTIMICROBIAL PHOSPHOLIPASE A2 OF Bothrops ROLE OF CYCLIC AMP PATHWAY asper VENOM
Bergantin LB, Souza CF, Miranda-Ferreira R, Smaili SS, Jurkiewicz NH, Fernández M1, Núñez V1,3, Lomonte B2, Merino V4, Sanz L5, Calvete JJ.5 Jurkiewicz A, Caricati-Neto A. 1Program of Ofidismos y Escorpionismo, Antioquia University, Colombia. E-mail: Department of Pharmacology – INFAR. Escola Paulista de Medicina, Federal [email protected] University of São Paulo, Brazil. E-mail: [email protected] 2Clodomiro Picado Institute, Microbiology Deparment , Costa Rica University, San José, Costa Rica 3Microbiology School, 4Pharmaceutical Tecnology Program, Valencia University, Spain. Previous studies showed that activity contractile of smooth muscles in 5Institute of Biomedicine of Valencia, CSIC, Valencia, Spain. response to transmitters released from sympathetic nerves is dramatically reduced by inhibition of Ca2+ influx through L-type voltage-dependent Ca2+ channel (L-type VDCC) or increase of cytosolic Snake venom is constituted by wide quantity of proteins, some with cAMP concentration ([cAMP]c) (Burnstock, Ann Rev Pharmacol Toxicol enzymatic activity, such as the Phospholipase A2 (PLA2s) which can be 2009). In recent study (Cell Calcium 2013, submitted), we showed that enzymatically active, if they have an aspartate in the position 49 or simultaneous administration of L-type VDCC blockers (verapamil) and inactive (homologous) if they possess a lysine or another amino acid in [cAMP]c enhancers (rolipram, IBMX and forskolin) potentiated the same position; these last ones can cause similar effects as the purinergic contractions evoked by electrical field stimulation of rat vas enzymatically active, several of them are myotoxic with rapid deferens, instead of strongly inhibiting. However, molecular installation effect and they are not neutralized antivenom; similarly, mechanisms involved in this “calcium paradox” are yet unclear. In the other studies have revealed the pharmacological potential of these present work, we showed that this potentiation of purinergic proteins; antimicrobial, antiplasmodial, antiaggregant. The described contraction of rat vas deferens was prevented by inhibitors of adenylyl work achieved the isolation of a 13.6 KDa, pl9.5, homologous PLA2 2+ cyclase (SQ 22536) and blockers of Ca uptake by sarco-endoplasmic through PLA2 of 13.6 KDa, with pl 9.5, through various chromatographic reticulum (thapsigargin), suggesting that this effect is mediated by steps, as well as confirms its identity by trypsinization and N-terminal, 2+ 2+ increment of cytosolic Ca concentration ([Ca ]c) mediated by cAMP. resulting in peptide of 38 residues. Biological characterization was To evaluate if combination of inhibition of Ca2+ influx and increase of made by in vivo and in vitro.The result was a protein with edemizing 2+ [cAMP]c produces increment of [Ca ], we studied effects of verapamil activity in 2 hours and a considerable myotoxic action. The cytotoxic and rolipram on fura-2 signals (Ca2+ probe) in chromaffin cells of rat action was tested using murine myoblasts and the results shown lower adrenal medulla using fluorescence microscopy. These assays showed values than those reported in the literature. Significant activity against 2+ that [Ca ]c in these cells was increased by combination of these agents. Staphylococcus aureus was observed. The pharmacokinetics was This effect was prevented by preincubation with thapsigargin, bicompartmental type, it was evaluated using a rat model and detection suggesting participation of Ca2+ from sarco-endoplasmic reticulum. In by ELISA, its presence in organs was restricted to kidney and without 2+ contrast, a reduction of [Ca ]c was observed when verapamil and systemic myotoxic activity. Additionally, the venom complete presents rolipram were incubated alone. Together, these results suggest that similar kinetic behavior. The isolated toxins study shows the 2+ 2+ reduction of [Ca ]c due to blockade of Ca influx through L-type VDCC importance of structure characterization as a tool to understand the could stimulate adenylyl cyclase activity increasing [cAMP]c that in structure-function relation. These essays complete the pharmacological response stimulates Ca2+ release from endoplasmic reticulum, resulting studies on phospholipase A2, which pursue the understanding of the in an increment of transmitter release from sympathetic nerves and processes implied in the kinetics (LADME). These processes describe contraction. This interaction between Ca2+ and cAMP signaling pathway the toxin behavior which supports matching, establishing differences could be important in the regulation of neurotransmission and in and evaluating its possible application in the pharmaceutical level, adverse effects of combined use of anti-hypertensive and anti- according to the diverse pharmacological properties. depressants.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S121
LATINFARMA 2013 Resúmenes/Abstracts
CO 198: ORGANOMETALLIC COMPLEXES WITH IRON AS CO 199: EFFECTS OF SOME ANGIOTENSIN-CONVERTING POTENTIAL CANCER THERAPEUTICS ENZYME INHIBITORS AND ANGIOTENSIN II RECEPTOR BLOCKERS ON EXPERIMENTAL INFLAMMATION Mojzisova G1, Mojzis J2, Mirossay L2, Bomba A1, Strojny L.1 Magyar I, Creț M, Cuparencu B. 1P. J. Safarik University, Faculty of Medicine, Department of Experimental Medicine, 2Department of Pharmacology, Košice, Slovak Republic. Department of Pharmacology, Faculty of Medicine & Pharmacy, 10 P-ța 1. Dec. 1918, University of Oradea, Romania E-mail: [email protected]
Objective: Our study was aimed at investigating the antiproliferative and antiangiogenic effects of iron complexes Q-603, Q-616/1 and Q- Introduction: Angiotensin-converting enzyme inhibitors (ACEIs) and 820 in in vitro conditions. angiotensin II receptor blockers are potent antihypertensive drugs and widely used worldwide. At the same time, due to an inhibition on Material and methods: Effects of these compounds were tested by kininase II they could have some effects in certain disease which employing MTT cytotoxicity assay, colony formation (CFA), DNA involve an inflammatory process. fragmentation, endothelial cell migration (ECM) inhibition and matrix metalloproteinase (MMP) activity. Material and method: The experiments were carried out in Wistar albino rats of both sexes, weighing 150-200 g. They were housed and Results: Incubation of Jurkat, HeLa, MCF-7, A549 and MDA cancer cells fed in standard conditions. The inflammations were induced as folows: with Q 603 at a concentration 106 mol/L for 72h caused 59.89, 77.66, 1). the hind paw edema evoked by the intraplantar injection of 0.1 mL 67.30, 92.20 and 91.50; with Q 616/1 at a concentration 10-5 mol/L for from a 10% aqueos kaolin suspension; the measurements of the paw 72h caused 65.96, 34.53, 57.70, 55.71 and 95.90% reduction in cell volume increases were performed plethismometrically at 1, 3.5 and 24 survival. The cytotoxicity of Q 820 is similar to that of Q 616/1. The hours after kaolin administration; 2). the insertion of a cotton pellet results obtained indicate that the tested compounds exerted cytotoxic weighing 50 mg into the scapulo-humeral region; after 3 days the activity upon the evaluated cell lines. pellet was removed and its weight determined. This procedures were CFA also confirmed growth-inhibitory effects of compound Q 603, Q- performed in light ether anaesthesia. In addition, the following bood 616/1 and Q-820. Pre-treatment of HeLa cells with Q 603 resulted in inflammatory markers were measured: fibrinogen and C-reactive marked apoptosis as detected by DNA fragmentation. The same protein (CRP). The tested drugs were: captopril (0.4-4.0-6.0 compound at a concentration 10-7mol.l-1 inhibited endothelial cell mg/animal), enalapril (0.2-2.0-4.0 mg/animal), lisinopril (0.2-2.0-4.0 migration in vitro. mg/animal), quinapril (0.2-2.0-4.0 mg/animal) and valsartan (4.0-8.0- 16.0 mg/animal). The drugs were administered intraperitoneally (i.p.). Conclusions: Our results suggest that iron complexes Q-603, Q-616/1 The controls recieved i.p. the same volume of saline. It is to note that and Q-820 may be useful agents for cancer chemoprevention and the used doses corresponded roughly to the human ones. The treatment but further studies are warranted. However, these results statistical evaluation was carried out by chi square and ʺsize effectʺ need to be confirmed in other in vitro but also in vivo experiments. procedures. Results: All ACEI exhibited in a dose-dependent and a time-related manner (in the case of rat paw edema) a proinflammatory activity. The most active compounds were: quinapril (in paw edema) and enalapril and lisinopril (in cotton pellet method). Valsartan was ineffective. Fibrinogen and CRP blood levels were increased by all ACEI. However, no clear dose-response relationships might be seen. Conclusion: From these data it may be inferred that the proinflammatory activity of ACEI was due to an accumulation of bradykinin, a phlogogenic peptide. It is well known that the converting enzyme besides its splitting effect of angiotensin I, leading to the genesis of angiotensin II has a kininase activity, i.e. it splits some peptide, including bradykinin.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S122
LATINFARMA 2013 Resúmenes/Abstracts
CO 200: EFFECT OF GESTATIONAL AGE ON C 045: SELECTIVE CYTOTOXIC ACTIVITY OF 1-O-UNDECYL PHARMACOKINETICS OF RANITIDINE IN NEWBORNS GLYCEROL
Lares Asseff I1, Villanueva Fierro I1, Benitez Gaucin G2, Juárez Olguín Hernández-Colina M1, Martín A2, Calero A, Del Toro G.1 H3, Toledo López A3, Camacho Vieyra G3, Sosa Macias M1, Galaviz 1Pharmacology &Toxicology Dept., Pharmacy and Food Institute. Havana, Cuba. Hernandez C1, Loera Castañeda V1, Pérez Guillé G3, Guillé Pérez A3, E-mail: [email protected] 1 Zaruma Torres F. 2Center for Genetic Engineering and Biotechnology, Havana, Cuba.
1 Centro Interdisciplinario de Investigación para el Desarrollo Integral Regional, CIIDIR-IPN Unidad Durango, México. 2Servicio de Pediatría y Neonatología del Hospital General de Durango, México. 1-O-alkylglycerols exhibit several pharmacological properties, which SSA. include sperm motility improvement, antidrepanocitary, anti- 3Laboratorio de Farmacología, Instituto Nacional de Pediatría, México, D.F. angiogenic and antitumor activity. The cytotoxic activity of this family of compounds has been reported previously by our workgroup, but it didn´t include the 11 carbon chain molecule, 1-O-undecylglycerol Objective: The aim of this study was to determine the effect of (C11). The aim of this work was to demonstrate the cytotoxic activity gestational age on pharmacokinetics of ranitidine in newborns. of several concentrations of C11 in tumor cell cultures of different Methods: Fifty children (20 females and 30 males) comprising of full- histological origins (A549, A375, MCF-7, MDA MB231), and compare term babies (babies born between 37 and 42 weeks of gestation) and with normal cell cultures (Vero cells, human primary fibroblast, pre-terms (those born before 37 weeks of gestation) were enrolled for 3T3A31, 184B5). Cytotoxicity was measured by MTT assay, and GI50 the study. The gestational age (GA) of the babies were as follows: 6 was determined using curve interpolation in GraphPad Prism v5.0. pre-term babies small for their gestational age (SGA) (weight < 10th Taking into account the lowest GI50, obtained in breast cancer cells percentile); 20 pre-term babies appropriate for their gestational age (MCF-7, MDAMB231), impedance measured by Real Time Cell Analyzer ® (AGA) (weight between 10 and 90 percentile); 4 pre-term babies large X-Celligence performance showed differential behavior and cell index for their gestational age (LGA) (weight > 90 percentile); 7 SGA; and 13 for cancer and normal breast cells treated with C11. The levels of AGA babies of full-terms. All the children were given 3mg/kg/day of caspase-3 and Akt after 3 and 24h of treatment with C11 changed in ranitidine. Two blood samples were collected at each of the following MCF-7 cells with respect to normal cells. We concluded that C11 has times: 0, 0.5, 0.75, 1, 2, 4, and 8 h from every newborn after drug selective and concentration dependent cytotoxic action on cancer cell administration. Ranitidine levels were determined using HPLC (High culture, which is more prominent in breast cancer cells, and mediated Pressure Liquid Chromatography) technique. by apoptotic activity and Akt modulation in MCF-7 cells. 1-O- undecylglycerol could be a good candidate for further studies in Results: Pharmacokinetics of ranitidine had a bi-exponential behavior selective anticancer therapy. with a half-life elimination (t1/2β) of 2.79 h, area under curve (AUC) of 1688 ng/mL, volume of distribution (Vd) of 1.44 L/kg and clearance (CL) of 5.9 L/kg/h. AGA and LGA pre-terms presented higher plasmatic concentration of ranitidine with a median value of 1,484 ng/mL and 1,337 ng/mL. The median plasmatic concentration in SGA pre-terms was 519 ng/mL while it was 343 ng/mL for AGA full-terms. The percentage of children with concentrations equal to or greater than 400 ng/mL was 68%, whereas those with 100 to 400 ng/mL was 22%, showing statistically significant differences (p<0.05). Conclusions: Plasma levels of ranitidine depend on the gestational age of the newborns. Based on respective characteristics, adequate dosage of ranitidine in children should take into consideration their gestational age.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S123
LATINFARMA 2013 Resúmenes/Abstracts
CO 201: ANXIETY AND STRESS BEHAVIOR ON ZEBRAFISH CO 202: EFFECT OF ESCULETIN IN EXPERIMENTAL MODEL (Danio rerio): A NEW WAY FOR DRUGS DISCOVERY OF INFLAMMATORY BOWEL DISEASE
Iturriaga-Vásquez P1, Herzog R1, Castro S1, Guerra N1, Prieto JP5, Moya Witaicenis Fantinati A, Chagas, AS, Tanimoto A, Almeida-Junior LD, P2, Reyes-Parada M3, Sotomayor R4, Scorza C5, Arias H.6 Fontes, PK, Castilho A, Di Stasi LC.
1Lab. de Qca. Biodinámica, Facultad. de Ciencias, U. de Chile., Chile. Laboratory of Phytomedicines, Pharmacology Department, IBB, UNESP, Botucatu, 2National Institute of Mental Healht, NIH. USA. SP, Brazil. E-mail: [email protected] 3Escuela de Medicina, Fac. de Medicina, USACH, Chile. 4Depart. de Fisiología, Fac. de Ciencias, U. de Valparaíso, Valparaíso. Núcleo Milenio Estrés y Adicción, Santiago, Chile. 5Lab. de Biología Celular, Inst. de Investigaciones Biológicas Clemente Estable, Introduction: Esculetin (6,7-dihydroxy-coumarin) is an antioxidant Uruguay. coumarin derivative with intestinal anti-inflammatory activity in 6Depart. of Medical Education, College of Medicine, California Northstate trinitrobenezene sulfonic acid (TNBS)-induced rat colitis, at the dose of University, USA. 5 mg/kg, however without elucidated mechanism of action. Our objective was to evaluate the effects of the esculetin up on the
inflammatory mediators and gene expression involved in intestinal In recent years, zebrafish (Danio rerio) has become an attractive model inflammatory process. for drug discovery. Zebrafish exhibits a short development time and is Material and methods: Anaesthetised rats (n=8) were treated daily easy to obtain large numbers of individuals for experimentation. In (p.o.) with 5 mg/kg of esculetin or 2 mg/kg of prednisolone (reference addition, they can absorb chemical substances from their tank water. drug) for 4 days and 2 hours prior to TNBS administration into the The potential of zebrafish for behavioral study has been applied using colon (preventive protocol) or 2 hours after this administration and different paradigms associated to complex behavior such as memory, daily until the 7th day (curative protocol). Biochemical (glutathione anxiety, stress, reinforcement properties of drugs of abuse and (GSH), myeloperoxidase (MPO), TNF-α, IFN-γ, IL-6, IL-10 and NF-κB), neuroprotection of dopaminergic neurons. The novel tank diving test gene expression (Heat shock protein (HSP70), Heparanase and NF-κB), has been used by different research groups as a model for anxiety and macroscopic parameters (damage score, extension of lesion, colonic stress studies in zebrafish. It is conceptually similar to the rodent open weight/length ratio) and scanning electron microscopic (SEM) were field test, because it takes advantage of the instinctive behavior of both evaluated. zebrafish and rats to seek refuge when exposed to an unfamiliar environment. The decrease of bottom dwelling has been used as Results: No treatments ameliorated macroscopic parameters in both parameters of the anxiolytic effects for different drugs. Here, we protocols. In preventive protocol, esculetin reduced colonic levels of compare the effects of different drugs that act by different ways such as IL-6 (37.35%) and IL-10 (25.57%) and prednisolone reduced the nicotinic receptors agonists and antagonists (Nicotine, Cytisine, colonic levels of IL-1β (37.49%) vs. control group. Both compounds Varenicline, PNU 282987, DHE and Erysodine) and serotonin, reduced the gene expression of HSP70 in 61.9 and 51.9%, respectively. dopamine and norepinephrine transporter ligands (SERT, DAT, NET) In curative protocol, esculetin promoted reduction in IL-1β levels in such as Flouxetine, MTA, PAL-287, Desipramine, Cocaine and 41.8% and counteracted the GSH levels in 35.6% and prednisolone Methylphenidate. Our results shows that nicotinic agonist produce a inhibited MPO activity in 67.8%. Esculetin promoted a better recovery decrease of the bottom dwelling, indicating an anxiolitic behavior like- in epithelial surface architecture in both protocols in SEM analysis. nicotine, whilst, the selective nicotinic agonist PNU 282987 don't produce any changes respect to the control. SERT ligands such as Conclusions: This study suggests that intestinal anti-inflammatory Fluoxetine and PAL-287, and the NET ligand Desipramine shows activity of esculetin is related with its antioxidant and immuno- similar effects decreasing the bottom dwelling in the novel tank test, in modulatory properties. Esculetin might be an interesting new anti- the other hand, the DAT blockers (methylfenidate and Cocaine) shows inflammatory drug for the treatment of inflammatory bowel disease. an opposite effects increasing the bottom dwelling behavior. Finally, we show a novel dual nicotinic antagonist and SERT ligand that exert an anxiolytic profile in the novel tank diving test.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S124
LATINFARMA 2013 Resúmenes/Abstracts
CO 203: POPULATION PHARMACOKINETIC ANALYSIS OF CO 204: ENDOTHELIAL INVOLVEMENT ON THE INDUCED TACROLIMUS IN MEXICAN PEDIATRIC RENAL RELAXATION BY ROSUVASTATIN, IN OBESE RAT AORTIC TRANSPLANT PATIENTS RINGS
Jacobo C1, García M2, Medeiros M2, Fernández I3, Castañeda G.1 Aranda-Zepeda L1, Valencia-Hernández I1, Morín-Zaragoza R1, Rodríguez-Choreño D1, López-Canales O1, López–Canales JS.1,2 1Department of Pharmacology, CINVESTAV-IPN, Mexico City, Mexico. E-mail: [email protected] 1Escuela Superior de Medicina del I.P.N., 2Instituto Nacional de Perinatología. 2Department of Nephrology, Hospital de México Federico Gómez, Mexico City, Plan de San Luis Santo Tomas, Miguel Hidalgo, 11340 Ciudad de México, Distrito Mexico. Federal. E-mail: [email protected] 3Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra, Pamplona, Navarra, Spain. Introduction: Obesity is the most common foodborne illness in the world and given it’s magnitude and implication in Mexico,is considered Introduction: Immunosuppressant tacrolimus is widely used to a public health issue. Also obesity is related to other comorbidities prevent graft rejection following renal transplantation (1). However such as hypertension, type 2 diabetes, myocardial infarction and tacrolimus is characterized by a poor bioavailability (2), narrow dyslipidemia. In this sense, studies have been made to study the therapeutic index (3) and extensive intra- and inter-individual beneficial effects of lipid-lowering therapy based on statins, because of pharmacokinetic variability making it difficult to dosing (2, 3, 4). The their pleiotropic effects mainly on endothelial function. With the aim to current study aims at to develop a population model to characterize provide relevant information, we evaluated the ability of rosuvastatin the pharmacokinetics of tacrolimus in pediatric renal transplant to induce endothelium-dependent relaxation in the thoracic aorta ofan patients and will help to improve dosing in these patients. obese rat model. Methods: From 51 concentration-time profiles of pediatric patients, a Methods and Results: Male Wistar strain rats were used for population base model was developed and validated using NONMEM experiments in vitro. We found that rosuvastatin (10-9 -10-5 M) induced ® ® version 7, PsN 3.4.2 and R 2.12.2. 51. relaxation in aortic rings of the control group as well as in the obese Results: Several models were tested, and based on OFV and goodness precontracted with phenylephrine rat group (10-6 M), however the of fit plots was chosen a 2-compartment model with first order effect was greater in non-obese rat aortas. This relaxant effect was absorption transit compartments as base model, which was validated almost completely inhibited by L-NAME (10-5 M), TEA (10 mM), -5 -5 with NPC (1000 simulated datasets, and CMAX and AUC12 used as cycloheximide (10 M) and indomethacin (10 M). Observed increased descriptors to compare numerically real data vs. simulations), and VPC expression of cyclooxygenase 1 and 2, as well as the endothelial and (1000 datasets were simulated using the base model, after 95- inducible nitric oxide synthase in obese rat aortas pre-treated with percentile intervals of simulated concentrations were generated, and rosuvastatin were performed by immunoblotting method. observed concentrations of tacrolimus were overlapped and compared Conclusions: These results indicate that rosuvastatin is able to relax visually); these studies showed good agreement between simulated the obese rat aorta despite of endothelial damage induced by obesity. and observed blood concentrations of tacrolimus using the base This relaxation effect appears to be mediated by nitric oxide, population pharmacokinetic model. prostaglandins and potassium channels. Rosuvastatin upregulates COX- Conclusion: This study intend to develop a population 1 and 2 as well as eNOS and iNOS. pharmacokinetic model to decrease the high inter-individual variability and have an optimal dosage of tacrolimus to prevent graft rejection events and serious side effects such as nephrotoxicity in pediatric renal transplant patients. Therefore it is of great interest to test different covariates as polymorphisms of enzymes that carry out the metabolism of this drug (such as CYP3A5 and ABCB1) in the model that was selected and validated as base model. Future activities: Build the final covariate model and find a bayesian estimator based on the final model that helps to optimize the dosage of tacrolimus.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S125
LATINFARMA 2013 Resúmenes/Abstracts
CO 205: ANTIANGIOGENIC EFFECT OF CHALCONE CO 206: EFFECT OF IBUPROFEN AND IBUPROPHENYL- DERIVATIVES IBUPROPHENATE ON GASTRIC MUCOSA LESIONS AND ACUTE TOXICITY Mirossay La, Pilatova Ma, Kutschy Pb, Mojzisova Gc, Mojzis J.a López A, Ferreyra O, Torres L, Pére J, Palacios F, Izquierdo T, Lozada aDepartment of Pharmacology; cDepartment of Experimental Medicine MC. Faculty of Medicine, bDepartment of Organic Chemistry, Faculty of Science. P.J. Safarik University, Kosice, Slovak Republic. E-mail: Universidad Autónoma Metropolitana-Xochimilco. México. E-mails: ado-lop- [email protected] [email protected], [email protected]
Introduction: Several clinical studies showed a positive correlation Introduction: Ibuprofen (Ib) is one of the most widely used non- between the number of vessels in the tumor and the metastases steroidal anti-inflammatory drugs (NSAID) to treat inflammatory formation and the prognosis of the disease. Therefore antiangiogenesis diseases. Its therapeutic effects are mediated mainly by inhibition of is an important area of therapeutic development for treatment of COX-2, whereas their side effects are primarily caused by COX-1 cancer, since tumor growth and metastasis depends on angiogenesis. inhibition; the most common of those are gastric injuries. Furthermore, there is evidence that gastric lesions caused by Ib are not only due to Chalcones are precursors of flavonoids in their biosynthetic pathway. the COX-1 inhibition, they are also caused by local irritation because to Variety of biological activities has been demonstrated for these the carboxylic group present in the molecule. Looking for the reduction compounds. However, there is only a limited amount of literature of gastric damage by carboxylic group present in the Ib, a molecule concerned with antiangiogenic effects of chalcones. which masks the functional group was synthetized, the ibuprophenyl- Material and methods: In the present work, we tested four newly ibuprophenate (Ib-Ib). This work describes the evaluation of synthesized chalcones (1, 2a, 2b 3) for their antiangiogenic effect ulcerogenic potential of Ib-Ib. using human umbilical vein endothelial cells (HUVEC). Effects of these Material and methods: In order to evaluate and compare the gastric compounds were tested by employing MTT cytotoxicity assay, capillary damage produced by oral administration of Ib and the new molecule tube formation (CTF), endothelial cell migration (ECM), gelatinase Ib-Ib, different doses (1, 2 and 3 times anti-inflammatory effective zymography or vascular endothelial growth factor (VEGF) detection. doses; where 30 mg/kg is the effective dose for ibuprofen and 39.07 Results: Only compound 3 possess significant cytotoxic effect on mg/kg for Ib-Ib) of each drug were assayed in stomach CD-1 female HUVECs. It also completely inhibited CTF by HUVECs in concentrations mice (25-30 g). As ulcerogenic agent indomethacin (50 and 100 mg/kg 10-7-10-8 mol/L. Moreover, this chalcone effectively block also ECM. In of body weight) was used. Ulcer index was calculated using ImageJ biochemical analysis, chalcone 3 in a concentration-dependent software. Additionally, acute toxic effects of Ib-Ib were evaluated by decreases the secretion of matrix metalloproteinase-9. Furthermore, Lorke (1983) procedure. Significantly differences were determined exposure of HeLa cells (cervix cancer) to chalcone 3 resulted in a dose- using ANOVA and P< 0.05. dependent decrease in the secreted VEGF level in conditioned media. Results: The gastrointestinal side effects were evaluated as total Conclusions: The present study demonstrates antiangiogenic ulcerated area caused by the administration of ibuprofen compared to properties of chalcone 3. Further studies are necessary to elucidate its Ib-Ib. At the current doses not statistically significant difference in mechanism of action, nevertheless, this compound might have a ulcerative index was observed between stomachs groups treated with potential to enter pre-clinical trials as a new angiostatic drug. ibuprofen and Ib-Ib. Detailed observation of stomachs reveled an important mucosa lost in groups administrated with high Ib-Ib doses. Besides, DL50 was determined > 5000 mg/kg. Conclusions: There was no difference between the ulcerative index on the stomachs treated with I band Ib-Ib, this compound results safe until 5000 mg/kg by oral way.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S126
LATINFARMA 2013 Resúmenes/Abstracts
CO 207: COAGULATION FACTOR Xa (FXa) AND ITS ZYMOGEN such as Vascular Endothelial Growth Factor (VEGF). FX has been shown FX INHIBIT ANGIOGENESIS in a knock-out model to have a role in vascular development and angiogenesis. We report herein that FX and FXa possess anti-angiogenic Valenzuela R1, Lange S1, Gonzalez I1, Arce M1, Aranda E1, Elliot M2, properties. Both the recombinant zymogen FX and recombinant FXa, Alvarez M3, Palma V2, Allende M3, Owen GI.1,4 but not a recombinant FX lacking the Gla-domain, inhibit the formation of tubular structures in an in vitro model of angiogenesis using the 1Departamento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile. Santiago, Chile. endothelial cell line EA.hy926 seeded in matrigel and in independent 2Departamento de Biología, Facultad de Ciencias, Universidad de Chile. Santiago. cultures of human umbilical vein endothelial cells (HUVECs) stimulated Chile. with VEGF. We demonstrate that FXa and FX use distinct mechanisms 3FONDAP Center for Genome Regulation. Facultad de Ciencias, Universidad de to mediate this activity, with only FXa being dependent on PAR-1 Chile. Santiago, Chile. activation. Also we showed that blockade of Endothelial Protein C R 4Biomedical Research Consortium Chile (BMRC), Alameda 440, Piso 13. Santiago, eceptor (EPCR) also inhibits the antiangiogenic effect of FX and FXa. In Chile. an in vivo setting, we show that FX and FXa are anti-angiogenic in a Zebrafish model of intersegmental vasculature formation and in the chick embryo chorioallantoic membrane. Our results shed further light Angiogenesis is the formation of new vascular segments from existing on the extra-coagulatory function of the factor Xa coagulation factor vessels. This process plays a fundamental role in cancer progression and present the first demonstration of a biological role for the zymogen and involves activation of multiple pro-angiogenic signaling cascades FX.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S127
LATINFARMA 2013 Resúmenes/Abstracts
Simposio de Productos Naturales / Symposium of Natural Products
CO 208: THE USE OF MEDICINAL PLANTS AND OTHER CO 209: THE OVERLAP OF TRADITIONAL AND ALLOPATHIC DIETARY SUPPLEMENTS FOR THE TREATMENT OF PAIN IN MEDICINE: A STUDY FROM MIDWESTERN UNITED STATES INTEGRATIVE CLINICS IN THE UNITED STATES Kiefer D, Tellez-Girón P, Bradbury J. Kiefer D. Department of Family Medicine, 1100 Delaplaine Court, University of Wisconsin- Department of Family Medicine, 1100 Delaplaine Court, University of Wisconsin- Madison, Madison, Wisconsin, 53715. E-mail: [email protected]. Madison, Madison, Wisconsin, 53715. USA. Email: [email protected]
Introduction: Herbal medicine use is common in the United States, Introduction: The use of medicinal plants and other dietary especially in immigrant populations. This topic transcends the supplements in the United States is common and increasing. Pain, from boundaries of many disciplines (i.e. anthropology, botany, clinical a variety of causes, is one of the more common symptoms for which medicine, etc.). In addition, there are significant gaps in the literature people in North America use dietary supplements. There is evidence in about the specific plants used, the overlap of allopathic and herbal the English-language medical literature supporting the use of some medicine, and the prevalence of use in the Midwest. natural products for pain due to arthritis, fibromyalgia, headaches, and Objective: To explore herbal medicine use by Latinos now living in low back pain. Madison, covering as many of the interdisciplinary aspects of an Objective: To review the medical literature for clinical trials on dietary ethnobotanical research project as possible. Specifically, the objective supplements for the most common pain conditions, focusing on was to document the sources of those plants and plant knowledge, and clinically-relevant, recent research. the health conditions for which the plants were used. Methods: A review of randomized, controlled clinical trials and meta- Methods: A convenience sampling method followed by “snowballing” analyses as listed in the PubMed database. inquiry was used to identify Spanish-speaking community members in Madison with knowledge about herbal medicine and retail Results: There is research exploring the use of a variety of dietary establishments stocking plants for Latinos; respectively, focus groups supplements for pain. Some of the research trials are small and of and visual surveys of herbal retail outlets were then used for data substandard methodological quality, while others are well-designed collection. Collaboration with colleagues in botany, primary care and and convey useful conclusions. Some of the dietary supplements being global health helped refine the research methodology and identify studied for pain include 5-HTP, ASUs, Boswellia serata, coenzyme Q10, study participants. omega-3 fatty acids, Petasites hybridus, riboflavin, SAMe, Tanacetum parthenium, and Zingiber officinale. The safety and efficacy of these Results: Eight focus groups consisting of 42 study participants yielded natural products will be reviewed in this presentation. 199 minutes of audio recordings. Fifty-eight different medicinal plants were mentioned. These plants were obtained from gardens, relatives, Conclusions: There are many dietary supplements, including medicinal friends, and ten retail establishments. Retail sites sold fresh and dried plants, possibly useful for headache, fibromyalgia, and joint pain. There plants, and packaged products, ranging from 20-150 plant products is varying scientific evidence supporting the use of these natural per site. Participants mentioned 35 distinct health conditions for which products for these conditions. Factoring in any relevant nutraceutical- herbal medicines were used; non-disclosure was the rule. Clinically- pharmaceutical interactions, an integrative approach to the treatment relevant confusions were also identified when common plant names of pain can safely and effectively utilize dietary supplements such as were compared with likely Latin binomial names. medicinal plants, while awaiting further research to refine and improve the use of these vitamins, herbs, and other compounds. Conclusions: Herbal medicine use by Latinos is both complex and extensive, making a compelling case for interdisciplinary research teams, and for health care providers to learn about the topic. Future work should involve other demographics, botanical identification, quantification of disclosure rates, and development of educational interventions.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S128
LATINFARMA 2013 Resúmenes/Abstracts
CO 210: HERBAL MEDICINES: NEW PARADIGM FOCUS CO 211: PROJECT FUNDING MODELS FOR RDI IN MEDICINAL PLANTS IN LATIN AMERICA Chico S, Catalano A. Desmarchelier C. National Administration of Drugs, Food and Medical Devices. Av. de Mayo 869, Ciudad Autónoma de Buenos Aires, Argentina. E-mails: [email protected], Ministry of Science & Technologyof Argentina (MinCyT). Godoy Cruz 2320, [email protected] Buenos Aires, Argentina. E-mail: [email protected]
Introduction: ANMAT is the Argentinian health authority with Project funding is an important instrument in the development of new competence in herbal medicines. Recently, it has adopted the new pharmaceuticals in industrialized countries. Several sophisticated paradigm based on regulatory science. This work aims to present the financing instruments have been developed for funding promising tools found to impulse traditional medicines control. In 2009 ANMAT research, development and innovation (RDI) projects in this sector. was recognized by t PAHO as National Reference Authority in Drugs These include private capital raising, secondary public offerings, long Regulation. Since 2013 ANMAT has been active member of the term investments, and government funding through specific agencies International Regulatory Cooperation for Herbal Medicines (IRCH) - such as the National Institutes of Health (NIH) in the USA, only to name WHO. Its constant searching, regulating inspections, and monitoring a few. activities on traditional medicines, in consonance with the developments achieved by Argentinian and Regional Pharmacopoeia However, in developing countries these instruments have not evolved commissions, have collected vast information on herbal products in the same degree as – for instance – in the USA, Europe or Japan. And valuable to be guided in favor of the public health. Whit appropriate if they have, they are mostly oriented to innovation in drugs from new tools it will be possible to achieve this objective. entities of a synthetic and/or biological nature. Few efforts have taken place in supporting the development of new drugs or active Objetives: Regulatory science paradigm was defined as the utilization, ingredients (i.e. APIs or active extracts) from plants. Furthermore, in each decisional act, of the best scientific evidence available as a companies that manufacture and market plant-derived products such result of the conjunction of professionals, academics, regulatory as phytopharmaceuticals and dietary supplements do not tend to use authorities and society. Under this new concept, for the control on this kind of instruments due to their culture, small size and family-style herbal products ANMAT has considerated the following tools: herbal management. products and companies strategies registration-permit, control market, good manufacturing practices, herbal medicinal products In recent years several public funding instruments have been vigilance, pharmacopoeia monographs and a technical advisor group developed in Argentina in order to encourage innovative initiatives in with expertise in the field. All this tools are found in the conjunction of small and medium-sized enterprises (SMEs), and are increasingly a working group harmonized. being used in the fields of pharmaceutical, biotech and agricultural technology. These instruments are either of a general purpose – that is Conclusion: Having regard to the particular characteristics of these to say that they can be used by any industrial sector – or oriented. They traditional medicines products, ANMAT has found that only by the include soft credits, tax benefits, or even direct subsidies for RDI contributions of all the tools available in different contexts will obtain projects that will ultimately lead to new and innovative products, harmonized information to serve to the community. Strengthening services or processes either in single companies or in private-public legislation concerning herbal medicinal products to adopt science- consortia. based legislation with participation of scientific and regulatory professionals, ANMAT has concluded is the best way to achieve it. We will present an overview of the main instruments available for the industry, together with some cases that have or could be eligible for funding in the field of RDI with medicinal plants.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S129
LATINFARMA 2013 Resúmenes/Abstracts
CO 212: EFFECT OF MANGIFERIN (Mangifera indica L.) ON CO 213: NEUROTOXICOLOGICAL EVALUATION OF AQUEOUS THE GASTRIC MUCOSA OF CD-1 MICE EXTRACTS OF Turnera diffusa (Turneraceae) AND Chrysactinia mexicana (Asteraceae) IN MICE, PLANTS USED Cervantes F1, Sánchez Z1, Sarmiento E1, Palacios JF2., Lozada MC2, Izquierdo T.2 AS TRADITIONAL APHRODISIAC REMEDIES. “Damiana de California and falsa Damiana” 1Maestría en Ciencias Farmacéuticas. 2Lab. Fitofarmacología. Lab. Síntesis Orgánica. Depto. de Sistemas Biológicos. División de CBS. Universidad Autónoma Ferreyra-Cruz Oa,b, Dorantes-Barrón Ab, Estrada-Reyes Rb, Cassani J.c Metropolitana–Xochimilco, México. aMaestría en Ciencias Farmacéuticas. Universidad Autónoma Metropolitana. Calzada del Hueso 1100, Col. Villa Quietud, Delegación Coyoacán, 04960, México D.F., México. E-mail: [email protected], [email protected] Introduction: Mangiferin (MNG), a xanthone C glycoside obtained bLaboratorio de Fitofarmacología. Instituto Nacional de Psiquiatría Ramón de la from the aqueous extract of the bark of Mangifera indica L. (family Fuente Muñiz. Anacardiaceae), presents an antioxidant, anti-inflammatory, and cCalzada México Xochimilco No. 101, Col. San Lorenzo Huipulco, Delegación antinociceptive profile. Its proposed action mechanism is through Tlalpan, 14370 D.F. México. inhibition of prostaglandins (PGs) synthesis as well as other alternate dDepartamento de Sistemas Biológicos, Universidad Autónoma Metropolitana mechanisms. PG inhibitors induce injuries in the gastric mucosa, Unidad Xochimilco. México, D.F.04960, México. ulcers, digestive bleeding. In this study we assessed the effect of MGF on the gastric mucosa in an experimental model. Introduction: Turnera diffusa Wild (Turneraceae) and Chrysactinia Material and methods: MGF was provided by the Organic Synthesis mexicana A. Gray (Asteraceae), widely used as aphrodisiacs in the Laboratory of UAM-X. We used six groups of female CD1 mice (n = 6) traditional medicine, are an alternative to treat the sexual health with a 12-h fasting. The first group received indomethacine (INDO) at problems. To our knowledge, there is not information available about 100 mg/kg orally. We evaluated three MGF oral doses: 60, 120, and the side-effects of the intake of these plants. The aim of this work was 240 mg/kg, and two negative vehicle controls. Mice were euthanized 6 to evaluate the neurotoxicological effects of aqueous extracts of T. h after administrations. Stomachs were removed, washed, and fixed in diffusa and C. mexicana in mice. 2% formaldehyde. Gastric injury was assessed through images of the ulcerated, bleeding areas, as well as hyperemic injuries; the Image J® Material and methods: Neuropharmacological effects produced by software was used to determine the ulceration index (UI) for each the oral administration of T. diffusa and C. mexicana aqueous extracts group. Data were analyzed with ANOVA-GraphPad Prism®- program were carried out employing Swiss-Webster male mice. Neurological and Tukey’s test; significance was set at P<0.05. effects were evaluated in open field, rota-rod and inverse-bar paradigms. The acute toxicity was evaluated through the LD50. Results: The UI assessed with the three MGF doses did not differ significantly from controls and was different from INDO (P<0.05). To determinate the chronic toxicity, behavior, weight and temperature Hyperemic injury was only observed with the higher doses. Topical body changes were monitored during thirty days of daily injuries, type mucosal erosion due to interruption of the gastric barrier administration. After this period the animals were sacrificed and the of epithelial cells, were observed at 60 (0.13%), 120 (0.82%), and240 morphology of kidney, liver, stomach and spleen were analyzed mg/kg doses in only two cases (0.12% and 0.74%). macroscopically. Conclusions: MGF has low incidence of damaging effects on the gastric Gastric toxicity was evaluated by determining the ulcer index by mucosa. This seems to be associated to the fact that it does not induce extracts-treat; the changes produced were compared to indomethacin. depletion of PGs, which is essential for the development of clinically The comparisons were made using the ImageJ-software. relevant gastric ulcers. Results: The T. diffusa and C. mexicana treatments did not cause the death of mice or alterations in behavior. Only at 5000 mg/kg dose a decrease in locomotor activity was observed. LD50 > 5000 mg/kg for both of them. The treatments did not induce neurological failures. Dosage range did not cause significant damage in the organs and unlike to indomethacin, treatments did not produce gastric ulcers. The therapeutic index for both species was upper than 75. Conclusions: The lack of toxicity implies that the intake of T. Diffusa and C. mexicana does not involve significant health risks. These findings supports the use of these aphrodisiac plants as a safety alternative to treat the sexual dysfunctions or for relief the side effects that derivate to some chronic diseases.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S130
LATINFARMA 2013 Resúmenes/Abstracts
C 046: METABOLIC SYNDROME AND PLANT DRUGS Diagnosis is based primarily on: (Enlarged abstract) Clinic (abdominal measurement) Alonso J. Blood analysis (lipid parameters and sugary) Liver ultrasonography (confirm or rule out fatty Asociación Argentina de Fitoterapia, Buenos Aires, Argentina. liver) Microalbuminuria (signal of endothelial dysfunction, kidney damage, disease CV) Insulin resistance, obesity, hypertension, and dyslipidemia are strongly ECG (Left Ventricular Hypertrohy) • associated with metabolic syndrome, which is considered to be a Blood Pressure reversible clinical stage before its evolution to coronary heart disease and diabetes. Metabolic syndrome is also known as metabolic syndrome X, cardiometabolic syndrome, syndrome X, insulin Treatment resistance syndrome, etc. Is a combination of the medical disorders that, when occurring together, increase the risk of developing Increase physical activity, reduce weight, treatment of diabetes and cardiovascular disease and diabetes. The term "metabolic syndrome" insulin resistance, treat hyperlipidemia, hypertension, stress and dates back to at least the late 1950s, but came into common usage in anxiety disorders, and the fatty liver (if any). Many drugs used in these the late 1970s to describe various associations of risk factors with cases (glitazones, metformin, statins, orlistat, pharmaceuticals, etc) are diabetes that had been noted as early as the 1920s. Kylin (1923) was a not exempt from risks, and have not always yielded the expected Swedish doctor who first defined the association between results. In such a way that many plant drugs recently have been hypertension, gout and hyperglycemia. positioned to be able to give a finished therapeutic coverage and wide in each of the clinical manifestations of this syndrome, without Marseille Jean Vague, in 1947 and then in 1956, showed that people generating the adverse effects so often observed. with obesity were predisposed to have in the future diabetes, atherosclerosis, thyroid dysfunction, and urinary calculations. In 1977, At the conference will be published the scientific work and clinical Haller employment for the first time the term "Metabolic Syndrome" in experiences with extracts of artichoke (Cynara scolymus), african academic circles to refer an association between obesity, diabetes mango (Irvingia gabonensis), greater nettle (Urtica dioica), milk thistle mellitus and fatty liver, describing in addition the risk factors for (Silybum marianum), guava (Psidium guajava), noni (Morinda arteriosclerosis. Some studies have shown the prevalence in the USA to citrifolia), rooibus (Aspalathus linearis), spirulina (Spirulina pratensis), be an estimated 25% of the population, and prevalence increases with turmeric (Curcuma domestica), roselle (Hibiscus sabdariffa), age. resveratrol, coenzyme Q-10. The World Health Organization 1999 criteria require the presence of any one of diabetes mellitus, impaired glucose tolerance, impaired fasting glucose or insulin resistance, and two of the following:
Blood pressure: ≥ 140/90 mmHg Dyslipidemia: triglycerides (TG): ≥ 1.695 mmol/L and high- density lipoprotein cholesterol (HDL-C) ≤ 0.9 mmol/L (male), ≤ 1.0 mmol/L (female) Central obesity: waist: hip ratio > 0.90 (male); > 0.85 (female), or body mass index > 30 kg/m2 Microalbuminuria: urinary albumin excretion ratio ≥ 20 µg/min or albumin: creatinine ratio ≥ 30 mg/g. Clasification The European Group for the Study of Insulin Resistance (1999) requires insulin resistance defined as the top 25% of the fasting insulin values among nondiabetic individuals AND two or more of the following:
Central obesity: waist circumference ≥ 94 cm (male), ≥ 80 cm (female) Dyslipidemia: TG ≥ 2.0 mmol/L and/or HDL-C < 1.0 mmol/L or treated for dyslipidemia Hypertension: blood pressure ≥ 140/90 mmHg or antihypertensive medication Fasting plasma glucose ≥ 6.1 mmol/L In the Metabolic Syndrome there are furthermore hyperleptinemia and, at the same time, resistance to the own leptin. This substance is secreted in the adipocytes (mainly). When the amount of fat stored in the adipocytes increases, leptin is released into the bloodstream, to inform the hypothalamus that the body has a number of reservations and that should inhibit the appetite. Leptin also increases the oxidation of fatty acids and decreases the TGC in the adipocyte.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S131
LATINFARMA 2013 Resúmenes/Abstracts
CO 214: SCREENING MEDICINAL PLANTS FROM CO 215: ANTI-Trypanosoma cruzi EFFECT OF ESSENTIAL OIL GUANAJUATO (MEXICO) FOR THE DETECTION OF NOVEL FROM Thymus vulgaris L (THYME) AND ITS MAIN ANTIPROTOZOAL PRODUCTS CONSTITUENT, THYMOL, IN MICE
Osegueda MS1, Calzada F2, Yépez-Muliac L3, Diosdado MGS1, Rojas Armas JP. Hernández MEG1, Márquez MRG1, Medellín SM1, Marrero JG1. Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú. E- 1National Polytechnic Institute (IPN). Engineering Interdisciplinary Professional mail: [email protected] Unit. Campus Guanajuato (UPIIG). 200 Mineral Valenciana Avenue. Industrial Park Puerto Interior, Zip Code: 36275. Silao de la Victoria, Gto, Mexico. E-mail: [email protected] 2Unidad de Investigación Médica en Farmacología, UMAE Hospital de Introduction: American trypanosomiasis caused by the protozoan Especialidades-2° piso CORCE Centro Médico Nacional Siglo XXI, IMSS, Av. Trypanosoma cruzi, affects 18 to 20 million people from Mexico to Cuauhtémoc 330, Col. Doctores, CP 06725, México, D. F. E-mail: Chile and Argentina. Only nifurtimox and benznidazole are available [email protected] for treatment, but have significant side effects, so it is urgent search for 3Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, new drugs and medicinal plants are an alternative. UMAE Hospital de Pediatría. Centro Médico Nacional Siglo XXI, IMSS. The aim of this study was to determine the effect of the essential oil from Thymus vulgaris and thymol on Trypanosoma cruzi in mice. Morbidity and mortality due to enteric protozoan infections are a Material and methods: albino mice Balb/c were randomly assigned to serious health problem in the world, particularly in developing the following groups (n = 15) infected and untreated (G1), infected and countries where there are poor sanitary conditions. Metronidazole is treated with essential oil from Thymus vulgaris 200 mg/kg (G2), the drug now most widely used in the treatment anaerobic infected and treated with thymol 200 mg/kg (G3), infected and treated protozoan parasitic infections, however, potential carcinogenic, with benznidazole 100 mg/kg (G4), non-infected and untreated (G5), teratogenic, embryogenic effects and clinical and laboratory- and infected and treated with Thymus vulgaris 200 mg/kg (G6). The generated drug-resistant strains of both protozoa have been treatment was performed from the eighth day post infection. reported. [1] In an effort to improve the therapy for giardiasis and Parasitaemia was checked individually every 2 days by direct dysentery, new drugs that retain therapeutic efficacy and are devoid microscopy counting parasites in 5 µL of blood. In 14, 21 and 28 days of adverse effects, should be discovered. Medicinal plants used to post infection, five mice from each group were sacrificed and the treat gastrointestinal disorders could be a source of such new drugs. hearts quickly removed and processed for histopathological analysis. In the course of a study of medicinal plants from Guanajuato Results: The essential oil from Thymus vulgaris and thymol (Mexico), the antiprotozoal activity of the crude extracts from significantly reduced the number of trypomastigotes in the parasitemia Brickellia veronicaefolia (Peixtó), Tecoma stans (Tronadora), peak from 57.60 ± 16.97 to 30.10 ± 15.18 (p < 0.05) and 10.90 ± 3.67 x Eysenhardtia polystachya (Palo Dulce) and Salvia patens var. 104 trypomastigotes/mL (p <0.001), respectively, and the number of Guanajuato, were evaluated using an in vitro antiprotozoal assay. amastigotes and inflammatory infiltrates in the heart tissue at the end The acetonic extracts from aerial part of the plants, were dissolved in of the experiment. a hydro-alcoholic mixture and extracted by liquid/liquid partition Conclusions: The essential oil from Thymus vulgaris and thymol have with solvents of increasing polarity: n-Hexane, CHCl3, and EtOAc. anti-Trypanosoma cruzi effect in vivo in mice. In the present work we report the evaluation of each extracts, and its partitions, using an in vitro antiprotozoal assay.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S132
LATINFARMA 2013 Resúmenes/Abstracts
CO 216: MANGIFERIN: A NATURAL GLUCOSILXANTHONE CO 217: CYTOPROTECTOR EFFECT OF METHANOLIC AND ITS THERAPEUTIC POTENTIALITIES EXTRACT FROM THE LEAF OF Erythroxylum coca IN GASTRIC INJURY INDUCED IN RATS Delgado-Hernández R1, Garrido Suarez BB1, Hernández I2, Rodeiro I2, Rodriguez JC1, Garcia L1, Acosta A3, Nuevas L4, Romero JA1, Salomon S1, Palomino de la Gala R, Arroyo J. Rodriguez C1, Vandama R1, Haegeman G5, Vanden Berghe W5. Facultad de Medicina Universidad Nacional Mayor de San Marcos. Lima Peru. 1Centro de Investigación y Desarrollo de Medicamentos (CIDEM), Plaza de la E-mail: [email protected] Revolución, La Habana. Cuba. E-mail: [email protected]
2Laboratorio de Farmacología, Centro de Bioproductos Marinos, Plaza de la Revolución, La Habana, Cuba. Objective: To demonstrate the gastroprotective effect of methanolic 3Tecnología Química, ISPJAE, Marianao, Cuba. extract from leaves of Erythroxylum coca through indomethacin and 4 Centro de Genética Médica, Playa, La Habana, Cuba. pyloric ligature in rats. 5University of Gent and 6Department Biomedical Sciences - University of Antwerpen, Belgium. Material and methods: Methanolic extract from leaves of Erythroxylum coca was prepared with leaves acquired from Empresa Nacional de la Coca S.A. Lima. Gastric protection was evaluated by Mangiferin (MF), a natural glucosilxanthone (2-beta-D-glucopyranosyl- inducing gastric injuries with indomethacin, it was considered normal 1,3,6,7-tetrahydroxy-9H-xanthen-9-one) has been obtained from control groups, indomethacin, omeprazole and ranitidine with three different natural sources, being ones of more reported in our country levels of doses of extract; congestion, edema, hemorrhage and ulcers. its isolation from the stem bark of Mangifera indica L. Mangiferin constitutes the active pharmaceutical ingredient (around 10-20%) of Results: It was proved a local congestion decrease from mucosa the Vimang, aqueous extract commercialized in Cuba from the stem gastric with omeprazole 10 mg/kg followed by the treatment with bark of Mangifera indica L. Several articles published in the last 15 Eritroxylom coca (EC) in doses of 50 mg/kg, 250 mg/kg y 500 mg/kg years explain the pharmacological properties of the Vimang in direct body weight. It was observed a similar behavior with edema and relationship with the presence in the extract of the mangiferin. hemorrhage, being in this last one the dose of EC 250 mg/kg the most However, the ecological sustainability of this obtaining process has effective; and in the evaluation of ulcers in the gastric mucosa, the been questioned and its feasibility has not been scientifically treatment with EC 500 mg/kg had an effect slightly superior at the demonstrated, for such reason others way have been explored for the ranitidine group in doses of 100 mg/kg. isolation and purification of mangiferin. Conclusions: It has been demonstrated in experimental conditions the The current work shows the main results of Mangiferin Project that methanolic extract from leaves of Erythroxylum coca is effective as have been conducted by a multidisciplinary group of researchers in the gastroprotective agent in rats with induction of gastric ulcer. Drug Research and Development Centre (CIDEM). The project has allowed obtaining mangiferin from the leaves of different species of Mangifera indica L. The investigation has been organized to study the best analytical, technological and pharmaceutical conditions with the objective of to obtain a natural active pharmaceutical ingredient pure, available and pharmacologically effective for to develop new phytotherapeutic drugs. On the other hand, considering the advantages to have mangiferin as active principle pharmaceutically usable for the preparation of new phytomedicinals and keeping in mind the pharmacologicals reports that show mangiferin as antioxidant, antiangiogenic, neuroprotective, analgesic among others properties, we have evaluated the possibility to develop new formulation with mangiferin for the treatment of different pathological conditions were result very important to modulate de proangiogenic and proinflammatory mediators. The main results of these pharmacological studies, with the corresponding deepening in the mechanisms of action involved in the biological activity of the mangiferin, are illustrated in this presentation. Other studies with antitumoral drugs broadly used in the oncological therapy, as the cis-platinum, in co-treatment in vitro with mangiferin against tumors cells have demonstrated a synergistic increment of cytotoxicity effects of antitumor drugs for actions of mangiferin. This results suggest the possibility of reduced the dose of antitumor drugs with a therapeutic scheme using mangiferin together with cytostatic drugs. These discoveries constitute the preclinical criteria to consider mangiferin as a future phytotherapeutic for the treatment of oncological processes.
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LATINFARMA 2013 Resúmenes/Abstracts
CO 218: PHYTOCHEMICAL EVALUATION, ACUTE TOXICITY Results: We reported alkaloids, flavonoids, cumarines, steroids, AND ANALGESIC, ANTI-INFLAM-MATORY AND PROKINETIC phenols, quinones, saponins and catechines. We observed sedation and EFFECTS OF Maytenus macrocarpa (CHUCHUHUASI) sterotipias with 4000 mg/kg and dead with 12,000 and 14,000 mg/kg LEAVES ON RODENTS without determination of the lethal50 dose. Amount 500 and 2250 mg/kg we found antinociceptive effect by the inhibition of abdominal Salazar-Granara A1, Castañeda-Castañeda B.2 contractions, being more effective than Diclofenac (ANOVA of one tail and multiple test of Bonferroni, p<0.05); so the effect was related to 1Doctor, Médico Cirujano, Centro de Investigación de Medicina Tradicional y the dose (r=0.5746 y r2=0.3302). With the tail shake test we found Farmacología (CIMTFAR), de la Facultad de Medicina Humana de la Universidad antinociceptive effect at 1000 and 1500 mg/kg being lower than de San Martín de Porres (FMH-USMP), Perú 2Doctor, Médico Cirujano General, Director del Instituto de Investigación, Tramadol ((p>0.05). The phases 1 and 2 of formalin test showed CIMTFAR, FMH-USMP, Perú. antinociceptive and anti-inflammatory effect at 750 and 1000 mg/kg, being higher than Diclofenac (p<0.05). The carrageenan test showed Objective: To determinate the phytochemical composition, the acute anti-inflammatory effect at 1000 and 1500 mg/kg lower than toxicity and the analgesic, anti-inflammatory and prokinetic action of Ibuprofen (p<0.05). Among 500 and 3500 mg/kg we observed increase Maytenus macrocarpa (chuchuhuasi ) leaves. of intestinal motility, against to atropine and effect related to dose (r=0.2609 and r2=0.06808). Methods: In vitro: we did the phytochemical march. In vivo: we used male rodents. The acute toxicity was determinated with the Irving test. Conclusion: It made evident phytochemical composition, toxic effects The antinociception was evaluated by the methods of abdominal and antinociceptive, anti-inflammatory and prokinetic effects of contortions, tail shake and the formalin test. The anti-inflammatory chuchuhuasi’s leaves. activity was determined by mean of formalin and carrageenan testes. The intestinal activity with the test of activated coal.
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LATINFARMA 2013 Resúmenes/Abstracts
Taller de Farmacovigilancia / Workshop on Pharmacovigilance
CO 220: REGULATORY REQUIREMENTS COMPARISON OF CO 221: CHARACTERIZATION OF ADVERSE DRUG MINISTRIES OF HEALTH AND ETHICS COMMITTEES FOR REACTIONS OF LOW FREQUENCY OF APPERANCE IN THE SAFETY REPORTS IN CLINICAL RESEARCH IN CENTRAL CUBAN DRUG SURVEILLANCE SYSTEM, 2004-2012 AMERICA AND CARIBBEAN Santos L, Jiménez G, Alfonso I, Romero MB.
Ramírez N1, Madrigal C2, Molina R.2 Universidad De Ciencias Médicas. Matanzas, Cuba. E-mail: [email protected] 1Faculty of Pharmacy, University of Costa Rica. E-mail: [email protected] 2Roche Servicios S.A. E-mails: [email protected], [email protected] Introduction: the adverse reactions of drugs constitute an emergent
pathology, with a big welfare, social and economic aftereffect. The Introduction: Clinical studies are important to provide information present investigation has the target to characterize the adverse about the effectiveness of the pharmaceutical products of companies in reactions of medicines that occurs in low frequency of appearance, real circumstances. That is why health regulation for Phase III studies received in the National Coordinating Unit of Pharmacovigilance from and Phase IV are important to ensure the safety of the subjects in the 2004 to 2012. presence of adverse effects. Method: we conducted an observational, descriptive, transversal Methodology: In this paper, the information about health laws or study, of drug surveillance, to characterize the reactions of low decrees of the countries of Guatemala, Dominican Republic, Trinidad frequency of appearance according selected variables like age, sex, and Tobago, El Salvador, Panama, Bahamas and Costa Rica were other treatments, severity and causality assessment. reviewed and focused in clinical research and regulations Ethics Committees. Local documents relating to clinical studies were Results: it is possible to appreciate with the course of the years an reviewed and specifically the aspects related with safety to subjects increase in the detection of adverse reactions of low frequency of (Reporting of adverse effects). The Information obtained was appearance, of which 40806 adverse reactions were evaluated. The compared and analyzed with respect to Report Adverse Events demographic characteristics in the reports of low frequency the adults (serious adverse event and suspected unexpected serious adverse as the group demonstrated of major notification (26864 cases for reaction, SUSAR) and was compared between each of the legislation in 65.8%), and the predominant sex was the feminine one with 26781 this aspect. reports for 65.6%. There prevailed the RAM moderated with 23135 reports (56.7%), those of type A with 29578 reactions (72.5%) and Results and conclusions: It was found that Guatemala, El Salvador and occasional with 12718 notifications (54.6%), falling ill in major Panama are those with greater protection for the subjects, because the quantity the skin and annexes as system of organs. Most of the deadline to report adverse events are more demanding and their detected effects were probable according to the causality 26326 regulations need more requirements and periodic reports. In Bahamas, (64.5%) expressing efficacy of the detection of the reports of low Nicaragua, Honduras and Trinidad and Tobago's do not have a national frequency. The serious RAM and of low frequency they totalized 783 entity to ensure clinical research regulations. In the case of Dominican reports, the penicillin and the pentavalent vaccine with 53 notifications Republic is one of the countries that have shown interest in this area (6.7%) there were the medicines that more serious reactions and of and created the National Bioethics and Health (CONABIOS). With low frequency they have provoked in this period. The antimicrobial respect to Costa Rica, the law repealed in 2010 and this does not allow and antineoplastic ones were the medicines that more mortal reactions clinical research and recently depends on approving a new law in produced. Biomedical Research. Conclusions: The notification of the suspicious adverse events of medicines, especially if they are slightly well-known or if they are of recent commercialization, allows knowing better its toxicity profile and helps to reduce the risks in the population.
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LATINFARMA 2013 Resúmenes/Abstracts
CO 222: COMPETENCE IN REPORTING ADVERSE DRUG CO 223: CHAGAS DISEASE: PHARMACOLOGICAL ALTERNATIVES REACTIONS AND MEDICATION ERRORS BY REGISTERED FOR VECTOR CONTROL NURSES IN A SPANISH TEACHING HOSPITAL Marin GH1, Dadé M1, Daniele M2, Mestorino N2, Errecalde J.1 Salcedo-Diego I, Serrano-Gallardo P, Revuelta-Zamorano M, de 1Cátedra de Farmacología Básica, Facultad de Ciencias Médicas, 2Catedra de Andrés-Jimeno B. Farmacología, Facultad de Ciencias Veterinarias, Universidad Nacional de la Hospital Universitario Puerta de Hierro Majadahonda-Universidad Autónoma de Plata. 60 y 120 s/n, 1900, La Plata, Buenos Aires, Argentina. E-mail: Madrid, Calle Manuel de Falla 1, 28220 Majadahonda, Spain. E-mail: [email protected] [email protected]
Introduction: Chagas is an endemic disease in South America that has Introduction: Although Registered Nurses (RN) have been included in very few treatment options to eliminate Trypanosoma cruzi, while the Spanish Pharmacovigilance System (PV) since its set up, they preventive actions consist in spraying homes with organophosphate. provide less than 10% of the drug related problems reports. The aim of Unfortunately these options have failed to control the spread of the the study is to assess the competence of hospital RN in reporting disease, and today, millions of inhabitants affected. adverse drug reactions (ADR) and medication errors (ME). Objective: To demonstrate the presence of avermectin inside Triatoma Methods: Cross sectional study. An electronic survey, designed for the infestans bodies after feeding them with blood loaded with purpose of the study, and which content and face validity had been ivermectine. Extensive populations of Triatoma infestans can be found previously explored, was sent to the universe of clinical nurses in domestic and peridomestic habitats such as corrals and chicken (N=760) of a public tertiary Spanish teaching hospital. The coops since they are sources of blood meal for triatomine bugs. In questionnaire included 32 items to measure their competence these context this study tested the efficacy of Ivermectin 0.5% injected (knowledge, attitudes and skills) in reporting drug related problems, subcutaneously to hens at a dose rate of 200 ug/kg against fifth instars’ as well as socio-demographic and professional variables. Descriptive nymphs of Triatoma infestans. and bivariate analysis (Chi-squared and Student´s t-test) was Methodology: Insects used in this study were fifth instars’ nymphs of performed. T. infestans. Nine hens were used during the experiment. Six hens were Results: The response rate was 40.8%. 89%of the responders were treated with Ivermectin 0.5% (subcutaneous route), and the other women, mean age was 37 years (SD 9.29); 85% administer medication three animals were used as control group, the control group was daily and 31% attended training in patient safety last year. Few RN had manipulated similarly but did not receive Ivermectin. The effects of ever seen the ADR (22%) or the ME (16%) reporting forms and the Ivermectin were measured in two different aspects: mortality and majority have not reported and ADR (98%) nor an ME (97%) during blood intake. Mortality was measured using six groups of 10 fifth last year. 76% think that all suspected ADR should be reported. 94% instars´ nymphs each, fed over the individually identified hens. The agreed that receiving training on PV in their Units could increase the groups were fed at two and seven days after the treatment with reporting rate. Based on the bivariate analysis, those RN working Ivermectin. Blood intake was measured as the difference between the evening and night shifts are more likely to know the ME reporting form weights of the groups, 10 fifth- instars´ nymphs each, before and after (p=0.029), as well as those who received training in patient safety each feeding. (p=0.092). Results: Ivermectin produced differential mortality rates in T. Conclusions: The lack of knowledge on the spontaneous reporting infestans fed on treated hens. Nymphs fed 2 days after treatment not systems might be a factor to explain the under-reporting of ADR and show differences with the control group. Nymphs fed 7 days after ME by hospital Registered Nurses. New training strategies need to be treatment showed 10% mortality. Groups fed 2 and 7 days after the considered to improve their competence in reporting, in order to treatment showed no difference in blood intake. On average each increase the knowledge of drug related problems in the hospital setting. nymph consumed 210 ± 67 mg of blood. Conclusions: This study shows that Ivermectin had only slight lethal effects after a single feeding on treated chickens. Further studies are needed to evaluate if changing certain parameters, such as route of administration and dose could increase the mortality rate of Ivermectin in T. infestans.
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LATINFARMA 2013 Resúmenes/Abstracts
CO 225: IMPLEMENTATION OF A PROGRAM OF ADVERSE CO 226: ADVERSE REACTIONS TO ANTIMICROBIAL AGENTS. EFFECTS NOTIFICATION FOR PATIENT. GUANTÁNAMO. CUBAN PHARMACOLOGICAL SURVEILLANCE SYSTEM, JUNE 2009 - FEBRUARY 2010 2003-2012
Trabanca Beltrán YA1, Jiménez G2, Alonso I.2 Alfonso Orta I, Fariñas Reynoso AT, Coutín Marie G, González R.
1Health Public Direction, Paseo St and Luz Caballero corner, La Habana, Cuba. Department of Pharmacoepidemiology. Ministry of Public Health, La Habana, Email: [email protected] Cuba. E-mail: [email protected] 2Center for the Development of Pharmacoepidemiology, National Pharmacovigilance Unit, 5ta Ave and 44 St, Miramar, Playa, Havana City, Cuba. Introduction: The antimicrobial effects related to account for 20% of visits to hospital emergency rooms for drug toxicities. In Cuba adverse Introduction: In the last years the drugs have become topic of reactions to antimicrobials are ranked first in the report from 2003 concern, every time they are more those that are marketed, increase until 2012. It is currently unknown features of these adverse reactions the consumption considerably and as a consequence adverse effects and their preventability have not yet been studied on time series to appear, for that becomes necessary the pharmacovigilance to classify describe the behavior of the same, allowing to forecast for the NHS. and to identify these effects that appear in the habitual clinical practice. In the Cuban system of health we works with the method of Method: An observational study, longitudinal descriptive. The spontaneous notification for the sanitary professionals, however the required information was obtained from case series annual report program does not exist where the patients notify their adverse effects adverse reactions to antimicrobials in the period from January 1, 2003 in a direct way. to December 31, 2012, reported to the national database pharmacovigilance Ministry of Public Health. We studied the trend and Material and methods: Observational, descriptive and traverse study, seasonality as part of the components of the time series and calculated that used the method of pharmacovigilance spontaneous notification of the odds. adverse reactions suspicions in the municipal main pharmacies of Guantánamo city to implement a program of notification of adverse Results: We reported a total of 40,391 adverse reactions to effects to drugs for patients. We designed a collection of data schedule antimicrobials, dominated by reactions to antibacterials (86.4%). Over that was designed for the patients' disposition in the 10 municipal 60% of adverse reactions occurred in female adults. The antibacterial main pharmacies of the city, in the period among June from 2009 to penicillin G caused the highest number of reports (8423 patients), the February 2010. most affected organ system was the skin (19 051 reports/47, 2%). More than 70% corresponded to probable reactions and low Results: The reports of adverse effects were more frequent in patients frequency. The 17.5% of adverse events were considered preventable, from 15 to 39 years of old and feminine sex. The pharmacological the indication being inadequate because of higher prevalence (52.2%). groups that prevailed were the antimicrobials, AINES and the vaccines, We identified the growing trend and seasonality in the series, except being the most frequent medications the influenza vaccine, Cephalexin adverse reactions to antivirals for being irregular. We calculated the and Captopril. The most affected organs systems were the digestive, forecast for 2013 and 2014 and will increase. skin and central nervous system. The light, probable and frequent adverse effects prevailed. Also the reports of adverse effects in their Conclusions: Adverse reactions to antimicrobial drugs are a health majority were of good quality. problem in our country that affected female adults. Predominated reports to penicillin G and skin. More than half were considered Conclusions: The implementation of a program of report of adverse moderate, probable and low frequency. The sixth of the reactions could effects for the patients is feasible and it provides important data to the be avoided and steps should be taken to prevent the same due to the sanitary system. clinical and economic consequences for the health system.
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LATINFARMA 2013 Resúmenes/Abstracts
CO 227: CHARACTERIZATION OF ADVERSE REACTIONS TO CO 228: ADVERSE DRUG REACTIONS NOT DESCRIBED IN NSAIDs IN ELDERLY IN BOGOTA DC 2012 THE ELDERLY. PHARMACOVIGILANCE SYSTEM. CUBA , 2008-2012 Chaves M. Furones JA1, Alfonso I2, Jiménez G2, Cruz MA1, López AF3, Broche L.2 Department of Pharmacology and Therapeutics. Universidad Militar Nueva Granada, Trasversal 5 No 49-00 Bogotá D.C. E-mail [email protected] 1Escuela Nacional de Salud Pública, La Habana, Cuba. E-mail: [email protected]
2Dpto. Nacional de Farmacoepidemiología del MINSAP. Cuba. 3 Introduction: Nonsteroidal anti-inflammatory drugs are frequently Facultad Ciencias Médicas Julio Trigo: UCMH. Cuba. prescribed in the elderly, despite their potential to cause side effects. Introduction: The main aims pharmacovigilance identify adverse drug Objective: Characterizing adverse reactions to NSAIDs in older adults reactions (ADR) were not detected in pre-marketing clinical trials, in Bogota D. C particularly in high-risk populations such as the elderly. Methods: We performed a pharmacovigilance study, which included Objective: To characterize ADR described in elderly reported to 39 reports of NSAIDs-ADR and PRM in adults over 44 years old, Pharmacovigilance system of Cuba from 2008 to 2012. included in the District Pharmacovigilance Program database of Bogota during 2012. Method: Cross-sectional study. The universe were not described ADR, unwanted effects not registered with Cuba Drug Formulary (DF) in Results: NSAIDs were the second group of drugs with more reports of patients 60 years and older, in the database of the pharmacovigilance ADR and PRM in elderly, with 39 reports 12.1% of notifications system. Outcome measures were age, sex, skin color, main RAM, received in the District Pharmacovigilance Program of Bogota. With an imputability, severity, medication, organ system, kind of health annual incidence of 1.86 per 100,000 adults over 44 years old, which reporter and source level of the report. Descriptive analysis was accounts for the morbidity associated with ADR - NSAIDs monitored in performed Bogota D. C. The drug more committed was metamizol with 48.7%. The skin and annexes was the most affected organ in 51.3% of cases. Results: 899 RAM reported undescribed. Women predominated According to mechanistic classification of 69.2% were type B ADR, (64.1%) and white skin (72.5%) with mean age of 70.10 years. The according to the severity 66.7% were moderate. more RAM reported were headache, hypertension and hypotension with 4.0% each, which affected more the cardiovascular system Given that older adults consume more medications than younger (22.1%). Heberprot-P® (5.5%), captopril (4.2%) and dipyrone (3.8%) adults and the prevalence of ADRs increases in this population, one were the drugs most associated with undescribed ADR. Conditional would expect a greater number of reports. But the spontaneous accountability and moderate severity were 90.3% and 55.2%, notification method ADR, has the problem of underreporting, it is respectively. The 80.9% of the notifications come from primary health estimated that the health personnel only detects the 5 to 15% of the care. ADR that arise, versus active pharmacovigilance methods Conclusions: There is a significant proportion of ADR undescribed in Conclusion: The behavior of ADRs to NSAIDs in adults over 44 years the elderly, whose main features are similar to ADR already old of Bogota is similar to that reported in the literature for this established in Drug Formulary, this does not allow to prevent their. population, regarding frequency of submission of the ADR and the affected organ system. But with respect to metamizol is necessary to note that in the United States and other developed countries is prohibited marketing.
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LATINFARMA 2013 Resúmenes/Abstracts
CO 229: PHARMACOVIGILANCE OF HEBERPROT-P® CO 231: WHY IS THERE A NEED TO SET UP A SPANISH-LATIN AMERICAN DILI NETWORK? Yera I, López P, Alonso L, Valenzuela C, Tuero A, Alvarez A, Debesa G, Moreira M, Marrero I. Bessone F, Hernandez N, Dávalos M, Paraná R, Schinoni MI, Lizarzabal M, Kershenobich D, Loaeza A, Arrese M, Ann-Chirino R, Méndez- Centro de Ingeniería Genética y Biotecnología, La Habana, Cuba. E-mail: [email protected] Sánchez N, Fay F, Bruguera M, Stephens C, Lucena MI, Andrade RJ.
Facultad de Ciencias Médicas. Servicio de Gastroenterología y Hepatología, Pharmacovigilance and post-authorization studies are key elements to Hospital Provincial del Centenario. Universidad Nacional de Rosario, Argentina. monitor the safety and effectiveness of drugs already in the market. CIGB have national and international vigilance of the Heberprot-P® since early stages of commercialization, combining methods of active The lack of a Latin American registry where physicians can centralize and passive surveillance. In the first national post marketing study in reports on hepatotoxic events occurring in the region constitutes a Cuba included 1851 treatment cycles on 1835 ulcers from 1788 major epidemiological deficiency in the liver toxicity field within our subjects were received the Heberprot-P® in secondary and primary continent. Information on hepatotoxicity in Latin American is scanty healthcare level. Complete granulation was obtained in 75.9% of ulcers and usually comes from case reports or small series of patients. The (95% CI; 73.9 – 77.8), in an average of 5 weeks. Re-epithelization of the lack of information regarding the incidence and particular lesion was achieved in 1012 (61%) of the 1659 ulcers seen during characteristics of DILI (Drug Induce Liver Injury) makes it necessary to follow-up. Amputations during the treatment period were necessary in implement a data registry system that would allow us to include all DILI 220 occasions (11.9% of the treatment cycles). Relapses during follow- data recorded prospectively over time. Physicians using a structured up occurred in 5.0% per person-year, and new lesions in 9.5% per and uniform report form protocol and methodologically trained would person-year. There was no relationship between these outcomes and provide valuable information to identify the characteristics of patients, the etiology, Wagner’s grade, or location of the initial ulcer. Follow-up drugs or herbals more frequently involved in DILI, pattern of liver information was obtained from 1620 subjects with 1659 lesions, injury and outcome. Furthermore, Latin America represents a group of median follow-up time was 425.5 days. The variables with significant 23 countries composed by different ethnicities (Hispanic, black, unfavorable influence on survival time were ischemic etiology, history mestizo, Amerindian and European). Such an ethnical diversity within of ischemic cardiopathy, older age, and amputation after treatment the same geographical area is both a challenge and a chance to enhance failure, whereas healing of the ulcer prolonged survival significantly. the knowledge on the ethnic influence in genetic susceptibility as well Adverse events were mostly mild. The serious adverse events were not as phenotypes of drug induced liver damage. Collaborative groups attributable to the product, but to the underlying conditions of the should not only contribute to improve the medical knowledge on liver patients. The results effectiveness in terms of granulation and complete toxicity but also intend to fulfill other specific issues such as: 1) healing promotion as well as amputations and relapses preventions Conduct drug surveillance studies, 2) Perform phenotypic and demonstrate the effectiveness of the product. The benefit (granulation genotypic studies in order to identify and individualize pathogenic or healing) - risk (moderate and severe adverse events + amputations) mechanisms specifically related to drug susceptibility, involved in assessment was favorable for all subgroups the patients. The efficacy different populations and ethnicities. 3) Establish new consensus and and safety of Heberprot-P® in clinical trials was confirmed by the to discuss new definitions of DILI phenotypes and outcomes. 4) To results of its use in clinical practice. further refine hepatotoxicity causality criteria by better weighing clinical information available. Adequate management of these factors will have a significant impact on clinical practice and would have an important bearing on Public Health.
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LATINFARMA 2013 Resúmenes/Abstracts
CO 232: THE SPANISH-LATIN AMERICAN DILI NETWORK: methodology in place at the Spanish DILI Registry. Identified cases PRELIMINARY RESULTS FROM A COLLABORATIVE would be remitted to the coordinating centre in Málaga for causality STRATEGIC INITIATIVE assessment and information storage. Bessone F, Hernandez N, Sanchez A, di Pace M, Arrese M, Brahm JR, Results: Seventy-three DILI cases have been analyzed up to November Ruiz A, Arancibia J, Kershenobich D, Loaeza del Castillo A, Girala M, 2012, having a meanage of 52 years (range 15-86) and female Paraná R, Schinoni MI, Mendez-Sanchez N, Medina-Cáliz I, González- predominance (60%). The therapeutic groups most frequently Jiménez A, Stephens C, Robles Díaz M, Lucena MI, Andrade RJ. implicated were NSAIDs (22%) including nimesulide (5 cases) and diclofenac (4 cases); anti-infectives (19%) including nitrofurantoin (3 Servicio de Gastroenterologia y Hepatologia, Hospital Provincial del Centenario, cases), herbal remedies (12%) including Morinda citrifolia, Peumus Rosario, Argentina. E-mail: [email protected] boldus and Monascus purpureus; hormonal therapy (12%) including cyproterone acetate (4 cases); and central nervous system drugs (11%). Hepatocellular injury (50%) was the most common type of liver Introduction and aims: Idiosyncratic hepatotoxicity induced by drugs damage. Jaundice was seen in 71% of cases, 53% required or herbal remedies (DILI) is an important health problem. DILI is hospitalization and 38% fulfilled Hy's Law criteria (66% of hormonal expected to differ across geographical areas due to differential drug therapy cases, 44%o f herbal cases). Positive autoantibody titers were polices, prescription habits, drug consumption and genetic factors. In present in 29% of cases, mainly antinuclear. Six cases were 2011 the Spanish DILI Registry contacted leading Latin American autoimmune hepatitis DILI (8%) and five cases had experienced a hepatologists in order to establish a Latin American DILI Registry. The second DILI episode (7%). objectives of this initiative were to stimulate detection and collection of well phenotyped cases to provide information on the Latin American Conclusions: This initial analysis demonstrates similar phenotypic DILI profile and corresponding risk factors. characteristics as observed in registers outside Latin America with respect to type of injury and severity. However, female cases seem to Methods: Reference hepatologists were identified in Argentina, predominate in Latin America. With regards to causative agents, Uruguay, Chile, Brazil, Mexico, Peru, Venezuela and Bolivia, who in turn elevated representation of NSAIDs, hormonal treatments and herbal were commissioned to establish national specialist networks remedies were evidenced. contributing to the project. Data would be obtained using the
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LATINFARMA 2013 Resúmenes/Abstracts
Simposio de Cronobiofarmacología / Symposium of Chronobiopharmacology
C 047: CHRONOPHARMACOLOGY C 048: THE ROLE OF ACTIGRAPHY IN THE STUDY OF THE SLEEP-WAKE CYCLE Valdés Y. Meira e Cruz M. Faculty of Pharmacy and Foods. 2317, 222nd St. La Coronela. La Lisa. Havana. Cuba. E-mail: [email protected] Portuguese Association of Chronobiology and Sleep Medicine. Cardiovascular Autonomic Function Lab, Lisbon Faculty of Medicine, Portugal. E-mail: [email protected] Biological rhythms influence many body functions like metabolism, sleep pattern, hormone production and physiology. Variations in these functions cause changes both in disease state and in plasma drug In the recent years activity-based sleep wake monitoring acquired an concentrations. Diseases, such as hypertension, asthma, peptic ulcer, important role as a measuring tool in sleep research and sleep arthritis, myocardial infarction, congestive heart failure, stroke, cancer, medicine. Although not as accurate as PSG for evaluating some sleep follow the body's circadian rhythm. Many systems in the human body parameters, actigraphy has the ability to record continuously for long such as hepatic and renal systems show variation in their function time periods and most often seems more reliable than sleep logs throughout a typical day. They are predictable systems, which require preventing the need of long time observations which are most of the different amounts of drug at predictably different times within the times unfeasible from a practical point of view. Adults and children circadian cycle in order to maximize desired and minimize undesired sleep patterns can be analyzed with the use of this technique which drug effect. Chronopharmacology considers that the drug therapy can provides important validated objective information either related with be optimized by tailoring the dosing schedule based on sleep and wake schedules, daytime and nighttime activity as well as chronobiological pattern. This has led to a new approach to the environment light. Actigraphic analysis may also have a role in the development of drug delivery systems. A number of chronotherapeutic medical care of patients with different sleep disturbances, namely medications, aiming at synchronizing medications and the intrinsic circadian rhythm disorders, insomnia, restless legs syndrome and rhythms of disease have been developed in recent years. In this lecture, periodic limb movements. More rarely actigraphy may be useful for the concepts of biological rhythms, chronobiology, chrono- selected patients with suspected sleep related breathing disorders. pharmacology and chronotherapy for various diseases will be Despite the different conditions for which actigraphy may be helpful, discussed. some methodological issues need to be respected in order to obtain clinically useful and reproducible data.
In this lecture, author will provide an overview about actigraphy as a tool with great value on sleep lab both for research and for clinical purposes.
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LATINFARMA 2013 Resúmenes/Abstracts
MR 005: SPORTS CHRONOBIOLOGY they are ruled by the suprachiasmatic nucleus and related to the psychoneuroendocrine system. They have diverse implications from his León A, Nicot G, Almenares E, Hernández A. application to the exercise, his performance, training, moment of sports Instituto de Medicina del Deporte. La Habana. Cuba. E-mail: [email protected] results, prevention and rehabilitation of sports injuries, as well as the more premature recuperation, analysis and use of drugs in circadian rhythm disorders like Jet Lag, united to the job of medicinal and acupuncture therapies as well as related others; all of them Chronobiology is the science of biological rhythms that applied in the contributing to achieve better results in the training and the human being has implications in many spaces of life and work. The competitions. The IMD exposes some investigations, methods and beginnings of this discipline applied to the Science of sports, rule a lot aftermaths used in Cuba with techniques, books and postulates of physiological activities ruled by the time, been born and timed in experienced at this field, of late years. linkage with the central nervous system and in independent activities
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LATINFARMA 2013 Resúmenes/Abstracts
Taller de Medicamentos Genéricos / Workshop on Generic Drugs
CO 233: A ROLE OF INNOVATION IN CUBAN CO 234: BIOEQUIVALENCE (OR BIOINEQUIVALENCE) OF PHARMACEUTICAL INDUSTRY GENERIC IMMUNOSUPPRESSIVE DRUGS: PHARMACO- DYNAMIC CONSIDERATIONS Carralero M, Gutiérrez A. Castañeda G. BioCubaFarma, La Habana, Cuba. Departamento de Farmacología, Centro de investigación y de Estudios Avanzados Introduction: This work discusses several aspects related to del Instituto Politécnico Nacional. Av. Instituto Politécnico Nacional 2508, 07360 development and technological innovation; and establishing an México, D.F. adequate infrastructure, including specialized institutional structures, for the evaluation of technology transfer and development in order to meet the demands made by human beings to the pharmaceutical Current bioequivalence criteria consider only pharmacokinetic data. If industry. The most important aspect is that innovation is no longer just the area under the curve and the peak concentration observed with a about the product itself, it is also centered on how an enterprise generic falls within a pre-established range with regard to the contributes to improving the health of patients. innovator, both products are considered bioequivalent, and hence Material and methods: We have constructed a table of dates collected interchangeable. However, blood concentration data cannot be directly from the introductions to basic drugs list in the 2009 - 2013 period and extrapolated as expressions of the pharmacological effect. The we do a review of technological innovation in the Pharmaceutical concentration-effect relationship is given by the Hill equation, yielding Industry. We compiled economical dates of these introductions and a sigmoid curve. For most drugs, the curves exhibit a smooth slope their health benefits. factor (h=1), in a way that a change in concentration yields a comparable change in the effect. However, calcineurin inhibitors, such Results: At the industrial level, generic drugs reduces the cost of as tacrolimus and cyclosporine, exhibit curves with a high slope (h=3). developing of new product and the overall costs of manufacturing that In such cases, small changes in concentration result in important could lead to reduced healthcare spending. Re-innovation by the changes in the effect. Therefore, the allowed variability in drug generic pharmaceutical industry can be observed in drug product concentrations permitted by current bioequivalent criteria can result design, formulation, process development and manufacturing in important changes in the effect, and thus in therapeutic failure. Our processes going back to the early stages of the product development results support previous reports on the non-interchangeability of cycle. innovator and generic products of calcineurin inhibitors. The challenge of new management systems in these innovative generic pharmaceutical enterprises is on product innovation: How to optimize product quality? How to reduce manufacturing costs? How to reduce the time to market? Conclusions: The innovation is widely regarded as an instrument to create competitive advantage, Cuba has developed a well-established pharmaceutical industry based on the formulation or manufacturing of generic medicines, originally to provide medicinal products for her own population and, more recently, to earn hard currency through exports. In order to strengthen pharmaceutical production is formed BioCubaFarma Group.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S143
LATINFARMA 2013 Resúmenes/Abstracts
CO 237: CARBON NANOTUBES AS PARACETAMOL CARRIERS CO 238: SIMPLIFYING AND STREAMLINING THE MARKETING FOR CONTROLLED DRUG DELIVERY: A THEORETICAL AUTHORIZATION PROCESS IN CUBA STUDY Suárez Y, Fernández M, Sánchez C. Hernández Valdés D, Enriquez Victorero C, Jáuregui-Haza U. Centro para el Control Estatal de Medicamentos, Equipos y Dispositivos Médicos, Instituto Superior de Tecnologías y Ciencias Aplicadas (InSTEC), La Habana, La Habana, Cuba. E-mail: [email protected] Cuba. E-mail: [email protected]
Introduction: The risk based approach can be applied both to the Single-walled carbon nanotubes (CNT) have ultrahigh surface areas product development, and as part of regulatory operations including that together with the advances on chemical functionalization of CNT assessment activities. This new approach was needed to be introduced for aqueous solubility aimed at exploiting nanotubes as in Marketing Authorization process by the National Center for State macromolecules for chemistry, biology, and medicine. For that reason, Quality of Control of Drug, Equipment and Medical Devices (CECMED), CNT can be used as carriers and/or excipients to obtain different drug in order to simplify and streamlining the review process in Cuba, delivery systems. In this work, a theoretical study of interactions ultimately based on patient protection and scientific principles. The between paracetamol, a widely used analgesic and antipyretic aim of this work was to apply the quality risk management approach in pharmaceutical, and a simplified model of NTC is presented. The licensing product process of synthetic and semisynthetic drugs. simplified CNT model consists of seven membered ring graphene sheet Methods: The state of art regarding risk approach and its (coronene) with a surface functional group (SFG), used to assess the implementation in marketing authorization was analyzed among influence of several SFG over the paracetamol adsorption on CNT. The selected National Drug Regulatory Authorities, Prequalification of MMH methodology was used to evaluate interactions between Medicines Programme of WHO and CECMED. Registered and rejected paracetamol and SFG (carboxyl, hydroxyl) and the graphene sheet. This products were characterized during the period 2007 – 2009. Two methodology combines quantum mechanical methods for the normative projects were elaborated according CECMED internal calculation of energy with statistical thermodynamic in order to obtain methodology. molecular association magnitudes. The structure of each complex was optimized using the PM6-DH2X dispersion augmented semiempirical Results: Differences were found among the selected entities regarding method, which includes empirical corrections for hydrogen bonding the implementation level on risk approach in marketing authorization. interactions. The pH influence over SG and paracetamol structures was During the studied period, 536 products were registered, 79% taken into account. The solvent effect using an explicit solvation model imported, 44% of imported products were previously approved by a with different hydration conditions was evaluated. The Molecular relevant regulatory authority or prequalified by WHO, and 38.2% Electrostatic Potential maps over the 0.002 AU electronic density complicated dosage forms. Two drafts were designed: Guidelines for isosurfaces were obtained for the isolated molecules using B3LYP/6- marketing Authorization for products provided for United Nations 31G//B3LYP/cc-pVDZ. Charged surface groups have stronger Programme or previously approved by any Relevant Regulatory interactions with water molecules and paracetamol than neutral Authority and the guideline for quality assessment applying a risk surface groups. The affinity order is: COO- > O- > COOH > OH > graphene. based approach. 4 trainings were developed for assessors from Drug The presence of graphitic carbon favors adsorption of negatively Departments. charged paracetamol at basic pH. Conclusions: The two drafts are in line with the new trends and adjusted to national characteristics, that propose an abridged procedure for products previously approved by selected Relevant Regulatory Authority or prequalified by the World Health Organization, including the elements of pharmaceutical development as a key on quality risk management and decision trees to classify drug product in two level of risk from quality point of view.
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LATINFARMA 2013 Resúmenes/Abstracts
CO 239: DRUGS DEVELOPMENT VS NEEDS OF HEALTH. A XXI World Health Organization (WHO) and the OPS, from 2007 to 2012. It CENTURY CHALLENGE was determined the most produced drugs by these and other pharmaceutical companies. It was identified the principal causes of Rodríguez AJR, Lafourcade PA. death for illnesses, among first and third world countries. Pharmacy Department, Natural Sciences Faculty. Universidad de Oriente. As a result, it was observed that strategic planning in terms of the Santiago de Cuba. Cuba. E-mails: [email protected]; [email protected] needs of health does not come true. That the drugs what are more produce are generic and some combinations of it. A lack of real innovation, prohibitive pricing and strict regulations on intellectual In the last years, Pharmaceutical Industry has become a worldwide property were observed, too. This provokes a low availability of drugs leader. A few pharmaceutical companies have the control of the 50 for more urgent illnesses and a fact-finding absence to produce drugs percent of the world market of pharmaceutical products. However, the for forgotten chronic illnesses. production of drugs not only is not conducted to supply the needs of health, but also to generate earnings. The objective of this work was to It can conclude that, in spite of the increase of chronic illnesses, the evaluate the formal and ethical issues that determine the existent increase of the epidemiologic loads and the population's aging in all divorce among the drugs production and the needs of health and the over the world, the real innovation does not exist, researches in terms play roll of generic drugs in the health systems in the third world of the needs of health do not project and there is little ethical countries. performance of the grand Pharmaceuticals Enterprise. This combination of factors reduces the availability of essential drugs and It was made a meta-analysis by using the annual reports of some of the they determine the unfairness in the access to the drugs of all over the bigger pharmaceutical enterprise (i.e. Sanofi Aventis, Pfizer; Bristol world. Meyer Squib, Takeda, Bayer and Novartis) and the emitted informs of
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LATINFARMA 2013 Resúmenes/Abstracts
Taller de Enseñanza de la Farmacología / Workshop on Teaching of Pharmacology
C 049: PERMANENT PHARMACOLOGY UPDATING, CO 240: HISTORY OF PHARMACOKINETICS AND INHERENT COMPETENCE TO PHARMA-CEUTICAL CARE BIOPHARMACY IN CUBA: ROLE OF THE UNIVERSITIES Sedeño C. Fernández-Sánchez E.
Foods and Pharmacy Institute, Havana University. 23 Ave. No. 21425. Coronela, Institute for Food and Drugs. University of Havana, Cuba. E-mail: Lisa. Havana, Cuba. E-mail: [email protected] [email protected]
In the past 20 years, the safe use of drugs has generated actions and A time goes by in the history of the development of the Science and changes in international health policy, due to the many iatrogenic Technology, the universities plays a particular advanced role. Cuba is procedures caused by them, some attributable to clinical investigations not different in the appearance of Pharmacokinetics and Biopharmacy performed with insufficient scientific rigor, other problems related to besides the interest of research and development of innovator drugs good prescribing, dispensing or administration practices by the health and biosimilars and possibilities to find more optimal bioavailability care professionals or improper use of drugs by patients has been for generic drugs. named. The aim of this presentation is to cover the different stages in the Multiple drugs from natural, synthetic or biotechnological source, search of a national knowledge, through the participation of the joined to the therapeutic arsenal in the last decades of the last century, university in several investigations on request of the production characterized by some new and different mechanisms of action, other centers. mechanisms of action already described, but with better risk benefit ratio and other designed especially for the treatment of emerging In this exposure we’ll cover the different highlights on the results diseases at the time. scientifically obtained in the Cuban universities applying different methodological topics: pharmacokinetic characterization of new The care pharmacist responsible for dispensing prescribed molecules, pharmacokinetic/pharmacodynamic relationship (PK/PD), medications to patients must ensure and check that the patient knows integrated PK/PD modeling, population pharmacokinetics, absorption the proper performance of the prescribed drug, warn of potential risks enhancers, in silic methods in conjugation to the biopharmaceutical and provide advice to any health problems related to drugs. In order to classification systems (BCS), bioavailability of pegylated proteins and do this effectively, this professional must maintain a systematic others. Mainly these results were obtained in biotechnological pharmacological update during the course of working life. molecules in relation with the recognized strenght of the Cuban Biotechnological Industry. These facts made that international government organization of health reanalyze the roles and responsibilities of pharmacists responsible for It proves the interaction between university and manufacturing and dispensing drugs in society. Among the main actions and changes that besides it the advanced development of the Pharmaceutical Sciences took place since the late nineties of the last century to the present are: according to the scientific worldwide paradigms, proved by the modification of the mission of Pharmaceutical Services, with special publication of papers in journals of high impact. emphasis on patient-oriented processes, the need for training Eight Star Pharmacist, with mastery of competencies as Care Provider, Decision Taker, Trainee and Educator Permanent to ensure exercise care in their actions. It is the responsibility of universities to systematically update and form pharmaceutical professionals that today’s society demands, which must be fully trained about drugs that allows them to respond to the scientific development challenges imposed by health issues that characterize this century.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S146
LATINFARMA 2013 Resúmenes/Abstracts
CO 241: APPLICATION OF PBL, ICTs AND ITS EFFECT ON CO 242: "SIMULA EXPERIMENTAL PHARMACOL": SOFTWARE ACADEMIC ACHIEVEMENT IN THE COURSE OF BASIC TO TEACH AND LEARN EXPERIMENTAL PHARMACOLOGY PHARMACOLOGY-2011, MEDICAL SCHOOL OF UNMSM WITHOUT USE LABORATORY ANIMALS
Placencia M1, Gonzales H1, Villanueva T1, Acosta O2, Atoccsa V3, Balderas JL, Alfaro A, Tapia G, Navarrete A. Tenorio L3, Núñez M1, Malca M.4 Facultad de Química. Departamento de Farmacia. Universidad Nacional 1Pharmacology Section DACD-Medical School, 2School of Pharmacy and Autónoma de México. Ciudad Universitaria Coyoacán 04510, México D.F., México. Biochemistry, 3Informatics Office, Medical School, UNMSM, Perú. E-mail: E-mail: [email protected] [email protected] 4Teaching Medical School UPC Lima Peru Introduction: The use of laboratory animals is restricted for undergraduate curses of pharmacology experimental, is also expensive Introduction: The Universidad Nacional Mayor de San Marcos is and not all the universities have laboratory-animal housing and increasingly incorporating PBL methodologies and new ICTs in laboratory with equipment in quality and quantity enough to perform education, particularly in the health sciences, including pharmacology pharmacology experiments. We developed software with real and course. However it has not been yet assessed the impact of this on simulated experiments of pharmacology to teach experimental student academic performance. pharmacology. This software can be also used both for students and researches to learn pharmacology methods. Objective: To determine the effect of PBL and ICT on academic performance during Pharmacology course of Medical School, UNMSM, Material and methods: For several years we registered real in vivo 2011. and in vitro experiments of pharmacology and they were integrated in software to have access in a random form according drug, dose and Material and Methods: Sample: Students who took the course of experimental type. Also some experiments such as dose-response Pharmacology in 2011 (n = 131) who voluntarily participated in PBL curves and lethality were simulated with algorithms in such form to modules related to the impact on public health, as well as those in obtain results close to reported data in the literature. Also we simulate which new ICTs were used (n = 62) compared with those that used in vitro records of polygraph of experiments of relaxation and traditional methodologies (n = 69). Methodology: Analytical contraction of different isolated organ preparations. All this based on comparative study. Chamilo platform was used as part of ICT for the 3Rs rule. virtual learning (pre-test, simulated labs, electronic consultation). PBL methodology was applied with seven modules constituting 50% of the Results: The software is friendly, clear, easy manipulation, nice to user course activities. Academic performance was assessed by overall and useful to cover the objectives of teaches-learn of an experimental average of all scheduled activities. Student´s t test was used to compare pharmacology curse. This software is a platform Adobe Flash© the mean scores of the course, of PBL modules, among students who compatible with Windows© and MacOS©. Each experiment contain used ICT and those that followed only traditional teaching. fundament of the test, detailed methodology description as a experimental pharmacology book, how to analyze the crude data, Results: Students using traditional methodology obtained a overall alternative test for the same objective, a demo experiment to average score equivalent to overall academic performance of 13.62 ± understand the test with instruction on the critical points that the user 1.27; in theory tests an average score of 13.50 ± 1.59 and 13.4 ± 2.0 in should put attention, then the user perform the experiment. In this PBL modules, while the ICT group obtained 14.10 ± 1.2 and 13.88 ± point exist instructions, for the user select drug, and a dose and then 1.84, and 13.4 ± 1.7, respectively; showing significant differences (p = start the experiment, obtain his/her results and analyze and discuss on 0.033) only when comparing the overall academic performance them with the instructor or theacher. between groups. Conclusion: This software is useful to teach and learn experimental Conclusions: We found that ICTs have a significant effect in improving pharmacology, resolve economic, technical, educational and ethical academic performance, which implies the need for further study of the problems in the teaching of experimental pharmacology. factors involved.
Project Code: 110114435 UNMSM.
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LATINFARMA 2013 Resúmenes/Abstracts
CO 243: CURRICULAR IMPROVEMENT OF THE SUBJECTS CO 244: TEACHING PHARMACOLOGY AS A MEANS OF PHARMACOLOGY I AND II IN THE CURRICULUM OF PROMOTING RATIONAL DRUG USE. AN EXPIERENCE WITH MEDICINE UNDERGRADUATE STUDENTS Rodríguez Ezcurdia R, López Guerra RL, Huguet Blanco Y, Pérez de López M, Speranza N, Telechea H, Catenaccio V, Pagano E, Ramos C, Armas A, Quintana Gómez F. Viroga S, Artagaveitya P, Goyret A, Tamosiunas G.
Medical College "Dr. Serafín Ruiz de Zárate Ruiz", Villa Clara, Cuba. E-mail: Montevideo Medical School. Department of Pharmacology and Therapeutics, [email protected]. Hospital de Clínicas, School of Medicine of the University of the Republic (UDELAR), Uruguay.
Introduction: Pharmacology is a discipline that provides medicine students of scientific basis in therapeutic for applying an integral Introduction: Within the framework of a curricular reform that has treatment to patients. It is assumed that relevant pharmacologic been developing since 2009 in the School of Medicine of the Republic knowledge is revisited during the clinical clerkships and the students (UdelaR), the Department of Pharmacology and Therapeutics has are adequately trained to prescribe drugs upon graduation. However, implemented pilot projects that encompass educational innovations. for many years it has been noted that pharmacological training is Objectives: To develop educational strategies that will help optimize sometimes insufficient and that inadequate and irrational prescription pharmacology knowledge based in problem-solving techniques in of drugs is a very common problem in clinical settings. order to promote Rational Drug Use (RDU). Objective: To design a proposal of curricular improvement of the Material and methods: We implemented workshops with small subjects Pharmacology l and ll to guarantee the general doctor's groups of undergraduate students. Initially, during 2011, the appropriate formation. workshops were optional, but during 2012 they were included as part Methods: An observational, cross-section, descriptive study was of the curriculum. The students worked with real life cases and carried out focused on a mixed quantitative and qualitative design at problems regarding drug information, RDU, pharmacovigilance (use of Medical College "Dr. Serafín Ruiz de Zárate Ruiz" Villa Clara; from antibiotics, emergency and urgency use of antihypertensive drugs, February 2012 to April 2013. The methodological design was gastrointestinal risks of NSAIDs, risks of Varencicline use and solving of conceived in three stages: 1st stage to specify the difficulties of the problems at the Center for Drug Information). The workshops took program of the subjects Pharmacology l and ll; the 2nd stage related place during the course of 4 months, with weekly face- to- face with the design of the proposal of improvement of the revised activities and also through the use of a virtual learning environment. programs and the 3rd stage to assess the formulated proposal. Continuous assessment and evaluation was performed through tests to evaluate knowledge as well as through field work and reports. Results: The main identified difficulties were related with their design such as: teaching organizational forms, contents and system of Results: Seventy students participated in 2011 on this pilot project. In evaluation. Starting from the identified difficulties a proposal of 2012, 300 hundred students were involved. They acquired skills in the curricular improvement of the program was designed which is field of information searching and analysis, designed small scale distinguished for methodological orientations that guarantee a pharmacoepidemiological studies and applied pharmacovigilance developer teaching-learning process. It has the following structure: methods. They were able to understand the importance of rational title, basis, identified difficulties, modifications and basis of the drug prescribing, of monitoring therapy response, of critical analysis of modifications. The proposal was characterized by its relevancy; information and of the quality of local records in pharmacoepidemio- usefulness; feasibility for their application and methodological logical investigation. scientific value. The same one was valued by the specialists selected as The results on antihypertensive prescription were informed to the appropriate keeping in mind the mentioned structure, being participant hospitals and two reports were included in the Bulletin of recommended its implementation in later coming courses to their the Department of Pharmacology. Some of the information gathered validation. during the workshops was relevant to update the list of drugs used at Conclusion: Our program constitutes an effort to medicalize the the University Hospital. teaching of pharmacology in medical schools. We expect that most Conclusion: This working methodology allowed students to learn medical school in Cuba will follow our guidelines as our program is pharmacology from a non-traditional perspective, based in actual applicable to all curricula modalities. clinical problems. Also, the data obtained during the process was useful to enhance and generate local knowledge.
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LATINFARMA 2013 Resúmenes/Abstracts
C 050: IMPLEMENTATION OF VIRTUAL SIMULATION CO 246: ASSESSMENT OF THE GENERAL PHARMACOLOGY SOFTWARE Microlab® and RAT CARDIO-VASCULAR in LEARNING/TEACHING PROCESS IN THE YEAR 2012 PHARMACOLOGY 2012, MEDICAL SCHOOL OF UNMSM Demurtas SL and Brizuela Nilda Y. Placencia M, Núñez M, Gonzales H, Silva J; Carreño J, Vásquez A, Malca Faculty of Medical Sciences. National University of Córdoba. Argentina. E-mail: M, Wilgemburg H. [email protected] Teaching and Research Faculty of Pharmacology. Medical School UNMSM Lima, Peru. Research Project Code 120114335 UNMSM Lima, Perú. Introduction: General Pharmacology is a subject that belongs to the
3rd year within the Medicine Course of Studies, and is prior to the Introduction: Constructive learning of pharmacology in medical subject Applied Pharmacology. In 2012, it was delivered in 120 hours. careers is a challenge for universities and a necessary condition for The subject was taken by 700 students distributed in 42 groups. Its rational therapy. In the teaching of pharmacology in The Medical aims and objectives are to be able to infer the impact of the different School of UNMSM, virtual simulation activities using Microlabs® routes of administration on pharmacokinetics, to explain the software on pharmacokinetics and pharmacodynamics labs were pharmacological effects as a result of the mechanisms of drug action, to incorporated. (Dr.Hendrik van Wilgemburg). detect risks and adverse reactions, and to differentiate individual The aim of this work was to optimize learning tools for virtual learning variations in the results. In order to develop the chosen topics, and and to assess the impact of this on academic performance. taking into account the current syllabus of the subject, different teaching methods were used. Methodology: Descriptive and analytic cross-sectional study with non- probability sampling, involving students in the 3rd year of Medical Objectives: to detect the students’ degree of knowledge on the aims of School taking Pharmacology course. (134 students, 85 men and 49 the subject and their opinion as regards the adopted teaching methods. women). Informed consent was prepared requesting their voluntary Methods and resources: 300 randomly chosen students were polled, participation, informing them about the purpose of the research and monitored by teachers who employ different teaching methods. the importance of the study. Unit of analysis: Average grades for scheduled activities, continuous assessments in virtual labs, software The survey used consisted of: Microlab® and Rat Cardiovascular applying ICTs. Statistical analysis: descriptive development and application of Student´s t and Mann- A header to be filled in with the students’ Whitney tests. SPSS statistical software version 18 was used. information. A questionnaire about the students’ knowledge on Results: There were 6 induction workshops and training of the aims and objectives of the subject (closed-ended pharmacology teachers on managing Microlab® software and questions with 5 options) and their opinion (open-ended Cardiovascular Rat. Results: 4 lab guidelines for the use of virtual questions). The answers were classified into different simulation software. Scores for the labs of basic pharmacokinetics with categories. clinical application in 2011 were 12.0 and 14.1 in 2012 (p = 0.001). In the labs of pharmacodynamics on the cardiovascular system, the score Results: 65% of the surveyed students showed having knowledge on was 12.0 in 2011 and 13.6 in 2012. (p <0.001). the objectives, while the remaining 35% makes reference to therapeutic application, which is not contemplated at this stage. Conclusion: The optimization of the instruments allowed a significant improvement of student academic performance in virtual activities of The teacher’s development of theory was approved by 20% of the pharmacology. polled students; the presentation on the part of the students, by a 10%, and the troubleshooting workshop, by a 70%. Finally, only 35% attends lectures, 95% of which is satisfied with them. Conclusions: there is a stronger approval of the workshop as a teaching method and there are problems with the timetables to attend theory classes.
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LATINFARMA 2013 Resúmenes/Abstracts
CO 247: TEACHING OF PHARMACOLOGY IN THE MODULAR CO 248: THE GAME IN PHARMACOLOGY: ANOTHER WAY OF SYSTEM: CONSTRUCTION OF THE TRANSFORMATION LEARNING TO LEARN OBJECT Yodú Ferral N, Peña Fleites C. Izquierdo-Sánchez T. “10 de Octubre” School of Medicine. Josefina, entre Revolución y Gelabert. 10 de Laboratorio de FitoFarmacología, Depto. de Sistemas Biológicos. Universidad Octubre. La Habana. Cuba. E-mail: [email protected] Autónoma Metrolitana-Xochimilco. México. E-mail: [email protected]
Introduction: Current trends in medical education point to the Introduction: For the formation of undergraduate students majoring construction of student-centered knowledge models. Therefore, in Chemistry-Pharmaceutics-Biology, interactions of drugs and teachers are required to devise methods that activate students’ organisms are approached from a paradigm considering the drugs as learning capabilities and help them “learn to learn”. Didactic games are modifiers of biological responses. The dynamic processes that articulate both a method and a means of teaching that is rarely used in higher homeostasis and the interactions of drugs in biological systems are education. Yet, they stimulate self-learning, team work, motivation and analyzed from this integrated perspective. The Modular system offers a creativity. Furthermore, they can be used as a tool to grade students’ construction model of a transformation object (TO) based on the progress. theoretical contents from a multidisciplinary perspective. Our goal has been to collect student opinions about the effectiveness of Material and methods: Teams of 4 to 5 students are constituted, and using games as a self-learning stimulation mechanism in the context of the TO is proposed and discussed as a Research Project. The work the complex subject of “Pharmacology Receptors and their Clinic starts by selecting a therapeutic group (TG) of relevance for the Importance.” morbidity and mortality profile prevailing in Mexico. The theoretical Material and methods: Third year medical students in the 2012-2013 framework is elaborated approaching: 1) Structure and course (n=50) were taught the previously mentioned subject. physicochemical properties of the drugs that are representative of the Afterwards, they were told to assemble in teams and create games that TG. 2) Characterization of the pharmacokinetic profile. 3) Exposure would help study the subject. Outside school hours and with the active and analysis of the pharmacological action mechanisms. 4) Analysis of participation of the whole group, each team presented a practical the mechanisms associated with toxicity/adverse effects. 5) demonstration of its game. Finally, students selected the game they Hypothetical development in study models, pre-clinical, and clinical liked the most, and produced and anonymous written evaluation of phase. Themes are organized for analyses and discussion in seminars, this experience. following the mentioned order. Laboratory work is adapted to assessment in appropriate experimental models. Results: All students produced positive comments about the activity. They agreed it helped stimulate self-study, team work, motivation, Results: For the elaboration of TOs, the interrelation of factors that creativity and the whole learning process. Around 79.4% pointed out determine de health-disease process is approached in an integrated they found the activity an interesting one, particularly because it was a fashion, from public health, epidemiological, socio-demographic and novelty that let them enjoy while learning. Approximately 20.5% sanitary view points, as well as from anatomic, physiological, indicated negative factors. These were mostly related to the scarce toxicological, biochemical perspectives, among others. Drugs of time assigned for demonstrations and discipline problems during their different TGs such as: NSAIDs, anti-epileptical, cytoprotective, anti- development. The games’ effectiveness as a grading mechanism was propulsive, etc., are analyzed dynamic process, in which intrinsic and also questioned. external factors interrelate in an inter-dependent manner as a connective function of the homeostatic processes that modulate repair Conclusions: Didactic games serve to stimulate self-study, creativity, mechanisms as a whole. motivation and team work in the context of Pharmacology teaching. They also serve as a feed-back mechanism that can be used to correct Conclusions: Construction of TOs eases the understanding of the learning errors. Games have the benefit of encouraging more active pharmacological profile as a dynamic process, in which intrinsic and student-teacher exchanges. external factors interrelate in an inter-dependent manner.
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LATINFARMA 2013 Resúmenes/Abstracts
CO 249: COMPARATIVE ANALYSIS OF CLINICAL PL 014: CAUSES OF DISEASES AND THEIR BOARDING FROM PHARMACOLOGY TRAINING PROGRAMS ACROSS THE THE PERSPECTIVE OF ORTHOMOLECULAR MEDICINE WORLD Llorente JR. Domínguez V, Speranza N, Goyret A, Tamosiunas G. Presidente Sociedad Española de Nutrición Ortomolecular. E-mail: Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad [email protected] de la República (UdelaR). Hospital de Clínicas, Montevideo, Uruguay. E-mail: [email protected] When speak about nutrition and feeding in colloquial terms, we adapt this to culinary sphere, that is to say, to the aspect and organoleptic Introduction: Clinical Pharmacologist is a wide spectrum discipline characteristic. Feeding is the only way of we dispose to provide an yielding professionals with a similar wide spectrum area of activities appropriate nutrition. As all we know, it is one of the markets more including clinical practice, research, drug regulation and industry. manipulated from different areas, social, economic and mediatic. The Therefore, clinical pharmacology (CP) training programs should consequence is a commercialized feeding and far from the designed include a variety of content in order to acquire specific knowledge, function. Every time is bigger the number of diseases and these are skills and attitudes to function as a specialist. presented to earlier ages affecting fundamentally to metabolic, hormonal and immunity areas, and the degenerative character as Objective: To characterize a non-random sample of CP training cancer. This reality should be as starting point to outline a different programs in different countries. boarding of illness, and this is exactly it makes the Orthomolecular Material and methods: We have reviewed six CP specialty training Nutrition. Orthomolecular Nutrition act by two ways: on one hand programs from different countries and compared their main proposing changes in the alimentary behavior and for other elaborating characteristics. The selection criteria were only based on easiness of treatments with specific active principles with recognized activity in public access. front of different illnesses. Leaving of the premise that the illness is a multifactorial phenomenon they are more and more the professionals Results: A descriptive analysis is presented. The following table that join efforts to demonstrate that we are in the correct way. summarizes the most relevant results. Nutrigenomic is one of the more recent supports that serves of great help to understand the indefectibly connection between illness and
UK Spain Australia Canada U.S.* Uruguay nutrition. The aims of this work is to propose a different boarding from the disease with contrasted and surprising results that it can be in itself
-MD in US a unique work method or a support for other therapies. But to treat any Internal or Canada & General illness forgetting the biochemical impact that will present is, without Medicine, Primary Internal Basic Emergency Specialty Basic site to doubts, to reduce the options that we will have to re-establish Medicine Pass the Admission physician Medicine, physician & Acute annual exam -Non the patient's health. requirements 3 year- Pediatrics, 7 year- Medicine (MIR) physicians training Anesthesia training (12 & Doctoral or months) degree in Psychiatry Medical sciences
Duration of At least 2 4 years 4 years 3 years 2 years 3 years training years
Is Clinical 18 months & encouraged No No 6 months Yes training shifts but not required
Drug research Yes Yes Yes Yes Yes Yes
Training in Regulatory Yes Yes Yes Yes Yes Yes aspects
Training for Industrial No Optional Optional Yes No Not yet Clinical Pharmacology
Toxicology Yes No Yes No Yes Yes
Not in all the Training in No CP Yes Yes Yes No teaching CP Departments
*American Board of Clinical Pharmacology Conclusions: There is considerable heterogeneity in the CP training programs across the world. The examples analyzed show differences in terms of both background admission requirements and content of clinical training. This is felt to be a major contributor to the perception that clinical pharmacology is an ill-defined discipline.
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LATINFARMA 2013 Resúmenes/Abstracts
SESIÓN DE CARTELES /SESSION FOR POSTERS
Martes 22 / Tuesday 22nd
TALLERES Y SIMPOSIOS / WORKSHOPS AND SYMPOSIA
Inmunofarmacología y Biotecnología / Immunopharmacology and Biotechnology
Métodos Alternativos / 3Rs Alternatives Methods
Nanofarmacología / Nanopharmacology
Estrés oxidativo y Ozonoterapia / Oxidative Stress and Ozonetherapy
Productos Naturales / Natural products
Neuroinmunomodulación / Neuroimmunomodulation
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S152
LATINFARMA 2013 Resúmenes/Abstracts
Inmunofarmacología y Biotecnología / Immunopharmacology and Biotechnology
PIF-BT 001: CHARACTERIZATION OF DRY POLYSACCHARIDES PIF-BT 002: DEVELOPMENT AND VALIDATION OF A FROM NEISSERIA MENINGITIDIS SEROGROUPS A, C, Y AND SEROLOGICAL TEST (ELISA) FOR DETERMINING TETANUS W135 TO BE USED AS INTERNAL CONTROLS ANTIBODIES AS A POTENCY MEASUREMENT IN MICE SERA Diaz D, Gutiérrez N, Hernández D, Chovel ML. Gutiérrez N, Ontivero I, Valle O, Núñez JF, Mandiarote A, Chovel ML. Finlay Institute. Quality Control Direction. Ave 27 No. 19805, La Lisa, La Habana, Finlay Institute. Quality Control Direction. Ave. 27 No. 19805, La Lisa, La Habana, Cuba. E-mail: [email protected] Cuba. E-mail: [email protected]
Introduction: Finlay Institute is a leader center in the development of Introduction: Tetanus is a serious disease considered as the third vaccines against Neisseria meningitidis. In the 90’s a clinically active cause of death among the immunopreventive illnesses. The vaccination vaccine based on Outer Membrane Vesicle was produced against the with Tetanus Toxoid is the only effective way for preventing the serogroup B. Recently, a tetravalent vaccine based on Polysaccharides disease. The quality and efficacy of these vaccines could be assured by from serogroups A, C, Y and W135 has been developed. To face the challenge Potency tests in animals. The in vivo seroneutralization test quality control of this kind of vaccines, new methods and references (L+/10/50) is one of the most used assays, but the test has limitations should be established. in terms of ethic issues and variability. That’s why some 3Rs alternatives have been evaluated in order to replace this test. Aims: The aim of this research is to obtain and characterize 4 polysaccharides to be used as internal controls during the quality Objectives: The aim of this paper was to standardize and validate a control tests to be performed for lot release. serological test (ELISA) in mice as an alternative for the L+/10/50 in order to determine the Potency of Tetanus Toxoid vaccines. Material and methods: The Reference Materials Laboratory formulated 4 different freeze-dried candidates starting from dry Material and methods: Working standards to be used as calibration purified polysaccharides of Neisseria meningitides serogroups A, C, Y curve and coating were characterized by L+ and Flocculation tests, and W135. Homogeneity studies were performed and the candidates respectively. The lineal range for the standard and samples was were characterized according to the intended use by O-Acetyl, Syalic established. Specificity, Accuracy, Robustness and Precision were acid, Phosphorous contents and migration time zone by capillary determined. A correlation study against the seroneutralization test was electrophoresis. Stability of these materials was monitored during two also performed. years (2011 and 2012). Results: The activity of the Standard serum was defined as 116 UI/mL Results: All lots were found to be homogeneous. Each sample was by L+ (golden standard). The optimum concentrations for the coating assigned with a certified value and uncertainty for the intended (2 Lf/mL) and the conjugate (1/7000) were established. A lineal range purposes. The internal controls were stable for 2 years and it was for the standard serum (1/800-1/51200, factor 2) and the samples possible to monitor in a consistent and reliable way the behavior of the (1/400-1/1600, factor 2) were also defined. Specificity, Robustness, test used for the quality control of Meningococcal Polysaccharides. Accuracy and Precision was successfully evaluated, according to the pre-defined criteria. A significant correlation between the serological Conclusions: Four polysaccharide lots were characterized and are and the seroneutralization test was obtained. available to be used as internal controls during the quality control and lot release of these polysaccharides Conclusions: It was developed and validated a serological test (ELISA) in mice able to replace the seroneutralization test for determining Potency of monovalent Tetanus Toxoid vaccines.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S153
LATINFARMA 2013 Resúmenes/Abstracts
PIF-BT 003: PRODUCTION OF AN STANDARD SERUM IN MICE PIF-BT 004: SDS-PAGE AND RELATIVE QUANTIFICATION BY FOR THE DETERMINATION OF Salmonella typhi ANTI DENSITOMETRY OF RELEVANT PROTEINS PRESENT IN THE POLYSACCHARIDE VI IgG OMV FROM N. meningitides, SEROGROUPS A AND W135 Valmaseda T, Aranguren Y, Acosta L, Álvarez M, Fernández S. Alvárez M, Valmaseda T, González H, Mandiarote A, Naess L, Norheim G, Tunheim G,Cardoso D, Rosenqvist E, Garcia L. Finlay Institute. Ave 27 # 19805. La Lisa, Havana, Cuba. E-mail: [email protected] Finlay Institute. Ave 27 # 19805. La Lisa, Havana, Cuba. E-mail: [email protected]
Introduction: Standard serum and standardized immune enzymatic techniques are required for the immunogenicity assessment of the Introduction: Meningococcal disease remains being a serious health Salmonella typhi conjugated vaccine. Both are parts of a quality system problem for many countries. About 90% of the cases suffering systemic and are a requirement for the vaccine medical dossier submissions. meningitis are caused by Neisseria meningitidis strains from The goal of this work was to prepare an anti-PoliVi standard serum in serogroups A, B, C and more recently W135. OMV-based vaccines have mice and a indirect standardized ELISA to measure the anti-IgG PoliVi demonstrated their efficacy and safety in preventing the disease. Salmonella typhi conjugated candidate vaccine immune response. Clinical trials with this kind of vaccines have shown the relevance of some of the proteins present in OMV, namely PorA, PorB, RmpM (class Material and methods: The standard serum was obtained mixing 4) and Opa/OpcA (class5) y NadA. The aim of this paper was to serum from immunized animals with capsular PoliVi conjugated to establish a SDS-PAGE method with a calculation of the relative diphtheria toxoid which showed a higher indirect ELISA optic density amounts of the immunogenic proteins present in OMV and bulks by value of 1.0. The antibody anti-PoliVi content was also correlated with densitometry. a passive haemagglutination technique. The standard curve was prepared with 6 point obtained by double serial of serum from the first Material and methods: Samples from OMV and bulks at 0.5 mg/mL to diluted point 1:100. The SE titration, the regression equation and the be applied at 5 and 10 ug per protein/column in the gels of final adjustment were performed in 3 different plates during 3 polyacrilamide at 12.5% were prepared. The gel staining was consecutive days. The mean value for each point of the curve was performed by using Brilliant Coomassie Blue R250. Repeatability and calculated as well as the standard deviation (SD) and the variation intermediate precision were evaluated. The relative concentrations coefficient (VC). were calculated by using an Image Processing GS-800, BIORAD. Results: For the IgG measurement was assigned 320 Results: Typical protein chromatographic profiles from N. meningitis, haemagglutination unity per mL (UHA/mL), due to the standard serum serogroups A and W135 were observed. The densitometry analysis mixture in a 1:100 dilution shown a HA titer of 320. The average showed the proteins PorA and Por B as the most frequent for both concentration and the VC between plates were lower than 10%. The serogroups, with lower presence of NadA proteins, the high molecular regression coefficients of the obtained curve was higher than 0.99 weight protein complex, Opa/OpcA and RmpM. Each main protein which demonstrate a higher linearity of the adjust model. calculated was assigned with a range of relative concentration. The intra and inter-laboratory variability were acceptable, with values Conclusions: The anti PoliV-TD standard serum showed an excellent lower than 20%. linearity and parallelism. The standard IgG anti PoliVi standard serum would be measured quantitatively in mice serum samples immunized Conclusions: It was evaluated a SDS-PAGE method with densitometry with S. typhi conjugated vaccine candidates. able to identify and quantify the relative concentrations of the main proteins present in OMV and bulks from N. meningitidis, serogroups A and W135, in a reliable way.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S154
LATINFARMA 2013 Resúmenes/Abstracts
PIF-BT 005: IMMUNOHISTOCHEMICAL ANALYSIS OF PIF-BT 006: MOLECULAR AND KINETIC CHARACTERIZATION B23/NUCLEOPHOSMIN (NPM) PROTEIN IN TUMOR OF PANULIRIN, A NOVEL TRYPSIN INHIBITOR FROM THE BIOPSIES FROM PATIENTS WITH CERVICAL CANCER STAGE HEMOLYMPH OF THE SPINY LOBSTER Panulirus argus IB2/II Perdomo R, Montero V, Corzo G, Besada V, Vega Vega Y, González Y, Reyes V, Perera Y, Ancizar J, Alba J, García I, Valenzuela C, Solares M, Perera E, Porto M. Sarduy M, Alonso D, Acevedo B, Gomez R, Lopez-Saura, Perea SE. Biochemistry Department, Center for Pharmaceuticals Research and Center for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba. Development, La Habana, Cuba. E-mail: [email protected]
Introduction: CIGB-300 is a peptide-based investigational drug that Introduction: Proteolytic enzymes account for ca. 2% of all protein- inhibits the CK2-mediated phosphorylation on the nucleolar B23/NPM encoding genes in humans, infectious organisms, and other life forms. protein with the parallel impairment of ribosome biogenesis and cell Their control over protein synthesis, turnover, and function enables cycle control. In line with this, CIGB-300 is rapidly located at the cell them to regulate important physiological processes. Proteases are also nucleolus and such subcellular deposit has been correlated to the crucial for the replication and transmission of pathogens, which cause sensitivity of tumor cells toward the proliferative effect of this peptide. infectious diseases in mammals, and for the proliferation of insects and On the other hand, CIGB-300 has been shown to be safe and well agricultural pests, which transmit diseases, damage plant crops and tolerated when administrated by local injections in patients with spread infections through animal stocks. Protease inhibitors with cervical malignancies. promising therapeutic applications are emerging in the treatment of diseases, such as cancer, parasitic, fungal and viral infections, and Material and methods: In this work, we investigated the effect of inflammatory, immunological, respiratory, cardiovascular, and CIGB-300 on the B23/NPM protein levels by immunohistochemestry neurodegenerative disorders including Alzheimer’s disease. using paraffin embedded tumor biopsies coming from patients with cervical cancer stage IB2/II enrolled in the Phase 1 clinical trial, Material and methods: Hemocytes were isolated and treated with CERVIFARM-II. CIGB-300 was administrated by local injections directly acetic acid 2M. The acid lysate extract was further purified by cation in the tumors in three consecutive-3 days cycles at two dose levels (35 exchange chromatography. Purity was evaluated using RP-HPLC. The and 70 mg). Seven patients in each dose level were included in the inhibition of enzymatic activity was evaluated by enzymatic assays and study and biopsies were taken before and twenty-four hours after the complete amino acid sequence was established by a combination of last injection of the third cycle. Edman degradation and mass spectrometry. Sequence analysis with regard to existent sequences in databases was established to Results: Interestingly, a significant decrease of the B23/NPM levels corroborate the appurtenance to a peptidase inhibitor family. was observed in tumors after treatment with CIGB-300. Furthermore, the inhibitory effect at the nucleolar compartment was observed in 10 Results: We present here the isolation and molecular characterization patients among both groups. However it was significant only in the of a novel peptidase inhibitor that we named panulirin since have been cohort that received 70 mg of CIGB-300. Importantly, the B23/NPM only found in the Panulirus genus so far. We found that panulirin is pre-treatment levels at the nuclear + nucleolar compartments did highly specific for trypsin among serine protease tested. correlated positively with the reduction of tumor size as assessed by Conclusion: Kinetic characterization indicates that panulirin is a Resonance Magnetic Images. competitive and reversible fast-tight-binding inhibitor of trypsin with a Conclusions: Altogether, data presented here indicate that b23/NPM Ki value of 8.6 ± 0.81 nM. protein meets potentialities as future CIGB-300 surrogate marker for Phase 2/3 clinical trials and also provide the first clues as a potential CIGB-300 response predictor marker.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S155
LATINFARMA 2013 Resúmenes/Abstracts
PIF-BT 007: THERAPEUTIC EFFECT OF AN ALTERED PEPTIDE PIF-BT 008: EXPRESSION OF THE EPIDERMAL GROWTH LIGAND DERIVED FROM HEAT-SHOCK PROTEIN 60 BY FACTOR RECEPTOR AND N-GYCOLYL GM3 GANGLIOSIDE AS SUPPRESSING OF INFLAMMATORY CYTOKINES SECRETION RECOGNIZED BY IOR EGF/R3 AND 14F7 MABS IN TRIPLE- IN TWO ANIMAL MODELS OF RHEUMATOID ARTHRITIS NEGATIVE BREAST CANCER Lorenzo N, Barberá A, Torres AM, Henández MV, Hernández I, Gil R, Alvárez I, Calvo A, Rengifo E, Escobar X, Franco S, Camacho R. Ancizar J, Garay H, Reyes O, Altruda F, Silengo L, Padrón GR and Domínguez MC. National Institute of Oncology and Radiobiology (INOR), La Habana, Cuba. E-mail: [email protected] Biomedical Research Department, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, Havana, Cuba. E-mail: [email protected] Introduction: Triple-negative breast cancers (TNBC, estrogen receptor-negative, progesterone receptor-negative, and HER2- negative) are a high risk breast cancer lacking the benefit of specific Rheumatoid arthritis is a systemic autoimmmune disease mediated by therapy that targets these proteins. Therefore, is a need to develop T cells. Productive engagement of T cell receptors by major alternative treatment strategies in those tumors. The expression of histocompatibility complex-peptide leads to proliferation, epidermal growth factor receptor (EGFR) and the N-glycolyl GM3 differentiation and the definition of effector functions. Altered peptide ganglioside (NeuGcGM3) would be considered as potential targets for ligands (APL) generated by amino acid substitutions in the antigenic both passive and active immunotherapy in this subtype of breast peptide have diverse effects on T cell response. We predicted a novel T cancer. cell epitope (E18-12) from human heat-shock protein 60, an autoantigen involved in the pathogenesis of rheumatoid arthritis. Three Aim: To evaluate the recognition of two Cuban monoclonal antibodies APLs were designed from this epitope and it was demonstrated that rose against the Nglycolyl-GM3 ganglioside (14F7) and EGFR (ior- these peptides induce the activation of T cells through their ability to egf/r3) in TNBC by immunohistochemistry. modify cell cycle phase’s distribution of CD4+ T cells from RA patients. Material and methods: A number of 1 509 formalin-fixed and Also, IL-17, TNF-α and IL-10 levels were determined in PBMC from paraffin-embedded tissues from Cuban women with diagnosis of these patients. Unlike the wild-type peptide and the other two APLs, breast cancer were taken. The expression of hormone receptors and APL2 increased the IL-10 level and suppressed IL-17 secretion in these HER2 were determined by immunohistochemistry and the TNBC group assays. Therapeutic effect of this APL in adjuvant arthritis (AA) and was obtained. The immunorecognition of both, 14F7 and ior egf/r3 collagen-induced arthritis (CIA) models was also evaluated. Clinical Mabs in TNBC were studied. score, histopathology, inflammatory and regulatory cytokine concentration were monitored in the animals. APL2 efficiently inhibited Results: ER, PR and HER2 expression were detected in 53, 49 and the progression of AA and CIA with a significant reduction of the clinical 23.7% of breast tumors respectively, while; the 19.9% of these and histopathogic score. Therapeutic effect of APL2 on CIA was similar malignancies were TNBC. 14F7 Mab showed a moderate to intense to that obtained with MTX; the standard treatment for RA. This effect reaction in the 100% of TNBC. The staining with 14F7 was localized was associated with a decrease of TNF-α and IL-17 levels. These results mainly in the plasmatic membrane but also in the cytoplasm of more suggest that the therapeutic effect of APL2 is mediated in part by down- than 95% of malignant cells. EGFR over-expression was observed in regulation of inflammatory cytokines and support the potential use of the 10.5% of these tumors. The classification of EGFR expression using APL2 as a therapeutic drug in RA patients. EGFR pharmDx™ Kit was 3+ (17.3%), 2+ (5.9%), 1+ (20.3%) and 0 (76.5%). Similar patterns of recognition were obtained with ior egf/r3 in 3+ and 2+ groups, however, group 1+ were not detected by ior egf/r3. Conclusions: The recognition of ior egfr/r3 and 14F7 Mabs in TNBC open up the possibility of use passive and active immunotherapy against EGFR and NeuGcGM3 ganglioside, along or combined with other treatment modalities in this orphan of effective therapies malignancy.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S156
LATINFARMA 2013 Resúmenes/Abstracts
PIF-BT 009: IMMUNOLOGICAL BIOMARKERS IN THE PIF-BT 010: CR3-HBcAg INTERACTION TRIGGERS HIV- PROGNOSIS OF PATIENTS WITH COLON CANCER SPECIFIC TH1 AND CTL IMMUNE RESPONSE AFTER TERAVAC IMMUNIZATION IN MICE Lahera T, Calvo A, Torres G, Arango MC, Quintero S, De Armas MC , Danta D, Vázquez JM, Bonet T, Salazar S. Rodríguez-Alonso I, García-Díaz D, Brown E, Rodríguez Y, Márquez G, Prieto Y, Vázquez A and Iglesias E. National Institute of Oncology and Radiobiology (INOR), La Habana, Cuba. E-mail: [email protected] Dept Vacunas, Centro de Ingeniería Genética y Biotecnología, La Habana, Cuba. E- mail: [email protected]
Introduction: Colorectal carcinoma (CRC) is one of the leading causes of cancer death in both developed and developing countries, including Introduction: TERAVAC-HIV is a multiantigenic vaccine candidate Cuba. Until now, the anatomic extent of tumor (TNM classification) has against HIV-1 developed by the Center of Genetic Engineering and been the most important factor to predict the prognosis of colorectal Biotechnology. This formulation includes three antigens: the cancer patients. However, in recent years, data collected from large recombinant HIV-derived chimeric protein CR3 comprising Th and CTL cohorts of human cancers demonstrated that the immune contexture epitope rich regions from different viral proteins and the nucleocapsid of the primary tumors can be an essential prognostic factor. (C) and surface (S) antigens of hepatitis B virus (HBV). Previous results demonstrated that subcutaneous administration in mice with Aim: To assess the prognostic role of tumor-infiltrating lymphocytes TERAVAC in alum, elicits a Th1 immune response characterized by (TILs) in colon cancer. proliferation of CR3-specific CD4 and CD8 T cells and secretion of IFN. Material and methods: Immunohistochemistry was used to assess the In the present work, we evaluated the effect of co-adjuvation and co- density of TILs that were positive for cluster of differentiation 3 (CD3) administration of the HBV antigens in the aforementioned anti-CR3 (T cell coreceptor), CD45RO (protein tyrosine phosphatase and response. memory marker), CD8 (T cell cytotoxic coreceptor), and Granzym B Material and methods: Balb/c mice were subcutaneously immunized (cytoplasmic granule) according to tumor site (intraepithelial and with different antigenic mixtures of CR3 with each or both antigens of stromal) in samples from 40 patients who underwent resection for HBV in alum at anatomical distal sites. Ten days after the last colon carcinoma at National Institute of Oncology, Havana, between immunization, CR3-specific immune response was assessed by IFN 2004 and 2007 years. These variables were evaluated for their association with histopathologic features along with overall survival ELISPOT and CFSE lymphoproliferation of CD4 and CD8 T cells. IL-4, (OS) and the estimated 5-year OS rates. IL-10 and IFN cytokine secretion in culture supernatant fluids was determined by sandwich ELISA. IgG1 and IgG2a subclasses were also Results: The mean age of patients was 62 ± 11.6. There were a assessed by ELISA. predominance of patients with moderately differentiated adenocarcinomas (61.2%), sigmoid localization (44.9%) and clinical Results: The coadjuvation of CR3 and C was the best antigen stage II disease (37.8%). There was an inverse correlation between combination to induce CR3-specific Th1 immunodeviation. We clinical stage and density of CD45RO (R Spearman = -0.55), which was observed anti-CR3 IFN secretion in the absence of IL-4 and IL-10 and + + statistically significant. OS and 5-years OS for patients who had high- higher levels of IgG2a. In addition, a CD4 and CD8 T cell proliferation density CD45RO, CD3 and CD8 expression were better compared with was achieved in response to CR3 antigen stimulation in vitro. patients who had low-density, in both intraepithelial and stromal Conclusions: Although C and S contribute to TERAVAC localization, with significant differences statistical for stromal CD3 and immunogenicity, these results in mice suggest that interactions CD45RO. between CR3 and C antigens during adjuvation are crucial to achieve Conclusions: Our preliminary results suggest that CD45RO and CD3 the best CR3-specific Th1 immunodeviation. TIL have a significant impact on the survival and could be a prognostic factor in patients with CRC.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S157
LATINFARMA 2013 Resúmenes/Abstracts
PIF-BT 011: INDUCTION OF DE NOVO HCV CORE-SPECIFIC PIF-BT 012: THE IL-2 MUTEIN IS BETTER TOLERATED IN CELL-MEDIATED IMMUNE RESPONSES AND BALB/C MICE THAN wtIL-2 ENHANCEMENT OF NEUTRALIZING ANTIBODIES RESPONSE Fuentes D, Carmenate T, Soto D, Acosta E, León A, González C, León K. BY CIGB-230, A DNA-BASED VACCINE CANDIDATE, ON TRIPLE THERAPY WITH IFN-Α PLUS RIBAVIRIN National Center for Laboratory Animal Breeding, Calle 3ra Nº 40759 entre 6ta y Carretera Tirabeque, Reparto La Unión, Boyeros, Havana, Cuba. E-mail: Amador-Cañizares Y, Martínez-Donato G, Álvarez-Lajonchere L, [email protected] Vasallo C, Dausá M, Aguilar-Noriega D, Valenzuela C, Raíces I,
Dubuisson J, Wychowski C, Cinza-Estévez Z, Castellanos M, Núñez M, Armas A, González YJ, Revé I, Guerra I, Pérez Aguiar A, Dueñas-Carrera Introduction: The high-affinity receptor for IL-2 (IL-2R) is composed S. of 3 subunits: the IL-2Rα (CD25), IL-2Rβ (CD122), and the γc chain Centro de Ingeniería Genética y Biotecnología, Ave 31, 158 and 190, Playa, P.O. (CD132). IL-2 has been used for treatment of melanoma and renal cell Box 6162, Havana, Cuba. E-mail: [email protected] carcinoma, but this therapy has limited efficacy and also induce severe toxicity. Actually, it is assumed that part of the limitation of IL-2 therapy efficacy in cancer patients, is due to the IL-2 driven expansion of Treg cells which in turn, dampen the antitumor immunity. Many Introduction: CIGB-230, a vaccine candidate based on the mixture of a attempts have been made for improving IL-2 based therapy, several of DNA plasmid, expressing HCV structural proteins, with recombinant them based in developing IL-2 variants with modified properties. The HCV core protein previously demonstrated to be safe and main objective of this work was to evaluate the effect of high doses of immunogenic in HCV-infected humans. IL-2 mutein in Balb/c mice, compared with wtIL-2. Material and methods: CIGB-230 was administered in different Material and methods: The mutein differs from wt IL-2 by four schedules regarding IFN-α plus ribavirin therapy. Paired serum and mutations at the interface with the alpha subunit of IL-2R. Balb/c mice, PBMC samples from baseline and end of treatment were analyzed. HCV 5 animals per group, were inoculated with 20, 40 or 80 µg of wtIL-2 or specific humoral response was tested by enzyme-linked IL-2 mutein and PBS for the control group. The treatments were immunosorbent assay (ELISA), neutralizing antibodies were evaluated administered during 5 days, twice a day. After that, mice were by HCVcc neutralization assays, PBMC proliferation was assayed by sacrificed, and lungs, spleen and livers were weighed. For histological carboxyfluorescein succinimidyl ester staining and IFN-γ secretion was study, organs were fixed in 10% formalin solution, and paraffin- assessed by ELISPOT. Data on virological and histological response and embedded sections were stained with hematoxylin/eosin. their association with immune variables are also provided. Results: A significant and dose dependent increment in weights of Results: From week 12 to week 48, all groups of patients showed a lungs, livers and spleens were observed in the group treated with wtIL- significant reduction in mean leukocyte counts. Statistically significant 2 but not in the groups treated with IL-2 mutein or PBS. Moreover, decrements in antibody titres were frequent, but only individuals histopathological studies evidenced perivascular lymphocytic immunized with CIGB-230 as early add-on sustained the core-IgG infiltrations in lungs and livers of high doses IL-2 treated mice, such response, and the neutralizing antibody response was enhanced only infiltrations were not observed in organs from IL-2 mutein treated in patients receiving CIGB-230. Cell-mediated immune responses also mice or in control group. tended to decline, but significant decrements in IFN-γ secretion and total absence of core-specific lymphoproliferation were exclusive of Conclusions: These results suggest that the IL-2 mutein was better the control group. Only CIGB-230-immunized individuals showed de tolerated in Balb/c mice than wtIL-2, consequently it could be used at novo induced lymphoproliferative responses against the structural highest doses than wtIL-2 in order to obtain better efficacy. antigens. Importantly, it was demonstrated that the quality of CIGB- 230-induced immune response depends on number of doses and timing of administration in relation to the antiviral therapy. Specifically, the administration of six doses of CIGB-230 as late add-on to therapy increased the neutralizing antibody activity and the de novo core-specific IFN-γ secretion, with a favorable impact in the virological response. Conclusions: CIGB-230, combined with IFN-α-based therapy, modifies the immune response in chronic patients. These evidences shed light in the design of more effective therapeutic vaccine interventions against HCV.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S158
LATINFARMA 2013 Resúmenes/Abstracts
PIF-BT 013: DETECTION OF ERYTHROPOIETIN AND ITS PIF-BT 014: DEVELOPMENT OF A POLYSTYRENE LATEX- ANOLOGOUS BY ISOELECTRIC FOCUSING AND DOUBLE- BASED DIAGNOSTIC SYSTEM FOR RHEUMATOID FACTOR BLOTTING TECHNIQUE Marrero G, Delgado LP, Carol H, Ortiz N, Mussachio A and Menéndez T. Domínguez R, García G, Domínguez D, Martínez D. Centro de Biomateriales, Universidad de La Habana, Ave Universidad entre Institute of Sports Medicine, Antidoping Laboratory, Street 100, Aldabó Havana, Ronda y G, Plaza de la Revolución, La Habana, Cuba. E-mail: [email protected] Cuba.
Diagnostic systems based on monodisperse polystyrene particles Introduction: Human erythropoietin (hEPO) is a 34 kDa glycoprotein, (latex) are widely used due to their simplicity, low cost and rapid synthesized and released by kidneys in response to blood oxygen performance. Rheumatoid arthritis (RA) is an autoimmune disease demands. The production of recombinant hEPO has made possible its affecting 2% of population worldwide. Rheumatoid factors (RF) are banned use in competition sports. Methods to analyze EPO and other immunoglobulins (IgG, IgM and IgA) founded in sera of 80% of RA erythropoiesis stimulating agents (ESAs) are necessary for doping patients. The target for RF is the Fc region of human IgGs. Detection of control. RF is the most frequently used criteria to diagnose RA. In the present work we developed a polystyrene latex-based diagnostic system to Aim: To validate an isoelectric focusing and double-blotting analytical detect RF. Polystyrene particles of 0.48 ± 0.075 µm with a Z-potential method with chemiluminescent detection following the World Anti- of -28 mV were obtained by the method of surfactant-free emulsion doping Agency (WADA) criteria. polymerization. Particles size and Z-potential were determined by light Methods: Human urine samples were concentrated from 20 mL to 50 scattering. Scanning electron microscopy observation showed µL, for isoelectric focusing (IEF) experiments, by ultra filtration using spherical and clean particles. Adsorption of human normal Centricon and Centricon plus 20 from Millipore (MW cut-off 30 kDa). immunoglobulins (HNIg) on particle surfaces was studied in glycine Then, the retentates of ultra-filtration were electrophoresed in a buffered saline at several ionic strength, pH and HNIg concentrations. polyacrylamide gel, pH gradient 2-6. The gel was then submitted to a The selected conditions for coating the particles were pH 8, 0.05M and classical semi-dry electro-blotting process. Following the electro- 150 mg/mL of HNIg. Reactivity of latex particles coated with HNIg was blotting, the membranes were processed for blocking, incubation with calibrated with an international calibrator serum for RF (WHO 64/2) the primary antibody and washing. The principle of the Double and controlled with positive and negative RF controls. Reactivity of the Blotting (DB) was to transfer the primary antibody separately from the developed diagnostic reagent with RF-positive and -negative human blot membrane to a new support called the DB membrane. The sera, was evaluated with normal and complement-inactivated (30 min membranes were incubated with a chemiluminescent substrate. at 56ºC) sera. When used heated sera, our reagent showed 100% of Detection of luminescence was performed either by exposure in a coincidence in results with a commercial diagnostic kit of specificity Luminescent Image Analyzer LAS 4000mini CCD camera (Fuji film). 80% and sensibility 93%. Conclusion: We have developed a polystyrene latex-based reagent to detect RF in human sera that could Results: The luminescence was evaluated sing a CCD camera and be used in the diagnostic of RA. showed that the DB process did not induce any significant change in the distribution of the irrelative intensities. We determined the detection limits of the technique for the different erythropoietin. For BRP (3000 mUL/mL- 500 mUL/mL), NESP (48 ng/mL - 12 ng/mL). Conclusion: This procedure has been developed to detection EPO isoelectric patterns in urine and has made possible the differentiation of endogenous and exogenous recombinant hormone for anti-doping control purposes The method was specific for detection of erythropoietin BRP (recombinant erythropoietin) and NESP (Novel erythropoietin stimulating protein ).
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S159
LATINFARMA 2013 Resúmenes/Abstracts
PIF-BT 015: ASSESSMENT OF THE IN VIVO GENOTOXICITY OF PIF-BT 016: SYNERGISTIC EFFECT EVALUATION ON THE THE 1E10 MONOCLONAL ANTIBODY BY MEANS OF THE COMBINATION OF THE CIGB-552 PEPTIDE WITH BONE MARROW MICRONUCLEUS TEST CONVENTIONAL ANTINEOPLASIC DRUGS ON LUNG AND COLON CANCER CELL LINES Curbelo A, Casacó A, Mancebo A, Arteaga ME, González C, Rivero Y, Legró M, Ocaña R, García-Somines J, Bada AM, Lemus M, Escalona MA. Gómez Y, Oliva B, Tamargo B, Guerra M.
Center of Experimental Toxicology, National Center for Laboratory Animal Center for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba Breeding, Boyeros, Havana, Cuba. E-mail: [email protected]
Introduction: Cancer is one of the main causes of death globally. Lung Introduction: Monoclonal antibodies (mAb) has become a primary and colon cancers represent the first and third cause of death tool in immunotherapeutic passive strategies, being reported their use respectively by this disease. Despite there exist multiple therapeutic in many malignant diseases and rejection of transplanted organs. modalities to treat cancer, the toxicity associated to treatment and the Center of Molecular Immunology has developed the 1E10 mAb. With development of resistance limit their use. That is why combination of the objective of assessing the genotoxicity of this mAb it was conventional drugs with target therapy is an attractive strategy. CIGB- performed the bone marrow micronucleus test in Cenp:NMRI mice. 552 has demonstrated antitumor activity in vitro and in vivo. This peptide has been associated with the inhibition of the transcriptional Material and methods: It was established three dose levels (100, 200 activity of the factor NFk-B, pathway involved in the development of y 400 µg/animal) and two control groups (negative: patient solution, resistance to chemotherapy. With this premise, we decided to evaluate positive: cyclophosphamide 40 mg/kg body weight). All substances the combination effect of CIGB-552 with conventional antineoplasic were administered via intraperitoneal injection scheduled in two drugs in human lung and colon cancer cell lines. treatments at 24-hour intervals, and samples were collected 24 hours following the final treatment. The proportion of immature among total Material and methods: We evaluate the combination effect of CIGB- (immature + mature) erythrocytes was determined for each animal by 552 with Paclitaxel and Cisplatin in NCI-H125 lung cancer cell line and counting 500 erythrocytes, and 1000 immature erythrocytes per the combination with 5-Fluoracil and Cisplatin in HT-29 colon cancer animal were scored for the incidence of micronucleated immature cell line. Growth inhibition was determined by MTT assay after 72 h of erythrocytes (MNPCE). continuous drug exposure. The interactions between agents were assessed by Combination Index analysis using Calcusyn (Calcusyn Results: Statistical analysis of the results allowed establishing that Version 2.0, 1997, Biosoft, USA). The cell cycle profiling was 1E10 did not showed significant increase of the MNPCE in two sexes, determined by PI staining and Annexin V/propidium iodide staining and in female mice is observed significant decrease in the proportion was used to discriminate between early and late apoptosis. of immature among total erythrocytes at the 400 µg/animal dose. Results: Paclitaxel and Cisplatin were the most potent drugs in NCI- Conclusions: The study showed that the 1E10 mAb did not produce H125 and HT-29 cell lines respectively. The combination of CIGB-552 mutagenic effects in bone marrow and induce cytotoxic effects in with Paclitaxel showed a higher synergistic effect on lung cancer while female mice at the 400 µg/animal dose. combination of CIGB-552 with 5-Fluoracil showed a superior synergism on colon cancer. Moreover, the four combinations provoked a prominent inhibition of cell cycle and induction of apoptosis when compared to monotherapies. Conclusions: We conclude that co-administration of a variety of chemotherapeutic agents with CIGB-552 was able to enhance cytotoxicity synergistically in vitro through premature apoptosis and cell cycle arrest.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S160
LATINFARMA 2013 Resúmenes/Abstracts
PIF-BT 017: EXPRESSION AND CHARACTERIZATION OF A PIF-BT 018: CD4+ T LYMPHOCYTES AND VIRAL LOAD IN HIV RECOMBINANT MOUSE ANTI-CD20 ANTIBODY PATIENT WITH PREMIERE OF AIDS THAT RECEIVE ANTIRETROVIRAL TREATMENT Harteman O, Casadesús AV, Sosa K, Dorvignit D, Aira LE, Hernández T, López A, Acosta CM. Hernández D, Pérez J.
Laboratory of Antibodies and Experimental Biomodels (CIM-LABEX). 23 ave and Instituto de Medicina Tropical Pedro Kourí, La Habana, Cuba. E-mail: Caney Highway, P.O. Box 4032, Santiago de Cuba 90400, Cuba. E-mail: [email protected] [email protected]
HIV infection is one of the biggest health problems, more than 33 Introduction: CD20 molecule is a non-glycosylated B lymphocytes cell million people they are infected in the world. The AIDS premiere is a surface protein whose expression is increased in some pathogenic B form of presentation of the illness caused by HIV that is characterized cells, thus becoming an attractive target for diagnosis and therapy. In by alteration of the patient's general state, waste syndrome, serious line with this, an anti-CD20 mouse/human chimeric monoclonal opportunist infections, neoplasia and neurological alterations. Were antibody (Rituximab) has been widely used for treating certain studied T CD4+ lymphocytes and viral load in patient with AIDS lymphomas and autoimmune diseases. In this work, we describe the premiere that receive antiretroviral therapy, to beginning and one year stable expression and preliminary evaluation of a mouse anti-CD20 after the treatment 55 patients were studied which had T CD4+ antibody with the similar variable regions to Rituximab, obtained by lymphocytes counts less to 200 cell/µL and high viral load before the genetic engineering. treatment. The values of T CD4+ cells recovered and the viral load Material and methods: For the expression of the mouse anti-CD20 diminished at non detecting levels in the evaluated patients, after a antibody, Rituximab variable regions were synthesized and lentiviral year of therapy, which evidences the benefits of antiretroviral vector pLW carrying the heavy and light chain were constructed. HEK treatment. T CD4+ lymphocytes low count and high viral load 293T cells were cotransfected with the vectors and the viral titers associated with opportunists illnesses, most frequent had neuro- were determined by ELISA. Lentiviral transduction was carried out in toxoplasmosis and Pneumocystis jiroveci pneumonia. It was also HEK293 expression system. The antibody was purified by protein-A observed an increase of waste syndrome. AIDS-related mortality in affinity chromatography from culture supernatants and analyzed by patients older than 50 years increased in people who had more of an SDS-PAGE and HPLC. The biological activity was performed by opportunistic disease. The results of this study confirm the benefits of evaluating the reactivity against different CD20-expressing human antiretroviral therapy, particularly for therapeutic combinations of tumor cell lines and B cells from human peripheral blood mononuclear 3TC, d4T, nevirapine and 3TC, AZT, nevirapine. cells from healthy donors and non-Hodgkin lymphoma patients by flow cytometry. Results: Effective viral loads were obtained with titers between 107 and 108 viral particles/mL. Transfectoma productivity obtained by lentiviral transduction was 40 ug/mL. There were no differences in the recognition pattern between mouse anti-CD20 antibody and Rituximab in the evaluated cells lines. In addition, the antibody recognized 5-15% of peripheral blood mononuclear cells from healthy donors, similar to values reported in the literature whereas it was able to detect about 50% increase in CD19+CD20+ cells from non-Hodgkin lymphoma patients. Conclusion: The mouse anti CD20 antibody obtained showed similar recognition properties to Rituximab suggesting that could be an important tool for the selection and/or monitoring of patients diagnosed with B-cell proliferative disorders.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S161
LATINFARMA 2013 Resúmenes/Abstracts
PIF-BT 019: EFFECT OF BLOCKADE OF EGF SYSTEM ON PIF-BT 020: HOMOLOGOUS RECOMBINATION INDUCED BY WOUND HEALING IN PATIENTS VACCINATED WITH RADIATION, ASSAYED BY DIRECT REPEATS DUPLICATION CIMAVAX® EGF ASSAY Fernández A, Acosta S, Neninger E, Barroso MC, Wilkinson B, Troche Cuétara Lugo E, Camacho-Carranza R, Sanchez-Lamar A. M, Martínez LB, Viada CE, Crespo T, Casacó A. Instituto de Oncologia y Radiobiología, La Habana, Cuba. E-mail: Center of Molecular Immunology. Havana, Cuba. E-mail: [email protected] [email protected]
The epidermal growth factor receptor signaling system is frequently Introduction: Due to de depletion of ozone layer and the widespread unbalanced in human malignancies due to increased ligand production, use of radiation in clinical practice, it is important for the scientific receptor overexpression, receptor mutations, and/or cross-talk with community to elucidate the mechanisms of DNA damage induction by other receptor systems. For this reason, the EGFR is an attractive target radiation and its repair. Homologous recombination (HR) is a for anticancer therapy. The epidermal growth factor also plays an universal mechanism for DNA repair which additionally generates important role regulating multiple facets of cutaneous wound healing biological diversity. (inflammation, wound contraction, proliferation, migration, and Material and methods: To study HR we used a bacterial model, angiogenesis). The Center of Molecular Immunology produced a cancer Salmonella enterica serovar typhimurium and the segregation of vaccine (CIMAvax EGF) that blocks the binding of EGF to its receptor. duplication assay (Seg-Dup). This kind of model are useful because it This blockade causes an inverse association between the anti-EGF reproducibility, low cost, quick results and the possibility of antibody titers and EGF concentration. Around 1500 patients have been extrapolate results for the conservation of cellular mechanisms for the treated, showing that this vaccine is safe, immunogenic, increases maintenance of genetic information. A considerable part of our survival and improves quality of life. Considering the therapeutic knowledge about HR comes from assays based in the use of double benefits of CIMAvax® EGF vaccination and the role of EGF-EGFR system strand DNA ends as initiators of HR, which favors repair by RecBCD in the wound healing process, we decided to conduct a retrospective pathway. Seg-Dup assay is able to evaluate exchanges between sister research with the aim of determining the effect to the CIMAvax® EGF strands without any recombination pathway. A collection of strains Vaccine on the wound healing process in patients undergoing surgical with defects in genes that codifies proteins involve in the two main treatment. To identify patients who had undergone surgical treatment, routes for HR known in bacteria, RecBCD and RecFOR, was medical records of 543 patients were reviewed. After identification of constructed. This collection was evaluated in terms of its ability to patient that received surgical treatment, further information was recombine spontaneously. Recombination was also measured after obtained from source documents, including medical records and treatment with radiation (UV light y Gamma rays). operative reports using an observational list that included different variables. Postsurgical Wound Healing Complications were identified Results: It was evidenced that: spontaneous lesions non-commonly using the National Cancer Institute Common Toxicity Criteria for detected by RecFOR route could be repaired efficiently by this Adverse Events (NCI-CTC) version 3.0. None of the 9 patients operated pathway when RecB is absent. SbcCD acts as recombination´s presented adverse events related with the wound healing. These repressor; RecBCD system has a crucial role in repairing UV-induced results suggest that the use of CIMAvax® EGF apparently does not DNA damage while RecFOR only acts when their substrates persist in produce a deleterious effect in the wound healing process. time. The applied methodology confirmed the existence of RecA- independent recombination in Salmonella and suggests the existence of an alternative route of recombination for the double mutant RecB- /RecF-. Conclusions: The assay and the strain collection made for this study have a potential use for genotoxicological and antigenotoxicological evaluation and the study of the mechanisms of action of drugs.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S162
LATINFARMA 2013 Resúmenes/Abstracts
PIF-BT 021: CLONING, EXPRESSION AND SEMI-PURIFICATION PIF-BT 022: RESULTS OF THE SAFETY EVALUATION OF OF A CHIMERIC PROTEIN ENCOMPASSING HEPATITIS C CANCER VACCINES DEALING WITH NOVEL TARGETS FOR VIRUS EPITOPES CANCER IMMUNOTHERAPY
Aguilar-Noriega D, Santana F, Dueñas-Carrera S. Mancebo A1, Bada AM1, Casacó A2, González B1, León A1, Arteaga ME1, González C1, Sánchez B2, Carr A2, Ledón N2, Iglesias A.2 Center for Genetic Engineering and Biotechnology, Ave 31, 158 and 190, Playa, Havana, Cuba. E-mail: [email protected] 1National Center for Laboratory Animals Breeding (CENPALAB), Boyeros, La Habana, Cuba. Teléfono: 6837225. E-mail: [email protected] 2Center of Molecular Immunology (CIM), Playa, La Habana, Cuba Currently, there is no vaccine available against HCV and registered treatments have limited efficacy, with significant adverse effects. The immunological parameters that correlate with protection against HCV Despite the many preventive and therapeutic modalities aimed at have not been completely defined. Different evidences suggest that curing cancer, it remains a serious health problem for the world. development of effective vaccine requires the selection of epitopes Promising recent developments suggest that cancer immunotherapy capable of inducing neutralizing antibodies, CTL response and helper T may be the next great hope for cancer treatment. EGFRs are receptor cells. In the present work, we have amplified by PCR the regions coding tyrosine kinases and it is considered an important therapeutic target for fragments of protein Core, E1 and E2 from the HCV, which contain related with tumor progression, and several types of molecular epitopes for generation of neutralizing antibodies and epitopes specific therapies, including monoclonal antibodies, small molecules, and of CD4+ and CD8+ T cells. The DNA regions were cloned in an E. coli vaccines, have been developed to target the HER family of receptors. On expression vector and a chimeric protein, Eq1, was expressed as a the other hand, gangliosides are membrane glycosphingolipids that fusion variant to the N-terminus of the protein p64K in GC-366 contain two variants of sialic acid, the N-acetylated (NeuAc) and the N- bacterial cells. Eq1 was purified from the insoluble fraction after cell glycolylated (NeuGc) variant. The high expression of this antigen disruption by a combination of methods based on differential specific molecule has been associated with malignant tumor solubilization and metal chelating affinity chromatography since the progression and immunosuppressive mechanisms, so ganglioside could protein comprises a six- histidines tag. Eq1 was specifically recognized be considered as target for cancer immunotherapy. We have been by specific monoclonal antibodies and anti-HCV positive human sera. working for several years in the safety evaluation of cancer vaccines The future evaluation of immunogenicity in animal models would targeting these two systems, the EGF receptor and ganglioside. We reveal the actual ability of generated chimeric protein for eliciting a presented in this work results of repeated dose toxicity studies relevant immune response. performed in Sprague Dawley rats and Cynomolgus monkeys, including clinical observations, body weight and rectal temperature measuring, clinical pathology analysis, gross necropsy and histological examination in rodent studies, and immunological evaluation. Immunizations were capable of inducing mainly inflammatory effects at the injection site, with findings largely attributable to the adjuvants used and probably enhanced by the immunological properties of the antigens. In general, these vaccines were shown to be well tolerated, and these studies in relevant species allow treating cancer patients with tumors during long periods with relative weight safety margin.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S163
LATINFARMA 2013 Resúmenes/Abstracts
PIF-BT 023: TOXICOLOGICAL SAFETY EVALUATION OF ACM PIF-BT 024: PROCESS DEVELOPMENT OF Dermatophagoides T1H BY INTRAVENOUSLY ROUTE IN CENP: BEAG DOGS siboney PURIFIED PROTEIN ALLERGENS AS THE ACTIVE PHARMACEUTICAL INGREDIENT FOR AN ADJUVANTED González Y, Mancebo A., Acosta E, Sosa I, León A, Blanco D, González C, Curbelo A, Prado P, Morgado L, Quesada R, Pérez A, Hugues B, Fuentes ALLERGY VACCINE D, Samada I, Casacó A, Sánchez S, Contreras F, Contreras B, Ballart N, Martínez D, Más A, Samalea R, Torralba D, Labrada A. Valdés O, Lemus M, Estévez T, Jaime U, Díaz Y, Peña A, Ronda M, Pérez 1, Escalona 1, Mantilla 1, Matos D. Allergens Dept, National Center of Bioproducts, Bejucal, Cuba. E-mail: [email protected] National Center for Laboratory Animals Breeding (CENPALAB), Boyeros, La Habana, Cuba. Introduction: Novel allergen vaccines intended for allergy immunotherapy are increasingly based on recombinant or purified The humanized AcM T1h is an antibody produced by the Center of natural allergen proteins and adjuvants. The allergens are regarded as Molecular Immunology. This product is proposed for the treatment of the active ingredients since they induce the adaptive immune Rheumatoid Arthritis. The objective of this study was to evaluate the response. The aim of this work was to assess the process consistency toxicological safety of the repeated endovenous administration (12 and effectiveness of the purification steps of a Dermatophagoides weeks) of AcM T1h to Cenp:BEAG dogs. We establish two experimental siboney protein fraction containing major allergens. groups Control and Treated (4X), of six animals each, 3 per sex. Measurements included clinical observations, body weight, rectal Methods: A purification process in pilot-scale conditions was followed temperature, clinical signs (cardiac and respiratory frequencies, starting from a freeze-dried allergen extract of D. siboney. The process arterial pressure and pulse), electrocardiogram, ophthalmological comprised a salting-out step and chromatography in SUPERDEX-200. evaluations, electrophysiological evaluations, neurological exams, and Der s1 allergen content was assessed by ELISA and the allergenic hematological and clinical chemistry. The study ended with 100% activity was measured using IgE competition assay. Purity was survival. The results showed that body weight, body weight gains and determined by SDS-PAGE. rectal temperature were not affected by the AcM T1h. There were Results: The process showed consistent results after 15 consecutive found significant differences between groups in cardiac and respiratory batches. The average concentration of Der s1 was 154 µg/mL, with a frequencies, but apparently not related with the test substance CV of 8.4%. Mean total protein content was 254µg with a CV of 15%. administration, since all values were found to be within those reported Purity of Der s1 and Der s2 components was higher than 90% for all as normal for dogs. Hematological and serum chemistry was unaffected the batches. Batch yield was 4.3 ± 0.6 mg. No batches were found out of by the test substance. The results obtained showed that the AcM T1h is the specification or ±3σ limits. The maximum failure probability safe in the used biomodel. according to process capability analysis was 3% for the Der s1 content and allergenic activity. These values are regarded as satisfactory considering the variability of the analytical methods, which is estimated to be much greater that the intrinsic process variability. Conclusion: It was demonstrated the consistency of the main quality parameters of the active ingredient for a novel allergen vaccine, which is relevant to the clinical development of the product.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S164
LATINFARMA 2013 Resúmenes/Abstracts
PIF-BT 025: IMMUNOLOGICAL CHARACTERIZATION OF MEN PIF-BT 026: GENERATION OF MOUSE MONOCLONAL X CONJUGATED AS CANDIDATE VACCINE IN BALB/C MICE ANTIBODIES AGAINST SEVERAL SEROTYPES OF STREPTOCOCCUS PNEUMONIAE USING A HEPTAVALENT Espinosa-Viñals C, Rodríguez L, González M, Martin Y, Nicot M, Amador A, Luque Y, Cedré B, Acevedo, R, García D, Valdés Y, Vérez V. CONJUGATED VACCINE
Group of Immunochemistry, Center of Biomolecular Chemistry, Havana, Cuba. E- Rodríguez Y, Martínez D, Rodríguez L, Martín Y, González M, Aragón H, mail: [email protected] Valdés R, García D. Laboratory of Immunology, Center of Biomolecular Chemistry, Havana, Cuba. E- mail: [email protected] Introduction: Neisseria meningitidis (Men) is considered a health problem by medical authorities. Serogroups A, C, Y and W135 are responsible of the majority of cases of meningitis, nevertheless the Introduction: S. pneumoniae is one of the most common pathogens serogroup X has been increased its incidence and has cause important causing respiratory tract infections and other invasive infections in outbreaks in the African “Meningitis Belt”. Develop of a new children. Although, more than 93 serotypes have been described, a polysaccharide conjugate vaccine against Men X is an option to prevent cumulative worldwide clinical experience shows that there are only and control the disease. This investigation has focused in the few serotypes (1, 3, 4, 5, 6B, 7F, 8, 9V, 14, 18C, 19F and 23F), which are immunological characterization of a Men X polysaccharide conjugated. responsible for about 80% or more of invasive pneumococcal Material and methods: Animal was immunized with Men X infections. That is why, this study sough to generate monoclonal conjugated to tetanus toxoid (TT) or diphtheria toxoid (DT). Serum antibodies against theses serotypes of S. pneumonia using as was obtained at 7, 14 and 21 days. Immunoglobulin G (IgG) was immunogen a heptavalent conjugated vaccine. quantificated by indirect ELISA with “in-home” reference serum. IgG Material and methods: Female Balb/c mice of 19 - 20 g, were specificity was determined using an inhibition ELISA. immunized every 14 days with a seven-valent pneumococcal conjugate Results: Men X - TT conjugated exhibit high immunogenicity at second vaccine, including serotypes 1, 5, 6B, 14, 18C, 19F and 23F and tetanus and third administration (2, 4 and 10 µg). One dose not generated toxoid protein. Antibody titer was measured by enzyme-linked antibodies against the polysaccharide in any of doses administered in immunosorbent assay (ELISA) seven days after each immunization. this study. Aluminum phosphate as adjuvant incremented the Then, splenocytes from the mouse with better titter were fused with immunoglobulin responses of Men X - TT conjugated. All doses of the X63/Ag8/653 myeloma cells in a ratio (17:1). conjugates evaluated developed good response of IgG and bactericidal Results: After sixth immunizations, animals were considered ready for activity. hybridoma generation(titer 1: 32000-64000). The cell fusion efficiency Conclusions: The Men X conjugates evaluated in this study are (number of wells showing hybridoma growth/total number of wells immunogenic in Balb/c mice. These results support the preclinical data used) was 98% and hybridomas specific for all serotypes were of this MenX conjugates as vaccine candidates against N. meningitidis obtained. serogroup X. Conclusions: The immunization of mice with the seven-valent pneumococcal conjugate vaccine was effective for obtaining hybridomas against seven serotypes of S. pneumoniae. This result could be useful for optimizing immunoenzimatic techniques used in preclinical studies of pneumococcal vaccines candidates developed in our institution.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S165
LATINFARMA 2013 Resúmenes/Abstracts
PIF-BT 027: EVALUATION OF IMMUNE RESPONSE IN DOSIS PIF-BT 028: IMMUNOGENICITY OF MONOVALENT STUDIES OF CONJUGATED HEPTAVALENT VACCINE OF CONJUGATES AGAINST SEROTYPES 7F, 9V AND 19A OF Streptococcus pneumoniae IN RABBIT Streptococcus pneumoniae Martín Y, Pérez A, Travieso M, Amador A, Luque Y, Serrano Y, Pérez A, Rodríguez L, Martin Y, Amador A, Mariño D, Santiesteban E, Rodríguez L, García D. Serrano Y, García D, Santana D, Valdés Y, Vérez V.
Laboratory Animal Breeding Group, Center of Biomolecular Chemistry, Havana, Group of Immunochemistry, Center for Biomolecular Chemistry (CQB), Havana, Cuba. E-mail: [email protected] Cuba. E-mail: [email protected]
Introduction: Streptococcus pneumoniae is a pathogen causing deaths Introduction: Streptococcus pneumoniae (Neumococco) is an from vaccine-preventable diseases in children under 5 worldwide. The encapsulated pathogen that can cause bacterial pneumonia, prevalence of resistant strains of the microorganism to antibiotics, has bacteremia, meningitis and otitis media. The vaccination with capsular caused a worsening of their occurrence, and thus represents an polysaccharides (PS) is ineffective in toddlers and young infants, due to effective alternative vaccine development. The aim of this work was to the T-independent nature of these antigens. The success of conjugated develop an immunization schedule to evaluate the immune response vaccines against Neumococco is due to PS are become immunogenic and the effect of different doses of Cuban candidate heptavalent for these groups of risk, because they are processed as T-dependent conjugate vaccine. antigen by immune system. Currently, the Center for Biomolecular Chemistry is working on developing a heptavalent conjugate vaccine Material and methods: NZW rabbits infants 4 weeks of age were against Neumococco, which is currently undergoing clinical trials. With used, which were immunized on days 0, 14 and 28 of the experiment, the aim of increasing the valency of the vaccine for greater protection subcutaneously with de heptavalent conjugate vaccine. Titers of IgG in susceptible this center has aimed at incorporating seven new antibodies raised against the polysaccharides of serotypes 1, 5, 6B, 14, serotypes of this bacterium. The immunogenicity of tree monovalent 18C, 19F and 23F, were determined by indirect ELISA. conjugates against serotypes 7F, 9V and 19A were evaluated. Results: No significant differences were found between the groups Material and methods: Balb/c mice were immunized with three immunized with different doses. doses s.c of conjugates 7F-TT, 9V-TT or 19A-TT (2 µg PS/dose). The Conclusions: A quarter of the human dose is enough to enhance an serum antibody response and the antibody avidity were evaluated by immune response in rabbits. These results are part of the preclinical ELISA. evaluation of heptavalent pneumococcal conjugate vaccine. Results: An improvement of the immunogenicity was found after second dose to all the conjugates. In first dose observed IgM high values of which begin to decline after second dose, from which is expressed predominantly IgG isotype. For all serotypes tested affinity maturation as measured by the antibody avidity for the antigen was significantly increased after the second dose for all serotypes reaching values greater than 80%. Conclusions: All conjugates were immunogenic in mice evaluated from second dose, describing a characteristic response of T-dependent conjugates.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S166
LATINFARMA 2013 Resúmenes/Abstracts
PIF-BT 029: ACUTE DOSE INTRAMUSCULAR TOXICITY OF PIF-BT 030: PHYSICOCHEMICAL AND IMMUNOLOGICAL Streptococcus pneumoniae VACCINE IN CENP: SPRD RATS PARAMETERS OF THE ANTI-ALLERGIC ADJUVANT HOUSE- DUST-MITE VACCINE Luque Y, González Y, Mancebo A, González B, Rodríguez L González C, Acosta E, Sosa I, Sánchez S,García A, Contreras B, Prida Y, Thomas A, Más A, Ramírez W, Oliva Y, Mateo M, Bourg V, Torralba D, Morales T, Torres Y, Mantilla N, Matos D, Mojena M, Escalona MA. Llama J, Labrada A.
Center for Biomolecular Chemistry (CQB), Havana, Cuba. E-mail: National Center of Bioproducts, Allergen Research Department, Havana, Cuba. E- [email protected] mail: [email protected]
Introduction: Streptococcus pneumoniae (pneumococcus) is an Introduction: Th1 promoting adjuvants, as the Proteoliposome from important human pathogen responsible for high morbidity and Neisseria meningitides (PL) seemed to be helpful for designing new mortality worldwide, being the causative agent of a large number of anti-allergic vaccines. The novel anti-allergic vaccine candidate infections (severe invasive processes and particularly in the elderly, comprising allergens from Dermatophagoides siboney mite and PL children and immunocompromised). Vaccine strategies to generate adsorbed onto alum, showed a protective anti-allergic response in immunological memory against serotypes most prevalent worldwide Balb/c mice. Evaluation of shelf-life stability of pharmaceutical have been based on obtaining conjugates of bacterial capsule products is required during the pharmaceutical development phase, polysaccharides to carrier proteins. However, these vaccines are not an prior to advancing to clinical trials. option for developing countries, because the high prices they are sold, making them unavailable to the third world. Centre for Biomolecular Aim: To test the physics-chemical and immunological parameters for Chemistry (CBC) is working on a research project aimed at obtaining a stability to real time of the new vaccine. conjugate vaccine, made from fragments of capsular polysaccharides Methods: Following the ICH methodology, samples of three pilot (CPS) to seven strains of S. pneumoniae. scale GMP batches were stored at 4°C and assayed at 0, 3, 6, 9, 12, Objective: To evaluate the toxicity of the heptavalent conjugate 18, and 24 months. Possible desorption from alum gel was vaccine against Streptococcus pneumoniae administered monitored, testing the supernatant for allergenic activity (IgE- intramuscularly in Cenp:SPRD rats. inhibition ELISA), Der s1 content (MAb-ELISA) and total protein content. Preservation of antigen's integrity was checked by SDS- Material and methods: Young adult animals were randomly assigned PAGE and Western-Blotting after forced desorption. Other tests into 4 experimental groups of 5 animals per sex: one control and three were applied for measuring preservative content, pH stability, and treated groups (low, medium and high dose, receiving 10, 100 and 200 sterility. Since, a potency test is not yet established for this new L of vaccine respectively). The control group received 200 L of vaccine, allergen-specific immunogenicity in Balb/c mice was Placebo. The observation period was 14 days, with daily detailed determined at the beginning and end of the study. clinical observations. Body weight values were determined on days 0, 7 and 14. Rectal temperature was measured before and four hours after Results: After 24 months no deviations of quality specifications administration. A complete necropsy of all animals was conducted were detected in any parameter. Although a slight tendency toward following sacrifice at the end of the study. increasing the allergen activity and Der s 1 content in the supernatant was noted, it was not statistically significant Results: The assay ended with a 100% survival, no clinical changes (regression analysis, p<0.05). The immunogenicity test showed the observed. The behavior of body weight showed no significant expected outcome regarding induction of allergen-specific IgG, differences between groups and sexes. There were no rectal IgG1 and IgG2a antibodies (is PL adjuvant effect dependent), temperature variations related to the administration of the vaccine. No similarly to initial results. macroscopic abnormalities were detected. Conclusion: This study proved the vaccine stability during 24 Conclusions: It was concluded that the heptavalent conjugate vaccine months as a basis for approval of a reliable expiration period, as against Streptococcus pneumoniae administered intramuscularly did part of the pharmaceutical development phase, permit to advancing to not produce toxicity in rats Cenp:SPRD. clinical trials.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S167
LATINFARMA 2013 Resúmenes/Abstracts
PIF-BT 031: CHARACTERIZATION OF THE CONJUGATES OF VI PIF-BT 032: CONJUGATES FROM Streptococcus pneumoniae POLYSACCHARIDE OF Salmonella typhi CAPSULAR POLYSACCHARIDE SEROTYPE 5PIF-BT 032: PREPARATION AND CHARACTERIZATION OF Padrón MA, Cabrera RA, Merchán Y, Rodríguez Y, Balboa JA, Soubal JP, Santana D, Ramírez U, Hechevarría JA, Cardoso F, Rey ED, Pérez JL, Mariño D, Chang J, Fáez I, Cabrera ME, Aliaga I, Martin Y, Pérez A, García L, Fernández S. Santana D, Valdés Y, Verez V.
Finlay Institute. Center for Research & Production of Vaccines and Sera, Lisa, Center of Biomolecular Chemistry. 200 /19 and 21. Atabey, Playa. La Habana, Havana, Cuba. E-mail: [email protected] Cuba. E-mail: [email protected]
Introduction: Typhoid fever continues to be a health problem Introduction: Streptococcus pneumoniae is the most common cause of worldwide with 21 million of cases and 600,000 deaths annually. None acquired pneumonia, meningitis, and bacteremia in children and of the two existing vaccines at present to prevent its disease is licensed adults. In Cuba, this bacterium is responsible for a high number of for use in children younger than 2 years, the highest mortality age cases of pneumonia and meningitis per year, mainly in children under group. Conjugation of flat polysaccharides to immunogenic protein 5 years old. Multivalent pneumococcal conjugate vaccine is, therefore, reverses the pattern of response of these towards the Thymus- a high priority for Public Health. Our laboratory has development a dependence and induces responses in infants. heptavalent conjugated vaccine against this bacterium in order to protect the Cuban children. This vaccine includes the serotype 5, which Objective: To evaluate lots of polysaccharide Vi of Salmonella typhi is highly virulent and is one of the 11 serotypes of highest incidence in conjugated with diphtheria toxoid as carrier protein. the age groups of children under six and adults over 60 years. This Material and methods: five batches were characterized by physico- work studied two different activation levels of polysaccharide with the chemical and immunochemical methods, such as contents of O-Acetyl aim to evaluate its influence in the efficient of conjugation reaction and groups, determination of the distributions coefficient (kD) by HPLC, immune respond against the vaccine candidate. content of proteins by Lowry and identity by Dot Blot. Material and methods: The following method was developed to Results: The results were similar for all batches in study without generate the conjugates: i) fragmentation of polysaccharide, ii) significant statistical differences of the studied parameters between activation and iii) conjugation to carrier proteins. We obtained two them. conjugates, these products were characterized by HPLC-SEC, colorimetric methods to determine protein to polysaccharide ratio Conclusions: It was demonstrated consistency of the formulated lots (w:w) and immunoenzimatic assay to evaluate the antigenicity of the which allows the continuation of the development of this vaccine modified polysaccharide. candidate. Results: Our results demonstrated that oxidized polysaccharides and the conjugates preserve the native capsular polysaccharide epitopic identity. The conjugates were immunized in rabbits and elicited high titers of total IgG able to recognize the capsular polysaccharide. Conclusion: the conjugates obtained using this methodology (with both levels of polysaccharide activation), are antigenic and immunogenic in rabbits.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S168
LATINFARMA 2013 Resúmenes/Abstracts
PIF-BT 033: INFLUENCE OF PHOSPHATE SALTS AND ALUM PIF-BT 034: PHYSICOCHEMICAL AND IMMUNOLOGICAL CONTENT ON TO THE IMMUNOGENICITY OF A COMPARISON OF VI POLYSACCHARIDE CONJUGATES Dermatophagoides siboney AFPL1-ADJUVANTED VACCINE AGAINST TYPHOID FEVER Samalea R, Ramírez W, Tamargo B, Torralba D, Morejón A, Martínez D, Soubal JP, González A, Soroa Y, Cardoso F, Rey E, Pedroso J, Aliaga I, Más A, Oliva Y, Infante JF, Bourg V, Huergo L, Pérez O, Labrada A. Garrido R, Santana D, Valdés Y.
National Center of Bioproducts, Allergen Research Department, Havana, Cuba. E- Center of Biomolecular Chemistry. 200 /19 and 21. Atabey, Playa. La Habana, mail: [email protected] Cuba. E-mail: [email protected]
Introduction: Allergen adsorption can be relevant for clinical efficacy Introduction: About 21 million people suffer Typhoid Fever annually, and safety of alum-adsorbed allergen vaccines, particularly, for the with 1 and 4% of fatality rate, including children of 1-2 years of age. novel experimental vaccine containing the combination adjuvant For this age group, conjugate vaccines are being developed from the AFPL1®. Phosphate ions interfere with adsorption of capsular polysaccharide Vi (PsVi) of the bacterium Salmonella typhi, Dermatophagoides allergens to alum hydroxide. On the other hand, the causal agent. The conjugation method employs carbodiimide- alum is associated to formation of granulomas at the site of injection, mediated condensation chemistry, primarily employing adipic acid so its content should be minimized. dihydrazide (ADH) as spacer. On the path to obtain a conjugate vaccine, several conjugation parameters must be defined. In this study, Aim: To evaluate the immunogenicity of formulation variants of a we compared physicochemical and immunological characteristics of Dermatophagoides siboney AFPL1-adjuvanted vaccine, using different conjugates derived from different process variants. content of phosphate salts and alum hydroxide. Material and methods: We studied four conjugate variants: PsVi to 3 Material and methods: A 2 experimental design was used for diphtheria and tetanus toxoids (DT and TT respectively) using ADH as evaluating the effect of phosphate (0-8.5 mmol/L) and alum content a spacer and PsVi-DT without spacer, with initial (0.5-2 mg/mL) on to adsorption of Der s1, as measured by ELISA. Six polysaccharide/protein ratios of 1/1 (w/w) and PsVi-DT using ADH as variants were further selected for immunogenicity testing in Balb/c spacer but with an initial polysaccharide/protein ratio of 1/2. The mice, regarding allergen-specific IgG, IgG1, IgG2a, and IgE antibodies. conjugates were characterized physicochemically and IgG antibody Results: Best variants regarding Der s1 adsorption were in the range response was evaluated in Balb/c mice. 0-4.26 mmol/L of HPO4 or 0-2.5 mmol/L of H2PO4, achieving values up Results: All conjugates had good polysaccharide recovery and retained to 99.9%. Decrease of Al(OH)3 content to 0.5 mg/mL did not suitable O-acetylation contents. Conjugates with initial 1/2 significantly (P>0.05) influenced adsorption. All variants induced IgG1 polysaccharide/protein ratio had about 10% of unbound protein, and IgG2a allergen-specific antibodies, after three immunization doses. whereas in 1/1 conjugates virtually all DT reacted. Animals vaccinated However, the low alum variant showed slightly significant reduction of with conjugates had higher IgG titer in comparison with the plane both IgG1 and IgG2a, although with less IgE and eosinophils in polysaccharide immunized group. Conjugate with spacer generated a challenged mice. Phosphate content did not significantly influence the response significantly better than the conjugate without spacer, and response. antibodies induced by the latter were no avid by the native Conclusions: Reduction of alum and phosphate content could be polysaccharide. The carrier protein and the polysaccharide/protein considered as pharmaceutical improvements with no disadvantages ratio had no significant influence on immune response. regarding immunogenicity of this experimental antiallergic vaccine. Conclusions: The proposed procedures allows to obtain conjugates with suitable physicochemical characteristics which generate a superior immune response that the plane polysaccharide. However, the procedures with initial polysaccharide/protein ratio of 1/1 employing ADH as spacer were the best, regardless of the carrier protein.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S169
LATINFARMA 2013 Resúmenes/Abstracts
PIF-BT 035: PURIFICATION AND CHEMICAL PIF-BT 036: OBTENTION OF PEPTIDES DISPLAYED ON M13 CHARACTERIZATION OF IMMUNOGENIC PNEUMOCOCCAL PHAGE RECOGNIZING A MAB AGAINST MENINGOCOCCAL CAPSULAR POLYSACCHARIDES TYPES 19F AND 23F GROUP A POLYSACCHARIDE Martínez Rodríguez JC, Gonzalez D, González H, Primelles F, Rivero K, Blaín K, Ramírez F, Reyes F, Otero O, Amin N, Camacho F. Pérez M, Lic Concepcion FG, Arjona D, Guerra M, Hernández M, Marrero N, Costa W, Díaz R, Achon L. Instituto Finlay, La Habana, Cuba
Finlay Institute. La Lisa, Havana, Cuba. E-mail: [email protected] Neisseria meningitidis causes meningitis and septicemia. Although capsular polysaccharide-based vaccines are effective at reducing the Streptococcus pneumoniae is the most common cause of community- incidence of meningococcal disease caused by serogroups A, C, Y, and acquired pneumonia and the common cause of bacterial meningitis. A W135, the presently available meningococcal vaccines are poorly multivalent pneumococcal vaccine is formed by immunogenic amounts immunogenic in infants and fails to induce long-lasting immunity in of purified pneumococcal capsular polysaccharide of several adults. The obtention of mimetic peptides of meningococcal group A pneumococcal types. The aim of this work is the evaluation of a critical polysaccharide could be explored as vaccine candidates to induce an purification step. Hexadecyltrimethylammonium bromide (cetavlon), antibacterial response. In this work, a bactericidal IgG2a MAb (7E1F7) with most of the pneumococcal types may be a critical separatory step. recognizing a unique epitope in MenA CPS was immobilized to a 96 well Under carefully controlled conditions serves either to precipitate the ELISA plate at 5ug/mL. A collection of 1010 random nine peptides polysaccharide preferentially to protein and nucleic acids exposed on the surface of filamentous phages was added to select contaminants, or in the reverse, preferentially precipitating ligands. After several washes phages were eluted and transformed in E. contaminants. After the pneumococcal bacteria types 19F and 23F have coli TG1 cells. After three selection steps, four phage clones displaying been grown by any suitable method of fermentation to stationary peptides were obtained. These clones were able to bind mAb 7E1F7 in growth phase, the fermentation is stopped by the addition of an competition with MenA CPS. These peptides obtained here could mimic effective amount of sodium desoxycholate to lyse all bacterial cells and the PscA epitope. release cell-associated polysaccharide into the medium. Cellular debris is removed from the medium to be followed by two alcohol precipitations. The cetavlon treatment of pneumococci, follows several alcohol precipitations, which effectively removes the cetavlon, to be most effective, being an improvement over use at earlier stages in the purification procedure. This general scheme is the broad procedure suitable with variations to a number of pneumococcal polysaccharide types. This purification scheme effectively removes protein and nucleic acids contaminants of immunogenic pneumococcal capsular polysaccharides types 19F and 23F.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S170
LATINFARMA 2013 Resúmenes/Abstracts
PIF-BT 037: PREPARATION OF GLYCOCONJUGATES FROM PIF-BT 038: PHARMACOLOGICAL EVALUATION OF A VEGF Streptococcus pneumoniae SEROTYPE 14 TO TETANUS BASED IMMUNOTHERAPY IN NON HUMAN PRIMATES TOXOID BY TWO METHODS OF CONJUGATION Morera Y, Bequet-Romero M, Ayala M, Puentes P, Castro J, Sanchez J, Serrano Y, Chang J, Pedroso J, Cardoso F, Valdés Y, Fernández V, Vérez Alba JS, Ancizar J, Cosme K, Gavilondo JV. V. Center for Genetic Engineering and Biotechnology, Playa, Havana, Cuba. E-mail: Center for Biomolecular Chemistry, La Habana, Cuba. E-mail: [email protected] [email protected]
Introduction: Vascular Endothelial Growth Factor (VEGF) is an Introduction: Streptococcus pneumoniae is a leading cause of attractive target for cancer immunotherapy, given its key position on meningitis, pneumonia, and severe invasive disease in infants and the modulation of tumor vascularization. Along this research line, our young children in Cuba and throughout the world. Pneumococcal groups have developed VEGF immunotherapeutics based on conjugated vaccines enhance immune responses in high-risk recombinant modified human VEGF antigen combined with population compared to polysaccharide vaccines, due to their T-cell immunostimulator compounds. Our previous experimental studies in dependent mode of action. Multivalent pneumococcal conjugated mice have shown that theses combinations have both anti-tumoral and vaccine is a high priority National Project in our country. Thus, the aim anti-metastatic activity. The present study expands our of this work is to develop different strategies to obtain monovalent immunopharmacological analyses to non human primates, and conjugates to be included as a vaccine component. evaluates the effects on physiological parameters. Material and methods: We studied two methods (Method A and B) to Material and methods: Immunopharmacological studies were carried generate polysaccharide 14 glycoconjugates by reductive amination. out in Cercopithecus aethiops sabaeus non human primates, using three Method A involves 2 steps: i) simultaneously depolymerization and different but related immunization schemes with 100 µg 200 and 400 activation by partial N-deacetylation followed by nitrous acid µg antigen doses combined with immunostimulator compounds. deamination, and ii) conjugation to carrier protein. On the other hand, Results: Our active immunotherapy approach induces the production Method B, includes 3 steps: i) fragmentation of capsular polysaccharide of Anti-VEGF IgG antibodies and specific T-cell mediated responses. by acid hydrolysis, ii) activation by peryodic oxidation and iii) Purified IgG from immunized monkey sera was able to impair conjugation to a carrier protein. In both cases, the modifications of proliferation and formation of capillary-like structures in Matrigel, for polysaccharide were followed by competitive inhibition ELISA and HMEC cells in culture. All animals appeared generally healthy and no NMR techniques. The activated polysaccharide fragments were changes in overall behavior, feeding, neuromuscular performance, life conjugated to tetanus toxoid as carrier protein. The conjugates were span, body weight and hematologic or blood biochemical parameters characterized by HPSEC, protein:polysaccharide (w:w) ratio and were reported. Additionally, no deleterious effects on the different antigenicity ELISA to evaluate the polysaccharide epitope integrity. stages of the wound healing process were recorded. Results: We generate glycoconjugates of radial structure (A) and, Conclusions: In summary, these data suggest an attractive safety and crosslinked network (B). Our results show that both conjugation immunogenicity profile for the clinical application of VEGF based methodologies guarantee the conservation of CPs immunological vaccines as a therapeutic approach in cancer patients. information in each intermediate, the main difference is the high remaining free protein percentage in the final conjugate obtained by method A. Conclusions: Method B is the best process for obtain of glycoconjugates to be included in the pneumococcal conjugate vaccine.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S171
LATINFARMA 2013 Resúmenes/Abstracts
PIF-BT 039: IMMUNOGENICITY AND REACTO-GENICITY OF A PIF-BT 040: IMMUNOTHERAPY WITH HOUSE DUST MITE BOOSTER DOSE OF TETANUS VACCINE, VAX-TET®-5 IN ALLERGEN VACCINES IN PEDIATRIC PATIENTS WITH TEENAGERS PERSISTENT MODERATE ALLERGIC RHINITIS Baró M, Águila L, Ávila Y, Armesto M, Mirabal M, Valmaseda T, Ochoa González JV. R, Menéndez J. Paediatric Teaching Hospital “Eduardo Agramonte Piña”, Camagüey, Cuba. E- Finlay Institute, Havana, Cuba. E-mail: [email protected] mail: [email protected]
Introduction: A controlled randomized double-blind phase II/IV Introduction: Sublingual immunotherapy with allergens is not widely clinical study was conducted to evaluate immunogenicity and studied in pediatric patients with allergic rhinitis. reactogenicity of the Cuban vaccine vax-TET®-5 with reduced Objective: To assess the immunologic and clinical efficacy of formulation in 472 students from 14 to 19 years old, using as reference sublingual immunotherapy with allergenic extracts VALERGEN, in the Tetanus vaccine, vax-TET®. pediatric patients with persistent moderate allergic rhinitis. Material and methods: The study was carried out according to the Material and methods: A controlled, randomized, clinical, diagnostic Good Clinical Products of ICH, in researches on infant population essay was carried out in 20 pediatric patients with persistent moderate (CPMP/ICH/2711/99), the Declaration of Helsinki and the national allergic rhinitis. Sublingual immunotherapy was given through the regulation of the Center for Quality control of Drugs (REGULATION No. deglutition technique with standardized allergenic extracts 165 – 2000) and was approved by the Ethics Committee of Researches VALERGEN, manufactured in BIOCEN: Dermatophagoid siboney, of the Institute of Basic and Preclinical Sciences “Victoria de Girón”. Dermatophagoid pteronyssinus and Blomia tropicalis. Clinical, humoral Immunogenicity was evaluated by ELISA by quantification of the levels immune and allergic response was assessed in vivo and in vitro, at the of tetanus antitoxin in two serum samples before and 28 days after beginning and a year after treatment. vaccination. Non- inferiority of the Tetanus antitoxin levels was compared corresponding to the values of long-lasting reliable Results: At the onset of the study, 100% of patients were sensitized to protection ( 1UI/mL), induced by the Tetanus vax-TET®-5, in relation domestic dust mites and presented large amounts of eosinophils in the to Tetanus vaccine vax-TET®. Reactogenicity was studied by active nasal cytogram, total Immunoglobulin E (IgE) was elevated in 55% of medical follow-up in the first seven days up to 30 days. the cases and it was determined that 30% of the patients had an associated Immunoglobulin A (IgA) selective deficiency. After a year of Results: The results of immunogenicity did not show differences treatment, eosinophil concentration in the nasal mucosa decreased. between both vaccines regarding long-lasting titers (>1 UI/mL), 80% of patients showed normal IgE values. Clinical improvement was therefore the design of non-inferiority was met. The manifestations of evident in all the patients and no collateral reactions were determined reactogenicity were of slight intensity, being observed in the first 48 during treatment. post-vaccinal hours. There was neither report of serious adverse events nor of unsolicited adverse events related to the vaccines. Conclusions: Sublingual Immunotherapy with allergenic extracts VALERGEN is a safe and viable treatment that controls clinical Conclusions: The non-inferiority of tetanus antitoxin levels 1 UI/mL, symptoms and improves immunologic response in pediatric patients ® ® induced by vax-TET -5 in relation to vax-TET was verified. with persistent moderate allergic rhinitis.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S172
LATINFARMA 2013 Resúmenes/Abstracts
PIF-BT 041: IDENTIFICATION OF ANTIGENIC COMPOSITION PIF-BT 042: ANTI-EGF/EGFR THERAPEUTIC ANTI-CANCER OF OUTER MEMBRANE VESICLES FROM NEISSERIA DRUGS AND THE WOUND HEALING PROCESS Meningitidis SEROGROUP X Casacó A, Fuentes D, Ledón N, Chacón L, Fernández N, Iglesias A, Rodríguez Y, Zayas C, Balboa JA, Acevedo R, Álvarez M, Cabrera RA, Fernández A, Hernández D, Sánchez B, Iglesias I, Crombet T. Padrón MA, Rosenqvist E, Norheim G, García L, Cardoso D. Center for Molecular Immunology, Havana, Cuba. E-mail: [email protected] Finlay Institute, Havana, Cuba. E-mail: [email protected]
Introduction: Cutaneous wound healing is a complex process Introduction: Meningococcal disease is a serious health problem involving blood clotting, inflammation, tissue formation, and tissue worldwide, it is caused by gram negative microorganism Neisseria remodeling. Many experimental and clinical studies have meningitidis. These bacteria can be classified into 13 serogroups demonstrated varied, but in most cases beneficial effects of exogenous according to the chemical structure of the capsular polysaccharide, growth factors on the healing process. The use of targeted anti-cancer however only 6 serogroups have been responsible for the majority of agents is increasing. It is common to utilize a multi-modal treatment reported meningococcal disease: A, B, C, W135, Y and X. There are approach towards solid tumors, often including surgical resection, and vaccines against serogroups A, B, C, Y, W135, but there is no vaccine it has become apparent that some targeted agents can impair wound licensed against serogroup X. healing or cause increasing risk of perioperative complications. There are limited data regarding the wound healing process of anti-cancer Aims: The aim of this work is to identify the main antigenic and target drugs blocking the EGF/EGFR system. The aim of this work is to possibly immunestimulatory components in the Outer Membrane review the effects of anti-EGF/EGFR drugs on the skin wound healing Vesicles serogroup X (OMVx). process after programmed or emergency surgical procedures. Methods: Protein antigens in OMVx were evaluated by SDS/PAGE with Material and methods: A review of the current literature and our Blue comassie staining and conditions for Two Dimensional clinical trials was undertaken. We included the monoclonal antibodies electrophoresis (2-D) were set. Additionally, specific silver staining cetuximab, panitumumab, nimotuzumab; the small tyrosine kinase was carried out to quantify lipopolysaccharide (LPS) in the vesicles. molecules erlotinib and gefitinib; and the EGF-based cancer vaccine; Finally, immunotransference assay was performed with specific CIMAvax and the EGFR-based cancer vaccine; HER-1 vaccine. monoclonal antibodies to identify the LPS immunotype and protein antigens in OMVx. Results: They suggest a nonappearance deleterious effect of the anti- EGF/EGFR drugs in the wound healing post-operative process. Results: The gels and transference membranes were analyzed with a GS-800 densitometer and "Quantity One" software. Four proteins with Conclusions: On the contrary, the fact that anti-EGFR treatments high and medium molecular weight were observed, being a protein of inhibit the wound drainage-induced tumor cell proliferation and the approximately 40 KDa a majority one and 2-D also confirmed this radiation induced migration of tumor cells suggests that these kinds of result. LPS was revealed by silver staining and quantified (3.48% of drugs could still be useful and the treatment could be maintained, with LPS/total protein). Identity of LPS was confirmed by special surveillance, during the post-surgical period. immunotransference as L-3,7,9 and protein antigens like RmpM, Por A 1.5 and OpcA, were identified in the OMVx. Conclusions: Important antigenic proteins were identified in the OMVx as well as immunestimulatory LPS.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S173
LATINFARMA 2013 Resúmenes/Abstracts
PIF-BT 043: PILOT TRIAL OF IMMUNOGENICITY AND PIF-BT 044: BREASTFEEDING AND HUMORAL IMMUNE PRECLINICAL TOXICITY OF Salmonella VACCINE RESPONSE AGAINST Tetanus AND Diphtheria TOXOID IN CONJUGATE IN SPRAGUE DAWLEY RATS CHILDREN OF 2 YEARS OLD
Fariñas M, Oliva R, Infante JF, Valdez BY, Nuñez D, Valmaceda T, Pérez La Rosa D, Montesino S, Ochoa R, Valmaseda T, Alerm A, Gómez E. V, Serrano D, Hernández T, Aranguren Y, Ponce A, Fernández S. Instituto de Gastroenterología, Plaza, La Habana, Cuba. E-mail: Finlay Institute, Havana, Cuba. E-mail: [email protected]; [email protected] [email protected]
Introduction: Since the impact of breastfeeding on the response to Introduction: All drugs and vaccines to be utilized in humans must vaccination is controversial. pass preclinical studies to prove its safety and benefits, in these studies is mandatory to have at least one relevant animal model. Therefore the Objective: To evaluate the effect of breastfeeding on humoral response aims of this work were to demonstrate the relevance of Sprague to tetanus and diphtheria vaccination in two years old children who Dawley (SD) for the evaluation of immunogenicity of the Salmonella have ended the immunization basic stage of the vaccination schedule. conjugate vaccine by ELISA, in addition to the preliminary evaluation Method: Forty-four children were selected, they were then divided of toxicological effect by clinical and pathological studied. into two study groups according to the time they were breastfeeding. Material and methods: Rats of both sex received 0.2 mL of vaccine Solid phase immunosorbent assays (ELISA) were used to determine candidate intramuscularly in two doses with a time interval of seven concentrations of diphtheria and tetanus antitoxin. weeks. Weekly serological, clinical and haematological determinations Results: After applying the Student test to results, it was proved that were made with a pathological examination at the end of the exclusive breastfeeding for six months or longer showed an increase in experiment in order to identify toxicological effects. the concentrations of diphtheria antitoxin, while there was no Results: Taking into evaluation the antibody response in both sex with difference of tetanus antitoxin concentrations detected among children the immunization schedule, the animal model demonstrated to be good exclusively breastfed for six months or more, with those breastfed for for the evaluation of the humoral immunogenicity of the conjugate lesser periods. vaccine. During the study were not evident signals of toxicological Conclusions: The duration of breastfeeding influences seroprotection alterations. against diphtheria toxoid. Conclusions: SD rats are useful model for the evaluation of immunogenicity of Salmonella conjugated vaccine without preliminary evidences of toxicity.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S174
LATINFARMA 2013 Resúmenes/Abstracts
PIF-BT 045: DESIGN OF A SEMIPURIFICATION STEP BASED IN PIF-BT 046: RESULTS OF A PHASE II CLINICAL TRIAL A TWO AQUEOUS PHASES SEPARATING SYSTEM FOR THE CONDUCTED IN NON-SMALL CELL LUNG CANCER (NSCLC) PHB-01 EXTRACTION FROM TOBACCO LEAVES PATIENTS TREATED WITH 1E10 MAB-ALUM, AN ANTI- IDIOTYPIC VACCINE Ferro W, Álvarez T, Geada D, Guevara Y, Montero JA, Tamayo A, López A, Valdés R. Valdés A, Toledo D, González Z, Viada C, Mendoza I, Guerra PP, Rodriguez E, Mazorra Z, Vazquez AM, Crombet T, Macías A. Departamento de Anticuerpos Monoclonales. Dirección de Producción Centro de Ingeniería Genética y Biotecnología, La Habana, Cuba. E-mail: Center of Molecular Immunology, P.O. Box 16040, Playa, Havana, Cuba. E-mail: [email protected] [email protected]
The plantibody PHB-01 is a murine antibody expressed in a non- Introduction: The anti-idiotypemAb 1E10 (Ab2) is specific to an Ab1 commercial tobacco cultivar plants, specific for the determinant of the mAb (P3) that react specifically with N-glycolyl containing Hepatitis B surface antigen. This plantibody is used as an gangliosides, sulfatides and Ags expressed in some human tumors. A immunoreagent on Cuban Hepatitis B vaccine manufacture by means of multicentric, randomized, open and controlled phase II clinical trial an immunopurification step. However the purification at large scale of was conducted in 63 advanced non-small cell lung cancer (NSCLC) PHB-01 from tobacco biomass imposes several difficulties, especially patients. when a solid-liquid purification design is carried out. Cost concerning the chromatographic matrixes is one of these difficulties, for example Material and methods: After first line chemotherapy, patients were due to its not so long matrix lifetime as consequence of the presence of randomized 1:1 to receive the vaccine or placebo. Treatment consisted vegetal components that seems to be able to bound matrixes. With the on 5 vaccine doses every 2 weeks and then, monthly re-immunization aims to solve this and other troubles at large scale purification of PHB- to complete 15 doses. Vaccinated patients were treated with 1mg of 01 plantibody a novel design based on aqueous two-phase extraction is the anti-idiotypemAb 1E10 (Ab2). We evaluated the immunological currently evaluated. The study was carried out using systems of response in 40 vaccinated patients. different compositions of PEG and potassium phosphate salt and/or pH Results: The vaccine was immunogenic and high titers of IgG in each of one or two partitioning stages. Of a total of 27 treatments or antibodies were obtained against 1E10 in all vaccinated patients. The variants 10 of them were selected, taking account the removal of more treatment also elicited high antibodies titers against NeuGcGM3 than 40% of vegetal proteins and the removal of less than 10% of IgG ganglioside of both isotypes, IgM and IgG. This humoral response content, as promising systems for a future large scale process. The best increased with the course of vaccination, reaching a pick after patients combination was observed for PEG 4000 and potassium phosphate in a received the fifth dose of the vaccine, corresponding with the end of relation of 10%/15% at pH 5.5. This system provides the possibility for induction phase. Hyperimmune sera of 30 evaluable patients were able a complete process automatic control, and also the potential to specifically recognize and induce cell death to murine and humans chromatographic matrix elimination in the future. NeuGcGM3 positive cells lines. Interestingly, the cytotoxic capacity of the sera was significantly associated with longer survival times. Conclusions: This is the first report in demonstrate that the functional capacity of the antibodies against NeuGcGM3 ganglioside induced by vaccination with 1E10 mAb has clinical relevance. These results show the advantages of this anti-idiotypic vaccine and confirm the relevance of NeuGcGM3 ganglioside as an important target for cancer immunotherapy.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S175
LATINFARMA 2013 Resúmenes/Abstracts
PIF-BT 047: HUMORAL IMMUNE RESPONSE INDUCED IN PIF-BT 048: PRELIMINARY RESULTS OF IMMUNOLOGICAL EARLY STAGE BREAST CANCER PATIENTS INCLUDED IN A BIOMARKERS IN PATIENTS WITH PSORIASIS TREATED PHASE III CLINICAL TRIAL USING A GANGLIOSIDE-BASED WITH ITOLIZUMAB VACCINE Aira Diaz LE. Valdés A, Mulens V, González Z, Perez K, Fernández LE, Crombet T and Center of Molecular Immunology, P.O. Box 16040, Playa, Havana, Cuba. E-mai: Mazorra Z. [email protected] Center of Molecular Immunology, P.O. Box 16040, Playa, Havana, Cuba. E-mail: [email protected] Psoriasis is a chronic inflammatory disease with a prevalence of
approximately 1-5% in the general population. The majority of Introduction: NeuGc-containing gangliosidesare overexpressed in diagnosed patients have plaque psoriasis, and about 20% have human breast cancer. A multricentric, closed, double blind and moderate to severe disease. Because of the chronic nature of psoriasis, controlled Phase III clinical trial in patients with stage II of breast patients typically need long-term treatment, even though traditional cancer is currently ongoing to evaluate immunogenicity and efficacy of systemic therapies are often associated with cumulative, dose-related a cancer vaccine composed by the NeuGcGM3 ganglioside inserted in a toxicities. Itolizumab, a new drug which has as a target, CD6 molecule, proteoliposome from Neisseria meningitidisusing Montanide ISA 51 as has demonstrated to inhibit in vitro ligand-induced proliferation and adjuvant. activation, reducing pro-inflammatory response when healthy peripheral mononuclear cells have been used. An open-label, multi- Material and methods: After first line chemotherapy, patients centric, open access clinical study was designed to assess the safety and included in the trial were divided in two groups according to the efficacy in induction and maintenance treatment of Itolizumab in Cuban number of positive lymphonodes and subsequently were randomized patients with moderate-to-severe psoriasis. We measured in PBMC of 1:1 to receive the vaccine or placebo. The group I included patients these patients’ precursor frequency of lymphocytes T activated with with 0-3 positive lymphonodes and the second group, patients with ≥4 CD3/CD28 beads and frequency of T cells producing INF-γ; in sera we positive lymphonodes. Treatment consisted on 5 vaccine doses every 2 measured interleukin levels; and in skin biopsies we determined weeks during induction phase and after, monthly re-immunizations to expression of CD6. Itolizumab was well tolerated in this study, with no complete 15 doses. In a previous reports from a phase I and II clinical serious adverse events reported so far and the majority of patients trials, the vaccine was safe and the most frequent adverse events achieving at least 75% improvement in Psoriasis Area and Severity consisted on reactions at the injection site, fever and chills. In the Index (PASI 75) at week 12. We demonstrated that there was a present study forty-six patients of Arm A and thirty-five of Arm B reduction in precursor frequency of T cell proliferation with treatment corresponding to both groups were selected for evaluating of Itolizumab at week 12 and a significant decrease in frequency of T immunological response. cell producing INF-γ was not observed in both weeks. There was not Results: The vaccine was immunogenic and high antibody titers of variation in the interleukine (IL)-6 levels in 9 of 10 patients evaluated, both IgM and IgG isotype were induced against NeuGcGM3 ganglioside but in 6 of them there was a decrease in IL-8 levels. There was a in patients of Arm A, independently of the group. Hyperimmune sera reduction in lymphocyte infiltration in 60% (3 of 5 patients) of the skin were able to specifically recognize and induce cell death to NeuGcGM3 biopsies analyzed at week 12. positive cells lines. Hyper-immune sera also showed the capacity of rescue CD4 expression on the surface of healthy lymphocytes treated with the NeuGcGM3 ganglioside. Conclusions: This is the first report demonstrating the effectors functionalities of the antibodies against NeuGcGM3 induced by vaccination with NeuGcGM3/VSSP/Montanide ISA 51 in an adjuvant setting, showing the advantages of this glycolipid vaccine and confirming the relevance of NeuGcGM3 ganglioside as an important target for cancer immunotherapy.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S176
LATINFARMA 2013 Resúmenes/Abstracts
PIF-BT 049: EGF CANCER VACCINE: TOWARDS A SCHEDULE PIF-BT 050: DIFFERENT STRATEGIES FOR THE OPTIMIZATION AND A BIOMARKER OF CLINICAL RECOMBINANT EXPRESSION OF THE DOMAIN 1 OF CD6, A RESPONSE HUMAN TARGET RECEPTOR INVOLVED IN AUTOIMMUNE DISEASES USING BACULOVIRUS EXPRESSION SYSTEM Popa X, García G, Viada C, Luaces P, Mazorra Z, Crombet T, Rodríguez C. Álvarez Y, Talavera A, Rodríguez JF, Mancheño JM.
Center of Molecular Immunology, P.O. Box 16040, Playa, Havana, Cuba. E-mail: Centro de Estudios Avanzados de Cuba, CITMA, Carretera de San Antonio km 2, [email protected] 17100 Habana, Cuba. E-mail: [email protected]
Introduction: EGF is a potent growth factor that enhance the The therapeutic, monoclonal antibody T1h has been proved with very proliferation of cancer cells by both paracrine and autocrine promising results in the treatment of various diseases such as psoriasis, mechanisms. Approximately 75–85% of non-small cell lung cancers rheumatoid arthritis, and multiple sclerosis. Its molecular mechanism (NSCLC) overexpress the Epidermal Growth Factor Receptor (EGFR) of action entails, among others, the specific interaction with the surface and its ligands, i.e. Epidermal Growth Factor (EGF). The concept of glycoprotein CD6, which is predominantly expressed on lymphocytes, immune-deprivation of the circulating EGF underlies the generation of and in particular with its N-terminal domain (CD6-1). We claim that the specific immunotherapy for the treatment of NSCLC patients. The knowledge of the structure of the complex between T1h and CD6-1 will present vaccine consists of human recombinant EGF, coupled to a provide relevant information that may guide the rational design of recombinant carrier protein P64K, from the meningitis B bacteria and novel drugs and probably leading to new treatments when combined adjuvated in Montanide ISA51 VG. In this study we characterize the with other medicines. We tackle this problem experimentally by humoral response and basal EGF serum levels and their relation with protein crystallography, which demands the preparation of large the clinical outcome of NSCLC patients treated with EGF in two amounts of pure and homogeneous protein. Since CD6 is a human, different immunization schedules: Vaccine-chemotherapy-vaccine glycosylated protein we have chosen the bac-to-bac baculovirus (VChtV) and Chemotherapy-Vaccine-Vaccine (ChtVV). expression system for recombinant CD6-1 expression and in particular we have designed two distinct approaches: extracellular and Material and methods: Depends on the vaccination schedule patients intracellular expression. This will permit us to compare the effect of were randomized 2:1 to receive the vaccine or BSC. Treatment glycosylation on CD6-1 production yield. In the case of the extracellular consisted on 4 vaccine doses every 2 weeks and then, monthly re- expression (glycosylated form) we designed a variant of the gen immunization of 2.4 mg of CIMAVAX EGF in 4 separated administration containing a leader sequence for protein export that would code for a sites. We evaluated the humoral response and basal EGF serum levels CD6-1 domain His-tagged at the N-terminal end. In the case of the in an evaluable subset of vaccinated patients. intracellular expression (non-glycosylated form), we used the same gen Results: Humoral response is not affected with the interruption of lacking the leader sequence. Currently, we are optimizing the immunization during first line chemotherapy. The survival of treated purification process, considering also two approaches: first, using patients is associated with the levels of EGF-specific humoral response immobilized metal affinity chromatography as a first purification step in both treatment schedules. Furthermore, EGF serum levels and secondly, by immunoaffinity chromatography. This latter approach determined before and after chemotherapy can predict clinical benefit involves the preparation of chromatographic matrices with T1h in NSCLC patients treated with EGF cancer vaccine. covalently bound. Preliminary expression results indicate CD6-1 is being produced. Conclusions: Basal EGF serum levels and EGF-specific humoral response may constitute predictive and surrogate markers of clinical response in NSCLC patients treated with this therapeutic vaccine.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S177
LATINFARMA 2013 Resúmenes/Abstracts
PIF-BT 051: INTRAMUSCULAR AND INTRANASAL PIF-BT 052: IMMUNOPROTECTOR POTENTIAL OF CELLULAR IMMUNIZATION WITH NEW ANTI-MENINGOCOCCAL VACCINE FORMULATIONS DEVELOPED FROM LEPTOSPIRA NANOPARTICULATE VACCINE FORMULATIONS AS INTERROGANS BALLUM USING MESOCRICETUS AURATUS AS PROTEO-LIPOSOMES AND COCHLEATES INDUCE AT-A- BIOMODEL DISTANCE CELLULAR RESPONSE Batista Santiesteban N, Arencibia-Arrebola DF, Rosario-Fernández Tamargo B, Fleitas C, Infante JF, Márquez Y, Ramírez W, Torralba D, LA, Infante-Bourzac JF. García L, Pérez V, Bourg V, Labrada A, Mouriño A, Sierra González VG. Finlay Institute, La Habana, Cuba. E-mail: [email protected] Finlay Institute, La Habana, Cuba. E-mail: [email protected], [email protected] In the last years, Leptospira spp Ballum has increased its representation in human clinical isolations in Cuba. Effective vaccines are needed to The development of new and effective vaccines has been limited given control this zoonotic disease. With the objective of developing a new the scarce availability of adjuvants. The nanoparticulate structures vaccine candidate able to generate an effective protection against this constitute very promising candidates given their immune-potentiating serovar, two monovalent formulations developed by two highly capacities and its in vivo slow antigen delivery to innate immune cells virulent strains were evaluated (FoBa and FoBb). Clinical isolates of related to Ag presentation/processing mechanisms. In this work new Leptospira serovar Ballum were subjected to serial passages in adjuvant formulations based on proteoliposomes of less than 40 nm hamsters and monovalent vaccines were produced by modified and cochleates of less than 100 nm, were evaluated using as antigen a methods developed for vax-SPIRAL®. The vaccine efficacy was tested in protein complex of Neisseria meningitidis B. Our objective was to both experimental and control hamsters. The Mesocricetus auratus evaluate its capacity to generate an immune cellular response type Th1 biomodel showed that both formulations generated a protection of by means of Delayed-type Hypersensitivity trial. Male Balb/c mice were 100% against the Ballum lethal infection together to high levels of IgG used; the formulations were administered intramuscularly and antibodies and were efficient in the elimination of homologous carrier intranasally. The percentage of swelling in the rear extremities was state but not heterologous carrier states. Both FoBa and FoBb vaccines determined while doing at the same time the histological analysis of were protective against leptospirosis with high IgG titers, absence of regions close to inoculation sites, also with the use of Flow Cytometry, clinical signs and dead, and absence of leptospires in kidney of TCD4+ lymphocytes were identified, which were present in the lymph sacrificed animals. nodes close to the administration site of vaccine formulations and control. The classical DTH-Test correlates well with the lymphokine pattern determined by RT-PCR. Results demonstrate that for all the studied variants, the percentages of induration were, statistically speaking, higher than negative control, which becomes evident by vascular congestion, type of cellular infiltrate and other observations in histological cuts. The increase of TCD4+ lymphocytes in vaccinated groups, as well as the Th1 lymphokine, with regard to the non- vaccinated one, corroborates the activation of this decisive cellular line, in the development of the effector mechanisms of an immune response. All formulations in the trial by both inoculation ways stimulate type- Th1 cellular immune response, similar or higher than positive control, which corroborates the potentiality of said formulations, as adequate vaccine-candidates.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S178
LATINFARMA 2013 Resúmenes/Abstracts
PIF-BT 053: PHARMACOLOGIC INHIBITION OF CASEIN PIF-BT 054: DELINEATING THE FUNCTIONAL MAP OF THE KINASE 2 (CK2)-MEDIATED SIGNALING TO INDUCE INTERACTION BETWEEN NIMOTUZUMAB AND THE APOPTOSIS IN ACUTE MIELOID LEUKEMIA (AML) CELLS EPIDERMAL GROWTH FACTOR RECEPTOR ANTIBODY
Cruz Y1., Perera Y2., Cruz LD3., Perea SE.2 Tundidor Y, García C and Rojas G.
1National Institute of Oncology and Radiobiology, Ave 29 and E, Vedado, Havana, System Biology Department, Center of Molecular Immunology, Havana, Cuba. E- Cuba. E-mail: [email protected] mail: [email protected],cu, [email protected] 2Laboratory of Molecular Oncology, Division of Pharmaceuticals, Center for Genetic Engineering and Biotechnology (CIGB), P.O. Box 6162, CP 10600, Havana, Cuba. 3Centro de Estudios Avanzados de Cuba (CEAC), Carretera San Antonio, km 1- The epidermal growth factor receptor (EGFR) is one of the most 1/2, Puentes Grandes, La Habana Cuba important targets in the development of antitumor drugs. Until this moment only three monoclonal antibodies (mAbs) directed against its extracellular region(er) have been approved for marketing: cetuximab, Introduction: Despite sustained advances in the treatment of AML, panitumumab and nimotuzumab. Recent evidences indicate that mortality rates are still unacceptably high, stressing the necessity to resistance to this kind of treatment can be associated to mutationin develop new therapeutic compounds. Recent findings suggest that erEGFR gene. This finding highlights the importance of defining the CK2alpha, the catalytic subunit of CK2 holoenzyme, is an unfavorable epitope recognized by each antibody, in order to predict response to prognostic marker and attractive therapeutic target in AML. Here, we treatment. Nimotuzumab (R3) is a humanized mAb, used in Cuba in the explore for first time the impact of the anticancer peptide CIGB-300, treatment of patients with head and neck, high grade glioma and designed to block CK2-mediated phosphorylation on AML cells. esophageal tumor. The epitope recognized by this antibody has not been defined yet. Methods: CIGB-300´s antiproliferative effect was assessed on AML cell lines (n=4) using the MTT assay while cytotoxicity was determined by Here, we constructed more than 150 variants of domain III of the flow cytometry. Peptide internalization and intracellular distribution human erEGFR. These variants were obtained by randomization of were determined by flow cytometry and confocal microscopy (30 selected position of the antigen by Kunkel mutagenesis and displayed µM/3, 10, 30 and 60 min), respectively. Pulldown experiments were on filamentous phage. The recognition of these variants, by performed using biotin-conjugated peptide (30, 50, 100 µM/10, 30 nimotuzumab and cetuximab was evaluated in order to decipher the min) and CIGB-300´s interacting proteins were identified by western functional epitope of nimotuzumab and validated our mapping blotting (WB) (target oriented) or mass spectrometry (exploratory). strategy, respectively. Validation of potential targets was done by WB using phosphospecific At this point, we identified the energetically critical residues previously antibodies (40 µM/0.5, 2, 5 h). described for cetuximab, so we can conclude that our mapping strategy Results: CIGB-300 exerted a dose-response antiproliferative effect on is useful to map the epitope recognized by nimotuzumab. We identified nimotuzumab functional epitope, composed by a contiguous region AML cells (IC50 mean= 26 µM) which can be explained by apoptosis induction. Based on response profile and relevant clinical-pathologic (S356, F357, T358, and H359) and a separate residue (R353). This last features two cell lines (OCI-AML3 and HL60) were selected for further residue, R353, is within cetuximab structural epitope, and explains the experiments. CIGB-300 was rapidly internalized (i.e. 3 min) in most of competition previously described for these two antibodies. This study the population of both AML cell lines (>95%). Interestingly, the peptide shows clearly, at a molecular level the bases of inhibitory effects of clearly accumulated in the nucleolar region of HL60 cells while nimotuzumab in EGFR signaling. Additionally, these results complete accumulation seemed more diffuse in OCI-AML3. Pulldown cetuximab functional map. Moreover our results could help to predict experiments indicate that CK2 substrates NPM/B23, AKT, C23, YBX1 response and guide treatment decision with nimotuzumab and and p130 interact with CIGB-300 while preliminary validation of CK2- cetuximab, in patients with mutations in domain III of human erEGFR. mediated phosphorylation impairment suggests that NPM/B23 may be an important target for this peptide in AML. Conclusion: Our data provide the first evidences regarding the suitability of pharmacological intervention on CK2-mediated signaling as anti-AML therapy.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S179
LATINFARMA 2013 Resúmenes/Abstracts
PIF-BT 055: RESULTS IN THE IMPLEMENTATION OF QUALITY Annex 13 (EMA), Handbook: QPBBR (WHO) & FDA guidelines. The MANAGEMENT SYSTEM DEVELOPMENT STAGE IN THE methods were Brainstorming, internal audits, flowcharts and CIGB benchmarking. Apezteguia I, Diago D, Martínez E, Torres D, González N, González T, Results: During the Development phase, the GQS Management Rodríguez M, Quintana M. established the Review Points, the process guideline and policy procedures for transferring of the research projects to the Center for Genetic Engineering & Biotechnology, Cubanacán, La Habana, Cuba. E- development stage and production system as well as the change and mail: [email protected] batch released control, complaints and validation. An updating of the documentary system, self-inspections, internal Audits and non- conformity control was carried out to follow up the compliance with Introduction: The Integration of Design & Development stage to the Good Manufacturing Practices applied according to the stage of the Quality Management System at the Center for Genetic Engineering and project. Biotechnology focuses on one of the current trends for quality systems established in ICH Q10 guideline. This paper aims at showing the Conclusions: The design of the QMS at the technological development progress made during these years. stage in the CIGB made progress in their implementation certified by Quality Assurance Management and received the Certification NC-ISO Material and methods: Materials used: ICH guidelines Q8, Q9 & Q10, 9001:2008 and AENOR issued by INOR & AENOR. Regulation ISO 9001:2008, Annex 7/Regulation 16:2006 (CECMED),
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S180
LATINFARMA 2013 Resúmenes/Abstracts
Métodos Alternativos / 3Rs Alternatives Methods
PMA 001: IN VITRO CELL-BASED APPROACHES TO ASSESS PMA 002: SIMILARITIES AND DIFFERENCES BETWEEN THE THE MECHANISMS UNDERLYING ANTITUMORAL ACTIVITY GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS OF METHOTREXATE VIA pH-SENSITIVE CHITOSAN AND THE MEXICAN NORM NOM-062-ZOO-1999 NANOPARTICLES Streber ML1, Ramirez A2, Pekow C.3 Nogueira DR1, Mitjans M1,3, Pérez L2, Infante MR2, Vinardell MP.1,3 1INCMNSZ, Vasco de Quiroga No. 15, Mexico City, Mexico, E-mail: 1Departament de Fisiologia, Facultat de Farmàcia, Universitat de Barcelona, Av. [email protected], fax + 55 56 55 10 76, phone +55 54 87 09 00, ext. 1+1301 2 Joan XXIII s/n, 08028, Barcelona, Spain. E-mail: [email protected] CENASA, SENASICA, SAGARPA, Tecamac, Mexico, Mexico. 3DACLAM, Chief, Veterinary Medical Unit, Veterans Affairs Puget Sound Health 2Departamento de Tecnología Química y de Tensioactivos, IQAC, CSIC, C/Jordi Girona 18-26, 08034, Barcelona, Spain. Care System, Seattle, Washington, USA. 3 Unidad Asociada al CSIC, Barcelona, Spain. Introduction: The Guide (G) is an internationally accepted primary Introduction: The encapsulation of antitumor drugs in reference. The eight edition has been updated since its first publication nanoparticulated systems is a promising approach that may enhance in 1963 and the purpose is to assist institutions in caring for and using the success of chemotherapy in many cancers. In this line, we animals in ways judged to be scientifically, technically and humanely investigated the role of an amino acid-based amphiphile with pH- appropriate. The G assists investigators in fulfilling their obligation to sensitive properties on the antitumor activity and intracellular plan and conduct animal experiments in accord with the highest behavior of methotrexate-loaded chitosan nanoparticles (MTX-CS- scientific, humane and ethical principles. The recommendations are NPs). Moreover, we assessed the mechanisms underlying cytotoxicity based on published data, scientific principles, expert opinion and induced by the encapsulated drug. experience with methods and practices. It is divided in 5 chapters and has 4 appendixes. The Mexican Norm (MN) or standard NOM-062- Methodology: NPs were prepared using a modified ionotropic ZOO-1999 “Technical specifications for production, care and use of complexation process, including a surfactant derived from Nα,Nε- laboratory animals” has been published first in 2001 and has not been dioctanoyl lysine with a lithium counter ion. NPs were characterized updated since its publication. It is divided in 10 chapters and 2 for their physicochemical properties, drug entrapment efficiency and appendixes. Similarities in aspects like: environment, some terrestrial in vitro drug release using medium of different pH. Antitumor activity species, housing and management, anesthesia and analgesia, of MTX-CS-NPs was compared to the free drug using a range of in vitro euthanasia, physical plant, transportation. cytotoxicity assays and tumor cell lines (HeLa and MCF-7). HaCaT keratinocytes were used as non-tumor control cells. Differences: the G includes key concepts like ethics and animal use, the three Rs, policies, principles and procedures, aquatic animals Results: Our results demonstrated that the pH-sensitive behavior of (amphibians, reptiles and fish) are not included in the MN but includes NPs, which enabled an accelerated release of MTX in acidic medium. chapters like biosecurity and verification not included in the G. One of Moreover, fluorescence microscopy analysis evidenced that the NPs the most important differences: IACUC (Institutional Animal Care and have a membrane-lytic pH-dependent activity. These features allowed Use Committee) has detailed descriptions for constitution, function the cytosolic delivery of endocytosed materials, which in turn can be and protocol review and post- approval monitoring. The MN is lack of directly related with the greater cytotoxicity of MTX-CS-NPs against detail for the IACUC. the tumor cells than the free drug. Moreover, MTX-CS-NPs were found to be more cytotoxic around tumor extracellular pHe than at Conclusion: the MN should be updated and the G is a good model to physiological pH. The combined effects of pH-triggered release, follow but also should be aware of other international cytotoxicity and membrane-lytic activity, together with induction of recommendations like the CIOMS Principles and the Basel Declaration. cell cycle arrest, apoptosis, lysosomal membrane destabilization and mitochondrial injury are proposed as the general mechanisms underlying the greater cytotoxicity of MTX-CS-NPs. Conclusions: Altogether, our results suggest that these NPs could be potentially useful as a carrier system for tumor and intracellular drug delivery in cancer therapy. Furthermore, the combination of assays used here is a reliable approach that offers an in-depth and comprehensive evaluation of the mechanisms implicated in the cytotoxic effects of novel nanomaterials.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S181
LATINFARMA 2013 Resúmenes/Abstracts
PMA 003: E-LEARNING AS A STRATEGY TO REDUCE THE PMA 004: ZEBRAFISH NEUROTRANSMITTER SYSTEMS AS NUMBER OF ANIMALS USE IN PHARMACOLOGY POTENTIAL PHARMACOLOGICAL AND TOXICOLOGICAL TARGETS Mourelle AC1, Herrero ME1, Asprea M2, Ricca M.1 Rico EP. 1Aula Virtual Bioterio, www.labanimalstraining.com; E-mail: [email protected] Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da 2Bioterio y Cirugía Experimental, Hospital de Pediatría Prof. Dr. Juan P. Saúde, Departamento de Bioquímica. Rua Ramiro Barcelos 2600 – Anexo Bairro Garraham; Buenos Aires, Argentina. E-mail: [email protected] Santa Cecília Porto Alegre – RS, Brasil. E-mail: [email protected]
The use of live animals in teaching at university level is the preferred Recent advances in neurobiology have emphasized the study of brain methodology used to show, different pharmacologic phenomena structure and function and its association with numerous pathological previously learned in the classes. and toxicological events. Neurotransmitters are substances that relay, Nowadays computer and internet are widely accepted tools on amplify, and modulate electrical signals between neurons and other education and research and in the last decades facilitated the cells. Neurotransmitter signaling mediates rapid intercellular development and implementation of new teaching strategies and communication by interacting with cell surface receptors, activating learning. These new available educational tools, give us the second messenger systems and regulating the activity of ion channels. opportunity to implement alternatives to animal use to achieve the Changes in the functional balance of neurotransmitters have been educational objectives set for the practical classes. E-learning is implicated in the failure of central nervous system function. In addition, defined as the production, distribution and use of electronic content abnormalities in neurotransmitter production or functioning can be for educational purposes. induced by several toxicological compounds, many of which are found in the environment. The zebrafish has been increasingly used as an The aim of this work is to show the contribution of this methodology in animal model for biomedical research, primarily due to its genetic the application of the principle of the 3Rs (reduction, replacement and tractability and ease of maintenance. These features make this species a refinement) and how an e-learning program well planned, can be a versatile tool for pre-clinical drug discovery and toxicological valuable tool to reduce the number of animals used at university level, investigations. Furthermore, zebrafish is studied regarding the role of not only in pharmacology, but in other subjects that currently use live different excitatory and inhibitory neurotransmitter systems, such as animals, and at the same time the students could learn the concept of dopaminergic, serotoninergic, cholinergic, purinergic, histaminergic, bioethics and respect towards animals. nitrergic, glutamatergic, glycinergic, and GABAergic, and emphasizing their features as pharmacological and toxicological targets. The There is a worldwide moral and legal statement that the use of live increase in the global knowledge of neurotransmitter systems in animals should be restricted only for those procedures where it is zebrafish and the elucidation of their pharmacological and toxicological strictly necessary to use them, and the countries of Latin America, aspects may lead to new strategies and appropriate research priorities where there is still a strong need to introduce the concept of the 3R´s to offer insights for biomedical and environmental research. principles, we have to move in that direction.
Our experience shows that replacement and reduces of animals as a first approach is possible with this education strategy.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S182
LATINFARMA 2013 Resúmenes/Abstracts
PMA 005: DEVELOPMENT OF A SEROLOGICAL TEST FOR PMA 006: DEVELOPMENT OF A VERO CELL METHOD FOR DETERMINING BIOLOGICAL ACTIVITY OF THE WHOLE DETERMINING SPECIFIC TOXICITY AND REVERSION TO CELL COMPONENT IN DPT VACCINES FOR PRECLINICAL TOXICITY FOR DIPHTHERIA TOXOID IN VACCINES STUDIES Herrera L, Monteagudo R, Bolaño G, Fidalgo O, Delgado I, Chovel ML. Blanco A, Gutiérrez N, Valle O, Núñez JF, Mandiarote A, Chovel ML. Instituto Finlay, La Habana, Cuba. Instituto de Ciencias Básicas y Preclínicas “Victoria de Girón, La Habana, Cuba. E- mail: [email protected] Introduction: Diphtheria toxoid active pharmaceutical ingredient of diphtheria vaccines is obtained by inactivation of the diphtheria toxin Introduction: Whooping cough is an infectious disease caused by the with formaldehyde, taking care of not affecting its immunogenicity. bacteria Bordetella pertussis. Inactivated vaccines (whole cells) have One of quality requirements for this product is the determination of been produced with a successful coverage and effectiveness the absence of residual active toxin and the potential for reversion to worldwide. World Health Organization recommends an intracranial toxicity. The aim of this work was to develop a Vero cell culture assay challenge method for determining the Potency of DwPT vaccine as an alternative method for testing specific toxicity in order to replace batches. Nevertheless, this methos has been deeply criticized in terms the in vivo method. of ethical, economical and technical issues. Recently, serological tests have been evaluated in order to replace the challenge test. The aim of Material and methods: The WHO Protocol described in the WHO this paper was to develop a relevant serological test for determining Technical Manual, was followed in order to verify its suitability in our the biological activity of the wP component in vaccine candidates working conditions. A working Reference Diphtheria Toxin in during preclinical studies. minimum cytotoxic dose and a Diphtheria Antitoxin were characterized. 8 batches of diphtheria toxoid produced at Finlay Material and methods: OF1 mice were immunized with DwPT Institute were evaluated by Vero cell test and the results were vaccines (0.5 mL, i.p.) and observed during 28 days. Then, mice were compared with those obtained by the in vivo method. Validation of the bled and the serum pools were tested for total antibodies by using a method was performed by determining its detection limit, specificity whole-cell ELISA. In order to characterize the immune response, the and robustness. antibody titres against FHA and PT and the antibody subclasses were also determined. The method was standardized according to the Results: Sensitivity to detect diphtheria toxin-induced toxicity in our defined criteria. conditions was shown by the characterization of the working reference materials. Absence of toxicity in the toxoids tested was demonstrated, Results: All the standardization parameters met the criteria a result that was consistent with those obtained by the in vivo method. established. Moreover, the serological method was able to correlate The validation parameters fulfilled the specified criteria, showing that with the challenge test, both discriminating among potent and sub- the Vero cell has a higher sensitivity that the Toxicity test in guinea- potent vaccine samples. Poor anti-PT and anti-FHA responses were pigs. obtained, as expected, thus demonstrating that for whole-cell component the global antibody response is more relevant than the Conclusions: It was developed a Vero cell test for Specific toxicity and individual ones. It was also demonstrated that the subclasses more Reversion to Toxicity of Diphtheria Toxoids in vaccines, able to replace involved in the antibody response were IgG2a and IgG3. the compendial in vivo test. Conclusions: The serological test is a valid alternative for replacing the challenge method for determining biological activity of wP component in vaccines during preclinical studies.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S183
LATINFARMA 2013 Resúmenes/Abstracts
PMA 007: IGY TECHNOLOGY: USE OF EGG YOLK ANTIBODIES PMA 008: ALTERNATIVE METHODS FOR TRAINING FOR DIAGNOSTIC, PREVENTION AND THERAPY OF PROSTATE PALPATION AND URETHRAL DISEASES CATHETERIZATION FOR DOGS IN VETERINARY TEACHING
Geoghegan P1, Cangelosi, A1 , Brero M1, Fernandez Miyakawa M2, Capilé K, Bones VC, Campos GMB, Santos LT, Ribeiro AC, Oliveira ST. Chacana P.2 Federal University of Paraná (UFPR), Depto. de Medicina Veterinária. Rua dos 1Centro Nacional de Control de Calidad de Biológicos, ANLIS “Dr. Carlos G. Funcionários, 1540, Juvevê. Curitiba-PR. CEP: 80035-050. E-mail: Malbrán”, Argentina. E-mail: [email protected] [email protected] 2CICVyA, INTA, Argentina
It is essential that veterinary students learn to perform several types of The production of antibodies (abs) in chickens and the extraction of relevant clinical exams to develop their skills. Examples of such exams specific Abs from egg yolk (IgY Abs) are increasingly attracting the include prostatic palpation and urethral catheterization which are interest of the scientific community, as demonstrated by the significant useful to assist diagnosis of urinary and prostatic diseases in dogs. growth of the IgY literature. Use of IgY has several advantages over These practices are traditionally trained in live animals, cadavers or are mammal IgG: antibodies can be extracted from the egg yolk, avoiding not performed. The inconvenient tissues of traditional methods include the bleeding of the animal; large amounts of antibodies can be obtained difficulty to find appropriate cadavers and negative consequences for from a single hen and therefore, the number of lab animals can be animal welfare. The aim of this work was to develop artificial models of reduced as well as the cost of the production of the immunoglobulins. vagina, urethra, rectum and prostate in order to provide better teaching There are well established methods for hyperimmunization of the hens tools in veterinary subjects such as small animal clinics and semiology. and purification of IgY from egg yolk; and the immunoglobulins can be The models were developed using dogs’ cadavers. An artificial vagina used in almost any assay that uses mammal polyclonal abs by just was reproduced from a matrix made with alginate and later filled with adapting the technique. silicone in order to simulate urethral catheterization; latex, silicone and play dough was used to make the rectum and the normal and abnormal Besides the use in diagnosis, since large amounts of abs at a low cost prostates to simulate prostatic palpation. Other materials such as can be obtained, many applications of IgY-technology have been styrofoam and toy parts were also used for the construction of the explored for both human and veterinary medicine, including strategies mannequins bodies. The models had low cost, were able to mimic the for prevention and treatment of diarrheas, Helicobacter pylori anatomy and consistency of a living animal and allowed the infection, dental caries and many others. In Argentina, IgY Technology performance of urethral catheterization and prostatic palpation has been introduced since more than 10 years ago and currently new techniques in dogs, similarly to the exams performed in a living animal. applications are being developed as, for example, the detection of shiga For these reasons, the models show advantages over traditional toxin (that causes haemolitic uremic syndrome in children) and methods from the ethical, logistical and technical points of view. formulation of food additives containing specific IgY to prevent the Considering these preliminary results we conclude that the artificial disease. Also, the potential of the use of IgY against snake venoms, models can be used as a teaching tool and contribute to the spread of microbial toxins or viruses to treat human cases is being explored, in alternative resources in veterinary medicine, this way generating order to replace the production of hyperimmune therapeutic sera in conscious attitudes in favor of animal ethics and responsible science. horses or goats.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S184
LATINFARMA 2013 Resúmenes/Abstracts
Nanofarmacología / Nanopharmacology
PNM 001: DETERMINATION OF ELASTIC PROPERTIES PNM 002: SYNTHESIS OF SELF-ASSEMBLED AMPHIPHILIC OF CANCEROUS CELLS BY ATOMIC FORCE PEG-PLA COPOLYMERS BY UGI FOUR COMPONENT MICROSCOPY CONDENSATION AS A POTENTIAL CONTROL RELEASE SYSTEM FOR CANCER TREATMENT Ramos JR, Szlagor J, Garcia R, Lekka M. Peña L, Agüero L, Castro A, Ramon J, Lopes M, Zaldivar D. Centro de Estudios Avanzados de Cuba, Carretera de San Antonio de los Baños, Km. 1 ½ Valle Grande. La Habana, Cuba. E-mail: [email protected] Center for Biomaterials (BIOMAT), University of Havana, Cuba. E-mail: [email protected]
The tumor grade is a description based on how abnormal the cancer The design of macromolecules is rapidly evolving, with contributions cells look under a microscope and how quickly the tumor is likely to from synthetic chemistry, material science, and biomedical engineering. grow and spread. On the other hand, the atomic force microscopy Macromolecule-based devices such as polymeric nanoparticles, (AFM) has become a powerful tool to distinguish cancerous cells and polymer−drug conjugates, and polymeric micelles have been used for tissues from non-malignant ones. The AFM studies are mainly based on controlled drug delivery (CDD), improved drug efficacy and safety. the elastic properties of the cell cytoskeleton. As a general rule, it has Amphiphilic block copolymers play an important role in the obtaining been found that non-malignant cells are stiffer than malignant ones. of those devices. For examples, polymeric amphiphiles can self- However, the relationship between malignancy degree and cell assemble into micelles display a nanoscopic structure with a elasticity hasn’t been reported in the literature. hydrophobic core and hydrophilic corona and they are very useful in In AFM spectroscopy studies, living cells are measured under control release systems for cancer treatment. In this work polymeric physiological conditions. The cells are indented with the cantilever tip. micelles obtained by self-assembling of amphiphilic copolymer of The Indentation curve can be correlated with the Young's modulus of polylactic acid (PLA) grafted to polyethilenglycol (PEG) and the cell. The AFM has an inverted microscope to control the position fluoresceine have been prepared and characterized. In particular, PLA where the force curves are performed. was polymerized and end functionalized by ring opening. Polymerization to give carboxylic and aldehyde end functionalized PLA. In this work, we study 4 cell lines with epithelial origin (bladder cells) Synthesized molecules were characterized by GPC, 1H-NMR, FT-IR and with different degree of malignancy. The AFM spectroscopy was used to UV- Vis. Also, two different amphiphilic copolymers of PEG grafted PLA determine the elastic properties of the actin cytoskeleton. The curves and conjugated to fluoresceine have been synthesized by Ugi four were performed in the area above the cell nucleus. The cantilever components condensation reaction (U4CC) and they were spring constant was 0.01 N/m and the tip had a pyramidal shape of few characterized by GPC, 1H-NMR, FT-IR and fluorescence´s spectroscopy. micrometers height and an opening angle of 20°. The Young’s moduli Self-assembled nanoparticles were prepared by deusing the method of were estimated for indentation depths from 100 to 500 nm. A solvent´s rotavaporation. These nanoparticles were characterized by population of 10 to 15 cells was studied for every cell line and the total light scattering and scanning electron microscopy. All samples of PLA number of force curves used to estimate the Young’s moduli was were successful activated with moderate yields of monomer conversion around 600. The Tukey-Kramer multiple comparison test (P=0.05) of (70-80%). The U4CC achieved goods yields of 65%. The fluorescent the elasticity measurements showed that non-malignant cells are stiffer amphiphilic copolymers synthesized by U4CC were able to form self- than the cancerous ones (P<0.001) but there were no significant assembled nanoparticles of 400 nm. differences between the cells with grades 2, 3 and 4.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S185
LATINFARMA 2013 Resúmenes/Abstracts
PNM 003: DEXAMETHASONE RELEASE FROM CHITOSAN PNM 004: SYNTHESIS, CHARACTERIZATION AND IN VITRO MICROSPHERES OBTAINED BY SPRAY DRYING AND EVALUATION OF CHITOSAN/APATITE NANOSTRUCTURED COATED WITH A NOVEL PH DEPENDENT INTERPOLYMER COMPOSITES AS PROMISING BONE SUBSTITUTE COMPLEX MATERIALS García J, Bada N, López OD, Nogueira A, Caracciolo P, Abraham G, Solís Y, Carrodeguas RG, Davidenko N, Da Silva E, Peniche C. Ramón JA, Peniche C. Centro de Biomateriales, Universidad de La Habana, La Habana 10400, Cuba. E- Center for Biomaterials (BIOMAT), University of Havana, Havana, Cuba. E-mail: mail: [email protected] [email protected]
Chitosan/apatite (CHI/Ap) composites are attracting great attention as Microencapsulation of drugs in polymer matrices is an alternative to biomaterials for bone repair and regeneration procedures. The reason reduce the irritating effects on gastric mucosa produced by many drugs, is their unique set of properties: bioactivity and osteoconductivity as well as directing release to specific sites. Chitosan has been widely provided by Ap and resorbability supplied by CHI among others. explored for this purpose because of its excellent properties: biocompatible, biodegradable and nontoxic. In this work, chitosan In this work a novel procedure for obtaining nanoestructured microparticles loaded with dexamethasone (DMT-CS) in several chitosan/apatite (CHI/Ap) composites was established. The method CS/DMT ratios were prepared by spray drying using a Büchi 191 Mini involves the co-precipitation of Ap in a two steps procedure, starting Spray Dryer. The particles were covered by a pH dependent with soluble precursor salts. The process allows employing different poly(acrylic acid)/poly(vinyl pyrrolidone) interpolymer complex by a proportions of the starting ingredients in order to obtain composites water-in-oil reverse emulsion technique. Drug content, yield and with different CHI/AP ratios. The rute employed resulted effective for encapsulation efficiency were determined. A slight decrease in introducing Si in the crystalline network of the Ap formed in the CHI encapsulation efficiency with increasing drug content was observed. matrix of the resulting composite. The microparticles have a rough surface and spherical shape, as Characterization of the resultant composites by scanning electron observed by SEM. Complex formation was confirmed by FTIR microscopy, X-ray powder diffraction (XRD), thermal analysis and spectroscopy. This technique enabled also to identify the presence of Fourier transform infrared spectroscopy confirmed the formation of dexamethasone in microparticles. Release studies were carried out in nanoparticles of sodium- and carbonate-substituted hydroxyapatite gastric (pH 1.2) and intestinal (pH 6.8) simulated fluids. Quantification [Ca10-xNax(PO4)6–x(CO3)x(OH)2] with diameters less than 20 nm within was performed by UV-Visible spectroscopy at 242 nm. Drug release the CHI matrix. Chitosan/apatite and chitosan/Si-doped Ap have from DMT-CS non-coated microparticles was similar in both fluids, greater particle size than corresponding inorganic materials. Adequate varying the amount released with drug content. Dexamethasone correspondence was shown between the experimentally determined released from coated DMT-CS was almost negligible, indicating the inorganic content by thermal analysis and the expected theoretical potential application of this interpolymer complex in specific site value. A decrease in both crystal domain size and cell parameters of the delivery systems, for instance, in colonic drug release formulations. in situ formed Ap with increasing CHI content was revealed by XRD. Si- doped apatite, higher chitosan content and low molecular weight chitosan based-composites showed the lowest physiological stability and the highest enzymatic degradation. A deposition on composites surface of an apatite layer was evidenced after immersion in simulated body fluid. Cytotoxicity tests evidenced that studied materials are cytocompatible under physiological conditions. The above results suggest that the composites obtained are promising materials for bone regeneration.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S186
LATINFARMA 2013 Resúmenes/Abstracts
PNM 005: THE ISO TC 229/IEC TC 113, ESSENTIAL TOOL IN PNM 006: IRON OXIDES NANOPARTICLES FOR MEDICAL CONFORMITY ASSESSMENT OF RESEARCH AND APPLICATION PRODUCTION OF NANO-SCALE DEVICES Díaz C. Valdés G, Díaz C, Veranes Y, Hernández M. Centro de Biomateriales, Universidad de La Habana, Av. Universidad e/ G y Centro de Biomateriales. Ave. Universidad e/ G y Ronda, La Habana, CP 10400, Ronda, Plaza, La Habana, Cuba. E-mail: [email protected] Cuba. E-mail: [email protected]
When the size of magnetic particles (for example permanent magnets) Nanotechnology breaks as a generator of welfare in all areas of our is bellow a critical value, which depend on temperature, they behave, lives, in the tetrahedron of NBIC Technologies Convergence from the instead of small magnets, like giant paramagnetic atoms and exhibit National Science Foundation of the United States (Nano-technology, superparamagnetic properties, meaning that they have a large Biotechnology, Information Technology and Communications and constant magnetic moment and fast response to applied magnetic Science of Knowledge) can be seen that this new technology is creator fields, but do not retain any magnetism after removal of the field. of synergy and brings with it various risks that must be properly These features make superparamagnetic nanoparticles very attractive addressed in its regulations. The International Organization for for a broad range of biomedical applications. Standardization (ISO) and the International Electro technical In particular, in the context of the emerging concern about the Commission (IEC), in close collaboration, created the Technical potential toxicity of nanoparticles, it is noteworthy that iron oxide Committees 229 and 113. These committees operate in four working particles are highly biocompatible, as the iron cell homeostasis is well groups: Terms and Nomenclature (JWG1), Characterization and controlled by the body. Measurements (JWG2), Health, Safety and Environment (WG3) and Specification of Materials (WG4). According to the rules established by In this work, iron oxide magnetic nanoparticles are prepared in two the ISO/IEC have been instituted more than 35 standards for different ways: Nanotechnology. It is essential to spread knowledge for nano-scale standardization and settling the cognitive gap between developing 1- In situ, using the alginate network as a template, by dropping Na- +2 countries and developed nations, between higher-level specialists, alginate into a FeCl3 solution, where the Fe cross-linked alginate producers and potential customers. The objective of this work is to beads were treated with an alkaline solution. As a result the Fe+2 ions present recommendations to be considered for the introduction of were partially oxidized in situ and a spinel structure is obtained. regulations in our country on important aspects as the conformity 2- Based on 2FeCl3·6H2O + FeCl2·4H2O + 8NaOH → Fe3O4 + 8NaCl + assessment of the research and production through the relationships 20H2O reaction, where the iron solution is added dropwise to the among metrology, standardization and accreditation. The nano hydroxide solution. The precipitated powder was isolated by using a medicine is a discipline that generates extraordinary possibilities from magnet. the point of view of the interfaces NANO-BIO-INFO, which will contribute to individualized treatment of patients, either from the use Samples were characterized by XRD, SQUID, Mossbauer spectroscopy of controlled drug dosage as well as the biomaterials for tissue and SEM. regeneration, besides the broad ranges of diagnostic devices that could be developed. In the first case, nanoparticles with diameters in the range 4-15 nm were obtained. Intermediate step products were characterized after beads formation and alkaline reaction. The final product was maghemite with a distribution of particles size with different maxima. Using the second rut, particle with sizes in the range 6-12 nm, were coated by sodium alginate or sodium oleate. A preliminary obtainment of magnetic liposomes was made. The obtained magnetic nanocomposites present potential applications in vitro and in vivo medical systems.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S187
LATINFARMA 2013 Resúmenes/Abstracts
PNM 007: CHITOSAN-ALGINATE POLYELECTROLYTE PNM 008: PH-SENSITIVE MICROPARTICLES BASED ON COMPLEX NANOPARTICLES AS DRUG CARRIERS FOR ORAL POLYELECTROLYTE COMPLEXES FOR ANTIBIOTIC ADMINISTRATION DELIVERY
Becherán L, Peniche C, De Geest B, Vervaet C, Remon JP. Agüero L, Valdés O, Zaldivar Silva D, Peña L, Lopes M, Ramón JA.
Institute of Materials Science and Technology, University.of Havana, 10400, Centro de Biomateriales. Universidad de la Habana. Ave. Universidad e/. Ronda y Havana, Cuba. E-mail: [email protected] G, CP 10400, La Habana, Cuba. E-mail: [email protected]
Polyelectrolyte complexes (PEC) are very interesting materials for Development of safe and efficient polymer-based drug carrier system is different applications because their properties (swelling, permeability, a widely studied way to enhance therapeutic properties of old and new and others) can be modified by external stimuli. Particular interest is active pharmaceutical ingredients. Polyelectrolyte complexes have currently found in the preparation of PEC particles with biocompatible been explored for their potential in colon-specific drug delivery due to polyelectrolytes in aqueous media to be used for the transport of their ease of preparation, avoidance of hazardous procedures and biological macromolecules and other therapeutic compounds possibility to fabricate a variety of combined structures. In this work, throughout living organisms. Because of their minute size, poly(acryloxyethyl–trimethylammonium chloride–co– N-vinyl-2- nanoparticles exhibit a number of distinct advantages for intracelullar pyrrolidone, poly(Q-co-VP)) was synthesized by radical polymerization transport of substances and they can be useful as carriers through at 60°C and it was bonded by electrostatic attraction with sodium intravenous, oral, and mucosal routes. In this work, chitosan–alginate alginate (NaAlg). This complex allowed the obtaining of pH-sensitive PEC nanoparticles loaded with metronidazole as a model drug were microparticles by coacervation. Seven different mole ratios of Q and VP prepared by coacervation under mild experimental conditions. The were studied to prepare synthetic copolymer. Actual copolymer particles were characterized in terms of their morphology and composition was determinate by potentiometry technique approach. composition by scanning electron microscopy, dynamic light scattering, Microparticles formed were used to deliver a model antibiotic drug, infrared spectroscopy and differential scanning calorimetry. The sodium cefatoxime. The encapsulation efficiency was around 80% and release profiles of metronidazole at pH=1.2 and 6.8 were obtained and release profiles were investigated in different simulated mediums using zero order, Higuchi, Ritger-Peppas and Peppas-Sahlin mathematical an UV/vis spectrophotometer. In vitro drug release was found to be models were used for the evaluation of the in vitro drug release dependent of pH and showed sustained release characteristic over kinetics. The chitosan-alginate nanoparticles obtained showed extended period of time for 24h. Electron microcopy showed the spherical shape and the mean diameter of the loaded particles was 536 poly(Q-co-VP)/NaAlg microparticles to be almost spherical with many ± 2 nm. No evidence of polymers-drug interaction was observed. At pH wrinkles on their surface. Particle size analysis was done by optical 1.2, the particles presented low release of metronidazole while a microscope indicating that the particles were in the size range of 400- significant higher release was observed at pH 6.8 (almost 90% after 6 850 µm (n=150), narrow unimodal distribution. hours). The release profiles showed higher correlation coefficients for the Ritger-Peppas model and it was observed that the system presented an anomalous mechanism of drug release, the diffusion and swelling mechanisms probably occurring simultaneously.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S188
LATINFARMA 2013 Resúmenes/Abstracts
PNM 009: ORGANIC-INORGANIC THIN FILMS CONTAINING PNM 010: STUDY OF COMPOSITION POLYMERIC INFLUENCE NANOCRYSTALLINE HYDROXY-APATITE PARTICLES ON THE CONTROLLED DRUG DELIVERY CAPACITY OF A HYDROPHILIC COMPOSITE Peón Avés E, El Hadad AA, Jiménez-Morales A, Barranco V, López FA, Muñoz-García C, Galván Sierra JC. Campos Y, Fuentes G, Delgado JA and Almirall A.
Centro de Biomateriales, Universidad de La Habana, Ave. Universidad e/ Ronda y Centro de Biomateriales, Universidad de La Habana, Ave. Universidad e/ Ronda y G, Plaza de la Revolución, La Habana 10400, Cuba. E-mail: [email protected] G, Plaza de la Revolución, La Habana 10400, Cuba. E-mail: [email protected]
Multifunctional organic-Inorganic hybrid coatings on Ti6Al4V surfaces Bone diseases have greatly affected the adult population denying them were prepared by co-hydrolysis and polycondensation of - a decent quality of life, that´s why a large number of investigations methacryloxypropyltrimethoxysilane (MAPTMS) and tetramethoxy- have been aimed to obtain materials that reduce traumatic conditions silane (TMOS). TMOS in hybrid coatings tend to impart durability, in patients with certain diseases. Compound materials have been scratch resistance, and improved adhesion to the metal substrates. studying with special attention because of their versatility. MAPTMS contribute to increase flexibility, density and to achieve tailored properties, such as hydrophobic properties. The resulting In this work the principal objective is the study of hydrophilic MAPTMS/TMOS hybrid was modified with the addition of composites loaded with hydroxyapatite (HAp), with the purpose to use hydroxyapatite (HA) particles during the sol-gel process with the aim of them, as factory supplies gives internal and external fixers and generating bioactivity and decreases the porosity of the hybrid film microfixers in bone lesions of great magnitude. This material most has through blocking effect. The effects of HA doping on the thermal to be capable to deliver any drug of controlled manner during the time, stability of the prepared hybrids were investigated by using thermal in order to avoid any infection around the implant site. It was carried analysis (TG/DTG). The application of X-ray Diffractometer (XRD) has out the synthesis of the hydrophilic composites of poly (acrylamide-co- provided information about the crystalline and/or amorphous features 2,3-epxypropyl methacrylate) from a statistical design using as of the prepared coatings. Attenuated total reflectance Fourier variables the monomeric composition, the load, the cross linking Transformer Infrared Spectroscopy (FTIR-ATR) has been utilized for content (N,N-metylen bis acrylamide) and the dispersant content studying the functional groups within the prepared coatings. The (sodium alginate), maintaining constant the initiator percent hydrophobic behavior and thickness of the prepared coatings were (potassium persulfate). evaluated by application of both Contact Angle and Profilemeter The swelling behaviour had a typical hydrophilic biomaterials profile measurements. Scanning Electron Microscopy (SEM) coupled with an giving absorption water values of 260% in the samples with greater Energy Dispersive X-ray (EDX) system has been applied to study the content of acrylamide (AA, hydrophilic monomer). The drug delivery surface morphology and composition of coated samples. capacity shows a result of 93% at 6 hours, in spite of the great influence of the filler. The sample with the best controlled drug delivery capacity was the one who has greater content of the hydrophilic component, same results to the swelling behavior. In the bioactivity study, the more swelling sample immersed in SBF reached an apatite layer at 15 days after begins the study. The specimen with the best properties for being used as a substitute of bone tissue and as a matrix for controlled drug delivery was the one who had the greater percent of the hydrophilic monomer (AA).
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S189
LATINFARMA 2013 Resúmenes/Abstracts
PNM 011: SYNTHESIS AND CHARACTERIZATION OF PNM 012: DENTAL MATERIALS’ MODIFICATION BY CARBON NANOMATERIALS CONTAINING NATURAL ACTIVE NANOPARTICLES INGREDIENTS FOR BIOMEDICAL APPLICATIONS Ageev O, Polyakov V, Kovalenko A, Polyakova V, Svyatchenko V. Soriano J1, Sánchez E1, Alvarado A1, Flores L1, Ortega R1, Vera A1, Southern Federal University, Taganrog, GSP-17A, Nekrasovsky st., 44, EEE 1 1 1 2 Mercado F , Vázquez R , Tejeda A , Dominguez M, Hernández L , Hirata Faculty, Russia. E-mail: [email protected] G3, Cachau R4, Pal U5, Juárez Z1, Miranda M1, Palacios T1.
1Biological Sciences, UPAEP, 21 Sur 1103 Barrio de Santiago, CP 72410, Puebla, México; 2Chemical and Biological Sciences, UDLAP, Puebla, México; 3CNyN-UNAM, For the last few years many reviews were devoted to properties and Baja California, México; 4SAIC-Frederick, NIH, Frederick, MA, USA; 5IFUAP, BUAP, manufacturing research of so called nanoconcrete. In substance Puebla, México. E-mail: [email protected] nanoconcrete is a classical mixture of sand and cement with carbon [email protected] nanoparticle additive. Cement compounds’ modification researchers achieved good results and approved the effectiveness of using additives. At the same time well known, that materials used in Nanomaterials have broadly employed to immobilize drugs to be stomatology are cements too. There are four types of dental materials: delivered inside the cell and to prevent denaturation and degradation zinc-phosphate, silicate, silico-phosphate and polymer. of the drugs inside the body. The objective of this project is to synthesize modified nanomaterials with active ingredients from In this research were studied carbon nanoparticle modification of medicinal plant extracts to evaluate their biological in vitro activity. phosphate cement (“Unifas-2”, Russia) and a silico-phosphate cement Matricaria chamomilla and Catharanthus roseus are being used to (“Silidont-2”, Russia). Carbon nanoparticles produced by CVD were obtain chloroform and hexane extracts, purified by column used as dental cement modifying additives. Investigated dried dental chromatography and characterized by proton (1H) and carbon (13C) powders were mixed with carbon nanoparticles in different nuclear magnetic resonance (NMR). Magnetic nanoparticles were percentages. After that were formed samples by mixing the compound prepared by coprecipitation using FeCl3, Na2SO3 and NH4OH. Polymeric with a hardener. nanocapsules were prepared by microemulsion using sodium alginate Using electron microscope Phenom (FEI Co) structure and morphology with the extracts, CaCl2 and dioctyl sodium sulfosuccinate. of the modified dental materials surface was explored. Also strength Nanomaterials were characterized by transmission electron characteristics of modified filling materials were explored with a microscopy (TEM), infrared (FTIR) and Raman spectroscopy, dynamic tensile testing machine and by nanoindentation on AFM NTegra (NT- light scattering (DLS) and confocal microscopy. The particle size range MDT, Russia). Results of experiments showed that modified dental of nanoparticles was between 6-10 nm with Fe3O4 as the main cements outperform standard ones in 2-4 times. Moreover modified crystalline phase. Regarding alginate nanocapsules, their particle size dental cements were revealed to show the greatest resistance to range was between 200-400 nm. With these results, we continued with aggressive medias, for example, orthophosphoric acid wide used in the biological activity evaluation of all the materials obtained different kinds of sodas. Destruction of modified filling materials under employing bacterial models. 0.1% of orthophosphoric acid and Coca-Cola is virtually absent. Such influence on the standard filling materials causes its destruction in 18- 24 hours. Experimental dependences obtained in this study give the possibility of choice of carbon nanoparticle modifying additives quantity to achieve the required result upon strength characteristics of forming filling and its resistance to acid media impact.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S190
LATINFARMA 2013 Resúmenes/Abstracts
PNM 013: THE SCANNING TUNNELLING MICROSCOPY IN THE PNM 014: NOVEL SOLIDS DISPERSION OF CYCLOSPORIN A CHARACTERIZATION OF MOLECULES STRUCTURES WITH FOR IMMUNOSUPPRESSION THERAPY APPLICATION IN PHARMACOLOGY Salomón S1, López OD1, Gómez M1, Romero JA1, Turiño L2, Tur MI3, Herrera JA, Martínez Pons J, Hernández MP. Iraizoz A4, Alejo P1, Nogueira A.1
Instituto de Materiales y Reactivos Electrónicos (IMRE), Universidad de la 1Centro de Investigación y Desarrollo de Medicamentos. CIDEM. Ave 26 n 1605 Habana, Zapata y G, Vedado, 10400 Plaza de la Revolución, Havana City, Cuba. E- e/ Boyeros y Puentes Grandes. Nuevo Vedado. CP 10600. La Habana. Cuba. E- mail: [email protected] mail: [email protected] 2Centro de Estudios Avanzados de Cuba (CEAC). Carretera de San Antonio km 1½, La Lisa, La Habana, Cuba 3Empresa Productora de Insulina y Carpules. Laboratorios LIORAD. Ave. 27 A No. Electrochemical Scanning tunneling microscope (ECSTM) is a useful 26402 e/ 264 y 268, San Agustín, La Habana, Cuba. tool for the characterization of the structures of surfaces and 4Instituto de Farmacia y Alimentos. Universidad de La Habana. Ave. 23 No. 21425 electrochemical reactions in solid-liquid interfaces. ECSTM finds entre 214 y 222, La Lisa, La Habana, Cuba. application in the study of the absorption of molecular structures by certain kind of surfaces. It combines the atomic scale resolution of SPM microscopes with the possibility of operating under environmental Cyclosporin A (CsA), a cyclic oligopeptide, is a potent immuno- conditions closer to the physiological condition of biomolecules. This suppressant and has been used primarily to prevent xenograft rejection work resumes an actualized update of the application of ECSTM and after organ transplantation. However, it is known that the oral our preliminary results concerning to the study of the absorption and bioavailability of CsA is usually very low due to the poor absorption, desorption of molecules, especially those with potential applications in which is related to the relatively high molecular weight, very high medicine. lipophilicity. In the present investigation, novel solid dispersion (SD) of CsA was developed for oral administration. SD formulations were prepared by CsA, SLS, Dextran-70 and PEG-4000 with water by Spray dried. Their physicochemical and technological properties were investigated. The SD significantly improved the drug solubility compared to powder and commercial microemulsion Sandimun Neoral. Our results suggested that this type was formed by attaching hydrophilic carriers to the surface of drug without crystal change: formed by microparticles (MP) containing nanoparticles (NP). FTIR data demonstrated no chemical interaction between drug and carrier. The appeared determinated by SEM as a typical hollow microsphere that suggested the formation of nanoparticles in the surface. The microparticle size distribution was 30.64 ± 15.82 mµ. The Z-average particle sizes ranged was 31.23 ± 0.097 nm. Specifications for drying performance, moisture content and cyclosporine were more than 70%, less than 2% and 90-110%, respectively. Three batches were obtained on an industrial scale, and specifications for drying performance, moisture content, cyclosporine, microparticles size and microbiological test were within the range. Thus, the CsA solid dispersion prepared with SLS, Dextran-70 and PEG-4000 with water by Spray dried is a promising candidate for improving the solubility and bioavailability of the poorly water-soluble CsA, and development of oral solid forms.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S191
LATINFARMA 2013 Resúmenes/Abstracts
Estrés Oxidativo y Ozonoterapia / Oxidative Stress and Ozonetherapy
PEO 001: OXIDATIVE STRESS IN OBESES CHILDREN PEO 002: LEVELS OF SOME ANTIOXIDANTS IN CHILDHOOD HYPERTENSION Fernández D, Heredia D, Alfonso J, García J, González E. Alfonso J, Heredia D, Fernández D, Ballestero M, González E. Unidad de Investigaciones Biomédicas. Universidad de Ciencias Médicas de Villa Clara. Carretera de Acueducto y Circunvalación Santa Clara, Villa Clara, Cuba. E- Unidad de Investigaciones Biomédicas. Universidad de Ciencias Médicas de Villa mail: [email protected] Clara. Carretera de Acueducto y Circunvalación Santa Clara, Villa Clara, Cuba. E- mail: [email protected]
Introduction: Children’s obesity has shown an increase during last decades reaching epidemic proportions not only in developed Introduction: A lot of mechanisms of hypertension have been countries. The presence of obesity in adult life is related with multiple characterized in recent years, such as, Reactive Oxygen Species. It has health problems, in particular cardiovascular diseases, hypertension, been found that antioxidant defenses are affected in hypertension. In type 2 diabetes and others like cancer, arthrosis or fatty liver with this work levels of superoxide dismutase (SOD), catalase (CAT), and consequences on morbility and mortality in this group of peoples. reduced glutathione (GSH) are determined in serum of normotense, Current evidences show oxidative stress as a major fact related with pre-hypertensive and hypertensive children according to sex, skin comorbility in obese patients taking accounts the body mass index. colour, age and BMI. Aims: To determine antioxidant enzymatic activity superoxide Material and methods: A number of 407 children participated, 205 dismutasa and catalasa as well as levels of reduced gluthatione and females and 202 males, between 8 and 11 years old. (237) were malonildialdehide in serum samples from 87 obese children and a classified in normotense, (133) in pre-hypertensive and (37) in control group. hypertensive. SOD was determined by means of Marklund´s Method, CAT by Aebi´s Method, GSH by Sedlak´s Method, and total proteins by Material and methods: It was used serum samples from obese Lowry´s Method. Among all studied groups a p< 0.05 was used for the children aged between 5 and 14 years from endocrinology surgery significant difference and a p< 0.10 for the significant moderately belonging to Paediatric Hospital “José Luis Miranda” of Santa Clara, difference. All tests used belong to the SPSS 17.0 package. Villa Clara. Biomolecular determinations were performed by spectophotometric techniques applying biostatistical test to evaluate Results: SOD and GSH were the most affected AO. SOD and GSH differences between both groups. reduction was concentrated in 8-year- old, white and hypertensive children. Male sex was the most affected one in SOD and female sex in Results: It was found statistical differences between obese children GSH, as well as, obese children were just affected in the last one and control group taking account all the antioxidant parameters mentioned before. studied in this work. Obese children showed a significant decrease in superoxide dismutase and catalase activity as well as reduced Conclusions: According to the importance in the system antioxidant, gluthatione. By the other hand it was found increased levels of SOD, GSH, as well as, the results obtained in this study, it is possible the malonildialdehide in this group as evidence of oxidative damage on presence of oxidative damage in hypertensive children. lipids.
Conclusions: Obese children show a compromised antioxidant enzymatic system unable to reach an oxidative equilibrium. This situation can provoke damage mediated by oxygen reactive spices to different cellular biomolecules including lipids.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S192
LATINFARMA 2013 Resúmenes/Abstracts
PEO 003: OXIDATIVE STRESS INDICATORS IN PROGRESIVE PEO 004: GLYCEMIC CONTROL AND OXIDATIVE DAMAGE IN RENAL DISEASE TYPE 2 DIABETES MELLITUS Heredia D, Fernández D, López J, Cruz R, Alfonso J, González E. Céspedes E, Riverón G, Alonso C, Cabrera E, Correa R.
Unidad de Investigaciones Biomédicas. Universidad de Ciencias Médicas de Villa Facultad de Ciencias Médicas “Gral. Calixto García”, La Habana, Cuba. E-mail: Clara. Carretera de Acueducto y Circunvalación Santa Clara, Villa Clara, Cuba. E- [email protected] mail: [email protected]
Introduction: It has been proposed that poor glycemic control, Introduction: Cardiovascular diseases are considering the major microalbuminuria and lipid profile alterations are risk factors for cause of morbi-mortality in patients with chronic renal disease. vascular complications in diabetes mellitus. These changes are Considering that traditional risk factors are not capable to explain this associated with oxidative stress. situation new risks factors are searched to understand the high incidence of cardiovascular events in this group of patients. Among Objective: To analyze whether the changes in the lipid metabolism them an increased oxidative stress could be an important were associated with oxidative damage in type 2 diabetes mellitus. cardiovascular risk in these patients. Methods: A cross-sectional descriptive study was done with 94 type 2 Aims: To study oxidative stress indicators in 100 patients with renal diabetic patients. Lipid profile, thiobarbituric acid reactive products disease (50 in pre dialysis and 50 under haemodialysis treatment) and (TBARS) and carbonyl groups (POX), as markers of lipid peroxidation compare them with a control group in order to determine the and protein oxidation, respectively, were determined. Activities of presence of an altered redox state. antioxidant enzymes were analyzed too. Data were stratified according to glycemic control (glucose <6.2 mmol/L vs glucose 6.2 mmol/L, Material and methods: It was determined enzymatic activity glycated hemoglobin <7% vs glycated hemoglobin 7%) and superoxide dismutase and catalase besides levels of reduced microalbuminuria (microalbuminuria <30 g/L vs microalbuminuria gluthatione and malonildialdehide from 150 serum samples. It was 30 g/L). used spectrophotometric methods in all cases and the results were compared using a statistical software SPSS. Results: High density lipoprotein cholesterol (HDLc) concentration was lower (0.67 ± 0.44 vs. 0.83 ± 0.57 mmol/L), and TBARS and POX Results: It was found a significant reduction of superoxide dismutase concentrations were higher in diabetics with glucose 6.2 mmol/L activity (p=0.021) and reduced glutathione (p=0.031) with a (2.90 ± 3.17 nmol/mL and 2.43 ± 1.93 nmol/mg protein, respectively) significant increase of Malonildialdehide (p=0.000) in patients under in relation to normoglycemic patients (2.46 ± 1.35 nmol/mL and 1.67 ± pre dialysis treatment. By the other hand haemodialysed patients 1.00 nmol/mg protein, respectively) . Triglycerides (TG) were showed reductions in superoxide dismutase and catalase activity significantly higher in conditions of poor glycemic control. It was (p=0.000) and (p=0.040) and reduced gluthatione (p=0.033) along verified a positive association between diabetes duration and TBARS with a significant increase of malonildialdehide (p=0.000). (r=0.271, p=0.008), and there was a negatively correlation between Conclusions: A progressive renal damage is related with an altered TBARS and HDLc levels (r= -0.449, p=0.000). redox state as consequence of a reduced antioxidant enzymatic system The highest TBARS and POX levels were observed in patients with poor that lead to oxidative damage to lipids. glycemic control but only TBARS was significantly increased in diabetic patients with microalbuminuria. Conclusions: The lowest concentrations of HDLc in diabetic patients as well as the highest concentration of triglycerides in diabetics with poor glycemic control contribute to lipid peroxidation, in correspondence with duration of the disease.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S193
LATINFARMA 2013 Resúmenes/Abstracts
PEO 005: PHENOLIC CONTENT AND IN VITRO ANTIOXIDANT PEO 006: EVALUATION IN HIV-INFECTED PATIENTS OF ACTIVITY OF Pleurotus SP EXTRACTS ANTIRETROVIRAL CONCENTRATION, REDOX INDEXES AND PROGRESSION MARKERS ON BLOOD SAMPLES Beltrán Y, Morris H, Batista P, Llauradó G, Quevedo Y, Lebeque Y, Perraud I Gravier R, Pérez D, Hernández D, Bermúdez Y, Tarinas A, Gil L.
Departamento de Biología. Facultad de Ciencias Naturales, Universidad de Instituto de Medicina Tropical “Pedro Kourí”, Autopista Novia del Mediodía Km. 6 Oriente. Avenida Patricio Lumumba s/n, Santiago de Cuba, Cuba. E-mail: ½, La Habana, Cuba. E-mail: [email protected] [email protected]
Introduction: Human immunodeficiency virus (HIV) infection is Introduction: Pleurotus sp. is a genus of higher fungi widely accompanied by severe metabolic and immunological dysfunctions. It distributed worldwide comprising edible and medicinal species of is generally accepted that oxidative stress is involved in HIV infection. great economical value. The limited knowledge of the phytochemical However, the role in oxidative balance of Highly Active Antiretroviral nature of compounds contained extracts from mycelium and fruiting Therapy (HAART) is still debated. This study assessed the effect of one bodies of Pleurotus and the insufficient experimental evidences of their HAART combination (zidovudine/lamivudine/nevirapine) on redox antioxidant pharmacological activity limit the development of indicators and progression markers of disease. preparations enriched in bioactive metabolites with therapeutical potentialities. Methods: Eighty HIV subjects (40 had no taking and 40 are taking HAART during 6 months) and 40 voluntaries which no showed Material and methods: The polyphenol content and the in vitro serological evidences for HIV were followed for 6 months. Peroxidation antioxidant activity of Pleurotus sp aqueous extracts (mycelium and potential (PP), glutathione, malondialdehyde, plasma lipid peroxides, fruiting bodies) and extracts from fruiting bodies of Pleurotus sp superoxide dismutase (SOD), catalase (CAT), advanced oxidation obtained with solvents of different polarity: n-hexane, ethyl acetate, protein products, viral load (VL) and CD4 lymphocytes T subsets (CD4) acetone, ethanol and water, with the assay radical scavenging DPPH were measured at baseline and at 6 months. were characterized in the present work. Results: The statistical analysis showed significantly modified values Results and conclusions: : The aqueous extracts from mycelium and (p <0.05) in all redox indexes at 6 months compared to the initiation of fruiting bodies have antioxidant properties demonstrated in assays of treatment (except in CAT activity and PP). The comparison between DPPHA. In this sense, the mycelial extract gave a better response in the HIV seronegative voluntaries and HIV patients groups showed scavenging of this radical. On the other hands , phenolic compounds significant differences (p <0.05) in all redox indexes (except in activity were detected in all five extracts of Pleurotus sp obtained, however the of SOD). Not significant differences were found between HIV-infected highest concentrations were observed in more polar solvents (water patients groups (with and without HAART) respect CD4. The seventy and ethanol) with 138.4 y 86.37 mg/100 g of values , dry weight , eight percent of patients receiving treatment showed a viral load respectively (p<0.05) values . These preparations are potential reduction. candidates for the design of functional foods, dietetic supplements or medicines useful in the management of diseases caused by oxidative Conclusion: This HAART combination increase oxidative stress in HIV- stress. infected patients beside its therapeutical benefits.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S194
LATINFARMA 2013 Resúmenes/Abstracts
PEO 007: ANTIOXIDANT ACTIVITY OF THE EXTRACTS OF PEO 008: ANTIOXIDANT ACTIVITY OF FLAVONOID – RICH THE LEAVES OF Terminalia muelleri FRACTION FROM Dichrostachys cinerea (MIMOSACEAE) LEAVES González Pérez M, Hijuelo Y, Hernández Sosa E, Perera Córdoba W, Pallo Hill A. Ribalta V, Torres L, Hernández E, Sueiro M, Armas Y, Ruz V.
Departamento de Biología, Facultad de Ciencias Naturales, Universidad de Departamento de Farmacia, Facultad de Química y Farmacia. Universidad Central Oriente. Patricio Lumumba s/n CP90500 Santiago de Cuba, Cuba. E-mail: de Las Villas. Santa Clara, Villa Clara, Cuba. E-mail: [email protected] [email protected]
Introduction: The aim of this study was to evaluate the “in vitro” Terminalia muelleri has been used traditionally in the treatment of antioxidant properties of a flavonoid-rich fraction of D. cinerea. various diseases. This study determines to the abundance of phenolic concentration and antioxidant capacity of this plant. The extraction Material y methods: Plant material: Leaves were collected in the was performed using 25 g of leaves and fruits wiht solvents of different forest surrounding Botanical Garden of Central University of Las Villas. polarity (water, chloroform, ethanol, methanol and n-hexane). The Plant sample was identify as Dichrostachys cinerea (Mimosaceae) by total phenols concentration obtained was determined by the Folin Orestes R. Mendez a taxonomic expert of this institution and deposited Ciocalteu method. The ethanol extracts (2) were used to evaluate the under register code UCLV- 9493. antioxidant activity by front DPPH and ORAC radicals. Extracting the Phytochemical procedure: Dry powder of leaves (30 g) of the plant was highest yield was obtained for the chloroform and less to n-hexane extracted with methanol (80%) using Soxhlet apparatus. The solvent showed the phenol concentration. The species presented a total phenol was then removed under reduced pressure to obtain the residue. After concentration greater than several of the species studied as removal of the solvent, the residue was dissolved in water and antioxidant capacity. subsequently partitioned with petroleum eter, ethyl acetate. The ethyl acetate fraction was evaporated under reduced pressure and concentrated in vacuum to obtain the flavonoids-rich fraction. Antioxidant properties of D. cinerea: The DPPH method was used as previous reported (Ohinishi, 1994) with slight modifications. Different doses of leaves of flavonoid-rich fraction were tested; rutin and ascorbic acid were used as positive control. Total antioxidant activity and reducing power were used to evaluate antioxidant activities too. Results: Phytochemical screening: The positive result was for flavonoids, coumarins, tannins and steroids in the flavonoid-rich fraction of D. cinerea leaves. Antioxidant activity: The flavonoid-rich fraction from D. cinerea leaves showed a powerful antioxidant activity. Conclusions: In conclusion this study showed as first time the powerful antioxidant activity of flavonoid-rich fraction of D. cinerea extracts and demonstrate that this plant possess potential health benefits on different diseases related with oxidative stress.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S195
LATINFARMA 2013 Resúmenes/Abstracts
PEO 009: URIC ACID AND LIPID PEROXIDATION IN PEO 010: EXPERIMENTAL EVALUATION OF 5- HYPERTENSIVE PATIENTS WITH CARDIOVASCULAR AMYNOSALICYLIC ACID AS A FREE RADICAL SCAVENGER DISEASE AND MYELOPEROXIDASE INHIBITOR, IN A TYPE 2 DIABETES MELLITUS MODEL Peña M, Céspedes E, Rodríguez K, Guerrero A, Olivares MC, Martínez D. Alemán González Duhart D, Tamay Cach F, Rosales Hernández MC, Instituto de Neurología y Neurocirugía, Ave. Universidad y J, La Habana, Cuba. E- mail: [email protected] Correa Basurto J, Mendieta Wejebe JE. Laboratorio de Biofísica y Biocatálisis, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n Colonia Casco de Santo Introduction: Oxidative stress and serum uric acid levels have been Tomás, México DF. E-mail: [email protected] associated with arterial Hypertension and Cardiovascular disease (CVD), but the importance of these associations remains controversial. Introduction: Type 2 diabetes mellitus (DM2) has been associated to Objective: To analyze the behavior of the uric acid and lipid oxidative stress due to different enzymatic systems such as peroxidation in hypertensive patients suffering from cardiovascular myeloperoxidase (MPO), having as a major consequence micro and disease. macro vascular complications which can lead patients to death. Methods: Serum uric acid, total cholesterol, triglycerides, and Aim: To evaluate in vitro and ex vivo 5-aminosalicylic acid (5-ASA), as thiobarbituricacid reactive products (TBARS) were determined in 80 a free radical scavenger and MPO inhibitor. hypertensive people (25 with CVD), 14 with CVD and 38 healthy people. The groups were stratified according to median of the uric acid Material and methods: 5-ASA was tested for antioxidant activity (300.50 mol/L). Low and high uric acid groups were analyzed. using the DPPH assay, ABTS technique, and FRAP assay. It was also tested as MPO inhibitor using the O-dianisidine assay. The compound Results: The lowest concentration of uric acid, cholesterol and TBARS was administrated to male Wistar rats pre-treated with nicotinamide were present in healthy people. There was hyperuricemia in some and streptozotocin for the induction of the model. Ex vivo, MDA and people of each group. Uric acid did not differ in hypertensive patients GSH in pancreas were calculated, so as inhibition of MPO and FRAP with CVD in relationship with those that did not present CVD, neither assay in plasma. among the non hypertensive with and without CVD, although in hypertensive men with CVD the uric acid levels are major compared to Results: 5-ASA had a good percentage of antioxidant activity in vitro other groups. There was a positive correlation between uric acid compared to the pattern in the corresponding assay. For the inhibition concentrations and systolic blood pressure. TBARS were not different assay, 5-ASA showed an IC50 of 0.45 µM. Finally, it was demonstrated among patients. Total cholesterol and TBARS were significantly that 5-ASA diminishes MDA levels, increases GSH, and inhibits associated in each group. Uric acid and TBARS were associated in plasmatic MPO. There was no significant difference among the groups hypertensive patients without CVD. for the FRAP assay. TBARS was lower in healthy women when median was 300.50 Conclusions: 5-ASA can be used as a coadjuvant in the treatment of mol/L, and there was a similar result with uric acid >300.50 mol/L. DM2 in order to prevent future micro and macro vascular However, TBARS was superior in hypertensive women and men in low complications, due to its antioxidant and MPO inhibition activities. uric acid group and there was not an increment of the damage with high concentration of uric acid. Conclusions: Uric acid was increased in hypertensive and CVD but there was not more incraesed in CVD. Lipid peroxidation was not more increased when there were high uric acid concentrations. The imbalance redox in hypertensive was not more severe in presence of CVD.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S196
LATINFARMA 2013 Resúmenes/Abstracts
PEO 011: ANXIOLYTIC EFFECT AND ANTIOXIDANT PEO 012: VIRTUAL SCREENING TO PREDICT THE POTENTIAL OF A SEMI-SYNTHETIC DERIVATIVE OF CLASTOGENIC ACTIVITY OF PHENOLIC ACIDS LIMONENE Guardado E, Matos MJ, Castro R, Santana L, Uriarte E, Molina E. Cardoso de Almeida AA1, Fonseca de Carvalho RR1, da Silva Oliveira J2, Pergentino de Sousa D3 and Mendes de Freitas R.1 Universidad de Camagüey “Ignacio Agramonte y Loynaz”, Camagüey, Cuba. E- mail: [email protected] 1Post-graduate Program in Biotechnology, Federal University of Piauí, CEP 64.049-550, Teresina, Piauí, Brazil. 2Graduate course in Pharmacy, Federal University of Piauí, CEP 64.049-550, Teresina, Piauí, Brazil. Phenolic acids have been reported to exert multiple biological effects, 3Department of Physiology, Federal University of Paraíba, CEP 58.051-900, João including their activity as pro-oxidants. Structural alerts to identify the Pessoa, Paraíba, Brazil. clastogenic activity of two important groups of phenolic acids (benzoic and cinnamic acids) with pro-oxidant activity were determined. The Introduction: Oxidation is a metabolic process that leads to methodology was based on a quantitative structure–activity production of energy in cells. However, the oxygen metabolism in relationship (QSAR) study. It was developed a virtual screening living cells also leads to production of free radicals called oxidants and, method for a clastogenic model using the topological substructural if not controlled, can cause extensive damage. The present study molecular design (TOPS-MODE) approach. The model has presented a evaluated the anxiolytic activity of the (+)-limonene epoxide through suitable probability of good classification for the external prediction the test to hide the ball and investigated its antioxidant potential in data set. Therefore, it was possible to establish the structural criteria vitro and in vivo on hippocampus of adult mice. for maximal clastogenicity (chromosomal aberrations) of pro-oxidant Material and methods: For the analyzes antioxidants in vivo mice reported phenolic acids. These criteria were: presence of methoxy were treated with 0.05% Tween 80 in saline dissolved 0.9% (or), and/or hydroxyl substitutions on the benzene ring and polarity of ascorbic acid 250 mg/kg (or) and (+)-limonene epoxide at doses 25, 50 these substituents. Fragments calculation remarked the negative and 75 mg/kg, (or). contribution for the activity of the alkyl chains and the positive contribution when the phenolic acids are esterified or substituted with Results: The results suggest that the anxiolytic effect of (+)-limonene polar groups such as hydroxyl groups, either asymmetric or epoxide, being observed a reduction in the number of hidden levels in symmetrically. In summary, the apolar regions of phenolic acid groups treated with (+)-limonene epoxide at doses of 25, 50 and 75 derivatives contributed negatively to the activity, while the polar mg/kg (or) and diazepam (2 mg/kg, i.p) when compared to vehicle, its groups favored it. This study can represents an interesting tool to reduction was observed after treatment with a single and repeated better understand the properties of natural substances in food, and doses, reinforcing the hypothesis that its terpenoid present anxiolytic also in the development of functional foods or nutraceuticals and drug effect. design. Conclusions: The results demonstrate an in vivo antioxidant effective 50% inhibitory concentration of 0.7342, 1.296 and 1.169 g/mL against the formation of nitrite ion, hydroxyl radical and reactive substances to thiobarbituric acid. (+)-Limonene epoxide treatment reduced the lipid peroxidation level and nitrite content, suggesting an antioxidant role in vivo since it was able to reduce the formation of reactive species derived from oxygen and nitrogen. Furthermore, the (+)-limone0ne epoxide increased antioxidant enzymatic activities (catalase and superoxide dismutase in mice hippocampus, suggesting that its antioxidant role may be due to modulatory effects in activity of these enzymes.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S197
LATINFARMA 2013 Resúmenes/Abstracts
PEO 013: RECOVERY FROM IRON DEFICIENCY ANEMIA WITH PEO 014: DETERMINATION OF DPPH FREE RADICAL DIFFERENT IRON SOURCE: EFFECTS ON LIPID SCAVENGING ACTIVITY OF VIMANG CONSTITUENTS PEROXIDATION AND ANTIOXIDANT ENZYMATIC DEFENSE Nuevas Paz L, Pardo Andreu GL, Louro Provedo Y, Acosta Esquijarosa García Y, Díaz-Castro J, López-Aliaga I, Alférez MJM, Ramos A, Hijano S, J. González R, Campos MS. Centro Nacional de Genética Médica de Cuba. Ave 31 esq 146 Rpto Cubanacán, Centro Nacional de Biopreparados, Bejucal, Mayabeque, Cuba. E-mail: Playa, La Habana, Cuba. [email protected]
Introduction: Vimang is the brand name of an aqueous extract of the Most of the oral Fe preparations contain ferrous salts, characterized by mango (Mangifera indica L.) stem bark extract (MSBE) of selected a low absorption and by the damage in the intestinal mucous in the half varieties. A phytochemical investigation of mango stem bark extract of patients. Trofin is a rich heme Fe source obtained by a partial has led to the isolation of xanthones mangiferin and homomangiferin hydrolysated of bovine blood, honey and propolis. Scarce information is and seven phenolic constituents: gallic acid (I), 3,4-dihydroxy benzoic available about the recovery of anemia with different Fe treatments acid (II), gallic acid propyl ester (III), (+)-catechin (VI), (-)-epicatechin (non heme, heme and mixture) on status oxidative-antioxidant. The aim (VII) and benzoic acid (VIII). The main components of Vimang is of this study was to assess the effects on lipid peroxidation and mangiferin, a compound witch several pharmacological activities. antioxidant defense in liver, erythrocytes, duodenal mucosa and plasma Previous experiments on that extract and have shown that it has during the recovery of anemic rat. Weanling female rat where divided antioxidant, analgesic, and anti-inflammatory properties. Stable free in two groups: a control group (n = 10) receiving a normal Fe diet with radical species such as 1,1-diphenyl- 2-picrylhydrazyl (DPPH•) is often FeSO4 (45.73 mg/kg) and an anemic group (n = 30) receiving a low-Fe used for the evaluation of the general radical scavenging capabilities of diet (6.92 mg/kg) for 45 days. For the next thirty days the anemic rats various antioxidants. was fed with FeSO4 (F diet), Trofin (T diet) or FeSO4 + Trofin (FT diet) Material and methods: In this work the antioxidant properties of for thirty days. The three anemic groups showed a positive these compounds and 30 industrial batches of Vimang were evaluated hematological recovery. After Fe replenishment, lipid peroxidation in using the DPPH method. duodenal mucosa was lower in anemic rats fed T and FT diets. SOD activity in duodenal mucosa was impaired by the Fe-deficiency (being Results and conclusions: The results shown that galic acid and propil higher in anemic for F and T diet than in control rats). The highest GPx gallate are the compounds with the highest antioxidant activity activity was observed in liver and erythrocyte cytosol of anemic rats followed by 3,4 dihydroxybenzoic acid, (-)-epicatechin, (+)-catechin, compared to control group, and no differences between anemic groups mangiferin, benzoic acid and homomangiferin in this order. The were recorded. However, the GPx levels in plasma and scrape of antioxidant activity was concentration dependant for each compound. duodenal mucosa were higher for F diet than in the others two anemic The results were used to establish the correlation between the groups. In conclusion, diets containing heme Fe (T and FT diets) in concentration mangiferin with the contents of total polyphenols and the anemic rats improve antioxidant/oxidative balance in duodenal total antioxidant activity of Vimang. They are a significative correlation mucosa. The recovery of anemia with heme or the mixture of between the mangiferin concentration and the antioxidant activities of heme/non-heme could be alternatives therapy to palliate the Fe- Vimang. deficiency.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S198
LATINFARMA 2013 Resúmenes/Abstracts
PEO 015: Phalaris canariensis EFFECT IN THE PREVENTION Results: the weight increased to 70% in rats with MS and the BP about AND CONTROL OF METABOLIC SYNDROME INDUCED FOR 140%. Glucose was increased 335%, with an initial value of 84 ± 4 HYPOCALORIC DIET. MODULATION OXIDATIVE STRESS IN mg/dL and reaching a value of 366 ± 25 mg/dL after 24 weeks. The RAT groups with therapy are below of problem group of 126 ± 11 mg/dL and prevention group with an average of 86 ± 9 mg/dL. Concerning the Alvarado Acosta JL, Noriega Alvarado RG and Yahuaca Mendoza P. percentage of glycohemoglobin we can see in the group where it was given only hypercaloric diet, the value was16.5 ± 1.5%, resulting in Doctorado en Farmacología de la Unidad Académica de Medicina Humana. 166% higher than the control group, its average percentage is 6 ± Universidad Autónoma de Zacatecas.Zacatecas, México. E-mail: 0.3%, in the treatment groups was of 7.5 ± 0.3%, representing 120% [email protected] below the problem group and prevention group show 4.3 ± 0.1%, the values of triglycerides we can observe an increase of 446% with respect to control. In the parameters of lipoperoxidation was increased Introduction: Metabolic syndrome (MS) is a combination of several in all tissues that were studied. Metabolic changes that occur with MS medical conditions that put them at risk of developing heart disease were successfully modulated by managing Phalaris canariensis, was and diabetes, concomitant with central obesity and generally insulin observed conclusively that there is a decrease in blood pressure, resistance. These chronic diseases are characterized by release of free glucose, triglycerides and oxidative damage (peroxidation), treatment radicals (FR); however, few has been used antioxidants in its control groups closely resemble those of the control animals. and has not considered the use of herbs high in antioxidants. The objective was to evaluate the antioxidant effect of Phalaris canariensis Conclusions: These results indicate that therapy with a natural in the prevention and control of experimental MS. antioxidant may be an effective control in the metabolic syndrome and prevent its complications, such that it can be used as an alternative Methodology: in Wistar rats was induced SM with phytotherapy. hypercholesterolemic diet, providing for 24 weeks. They were divided into groups: Control, SM, treatment and prevention. Were monitored weight and blood pressure (BP), as well as metabolic indicators (glucose, glycated hemoglobin, and triglycerides), lipid peroxidation oxidative stress in liver, pancreas, kidney, and heart.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S199
LATINFARMA 2013 Resúmenes/Abstracts
Farmacología de Productos Naturales / Pharmacology of Natural Products
PPN 001: Cardiospermum corindum (SAPINDACEAE) PPN 002: Bidens pilosa L. (ASTERACEAE) INHIBITS INHIBITS HYPERACTIVITY GASTROINTESTINAL ON RATS HYPERACTIVITY GASTROINTESTINAL ON RATS IN VIVO IN VIVO AND IN VITRO AND IN VITRO Silva VA, Nascimento PF, Silva FL, Barbosa-Filho JM, Nouailhetas LA, Costa LA, Lima PCO, Silva FL, Barbosa-Filho JM, Nouailhetas LA, Silva Silva JLV. JLV.
UNINOVE, UNIFESP, São Paulo-SP, UFPB, João pessoa-PB, Brasil. E-mail: UNINOVE, UNIFESP, São Paulo-SP, UFPB, João pessoa-PB, Brasil. E-mail: [email protected] [email protected].
Introduction: Cardiospermum corindum is known as “balãozinho” and Introduction: Bidens pilosa is known as “picão-preto” and is a weed is found mainly in Cerrado biome (Brazil). There is not effects reported found in Brazil. Its aerial parts are used to treat pain, diabetes, for species, thus the aim of this study was to investigate the effects of infection and inflammation, but there is not reported of the stalk for the ethanol crude extract obtained from the aerial parts of C. corindum species, thus the aim of this study was to investigate the effects of the (Cc-EtOH) on gastric ulcer ethanol-induced in vivo and ileum ethanol crude extract obtained from the stalk of B. pilosa (Bp-EtOH) on contractile response-induced in vitro, experimentally in rats. gastric ulcer ethanol-induced in vivo and ileum contractile response- induced in vitro, experimentally in rats. Material and methods: Wistar rats (200-250 g), in fasted (24h), were treated with Cc-EtOH (50, 150 and 500 mg/kg, o.r.) or omeprazole (4 Matherial and methods: Wistar rats (200-250 g), in fasted (24 h), mg/kg, i.p.) following ethanol P.A (1 mL/kg, o.r.). The ulcerative lesion were treated with Bp-EtOH (500 mg/kg, o.r.) or omeprazole (4 mg/kg, area (ULA) of each stomach was calculated (mm2) and compared. The i.p.) following ethanol P.A (1 mL/kg, o.r.). The ulcerative lesion area antispasmodic activity was investigated on ileum isolated from rats (ULA) of each stomach was calculated (mm2) and compared. The were fasting (24h) in glass baths containing Krebs modified solution, at antispasmodic activity was investigated on ileum isolated from rats 37°C, 1g resting tension, bubbled O2. The contractions were registered were fasting (24h) in glass baths containing Krebs modified solution, at by force transducer and increased by addition of KCl (40mM) or CCh 37°C, 1 g resting tension, bubbled O2. The contractions were registered (1M) and verified in presence of Cc-EtOH (27, 81, 243 or 500 μg/mL). by force transducer and increased by addition of KCl (40 mM) or CCh The p<0.05 values from Student “t” test or ANOVA were considered (1 M) and verified in presence of Bp-EtOH (500 μg/mL). The p<0.05 significant. All procedures were approved for the Ethical Committee. values from Student “t” test or ANOVA were considered significant. All procedures were approved for the Ethical Committee. Results: The ethanol promoted damage gastric (UHA= 367.5 ± 89.3 mm2, n=4) that was reverted in a dose-dependent manner and Results: The ethanol promoted damage gastric (UHA= 367.5 ± 89.3 significantly (p<0.01) by Cc-EtOH (ULA= 210 ± 55.8; 119.2 ± 39.3 and mm2, n=4) that was reverted in a dose-dependent manner and 47.7 ± 13.2 mm2, respectively) as soon as omeprazole (ULA= 145.7 ± significantly (p<0.05) by Bp-EtOH (ULA= 96.3 ± 11.8 mm2, n=3) as 20 mm2, n=6). Also, Cc-EtOH (27-500 μg/mL) impaired in a soon as omeprazole (ULA= 145.7 ± 20 mm2, n=6). Also, Bp-EtOH (500 concentration-dependent and potentially (p<0.01) manner the ileum μg/mL) impaired in a concentration-dependent and potentially (n=4) pre-contracted both KCl (Emax= 97.9 ± 2.0; 55.2 ± 5.3; 41.9 ± 3.8 (p<0.05) manner the ileum (n=3) pre-contracted both KCl (Emax= 74.9 ± and 26.9 ± 7.3%, respectively) or CCh (Emax= 78.1 ± 8.6; 75.4 ± 5.8; 50.6 14.3%) or CCh (Emax= 73.3 ± 2.8%). ± 3.4 and 42.8 ± 3.9%, respectively). Conclusions: These results demonstrate that stalks from Bidens pilosa, Conclusions: These results demonstrate that the aerial parts from as soon as its leaves, have actives principles and are able to inhibit Cardiospermum corindum have actives principles and are able to inhibit gastrointestinal activity. gastrointestinal activity.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S200
LATINFARMA 2013 Resúmenes/Abstracts
PPN 003: INHIBITORY EFFECT FROM HYDROMETHANOLIC PPN 004: HYDROMETHANOLIC EXTRACT OF Struthanthus EXTRACT OF Struthanthus venetus (BLUME) LEAVES,ON venetus (BLUME) LEAVES ATTENUATES THE METABOLIC THE PROLIFERATION OF HUMAN BREAST CANCER CELLS SYNDROME INDUCED BY HIGH FRUCTOSE DIET IN WISTAR (MCF-7) IN CULTURE RATS Lorenzana- Jiménez M, Magos Guerrero GA, Medina Jiménez M, Ávila Lorenzana-Jiménez M, Magos Guerrero GA, MendiolaAlmaraz L, ME, Figueroa A and Lemini C. Escobar Ramirez JL.
Department of Pharmacology, School of Medicine, University National Department of Pharmacology, School of Medicine, University National Autonomous of Mexico, Mexico, D.F. C.P 04510. E-mail: [email protected] Autonomous of Mexico, Mexico, D.F. C.P 04510. E mail: [email protected]
Introduction: A methanolic extract from Struthanthus venetus (Sv), Introduction: In previous studies we have shown that the methanolic epiphyte plant of Lorantaceae Family, showed cytotoxic and mitotic extract from Struthanthus venetus (Sv) leaves, known as "graft or effects on vascular endothelial cells and myocardial fibers of adult male matapalo", induced hypotensive and cardiotoxic effects over the guinea pig Hartley strain. anesthetized rats. Moreover, the same extract also significantly decreased triglycerides and cholesterol blood levels. Supporting the Objective: The aim of this study was to evaluate the effect of an extract use of botanical extracts as botanical drugs, in the present study we hydromethanolic of Sv (EHM-Sv) on the proliferation of MCF-7 human examined the effect of a hydromethanolic extract from Sv leaves on breast cancer, using the E-screen method modified by Körner. blood pressure, lipid profiles, and glucose of rats with metabolic Material and methods: MCF-7 cells were cultured in Dulbecco´s syndrome induced by high-fructose diet. Modified Eagle Medium (DMEM) with bovine fetal serum free of Material and methods: Two adult rat groups were studied: a control hormones and treated for six consecutive days with concentrations of group received regular rodent Chow (Purina) and drinking water ad - 0.5, 5 or 50 ng/mL of EHM-Sv, in the absence and in the presence of 10 libitum and other fructose group was fed on 20% fructose diet and 12 -11 -10 -4 , 10 or 10 M estradiol (E2) or 1.7 x 10 M of fulvestrant 20% solution in drinking water. (ICI182780) or tamoxifen (Tmx). In all experiments was used as control group, untreated cells. Results: After 8 weeks the fructose group developed signs of metabolic syndrome, including elevated abdominal fat deposition, abnormal Results: The results show that E2produced dose-dependent plasma lipid profile, and hypertension. This last group showed that the proliferative effect on MCF-7 cells that was antagonized by ICI 182780 hydromethanolic extract administered orally (310 mg/kg) everyday and Tmx. However, the EHM-Sv inhibits cell proliferation and during two months, produces antihypertriglyceridemic and significantly antagonizes the proliferative effects of E2, ICI and Tmx. antihypertensive effects. In this last effect probably the polyphenol The composition chemical of EHM-Sv shows the presence of identified to NMR 1H and NMR C (CD3OD) as catechin, is the active flavonoids, which produced beneficial effects in the treatment of compound. human breast cancer. Conclusions: These results suggest that the hydromethanolic extract Conclusions: These findings indicate the need for further of Sv contains polyphenols with potential properties to treatment of phytochemical-pharmacological studies of EHMSv for confirm if this metabolic syndrome, which need further investigation. herbal product has antineoplastic activity.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S201
LATINFARMA 2013 Resúmenes/Abstracts
PPN 005: ANTIHYPERTENSIVE AND VASORELAXANT PPN 006: USE OF TRADITIONAL MEDICINE AS AN EFFECTS OF A METHANOLIC EXTRACT FROM ALTERNATIVE METHOD FOR THE TREATMENT OF Chiranthodendron pentadactylon (LARREAT) IN RATS DIABETES MELLITUS IN PATIENTS IN THE COMMUNITY OF YAXCABÁ, YUCATÁN, MEXICO Magos Guerrero GA, Lorenzana-Jiménez M, Mendiola Almaraz L, Escobar Ramirez JL. Cen J, Ortiz R, Ramírez M, Torres J.
Department of Pharmacology, School of Medicine, University National Facultad de Química, Universidad Autónoma de Yucatán (UADY), Mérida, Autonomous of Mexico, Mexico, D.F. C.P 04510. E mail: Yucatán, México. E-mail: [email protected] [email protected]
Introduction: Traditional medicine consists of all the knowledge and Introduction: Chiranthodendron pentadactylon (Chp) known as “flor empirical practices transmitted from generation to generation. It is de manita” or “macpaxochitl”is a plant commonly used in folk medicine used to prevent or eradicate mental of physical illnesses. Currently, it to control heart disease and gastrointestinal disorders such as diarrhea is still being used worldwide with medicinal plants as its main and dysentery. Today, this plant for its medicinal properties is a therapeutic resources which have had a growing use for the treatment species threatened with extinction. of diabetes. Objective: Aim of the study is assess the cardiovascular activity which Material and procedures: An observational, prospective and cross- supports the therapeutic use of Chp to treat arterial hypertension. sectional study was carried out. A questionnaire was designed and Material and methods: a methanolic extract from Chp flowers given to the people with diabetes in Yaxcabá, to identify patients who (MEChpF), was evaluated on blood pressure of normotensive and use traditional medicine. Those patients were given another hypertensive rats, in aortic rings preparation (ARP) and on perfused questionnaire in order to know which medicinal plants are used. The mesenteric vascular bed preparation (PMVBP). statistical population had HbA1c at the beginning and three months later. The data was contrasted with a control group of patients who Results: Oral doses (100 mg/kg) or an intravenous dose (31 mg/kg) of said not to have used medicinal plants. MEChpF induced hypotensive and antihypertensive effects in normotensive and hypertensive rats, respectively. MEChpF shows Results: 165 people with diabetes were given a questionnaire. Only 15 vasorelaxation endothelium-dependent on the contraction induced by people use medicinal plants. 46.66% consumes ‘chaya’ (Cnidoscolus norepinephrine in ARP and PMVBP. This vasorelaxation is mediated by chayamansa) and the rest uses a wide range of plants. During the test nitric oxide because it is inhibited by N-nitro-L-Arginine Methyl Esther. period, the levels of glucose and HbA1c in the focus group were A flavonoid was isolated by bioassay-guided purification, and showed reduced by 14.63% and 19.17% respectively, whereas the control moderate cardiovascular activity. group 14.65% and 13.07%. 33.33% consumes ‘chaya’ every day and their levels of glucose and HbA1c reduced by 30.81% and 34.92% Conclusions: The results of the present study lend some support to respectively. 66.67% consumes ‘chaya’ once or twice a week and their the popular report for the medicinal use of the flowers of Chp in the level were reduced by 26.73% and 4.81%. control of blood pressure. However, the failure to identify all substances with cardiovascular activity, and the quick loss of life of this Conclusions: The focus group obtained better results by diminishing plant, can negatively affect the discovery of new drugs. their levels of HbA1c in contrast with the control group. The patients who consume ‘chaya’ every day obtained the most favorable results. This project was supported UNAM, DGAPAIN221010-2 This is supported by the state of the art about ‘the quality of the chaya’ by having Hypoglycemia effects in a dependant dosage manner. This study will allow us to keep track of the focus group and carry out future studies which will evaluate the antidiabetic side effects from the ‘chaya’ in the organism that will allow a right use, ensure its quality and lay the foundations to create phytodrugs in a long term.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S202
LATINFARMA 2013 Resúmenes/Abstracts
PPN 007: DRUG INTERACTIONS OF HERBAL MEDICINES PPN 008: THE ROLE OF Bidens pilosa L. AND Physalis USED IN URUGUAY angulata L. IN OBESE MICE
Moreale J, González T. Ribeiro JR1, Masago F1, Del Ben A1, Machado LO1, Quaglio AE1, Checon J1,2, Diemant G2, Velasquez MC2, Di Stasi LC.1 Biomedical Science Center, Montevideo University, Montevideo, Uruguay. Address: Puntas de Santiago 1604. Tel: (598) 2 604 25 44. Montevideo, Uruguay. 1Laboratory of Phytomedicines, Department of Pharmacology, Institute of E-mail: [email protected] Biosciences, Universidade Estadual Paulista (UNESP), Botucatu/SP, Brazil. E- mail: [email protected] 2Chemyunion Química Ltda – Research and Development – Sorocaba/SP, Brazil. Introduction: According to WHO, 80% of the world population uses herbal medicines (HM). In practice this means a segment uncontrolled drug therapy, with significant growth in most countries, with potential Introduction: Obesity and overweight are chronic inflammatory therapeutic effects, toxic and/or interactions. Information of disease that has been considered one of the most serious public health interactions between HM and drugs are often based on observational problems in the world. Several ethno pharmacological studies indicate studies, due to controlled clinical trials (CCTs) in humans are generally plant species for treatment of several disorders, such as obesity. not available. Therefore, the aim of this study was to evaluate the effects of Bidens pilosa L. and Physalis angulata L. in mice with high fat diet induced Objectives: Know the main HM available in the market of Uruguay. obesity (DIO). Researching about the legal framework regarding their registration. Analyze the evidence for clinically relevant drug interactions of yerba Material and methods: We have divided the animals into three mate (Ilex paraguariensis), black tea (Camellia sinensis), HM and groups: Non obese, Obese, Pair Feeding, and two treatments groups: tisanes (or infusions) sold “over the counter”. Bidens and Physalis were treated with each plant per os.for 21 days, all n= 8. Consumption and weight was measuring daily. After the Methodology: We performed an observational, descriptive literature treatment, samples were collected for quantification of serum: C- review type. First, we request an interview with the competent reactive protein and Leptin were measured by ELISA; and Adiponectin authority in the field of HM at “Registering Vegetable Specialties” of the gene expression in adipose tissue by qRT-PCR. All data were analyzed Drug Department of Ministry of Public Health (MPH). Secondly, we by ANOVA with Tukey post test, p < 0.05. conducted a systematic search for information in an electronic database (PubMed), including all articles on herbal-drug interactions Results and conclusion: The group B. pilosa L. decreased CRP (25.7 ± with clinical implications, and excluded articles of theoretical and/or 1.49 vs. 34.8 ± 1.23) and Leptin (956.43 ± 617.09 vs. 5864.6 ± 1875.4); no clinical relevance herbal-drug interactions, “in vitro” and “in vivo” and increased Adiponectin (46.20 ± 6.84 vs. 3.52 ± 1.97). However, animal experiments. group P. angulata L. did not change significantly when compared to the obese in CRP and Leptin, and increased Adiponectin (37.48 ± 11.92 vs. Results: Yerba Mate, Black Tea and aromatic herbs are recorded in 3.52 ± 1.97). According to the results, extract of B. pilosa L. Food Division of Montevideo Municipality. The HM included in demonstrated potential for treatment of obese individuals. composted yerba mate (n=27) and tisanes (n=73) are recorded in the Vegetal Specialities Division of the Medicines Department of the MPH. 69 searches were peformed, and found: 7 case reports, 3 open clinical trials, 2 CCT and 2 literature reviews; about: eight HM, corresponding to Camellia sinensis, Chamomilla recutita, Echinacea spp, Ginkgo biloba, Passiflora spp, Hypericum perforatum, Panax ginseng and Zingiber spp. Drugs involved in the interaction were: antineoplastics, warfarin, etoposide, caffeine, midazolam, talinolol, lorazepam, clozapine, oxycodone, cyclosporine, protease inhibitors, oral contraceptives and imatinib. Conclusions: Use HM is not innocuous. Develop CCTs to study clinical implication of interactions is appropriate and necessary. Patient information on HM that could interact with their medications is necessary. Develop “Phytovigilance” is essential.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S203
LATINFARMA 2013 Resúmenes/Abstracts
PPN 009: CYTOTOXIC ACTIVITY OF AN AVOCADO SEEDS PPN 010: Valeriana officinalis ATTENUATES THE EXTRACT (Persea americana Mill.) IN A PANEL OF CANCER ROTENONE-INDUCED TOXICITY IN Drosophila CELL LINES melanogaster Martínez M, Cortés E, Padilla E, Ramos M del R, Villanueva S and Vargas N, Haigert J, Teixeira J. Winterhalter P. Universidade Federal de Santa Maria, Departamento de Química, Avenida Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco, Roraima 1000, Bairro Camobi, CEP 97105-900 - Santa Maria, RS, Brazil. E-mail: AC. Av. Normalistas 800, Col. Colinas de la Normal. C.P. 44270, Guadalajara, [email protected] Jalisco, México. E-mail: [email protected]
Introduction: It is well known that environmental exposures may Introduction: Avocados (Persea americana Mill.) are very popular and determine the onset of Parkinson´s disease (PD). In this study, we recognized healthy fruits, cultivated in many tropical and subtropical investigated the possible protective effects of plant Valeriana areas of the world. After industrial fruit processing, avocado seed officinalis (V. officinalis) on the toxicity induced by neurotoxin material is generally disposed, although it could be a potential source rotenone in Drosophila melanogaster (D. melanogaster), an alternative for food supplement and medicinal products. In the present study, a animal model amply accepted to study the molecular mechanisms petroleum ether extract of avocado seeds was tested with regard to its involved in neurodegenerative diseases. cytotoxicity, using a panel of cancer cell lines. Material and methods: Adult wild-type flies (both gender) were Material and methods: Non-small cell lung cancer cell line A-549, concomitantly exposed to rotenone (500 µM) and V. officinalis cervicouterine cancer cell line HeLa, hepatocarcinoma cell line HepG2 aqueous extract (10 mg/mL) in the food during 7 days. and prostate adenocarcinoma cell line PC-3 were maintained as a monolayer in DMEM containing 10% fetal bovine serum at 37°C in a Results: Rotenone-fed flies had a worse performance in the negative humidified atmosphere of a 5% (v/v) CO2 in air. Cells were seeded in geotaxis assay (i.e. climbing capability) and open-field test (i.e. 96-well plates and exposed to several petroleum ether extract mobility time) as well as a higher incidence of mortality when concentrations (10 - 100 µg/mL) of the avocado seeds for 24 hours. compared to control group. V. officinalis treatment offered protection Then, MTT was added to each well, dissolved in DMSO after an against these detrimental effects of rotenone. In contrast, the incubation of 4 hours and read at 590 nm. decreased number of crossings observed in the flies exposed to rotenone was not modified by V. officinalis. Rotenone toxicity was also Results: In order to study the possible antineoplasic activity of associated with a marked decrease on the total-thiol content in the avocado seeds extract, in vitro cytotoxic analyses in a panel of cancer homogenates and cell viability of flies, which were reduced by V. cell lines were performed. Petroleum ether extract produced a viability officinalis treatment. Indeed, rotenone exposure caused a significant decrease dependent on the concentration. This effect was found at a increase in the mRNA expression of antioxidant enzymes superoxide concentration as low as 10 µg/mL. In HeLa, PC-3 and HepG2 cell lines, dismutase (SOD) and catalase (CAT) and also in the tyrosine LC50 values of the avocado seeds extract ranged from 60 - 80 µg/mL, hydroxylase gene (TH). The expression of SOD and CAT mRNAs were whereas A-549 cell line was less sensible to the extract, showing a LC50 normalized by V. officinalis treatment. value over 100 µg/mL. Conclusion: Our results suggest that V. officinalis extract was effective Conclusions: Petroleum ether extract from avocado seeds was found to in reducing the toxicity induced by rotenone in D. melonogaster as well be highly toxic against a panel of cancer cell lines. Lipophilic as confirm the utility of this model to investigate potential therapeutic compounds such as acetogenins could be responsible to these effects. strategies on movement disorders, including PD. Avocado seeds, therefore, could represent a source of new bioactive anti-tumor agents.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S204
LATINFARMA 2013 Resúmenes/Abstracts
PPN 011: PRELIMINARY EVALUATIONOF Brassica PPN 012: CONTRIBUTIONS TO THE QUALITY OF MEDICINAL campestris AND Coffea arabica EFFECTS IN OBESITY PLANTS NEGOTIATED IN THE STATE OF RIO DE JANEIRO, BRAZIL Del Ben A1, Machado LO1, Ribeiro JR1, Masago F1, Quaglio AEV1, CheconJ1,2, Diemant G2, Pereda MCV2, Di Stasi LC1. Marques CA, Nascimento AM, Nagashima JY, Vieira FS, Villas LB, Violante FA, Torres JC. 1Laboratory of Phytodrugs. Department of Pharmacology, Institute of Biosciences, UNESP, Botucatu, SP. Brazil. Instituto Federal do Rio de Janeiro (IFRJ). Rua Lúcio Tavares, 1045, Nilópolis, RJ, 2Chemyunion Química Ltda, Department of Research and Development, Brazil. CEP: 26530-060. E-mail: [email protected] Sorocaba, SP, Brasil. E-mail: [email protected]
Medicinal plants are very used by Brazilian population, being easily Introduction: Obesity has been considered one of the most serious found in popular markets. To verify the quality of these products was public health problems of the world, especially for being theme in risk made the authenticity study of feedstocks, secondary metabolites factor form some diseases such as heart disease, diabetes mellitus type detection tests, after thin layer chromatography, labels analysis and II, hypertension and some types of tumors, which are associated with dirt presence. The 34 analyzed samples were obtained in Rio de Janeiro high mortality rates. Several ethnopharmacological studies indicate state. Were analyzed: Ziziphus joazeiro Mart., “sene tea” (Cassia medicinal plants for the treatment of disorders associated with weight angustifolia Vahl. and/or C. acutifolia Del.), two different “slimming gain. Thus, the aim of this investigation was to evaluate the effects of teas”, composed by 13 and 30 species and Ginkgo biloba L. In Z. joazeiro, Brassica campestris L. and Coffea arabica L. extracts in animals with “sene tea” and G. biloba were verified the feedstocks authenticity, but high fat diet-induced obesity. one of Z. joazeiro samples had leaf fragments of another species. In the “sene tea” the samples had, beyond leafs, fragments of stem, fruits and Methods: The animals were divided into 3 groups without treatment: Poaceae leafs. In the “slimming teas”, the most species wasn´t found. non-obese, obese and pair-feeding, and 2 treated groups: C. arabica The fragments ratio of stems and petioles in these teas was high (over and B. campestris that were treated per os for 21 days. Food intake and than 35%), but in the most of species presents the leaves were weight were measured daily. At the end of the procedure, samples of mentioned like the main element. Another species were found too, the adipose tissue were collected to perform the gene expression of probably replacing absent species. The packings and labels revealed aquaporin-7, resistin and neuropeptide Y. Statistical analysis was damages in the “sene tea” and G. biloba, justifying the high percentage performed by ANOVA followed bya post hoc Tukey's test. of humidity found. Insects’ fragments and stones were discovered in Results and conclusion: Animals treated with C. arabica significantly the slimming teas and “sene tea”. The phytochemical tests, after thin reduced the weight even with an increase in consumption and the layer chromatography, in the ethanolic and hexanic extracts revealed genes analyzed had expression similar to non-obese group. Differences the presence of saponins, phenols, tanins, alkaloids, steroids and in consumption and weight loss couldn’t be observed in the treatment triterpenoids in Z. joazeiro, but positive results to flavonoids presence with B. campestris. Furthermore, the genes analyzed showed an occurred in the same sample that had fragments of another species. In increased expression compared to non-obese group. According to the the “sene tea”, was verified the presence of quinones, however, one of results, the extract of C. arabica denotes a promising treatment for the samples showed negative results to glicosides, triterpenes and obesity, decreasing body weight gain even increasing food intake. steroids, another sample revealed negative result to phenols. In the “slimming teas” the many species mentioned like components doesn´t corresponded to variety of secondary metabolites found. The obtained results confirmed the need of more control and supervision of these products.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S205
LATINFARMA 2013 Resúmenes/Abstracts
PPN 013: HYPOGLYCEMIC EFFECT OF SWEET LIME (Citrus PPN 014: ANTI-Helicobacter pylori, ANTI-INFLAMMATORY, limetta) PEEL AND TOXICOLOGICAL EVALUATION OF ROOT EXTRACTS FROM Hippocratea celastroides Padilla E, Villanueva S, Gutiérrez Y, Flores JM and Martínez M. García G, Cardoso-Taketa A, Monroy A, García S, Nuñez P, Escobedo W, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco,
A.C. Normalistas 800, Colinas de la Normal C.P. 44270 Guadalajara, Jal. México. E- Romero I, Villarreal ML. mail: [email protected] Centro de Investigación en Biotecnología, Universidad Autónoma del Estado de Morelos. Av Universidad 1001, Col Chamilpa, Cuernavaca, Morelos 62209, México. Tel +52 777 329 7057, Fax 52 777 329 7030. E-mail: Introduction: The sweet lime peel is a byproduct of the industry fruit [email protected] processing. Previous studies have shown that it contains high amount of dietary fiber and phenolic compounds which could help in the glucose control. In this work, the hypoglycemic activity of sweet lime Introduction: Hippocratea celastroides commonly known as peel was evaluated by both in vitro and in vivo testing. “cancerina” is used in Mexican Traditional Medicine for the treatment of gastric and intestinal infections, inflammation, injuries and gastritis. Material and methods: The sweet lime peel was dehydrated and sieved to produce a meal. Material and methods: A methanolic (MeOH) extract was prepared, and submitted to total acid-base extraction to obtain the ethyl acetate Glucose absorption capacity: The sample was mixed with a given and aqueous fractions. Ear edema was induced in Balb/c mice with 12- glucose concentration and after an incubation period, the glucose O-tetradecanoylphorbol (TPA) in order to study the anti-inflammatory content was measured in the supernatant. Cellulose was utilized as activities of the extract and fractions. The anti H. pylori activity of the control. extract was tested with a broth dilution method (in vitro killing essay). Glucose dialysis retardation index: The sample was placed in a dialysis In vivo acute toxicity was performed in female Balb/c mice by oral membrane with a glucose solution, then it was dialyzed against administration of the extract and fractions at doses ranging from 10 to distilled water, glucose was measured in the dialysate. In vivo, the 5000 mg/kg; while for the subacute study, the extract was given to postprandial hypoglycemic activity was evaluated in mice by male and female Balb/c mice a dose of 2000 mg/kg body weight. administering maltose orally. Simultaneously, sweet lime peel was Animals were observed daily for toxic signs. administered at a concentration of 500 mg/kg body weight; acarbose Results: Compounds of low polarity were identified in the root was used as a control. 30 minutes after treatment, glucose was methanolic (MeOH) extract and aqueous fraction of H. celastroides. measured with a glucometer in blood drawn from the tail vein. Root MeOH extracts as well as aqueous and ethyl acetate (EtOAc) Results: Sweet lime peel showed increased glucose absorption fractions of H. celastroides also showed significant anti-inflammatory capacity compared with cellulose and showed an inhibitory effect on effects. The extract and its aqueous fraction inhibited the growth of H. glucose diffusion, which was maintained for 180 minutes, whereas pylori with a MIC value of 31.5 µg/mL. The oral LD50 values of the cellulose effect remained only for 60 minutes. MeOH extract and of the EtOAc fraction were indeterminable. The LD50 of the aqueous fraction was 1233.33 mg/kg. Under the subacute Regarding the postprandial hypoglycemic activity, results showed that administration, neither mortality nor any signs of toxicity were sweet lime peel regulates the glucose level in maltose loaded mice after observed when the ethanolic (EtOH) root extract was administered. 30 min. These results are better than those reported previously for There were no significant alterations in biochemical parameters. orange peel. Conclusions: The roots of H. celastroides bear pharmacological Conclusions: It is possible that sweet lime peel absorbs glucose by activities that make it promising for the treatment of H. pylori infection increasing the intestinal viscosity. The delay in glucose diffusion could and its inherent chronic inflammation. No signs of toxicity from the postpone its absorption in the gastrointestinal tract. Hypoglycemic plant extracts were observed. Our findings contribute to confirm the activity studies in animals suggest that sweet lime peel could be used ethnopharmacological applications of H. celastroides. for controlling glucose levels in diabetics.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S206
LATINFARMA 2013 Resúmenes/Abstracts
PPN 015: ACUTE TOXICITY AND HYPOCHOLESTEROLAEMIC PPN 016: ANTIDIABETIC ACTIVITY OF Annona cherimola EFFECT OF A HYDROALCOHOLIC EXTRACT OF Eryngium MILL. (ANNONACEAE) ON TYPE 2 DIABETIC RATS heterophyllum IN C57BL/6 MICE Solares JI,1,2 Calzada F1 and Olivares IM.2 Castro-Torres IG, Martínez-Vázquez M. 1UIM Farmacologia Hospital de Especialidades CMN SXXl, IMSS, Av. Cuahutemoc Instituto de Química. Universidad Nacional Autónoma de México, Circuito 330 Col. Doctores Del Cuahutemoc CP 06725. E-mail: [email protected] Exterior, Ciudad Universitaria, Delegación Coyoacán 04510 México, D.F., México. 2Escuela Superior de Medicina del Instituto Politécnico Nacional, México, D. F.
Introduction: Eryngium heterophyllum belongs to the Introduction: Since ancient times, plants and herbal preparations Umbelliferae/Apiaceae family, and it has important ethnobotanical have been used as medicine. Research carried out in last few decades uses for the treatment of hypercholesterolaemic disease in the Mexican has certified several such claims of use of several plants of traditional traditional medicine. In Central Mexico, this plant is known by the medicine. Popularity of Annona cherimola Mill is used in Mexican popular name of “hierba del sapo" (toad grass). Hydroalcoholic extract traditional medicine for several ailments such as diarrhea, dysentery, of this specie was evaluated in an acute oral toxicity test using female abdominal pain, pneumonia, purgative, rheumatism, fever and as well C57BL/6N mice, according with OECD guidelines. as antidiabetic. Material and methods: The extract was evaluated also in a model of Material and methods: Alloxan-induced diabetic rats were treated hypercholesterolaemia in male C57BL/6N mice at 10 and 100 mg/kg with 300 mg/kg/d of ethanol extract from Annona cherimola (EEAC) or doses. vehicle for 4 weeks. The effect of EEAC on fasting blood glucose (FBG), and body weight in type 2 diabetic rats were measured. Results and conclusion: The results showed that the extract is not Results: After 4 weeks of treatment, EEAC administration showed toxic since it showed a DL50 over 5000 mg/kg. The results also showed that the mice significantly decreased cholesterol levels, after treatment significantly lower FBG levels (from 290 mg/dL to 108 mg/dL since the with extract at doses of 100 mg/kg for two weeks (p<0.05). Although second week) compared to the diabetic control group (from 290 the extract also induced a decrease in triglyceride levels, however it mg/dL to >500 mg/dL). In addition, EEAC showed no effect on body did not show a significant difference in comparison with the control weight in diabetic rats. group. In short in this paper experimental data are given which justify Conclusion: The findings from this study suggest that EEAC can the ethnobotanical use of this species in the Mexican traditional alleviate hyperglycemia of type 2 diabetes. medicine.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S207
LATINFARMA 2013 Resúmenes/Abstracts
PPN 017: ANTI-INFLAMMATORY ACTIVITY IN MICE BY PPN 018: CONSUMPTION STUDY ON RED QUINOA AREQUIPA ETHANOLIC EXTRACT OBTAINED BY GRAPE SEED OIL PROVINCE, AREQUIPA, PERU-2013
Flores L1, Izquierdo-Sánchez T. 2 Reyes Schultz R, Burgos Macedo C, Lazarte Ordoñez B.
1Maestria en Ciencias Farmacéuticas, Universidad Autónoma Metropolitana- Universidad Andina Néstor Cáceres Velásquez. Juliaca, Puno, Perú. E-mail: Xochimilco, E-mail: [email protected] [email protected] 2Lab. Fitofarmacología, Depto. Sistemas Biológicos, UAM-Xochimilco, (México).
Quinoa for their nutritional value, nutritious, its adaptability to Introduction: Grape seed oil is used in cooking and cosmeticology. different agro-climatic conditions have generated considerable interest Grape seeds are rich in lipids, proteins, carbohydrates and phenolic among producers, farmers, agribusiness companies, public and private, compounds. Resveratrol is well known as antioxidant and anti- national and international, in recent years. inflammatory in vitro and in vivo. Methanolic and ethanolic extracts of grape leaves have shown anti-inflammatory and analgesic activities in The present study has important significance and justification, because several experimental studies. The aim of this study was to evaluate the it is a substantial contribution in nutrition, public health. Given that anti-inflammatory activity of an ethanolic grape seed oil extract (EGSE) Arequipa city is the focus of migration in the Andean region of our in mice, and the characterization of the main components. Peru. Material and methods: An ethanolic extraction was performed to In Peru is produced by small farmers in a wide range of agro-climatic commercial grape seed oil. For this assessment, 42 healthy male CDI and ecological zones with traditional systems of production, mice (weighting 22-28 g), after 18 h fast period, were administrated processing, storage and distribution. Arequipa, quinoa is not cultivated, per os with EGSE (55, 100, 180 and 315 mg/kg) emulsified in tween 80 since the land is not suitable, even that is conducive to this altitude. solution (2%). Diclofenac 10 mg/kg was used as control. Acute edema Was provided by the results achieved, the suggestion Nutrition was induced by subcutaneous injection of carrageenan 0.2% in saline, Program of the Ministry of Health, the inclusion within the nutritional into the plantar tissue of the right hind paw, one hour after of each package for the low-income population. treatment administration. Records of paw swelling were taken as volume displacement by a plethysmometer (Ugo-Basile).The The main purpose of the study was to determine the rates of presumptive characterization of the extract was performed using FTIR, consumption of quinoa in the population of the city of Arequipa. and the identification of the constituents was done using GC-MS after methyl esterification. The instrument used was the survey, where data were entered on the consumption of quinoa, the amount of information that people have Results: The preliminary FTIR characterization showed that the about the red or quinoa grain and consumption of other food components of the extract have a carbonyl group and no aromatic substitutes. rings. The extract showed anti-inflammatory activity in a dose- dependent manner and showed maximal activity at 180 mg/kg dose, The representative sample was drawn based on six districts of the city equivalent to that of 10 mg/kg diclofenac. of Arequipa, which have been surveyed, obtaining the results: Rice 20 kg, per month, per family of five, 11 kg Noodles, Quinoa 1.5 kg. Conclusions: The EGSE showed dose-dependent anti-inflammatory effect; however, after presumptive characterization with FTIR no We conclude that consumption of quinoa is very low, therefore it is phenolic compounds were found in the extract. The GC-MS showed that suggested that the Peruvian State, raise public awareness on the the main components of the extract are linoleic, oleic, and palmitic nutritional benefits quinoa has further include in the Nutrition acids, then we concluded that these compounds may be responsible for Program, Red Quinoa. the effect.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S208
LATINFARMA 2013 Resúmenes/Abstracts
PPN 019: THE THERAPEUTIC POTENTIAL AND PPN 020: MECHANISMS OF ACTION INVOLVED IN THE TOXICOLOGICAL PROFILE OF Pimenta dioica (pimento) GASTROPROTECTIVE EFFECT OF THE ESSENTIAL OIL OF Hyptis martiusii BENTH. (LAMIACEAE) Campbell-Shelly J. Almir GWa, Germana FRCa, Alice VAa, Alisson RSOa, Jacinto CSNa, José
GMCb Introduction: Pimenta dioica (pimento) from the family Myrtaceae is aFederal University of Pernambuco, Recife, Brazil. one of the major spices produced in Jamaica and in folklore it is often bRegional University of Cariri, Crato, Brazil. used in the treatment of arthritis. In this study the validity of this claim was explored by examining the effects of pimento oil on joint swelling, and cartilage degradation in an adjuvant-induced mono-arthritic Introduction: Recent studies conducted by our laboratory murine model. demonstrated that the essential oil from the leaves of Hyptismartiusii Material and methods: Arthritis was induced in Sprague-Dawley rats (EOHM), an aromatic plant used in Brazilian traditional medicine to (250-300 g) with a single injection of 0.5 mL of (1 mg/mL) Complete treat gastric disorders, presents antiulcerogenic and antisecretory Freund’s adjuvant (CFA) in the synovial cavity of the right knee of each activities (Caldas et al., J. Ethnopharmacol. 137:886-892, 2011). The rat and arthritis allowed to developed over 26 days. A day before CFA aim of this study was to elucidate the mechanisms of action involved in injection and throughout the experimental period, control rats the gastroprotective effect of EOHM. received a daily dose of corn oil (360 mg/kg)) while test animals were Material and methods: EOHM was administered orally at the dose of given pimento oil (420 mg/kg), (Shama, 1994). 400 mg/kg in Wistar rats (n = 6/group). It was evaluated the Results: The knee joint was observed for signs of edema over 26 days. antisecretory activity stimulated with the agonist of the receptors of Changes in the knee joint circumference were measured using a the parietal cell by using the pyloric ligature method; the involvement flexible tape measure (Yun Cho, 2002). Rats were subsequently of NO and sulfhydryl groups and the levels of mucus, malondialdehyde sacrificed on day 26 and histological sections of the knee joint (MDA) and non-protein sulfhydryl groups (GSH), by using the ethanol- prepared and examined. induced ulcer model. The acetic acid-induced gastric ulcer model was used to evaluate the healing ability of the mucosa. Acute toxicity studies were carried out with pimento oil and the LD50 calculated. Sub-chronic toxicity studies were also done for 26 days and Results: EOHM altered the gastric acid secretion stimulated by the effects of the drugs on the stomach, liver and kidneys were secretagogues, by significantly reducing the volume (4.2 ± 0.2 and 3.4 ± observed. 0.2 mL vs. histamine 6.3 ± 0.7 and pentagastrin 7.1 ± 1.4mL, respectively) and acidity (24.8 ± 2.9 and 14.6 ± 3.4 On day 3 of 26 control rats displayed prominent swelling of the knee mEquiv.[H+]/mL/4h vs. histamine 52.8 ± 9.9 and pentagastrin 45.0 ± joint. By comparison there was a significant reduction (p<0.05) in joint 7.8 mEquiv.[H+]/mL/4h, respectively). The inhibition of the sulfhydryl swelling in animals treated with pimento oil. groups reduced the gastroprotective effect of OEHM). EOHM increased Preservation of the integrity of the synovial membrane and cartilage the levels of mucus by 54.8% (7.6 ± 0.5 vs. control 4.9 ± 0.4 µg/g was evident in animals treated with pimento oil, whereas the control tissue), reduced the levels of MDA by 72.5% (4.2 ± 0.8 vs. control 15.3 rats showed denudation of the synovial membrane. ± 1.5 µmol/g tissue) and prevented the depletion of GSH by 73.8% (78.2 ± 6.0 vs. control 45.0 ± 8.7 µg/g tissue) in the gastric mucosa. Conclusions: The study confirmed that pimento oil caused a reduction EOHM decreased (70.3%) the area of chronic ulcer, promoting in inflammatory swelling and preserved the synovial membrane in a regeneration of the mucosa and restoration of mucus production. rat arthritic model. Conclusion: The results indicate that the gastroprotective effect of Additionally the results of the study support the use of pimento in EOHM may be partly attributed to its antisecretory activity and partly Jamaican folklore for the treatment of joint swelling and the need for to cytoprotective mechanisms and antioxidant action. They also suggest pimento to be explored as a potential treatment for arthritis. that EOHM is a promising candidate for the treatment of gastric ulcers.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S209
LATINFARMA 2013 Resúmenes/Abstracts
PPN 021: EFFECTIVENESS OF A CREAM MADE OF PLANTAIN, PPN 022: CARNOSOL QUANTIFYING IN ROSEMARY NETTLE, AND FLAXSEED COMPARED WITH THE CREAM (Rosmarinus officinalis L.) EXPLANTS CULTIVATED UNDER CALMARTRIT IN ELDERLY (DISTRICT OF SELVA ALEGRE - A TEMPORARY IMMERSION SYSTEM (TIS) AREQUIPA) Villegas E1, Osegueda MS1, González J1, Alonso M1, Núñez H2, Herrera Burgos Macedo C, Corzo Salas A, Reyes Schultz R L.1
Universidad Andina Néstor Cáceres Velásquez. Juliaca, Puno, Perú. 1National Polytechnic Institute (IPN). Engineering Interdisciplinary Professional Unit. Campus Guanajuato (UPIIG).200 Mineral de ValencianaAvenue. Industrial Park Puerto Interior, Zip Code: 36275. Silao de la Victoria, Guanajuato, Mexico. Tel. (472)774748686. E-mail: [email protected] Introduction: Since plantain, nettle and flaxseed are medicinal plants 2University of Guanajuato. Campus Irapuato-Salamanca. LifeSciencesDivision. that can be used internally and externally in various diseases of the Ex Hacienda El Copal, k.m.9. Irapuato-Silao Road. Zip Code: 36500. Irapuato, body as a medicinal use. According to research these medicinal plants Guanajuato, Mexico. Tel. (01)4626241889. E-mail:[email protected] very well act as analgesics, anti-inflammatory and in combination like anti-arthritic. Rosemary (Rosmarinus officinalis L.) belongs to Labiate family, and it Material and methods: The research is experimental, experiments has small, deep-green color, and hairy leaves, which are able to corresponds to pure, its design is multiple, with experimental group produce and accumulate a bunch of poly-phenolic secondary and comparison group, quantitative approach to the experimental metabolites, including rosmarinic and carnosic acids, and carnosol, method. Depending on the number of variables is binary because it has being the last one an orto-diphenolic diterpene with a lactone and two variables, independent and dependent. According to its abietane skeleton. The carnosol is directly produced, by oxidation, temporality is prospective because the study was performed in the from carnosic acid, and it has anti-inflammatory, -oxidant and - future. According to his research problem is theoretical-practical for carcinogenic properties. In this study, the Rosemary in vitro culture collecting the information in various time periods observed. conditions for TIS were improved in order to obtain a substantial Where: G1: control group "B"G1 (GC): G2: experimental group "A" production of carnosol, which was detected and quantified by UV- plantain, nettle, and flaxseed. G2: Ol X1 X2 O2, O3 X3, X4 O4, O5 O19 VIS-HPLC. X5. G3: pharmacological group "C" (cream Calmartrit). Internode explants, approximately 2 cm long, were obtained from a The population is the set of people who will be grouped on the basis of greenhouse-grown Rosemary plant, and they were superficially one or more common characteristics that are under investigation, in disinfected with a 15% Sodium Hypochlorite solution, which had a this case consists of seniors (41, 42 and 46 years) the cheerful jungle 0.1% (v/v) commercial liquid soap. Subsequently, explants were in district high . vitro cultured on Murashige & Skoog (MS) semi-solid medium for nine days. Afterwards, different Rosemary explants were transferred Results: When applying the cream made of plantain, nettle, and to several treatments, containing different Plant Growth Regulator flaxseed for the treatment of arthritis was satisfactory reducing combinations; e.g. 0.2, 2.5 and 5 mg/L Benzyladenine (BA), and 0.5, 1 inflammation and pain in the joints of the hand to improve the state of and 2.5 mg/L Naphthalene acetic acid (NAA). Several frequency arthritis in 18 days, one day earlier compared with the cream immersion schedules were tested on Rosemary explants and their calmartrit. effect on shoot number production was evaluated. At the end of the pilot scheme concluded that the cream made from In order to quantify the carnosol from Rosemary explants a BAS medicinal plants (plantain, nettle, and flaxseed) the results were HPLC equipment was used, bearing a Hypersil C18 BDS (250x4.6mm, excellent because the pain and swelling decreased markedly testing our 5μm) column. The mobile phase was 10 mM formic acid (pH 3.0)- assumptions and goals outlined in our research. Acetonitrile (60:40), with a 1.2 mL/min rate flow and 30 min for the whole analysis. Carnosol was detected at 290 nm and 320 nm, and it was eluted as a single peak at 11.6 min. The greatest shoot number per Rosemary explant was 55, when 5 mg/L BA was used. Different carnosol concentrations were obtained depending on Plant Growth Regulator treatment applied to Rosemary explants.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S210
LATINFARMA 2013 Resúmenes/Abstracts
PPN 023: TOXICOLOGICAL ANALYSIS OF ROSEMARY PPN 024: GASTRIC HEALING PROPERTIES OF PROTEOLYTIC BIOACTIVES WITH POTENTIAL USE IN CLINICAL FRACTIONS FROM Vasconcellea cundinamarcensis LATEX APPLICATIONS AGAINST BACTERIA-RESISTANT IN Araujo e Silva A1, Menezes-Souza D2, Costa F3, Fujiwara R2, Salas C3, RABBITS Lopes MTP1 1 2 2 3 Ojeda-Sana AM , Cáceres Guido PA , Asprea M , Van Baren C , Departments of 1Farmacologia,2Parasitologia, 3Bioquímica e Imunologia – Balbarrey Z2, Adriana Macchi2, Filippo D2, Moreno S.1 Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. E-mail: [email protected] 1Fundación Instituto Leloir, IIBBA-CONICET, CABA, Argentina. 2Hospital de Pediatría Prof. Dr. Juan P. Garrahan, CABA, Argentina. E-mail: [email protected] 3IQUIMEFA (UBA-CONICET), Facultad de Farmacia y Bioquímica, UBA, CABA, Introduction: P1G10 a fraction obtained from V. cundinamarcensis Argentina. latex is rich in cysteine proteinases and displays gastric protective and healing activities, evaluated in rodent models. In this study, we investigated the gastric healing effect of sub fractions of P1G10, CMS1 Introduction: this work documented plant drug exposure of rosemary and CMS2, and some mechanisms of action using in vivo and in vitro bioactives in the skin of rabbits. Previously, we demonstrated their techniques. pharmacological potential in vitro and in two skin infection models in mice against human pathogenic bacteria1-4. However, remains to Methods: Gastric lesions were induced on female Wistar rats (180-200 investigate if they have no toxicological effects on the skin. The aim of g) with acetic acid 10%. After 24 h, daily treatment (v.o.) was initiated this study was to evaluate induction of irritation/dermal corrosion, in all groups (n=6): vehicle (control), CMS1 (1-30 mg/kg), CMS2 (3-30 and inflammatory reactions of the rosemary bioactive in skin of mg/kg), P1G10 (10 mg/kg) or Ranitidine (100 mg/kg). After 7 days, rabbits. animals were sacrificed and the stomachs removed to measure the ulcer area and the expression of growth factors by Real Time PCR. In Material and methods: toxicity of three doses of topical cream vitro studies using epithelial gastric cells (AGS; ATCC CRL1739) and containing bioactive or vehicles at 0, 24 and 48 h was assessed by endothelial cells (HUVEC-CS; ATCC CRL2873) were carried out to determination of erythema by photographic analysis at 1, 24, 48 and evaluate proliferative and migration stimulatory activities of the 72 h of treatment on four skin areas of 4 cm2 on each animal. The fractions. edema was investigated by ultrasound analysis (echography) of the dermis thickness. The animals were euthanized after 72 h and Results: CMS1 (1 mg/kg) and CMS2 (30 mg/kg) presented significant histopathological analyzes of the skin were performed in biopsy gastric healing effect, with reduction on the ulcer area by 62 and 44%, specimens. Also, pharmacokinetic parameters of plant compounds respectively. This activity was similar to P1G10 (52%) and Ranitidine were studied in the serum of the animals by gas chromatography after (49%). In the ulcerated mucosa, CMS1 increased the expression of 30 min, 1 h or 24 h of treatment. bFGF and VEGF in almost 20 and 4-fold, respectively, but did not alter EGF expression. CMS2 increased EGF, bFGF and VEGF by 80%, 510% Results: the skin treated with the plant compounds did not show and 267%, respectively. In vitro both, CMS1 and CMS2 (10 ng/mL), significant signs of swelling redness, blisters, peeling or ulcerations stimulated proliferation rate of AGS and HUVEC-CS cells by ~1.8 and after 4 days of treatment and three consecutive doses. In addition, skin ~1.4-fold, respectively. Cell migration was also stimulated by 79 and areas showed the same thickness in the groups treated with the active 68%, in AGS and by 55 e 50% in HUVEC-CS, respectively. plant and treated with the vehicle or without treatment after ultrasound examination (1.50 ± 0.22; 1.81 ± 0.28 or 1.75 ± 0.25 mm, Conclusion: The results suggest that CMS1 and CMS2 display respectively). Therefore, our results showed no adverse effects of the interesting gastric healing activities through modulation of growth formulation containing antimicrobial rosemary bioactive at the doses factors expression, cell proliferation and migration stimulus. tested on the skin. Financial Support: CNPq, CAPES and FAPEMIG. Conclusions: this work has a direct impact on areas of health, since we developed innovative formulations based in herbal alternatives, not only effective but also safe, for the treatment of bacterial resistant infections.
1Free Rad Res 2006,40:223; 2BLACPMA 2009,8:219; 2Pediatric Res 2012,72:109; 3Food Control 2013,31:189.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S211
LATINFARMA 2013 Resúmenes/Abstracts
PPN 025: PHARMACOVIGILANCE STUDY OF UNREGISTERED PPN 026: Lopezia racemosa Lag, MEXICAN MEDICINAL PRODUCTS COMMERCIALIZED IN COSTA RICA, THE CASE PLANT WITH ANTINOCICEPTIVE ACTIVITY OF MANZINOP™ CONTAINING CHAMOMILE (Matricaria Velázquez-González C1, De la O-Arciniega M1, Avendaño-Morales C2, chamomille) AND TETRAHYDROZOLINE Bautista-Ávila M1, Gayosso-De Lucio JA1, Villagómez-Ibarra JR2, Castillo M, Chaves P. Betanzos-Palmeros Z.2 1Área Académica de Farmacia, Instituto de Ciencias de la Salud, Universidad Faculty of Pharmacy, University of Costa Rica. E-mail: Autónoma del Estado de Hidalgo, Carretera Pachuca-Tilcuautla S/N Municipio [email protected] San Agustín Tlaxiaca, Hidalgo, México. E-mail: [email protected] 2Área Académica de Química, Instituto de Ciencias Básicas e Ingeniería, Natural products have been widely used in the belief that they have no Universidad Autónoma del Estado de Hidalgo, Km 4.5 Carretera Pachuca– harm to the health of people, however, it has been shown that this type Tulancingo, Mineral de la Reforma, Hidalgo, México. of products similarly could cause unwanted reactions in the population, which often doesn’t know this and can’t take the necessary precautions. A pharmacovigilance study for determination of the Introduction: Lopezia racemosa Cav. (Onagraceae) is known as minimal quality control specifications of an ophthalmic product sold “perilla”, is used in Mexico by traditional medicine practitioners to under the name Manzinop® was conducted, this product reports in its treat stomachache, toothache, pain and as antipyretic (UNAM, 2009). quali-quantitative formula the presence of an extract of Chamomile In this study we investigated the antinociceptive activity of the ethanol (Matricaria chamomille) and Tetrahydrozoline. extract of the aerial parts of L. racemosa in mice. An analysis of the current legislation in Costa Rica for natural products Material and methods: Antinociceptive activity of extract was tested and drugs was performed; it was also examined whether the product using a model of visceral pain induced by acetic acid in mice (writhing meets the minimal information that must contain the primary test). CD1 mice (n=6) were treated with vehicle (Tween 80, 1% in packaging and secondary packaging. Furthermore, it was used a thin water) or ethanol extract (150, 300 and 600 mg/kg, p.o.) and as drug layer chromatography to identify the presence of chamomile controls, diclofenac (10 mg/kg, p.o.) and acetylsalicylic acid (200 (Matricaria chamomille) and Tetrahydrozoline in the product and for mg/kg, p.o.) were used, 30 min before the acetic acid injection. The this it was used as standard substances Kamillosan™ solution and antinociceptive effect was studied for the individual observation and Visine ™ solution. In addition, physicochemical properties of the the total number of the abdominal contractions was counted in periods product were determined such as pH and osmolarity, and of 5 min for the following 25 min after intraperitoneal injection with microbiological tests were also performed with the product in order to 0.1 mL/10 g body weight of 0.6% (v/v) of acetic acid solution in verify for sterility. distilled water. Antinociceptive activity was expressed as the percentage change from writhing controls. A significant reduction As a result, it was found that there is a noncompliance with the law, (P<0.05) in the number of writhings by some treatment as compared since such products can not be classified as a natural product; in to controls injected with vehicle was considered to be a positive addition, the product does not meet the tests, labeling, identification antinociceptive response. All experimental procedures followed the and physicochemical properties or the microbiological tests provided Guidelines on Ethical Standards for Investigations of Experimental by the law of Drug Registration and Control. Pain in Animals. Results: Ethanol extract administration showed an antinociceptive effect at 150, 300 and 600 mg/kg, (88.83, 46.32 and 80.65% of inhibition, respectively). It is important to notice that the extract showed better activity than drug controls, diclofenac at 10 mg/kg (40.39% of inhibition) and acetylsalicylic acid at 200 mg/kg (40.39% of inhibition). Conclusions: Lopezia recemosa showed antinociceptive activity in writhing test, this study may give a support for traditional use of L. racemosa to treat pain.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S212
LATINFARMA 2013 Resúmenes/Abstracts
PPN 027: SYNTHESIS OF MASTICADIENONIC ACID PPN 028: INHIBITION OF NARINGENIN ON CYP1A1 ACTIVITY DERIVATIVES Santes-Palacios R, Camacho-Carranza R, Espinosa-Aguirre JJ. Marrero JG1, Rodriguez NVA2, Montaño RG2, Ortega A3, Maldonado E.3 Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de 1National Polytechnic Institute (IPN). Engineering Interdisciplinary Professional México, Apartado Postal 70228, Ciudad Universitaria, 04510, Distrito Federal, Unit. Campus Guanajuato (UPIIG). 200 Mineral Valenciana Avenue. Industrial México. E-mail: [email protected] Park Puerto Interior, Zip Code: 36275. Silao de la Victoria, Gto, Mexico. E-mail: [email protected] 2 Facultad de Química, Universidad de Guanajuato, Noria Alta S/N, Guanajuato, Introduction: Grapefruit juice (GJ) is a well known CYP inhibitor; México C.P. 36050 3Instituto de Química, Universidad Nacional Autónoma de México, Circuito CYP3A is one of the most affected subfamily leading to Exterior, Ciudad Universitaria, Coyoacán, México, D.F. 04510, México. anticarcinogenic and antimutagenic effects when GJ is administered to experimental animals in combination with mutagenic/carcinogenic agents metabolized by CYP3A. Naringin is one of the main constituents contained within GJ and its inhibitory effect against CYP3A4 has been Amphipterygium adstringens (trivial name ‘‘cuachalalate’’) has been well documented. Naringin is metabolized in vivo by α-ramnosidase widely used in traditional medicine as a gastroprotective, and β-glucosidase generating naringenin, the active inhibitory hypocholesterolaemic, anti-inflammatory, antiprotozoal and cytotoxic molecule affecting CYP3A4 activity. Reports suggest that CYP3A is not agent. Many of these properties have been attributed to the presence of the only one affected but CYP1A and 2B are also affected by masticadienonic acid. naringenin. As part of our efforts in developing pentacyclic triterpenes as Material and methods: The EROD (CYP1A1 ethoxyresorfin O- therapeutic agents, we were in pursuit of novel bioactive compounds deethylase associated activity), MROD (CYP1A2 methoxyresorufin O- based on masticadienonic acid, which enhance physical-chemical and demethylase associated activity), PROD (CYP2B1 penthoxyresorufin O- pharmacokinetic/pharmacodynamic properties. In this sense, dealkylase associated activity) and BROD (CYP2B2 benzyloxyresorufin synthetic approaches that rapidly generate molecular diversity and O-dealkylase associated activity) were measured in hepatic complexity in masticadienonic acid may be of great interest for microsomes from rats treated with the combination of phenobarbital medicinal chemistry. Considering the unraveling way by which and β-naphtoflavone. The inhibitory effect of naringenin was isocyanide-based multicomponent reactions (I-MCRs) generate characterized with kinetic parameters IC50 and Ki values. structural diversity with minimized synthetic cost, we envisioned the implementation of these reactions in the synthesis of structurally Results: We tested the in vitro capacity of naringenin to inhibit the diverse masticadienonic acid conjugates. activity of CYP1A and 2B subfamilies and found that naringenin showed the strongest inhibitory effect on CYP1A1 (IC50=436.7 nM). Herein we report on the utilization of Ugi four-component reactions Therefore, we decided to biochemically characterize the inhibitory (Ugi-4CRs) as a general multicomponent approach toward new properties of naringenin. CYP1A1 Supersome® used in this study masticadienonic acid derivatives. The Ugi-4CR is currently considered showed a Km=0.365 µM and a Vmax=6089 pmol/min*mg protein with one of the most versatile synthetic tools for the generation of molecular substrate ethoxyresorufin, and the biochemical characterization of diversity and complexity. naringenin CYP1A1 inhibitory effect revealed that it is a mixed inhibitor with a Ki=184.2 nM. Conclusions: The results suggest that naringenin is a selective inhibitor of CYP1A1 that might cause drug-drug interactions when co- administrated with CYP1A substrates.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S213
LATINFARMA 2013 Resúmenes/Abstracts
PPN 029: ANTIDIABETIC EFFECT OF AQUEOUS EXTRACT PPN 030: COMBIFER: NEW FORMULATION WITH HEM AND AND FRACTIONS FROM Allophylus cominia (L) SW LEAVES NO HEM IRON FOR ANAEMIA PREVENTION IN PREGNANT WOMEN. COMPARISON OF THE BIOAVAILABILITY OF Sánchez J, Young L, Marrero E, Harvey A. FERROUS SELTS Department of Chemistry, Pharmacology and Toxicology, National Centre for Animal and Plant Health, CENSA, Aptdo #10, San José de Las Lajas, Mayabeque, González Hernández R, Aznar García E, Súarez Fundora S, Varela A, Cuba. E-mail: [email protected] Silva N, Fernández J, González Pérez M, Díaz Barroso Y, Rodríguez S. Centro Nacional de Biopreparados, BIOCEN, Mayabeque, Cuba. E-mail: [email protected], [email protected] Introduction: Allophylus cominia (L) Sw. is a characteristic tree of Cuba, which is attributed several medicinal properties in traditional medicine, particularly as antidiabetic. This study was designed to Introduction: Iron deficiency anemia is one of the highest deficiencies explore the in vitro and in vivo antidiabetic potential of the A cominia prevalent in the world, mostly in pregnant women and children. We leaves aqueous extract and its fractions. use a natural anti-anemic product (Trofin®) composed of heme iron Material and methods: The aqueous extract of A cominia leaves was with high absorption and bioavailability. Combifer is a natural product partitioned successively with solvents mixtures of n-hexane, di-chloro origin. The composition is with d by heme (Trofin) and nonheme iron methane, n-butanol, methanol and water, increasing of polarity, in complexes. order to obtain ten fractions. The extract and its fractions were tested These one contribute to the balance between iron absorption and body for their possible antidiabetic activities on therapeutic targets of type 2 iron homeostasis and makes it an attractive product for increased the diabetes: protein tyrosine phosphatase 1B (PTP1B), dipeptidyl prevalence of the anaemia iron deficiency state, especially in peptidase-IV (DPPIV), glucose uptake in adipocytes 3T3-L1, plasma pregnancy. The objective of this study was to compared iron glucose levels in a model of type 2 diabetic rats and antioxidant effects. absorption and the effectiveness in the prevention of iron deficiency A cominia aqueous extract (0.25, 0.5 and 1.0 g/kg) was administrated anemia in pregnant women from ferrous fumarate in prenatal daily to type 2 diabetic rats orally during 21 days, streptozotocin was formulations. used for diabetes induction. Antioxidant properties were evaluated by two methods: DPPH and dichlorofluorescin (DCF) assays; resveratrol Material and methods: Combifer was compound by Trofin (Heme was used as antioxidant standard. iron) 300 mg, ferrous fumarate 50 mg (nonheme iron), vit C 60 mg, folic acid 0.02 mg. Prenatal haven´t heme iron. Ferrous fumarate 100 Results: A cominia extract inhibited the enzymatic activity of PTP1B mg. The iron absorption is 28% in Combifer with high bioavailability (IC50= 2.3 µg/mL) and DPPIV (IC50= 218 µg/mL) in an extract and 8% in prenatal. concentration dependent manner, resulting more active the more polar fractions in the PTP1B assay, while fractions showed a slight inhibition Resultds: The study with a total of 164 pregnant women with of DPPIV. A cominia extract enhanced glucose uptake in 3T3-L1 hemoglobin (Hb), hematocrit (HCT) and serum iron (FeS) were adipocytes, resulting more active fractions 6 and 10. The extract analyzed every 8 weeks since the beginning of the study, until delivery. exhibited antioxidant properties, evidenced in a scavenger activity on The occurrence of adverse reactions was also monitored. DPPH radicals and protective effect on fibroblasts L929 exposed to oxidative stress, a great variety of fractions showed antioxidant Conclusion: The new product Combifer was effective and safe for the activity in these assays. A cominia extract at 0.5 g/kg recovered the treatment of iron deficiency anemia in pregnant woman, without normal glycaemic values in type 2 diabetic rats. adverse events. Conclusion: A cominia aqueous extract and its fractions AcF6 and AcF10 are promising candidates for the development of antidiabetic phytopharmaceuticals.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S214
LATINFARMA 2013 Resúmenes/Abstracts
PPN 031: SUPPLEMENTAL SAFETY PHARMACOLOGICAL PPN 032: HYPOLIPIDEMIC EFFECTS OF CHITOSAN AND STUDIES OF BM-21, AN AQUEUS-ETHANOLIC EXTRACT CHITOSAN ACIDS SALTS ON TWO MODELS OF INDUCED FROM THE SEA GRASS Talassia testudinum HYPERLIPIDEMIA IN MICE Morales RA, García T, García N, Palmero A, Valdés Suria, Rodriguez JC, Bellma Menendez A, Menendez Soto del Valle R, Phuong DT, Phuong Laguna A, Valdés O, Menéndez R. NT, de la Paz N, López O, Fernández Cervera M, Nogueira A.
Centro de Bioproductos Marinos, Agencia de Medio Ambiente, Ministerio de Laboratorio Control Biológico, Centro de Investigación y Desarrollo de Ciencia, Tecnología y Medio Ambiente, La Habana, Cuba. E-mail: Medicamentos (CIDEM). Calle 17 No. 6208 e/ 62 y 64. Playa, Habana, Cuba. E- [email protected] mail: [email protected]; [email protected]
Introduction: BM-21 is the extract from the sea grass Thalassia Introduction: Hyperlipidemia is currently considered to be one of the testudinum standardized to thalassioline B (5.8 ± 0.9%). Although the most important cardio-cerebral vascular disease risk factors. preclinical efficacy and safety studies so far reasonably suggest the Cardiovascular disease is the main cause of death in developed potential use of BM-21 as herbal medicine due to its anti-oxidant, anti- countries; it is now widely recognized to be closely related with inflammatory, antinociceptive and neuroprotective effects, elevated blood lipids. Lipids mainly refer to the serum cholesterol and identification of possible accidental and undesirable effects by means triglycerides. Hyperlipidemia refers to either or both of increasing of a preclinical approach is necessary. Thus, the aim of the present levels of cholesterol or triglyceride. The purpose of this study was to study was to initiate the evaluation of the safety pharmacology study of determine the effect of chitosan obtained by deacetylation of chitin BM-21 on several vital organ systems. from lobster (Panurilus argus) shells and its salts on prevention of hyperlipidemia in mice induced by Triton WR 1339 and fed high Material and methods: Due to the pharmacological profile of BM-21 cholesterol diets. we studied the consequences of its oral administration on some function of CNS in mice and gastric mucosa in rats. According to the Material and methods: Hyperlipidemic Swiss mice were treated with experimental model, animals were orally administered once-a day with chitosan and its acetate and lactate salts at dose of 200 mg/kg. BM-21 in a doses interval between 4 - 1000 mg/kg prior to the Fenofibrate and colestyramine were used as positive control. experiments. Control groups were administered with vehicle and classical drugs were used as positive controls. Exploratory behaviour Results and conclusion: Chitosan and its acids salts caused a in open field, forced swimming, marble-burying, elevated plus-maze, significant decrease in total cholesterol (TC) and tryglicerides in serum maximal electroshock seizure and rota-rod test were used to measure compared with control group and had an inhibition for above 50%. The some potential effect on behavioral models. The potential pro/anti- data generated by this study demonstrated that chitosan and its acids ulcer effect of BM-21 was studied by means of ulcer induced by salts at 200 mg/kg dose are effective in lowering the hyperlipidemia indomethacine, diclofenac, ethanol and pylorus-ligation and was conditions produced by Triton and high cholesterol diet in mice. evaluated by the number and the gravity of erosions and histopathological evaluation of gastric mucosal tissue.
Results: Prolonged administration of BM-21 neither had general sedative and/or excitatory effects nor depressant/antidepressant activity. The extract did not behaved as an anxiogenic or anxiolytic agent, had no potential proconvulsivant/anticonvulsivant effects on maximal electroshock seizure and did not showed effect on motor coordination. Oral administration of the extract showed a dose dependent antiulcer effect against all experimental models, although the gastroprotective efficacy afforded by BM-21 in pylorus-ligated and ethanol-induced gastric ulcer models was superior to those observed in NSAIDs-induced gastric ulcer that is consistent with its anti- inflammatory activity observed previously. Conclusions: The present work has shown that the administration of BM-21 did not produce collateral pharmacological effects, of undesirable nature at least in the models used. This that may has potential future clinical impact.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S215
LATINFARMA 2013 Resúmenes/Abstracts
PPN 033: BIOCHEMICAL CHARACTERIZATION AND IN VITRO PPN 034: ANTIOXIDANT ACTIVITY OF THE EXTRACTS OF CYTOTOXIC EFFECT OF A POLYPEPTIDE AND PROTEIN MIS THE LEAVES OF Spondias mombin L. (JOBO) DERIVED FROM THE Rophalurus junceus Perez-Portero Y, Hijuelo Y, González Pérez M, Hernández Sosa E, Rodríguez A, Hernández O, Rodríguez A, Aguila M, Compte O, Méndez Perera Córdoba W, Pallo Hill A. MC, Fernández Y, Tuduri H, Junco J. Laboratorio de Fitoquímica, Instituto de Ecología y Sistemática, Universidad de Universidad Médica de Camagüey, Circunvalación norte y Ave Finlay. Camagüey, Oriente, Santiago de Cuba, Cuba. E-mail: [email protected] Cuba. E-mail: [email protected]
Introduction: Spondias mombin L. (jobo) has been used traditionally Introduction: Pharmacological evaluation of extracts of organisms in the treatment of various diseases such as: antidermatofític, and their isolation is an essential aspect in the process of discovering antimicrobial, antiseptic, astringent, among others. It is suggested that and developing a drug. these properties are related to the abundance of phenolic compounds of this plant, the antioxidant capacity is also directly related to the In the present work an in vitro therapeutic evaluation of a mixture of presence of phenolic compounds. The present work is to determine the polypeptides and proteins derived from venom of Rophalurus junceus, total phenol concentration, the activity against DPPH, ORAC radicals popularly known as blue scorpion, is carry out. and also the reducing power. Material and methods: To accomplish this work, we used a fluid Material and methods: The extraction was performed using 25 g of extracts from Rophalurus junceus hatcheries at Labiofam Laboratories leaves with solvents of different polarity (water, chloroform, ethanol, in the province of Camaguey. To biochemically characterize the crude methanol and n-hexane). The total phenols concentration obtained was fluid extract of the Rophalurus junceus we conducted the protein and determined by the Folin Ciocalteu method. We evaluated the polypeptides purification through a high pressure chromatography antioxidant capacity of the ethanolic extract by DPPH and ORAC system (HPLC). Meanwhile, the protein pattern eluted from the methods. It was further determined the reducing power by the Yen and purification system was evaluated using a 15% polyacrylamide gel Chen's technique (1995). electrophoresis (SDS-PAGE). For cell cytotoxicity determination a metabolic damage assays and staining with neutral red was used. Results and conclusions: The highest yield was obtained from the chloroform extract and n-hexane, although the lowest was for the Results: As result, it was found that the fluid extract of Rophalurus other solvent, and similar behavior showed the phenol concentration. junceus contains at least 13 fractions, in which about 50% consists of The highest values of antioxidant capacity were obtained by the ORAC polypeptides of less than 14 kDa. In vitro cytotoxic effect evaluation of method. There is a dependency relationship between the concentration the fluid extract in the prostate cancer line Dunning R3327-G revealed of the fractions and reducing activity. The highest value of reducing that the dose of 100 μg produced the greatest inhibition of tumor power belongs to the aqueous extract and the ethanol. The antioxidant growth in this cell line, while in the murine myeloma model P3- capacity of the extracts of the leaves of Spondias mombin is a X63/AG8/653 the greatest cytotoxic effect was observed at doses contribution to the pharmacology of natural products and helps us to between 1 and 10 μg. have scientifically arguments about the traditional uses of this species. Conclusions: We can state that the fluid extract from Rophalurus junceus venom contains a mixture of polypeptides and proteins responsible of their cytotoxic effect, which support its therapeutic function on cancer.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S216
LATINFARMA 2013 Resúmenes/Abstracts
PPN 035: CHEMICAL COMPOSITION, ANTIOXIDANT PPN 036: ANTIOXIDANT ACTIVITY OF THE EXTRACTS OF PROPERTIES OF THE ESSENTIAL OIL OF Piper Capraria biflora L. angustifolium LEAVES Cadenas-Perez X, Quesada-Yero S , Vicet-Muro L, Jorge-Rodríguez E. Monteagudo Romero U, Jorge Rodríguez E, Saucedo-Hernández Y. Departamento de Farmacia, Facultad de Química, Universidad Central “Marta Departamento de Farmacia, Facultad de Química, Universidad Central “Marta Abreu” de Las Villas, C-54830 Santa Clara, Cuba. E-mail: [email protected] Abreu” de Las Villas, C-54830 Santa Clara, Cuba. E-mail: [email protected] The ethereal, ethanolic and aqueous extracts of Capraria biflora L., leaves of Cuba, were investigated as antioxidant activity. The phenolic Introduction: The essential oil of Piper angustifolium L leaves from the content of the ethereal extracts, ethanolic and aqueous, was evaluated mountains of the Central Region of Cuba, were investigated as by the Folin-Ciocalteeau method, was found to be equivalent to 152.31, antioxidant activity. 391.97 and 94.90 mg AG/g for the ethereal extracts, ethanolic and aqueous. The antioxidant activity the ethereal extracts, ethanolic and Material and methods: The antioxidant activity of essential oil was aqueous of Capraria biflora L. was evaluated by 2,2′-diphenyl-1- evaluated against Cucurbita seed oil by peroxide, thiobarbituric acid picrylhydrazyl and the power to reduce Fe3+ to Fe2+ (reducing power). and p-anisidine methods. Moreover, this antioxidant activity was The antioxidant activity the ethereal extracts, ethanolic and aqueous of supported by the complementary antioxidant assay in the linoleic acid Capraria biflora L. showed moderate results in all assays tested, with system and 2, 2′-diphenyl-1-picrylhydrazyl. respect to antioxidants used patterns. Results and conclusions: The essential oil of Piper angustifolium L leaves obtained by hydrodistillation was analyzed by gas chromatography-mass spectrometry. Eighteen compounds, accounting for 95.1% of the oil were identified. The phenolic content of the oil, determined by the Folin-Ciocalteeau method, was found to equivalent to 128.04 µg pyrogallol/mg for essential oil of P. angustifolium. The antioxidant activity of essential oil showed moderate results in all assays tested, with respect to antioxidants used patterns.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S217
LATINFARMA 2013 Resúmenes/Abstracts
PPN 037: ANTIOXIDANT, ANALGESIC AND TOXICOLOGICAL PPN 038: PHYTOCHEMICAL AND PHARMACO- EVALUATION OF AN HYDROALCOHOLIC EXTRACT TOXICOLOGICAL STUDIES OF AN EXTRACT FROM OBTAINED FROM Piper ossanum Trel (PIPERACEA) Syringodium filiforme A MARINE PLANT WITH PROMISSORY RESULTS TO BE USED AS A NATURAL DRUG Gutiérrez Gaitén Y, Casado Martín C, Delgado Roche L, Herrera Ledesma Y, Valdivieso García A. Fernández Pérez MD, Rodríguez García M, Valdez Iglesias O and González García K. Instituto de Farmacia y Alimentos, Universidad de la Habana, Ave 23 e/ 214 y 222 # 21425, C.P. 13600, La Coronela, La Lisa, La Habana, Cuba. E-mail: Centro de Bioproductos Marinos, Loma 37, Nuevo Vedado, Plaza de la [email protected], [email protected] Revolución, Habana, Cuba. E-mail: [email protected]
Introduction: Piper ossanum Trel is a Cuban endemic plant. It has been Introduction: Seaweed extracts have been used as nutritional traditionally used as haemostatic, diuretic, antiseptic and supplements to alleviate or cure certain pathologies. Phytochemical antirheumatic. Antioxidant, analgesic and dermal toxicity evaluations and pharmaco-toxicological characterization of a standard aqueous were carried out in order to provide concrete evidences on its extract from Syringodium filiforme is reported at this work. effectiveness and safety. Phytochemical characterization was also developed for the hydroalcoholic extract. Material and methods: The sample was dried and a total extract prepared; three extracts were prepared with the use of solvents of Material and methods: The antioxidant activity was conducted by increasing polarity. For the total extract and fractions antioxidant FRAP and DPPH techniques. Analgesic effect was determined whit the activity were evaluated by using the free radical scavenging activity acetic acid - induced writhing assay in mice; dermal acute toxicity was assay with 1,1-Diphenyl-2-picrylhydrazyl reactive (DPPH´s method). also evaluated. The extract was chemically characterized by We evaluated the effect of topical application of the extract to murine phytochemical screening and gas chromatography-mass spectrometry skin damage by UVB acute radiation exposure. Its acute toxicity was (GC-MS) analysis. Total phenols content was determined by Folin evaluated in rats by oral and dermal administration and its possible Ciocalteu method. sensitizing effect on the skin of guinea-pigs was also studied. Results: Antioxidant activity using FRAP technique showed superior Results: The phytochemical screening detected the presence of high reduction potentials compare to the reference substance (Vitamin C). concentrations of flavonoids, phenols, terpenes, antocyanins and DPPH rehearsal also showed evidences as antioxidant. A 94.4% of reducing sugars. The total extract and methanol fraction showed analgesic effect was obtained with a 400 mg/kg dose. No clinical sings significant free radical scavenging properties, while the petroleum were observed during and after the toxicological evaluation, ether fraction showed moderate activity, and the chloroform fraction macroscopic damage was not observed either in the examined organs. didn’t show antioxidant properties against free radicals. On the other The phytochemical screening suggested phenols presence, especially hands, topical application of S. filiforme leaves hydroalcoholic extract flavonoids. GC-MS study allowed the identification of 23 compounds, to the irradiated skin 0.5 h before exposure avoided of the skin the majority ones were Phytol and other constituents from the macroscopic alterations, this protection occurred at a dose of 0.5 essential oil, many of them not reported previously for the species. mg/cm2. The protective effect is consistent with the antioxidant action Total phenols content was 0.63%. commonly observed in such phenolic structures, because pro-oxidant Conclusions: From the preclinical point of view, a high antioxidant and states may contribute to initiate UV-induced skin damage. Under our analgesic activity was demonstrated for the extract. The product didn't experimental conditions, it showed no lethality at the limit doses of produce toxic effects in the experimentation animals under the the total extract (2 000 mg/kg) and no adverse effects were found. rehearsed conditions. The phytochemical characterization of the The extract is not a potential allergen according to the results extract, allowed to suggest the presence of compound that may be obtained in the test. associated with the pharmacological properties demonstrated for the Conclusions: The results confirmed the potentialities of this species plant. for biological purpose and it is not toxic product on these experimental conditions.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S218
LATINFARMA 2013 Resúmenes/Abstracts
PPN 039: IMMUNOSTIMULATING EFFECTS AND PPN 040: ANTI-INFLAMMATORY EFFECTS OF Zuelania PHARMACOLOGICAL POTENTIAL OF THE EDIBLE guidonia SP. MUSHROOM Pleurotus SP. Puente E, Salas H, Berenguer C, Pineda E. Aguirre R, Álvarez Y, Morris H, Llauradó G, Lebeque Y, Fontaine R. Centro de Toxicología y Biomedicina. Autopista Nacional Km 1.5. Santiago de Departamento de Biología, Facultad de Ciencias Naturales, Universidad de Cuba, Cuba. E-mail: [email protected]; [email protected] Oriente. Patricio Lumumba s/n, Santiago de Cuba, Cuba. E-mail: [email protected] Introduction: The constant search for new natural products with Introduction: The genus Pleurotus comprises several edible species of pharmacological activities inclines us towards the preclinical high nutritional value, which also possess pharmacological potential, assessments of new formulations based on plants which have long including the immune system modulation. However, there are been used in the rural areas of our country without a scientific insufficient experimental evidences that thwart the development of rationale. bioactive-enriched formulations with therapeutical applications. This Material and methods: The anti-inflammatory activity of the Zulenia work’s aim is the evaluation of in vivo immunomodulatory properties guidonia sp aqueous extract was assessed using the 1% formalin of mycelium and fruiting bodies extracts from Pleurotus sp. solution method (proinflammatory) in the Sprague Dowley rat´s leg, Material and methods: The extracts were obtained through thermic using Ibuprofen as a positive control. Three dosage levels were used to treatment of the biomass (Cuban patent No. 23717, 2011). achieve the dose response curve. Immunomodulatory activity was evaluated on male Balb/c mice Results: The anti-inflammatory effect of the aqueous extract was administered intraperitoneally for seven days. observed from the dose of 300 to 150 mg/kg body weight. It has been Results: The extracts showed immunopharmacological effects judging proved the pharmacological actions of the phytochemical compounds by the bone marrow haematopoiesis, the splenic cellularity and the making up this plant´s structure, such as coumarins, phenols and serum protein concentrations. They also increased the count of total flavonoids, which could be responsible for the entire or the separate and differential leukocytes in peripheral blood, the number of anti-inflammatory activity. peritoneal macrophages, the vascular permeability in the peritoneal Conclusions: Thus, it is confirmed that we are in the presence of a cavity and the cellular immune response. plant capable of providing valuable raw materials with anti- Conclusions: The results evidenced a higher immunopotentiation in inflammatory activity. mice inoculated with Pleurotus sp. extracts, compared to those of the control group, suggesting they are potential candidates for functional foods and dietetic supplements useful on the nutritional modulation of the immune system.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S219
LATINFARMA 2013 Resúmenes/Abstracts
PPN 041: PROTEOLYTIC ACTIVITY EVALUATION ON Morinda PPN 042: THEORETICAL MODELING OF THE CHEMICAL citrifolia L. FRUITS INTERACTION BETWEEN THE 2,4-DITERBUTILPHENOL AND PROMUTAGENIC AROMATIC AMINES: METAPHENYL- Álvarez Jiménez E, Miranda Martínez M, Scull Lizama R, Abreu Payrol J. ENEDIAMINE, 4-AMINOBIPHENYL AND 2-AMINO-1- METHYL-6-PHENYLIMIDAZO [4,5 B] PYRIDINE AS DNA Farmacia Comunitaria (U- 626). Empresa Provincial de Medicamentos del Oeste. PROTECTIONS MECHANISM La Habana, Cuba. E-mail: [email protected] Marrero-Gutiérrez J, Sánchez-Lamar Á, Morera-Boado C.
Facultad de Biología, Universidad de La Habana. Calle 25 N0455, e/. J e I, Vedado, Introduction: Morinda citrifolia L. (Rubiaceae), known in Cuba since La Habana, Cuba. E-mail: [email protected] the first half of the nineteenth century with the common name of Indian Mora and more recently as Noni, has a large and recognized use in traditional herbal medicine for numerous conditions. Nowadays, it Isolated from vegetal specie Phyllanthus orbicularis K, the 2,4-di- has been a growing interest in a deeper understanding on the chemical tertbutilphenol (DTP) phenolic compound demonstrated a significant and pharmacological properties of this species. In this context and reduction of DNA damage produced by promutagenic aromatic amines: taking into account that many fruits have proteolytic enzymes or meta- phenylenediamine (m-PDA), 4-aminobifenil (4-ABP) y 2-amino- proteases, which are responsible for fermentation processes in the 1-metil-6-fenilimidazo[4,5-b]piridine (PhIP) by means of “in vitro” own fruit or for different pharmacological activities, we decided to assays. A putative action mode to explain DTP’s protective capacity is carry out this research. the chemical interaction with these amines, which inhibits the Material and methods: Proteins concentration at different stages of formation of active amines structures. However, up to date it has not the fruit was determined by means of a spectrophotometric method, been informed a molecular mechanism to explain these interactions. employing Coomassie Brilliant Blue G - 250 II (CBB). Proteolytic Owing this, the present research has been carried out to elucidate the activity was assessed by spectrophotometric determination of soluble feasibility of the phenol-amine interaction proposing stable association peptides resulting from the action of proteolytic enzymes on casein models using computational tools. substrate, type Hammarsten, at 280 nm. In order to create these models the first step done was the electronic Results: The highest proteins concentrations were observed in mature and geometrically characterization of phenol and amines structures, fruits, followed by the fermented ones, the green fruits showed the defining the less energy geometries and the potential molecular lowest concentration. In contrast to protein concentration, the interaction sites with the support of functional M05-2X and the base 6- proteolytic activity was higher in the ripe fruit, but does not differ 31G(d,p) corresponding to the Density Functional Theory. Afterwards appreciably from the green ones, the lowest proteolytic activity was employing the Minimum Multiple Hypersurfaces Methodology, observed on fermented fruits. different phenol-amines association models were generated, from which the most stables were identified and studied at M05-2X/6- Conclusions: Proteolytic activity is informed for the first time for 31G(d,p) level. As well, using the Atoms in Molecules and Natural Bond Morinda citrifolia L. and its superior for the green and mature fruits. Orbital Theories, the intermolecular interactions were characterized. Hydrogen bond and Van der Waals interactions were identified as the interactions responsible to warranty different association stability, being the interaction between the amine free pair of exocyclic nitrogen and sigma orbital anti-bond of hydroxyl group, the strongest hydrogen bond among all complexes and also represent the highest contribution to the stability. The main modification that conduces to pro-mutagenic aromatic amines activation was the N-hydroxylation of exocyclic nitrogens, which proposed that phenol interaction with this position would reduce its accessibility to the enzyme and therefore it would be possible to explain the DTP anti-mutagenicity. The complexes stability order proposed and as consequence the protection order against amines is: DTP/PhIP> DTP/m-PDA >DTP/4-ABP.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S220
LATINFARMA 2013 Resúmenes/Abstracts
PPN 043: ACUTE INFLAMMATORY EVALUATION OF PPN 044: DETERMINATION OF DIURETIC POTENTIAL OF VEGETABLE OIL Cucurbita moschata DUCH Commelina elegans HBK AND Bryophylum pinnatum LAM Sueiro-Oyarzun ML, Williams OE, Hernández-Barreto E, Saucedo- Valdovinos N, Ferrandiz D. Hernández Y, Cabrera-Santos K, Jorge-Rodríguez ME. Universidad de Camagüey. Circunvalación Norte, Km 5 ½. Camagüey, Cuba. E- Departamento de Farmacia, Facultad de Química y Farmacia, Universidad Central mail: [email protected] de Las Villas, Santa Clara, Cuba. E-mail: [email protected]
Introduction: A few years ago, the National Program for Medicinal Introduction: Therapeutic control of inflammation has gone through Plants was created. The province of Camaguey was then assigned the various stages, but none has achieved a complete success, because it is task of working on diuretics. In this work, plant diuretic capacity was difficult to manipulate a phatophysiologic event where so many factors contrasted to a commercial diuretic (hydrochlorothiazide). The plants are involved. The use of medicinal plants has been booming since the studied were Commelina elegans HBK, and Bryophylum pinnatum Lam. introduction of traditional medicinal resources in health systems. The Cucurbita moschata is a medicinal plant with several therapeutic Material and methods: The plants were decocted to a concentration properties and few have been scientifically proven. Anti-inflammatory of 20% w/v and after 2h of rest they were filtered. Some physical and property is one of them and could be ascribed to the metabolites of the chemical parameters were determined, such as, total solids, pH, and oil seeds. The objective of this work was to evaluate the acute anti- sodium and potassium contents. For the diuretic study of plants 50 inflammatory activity of Cucurbita moschata vegetable oil. Wistar rats (25 males and 25 females) from the Camaguey Medical University Animal Lab. were used. The diuretic effect of the decoction Material and methods: The evaluation of the acute anti-inflammatory was tested at 200, 400 and 800 mg/kg doses per body weight. The activity of the vegetable oil is conducted through the technique of natriuretic and kaluretic effects of the decoction on the negative and induced plantar edema agents: λ-carrageenan, fresh egg albumin positive control groups were contrasted. undiluted, dextran and histamine in Wistar rats and by the technique induced ear edema agent: 12-o-tetradecanoylphorbol-13-acetate in Results and conclusion: The positive control group had a qualitative Balb/c mouse. Oral doses of 2, 4 and 8 mL/kg for plantar edema higher volume of urine. The decoction of Commelina elegans had the technique were administered and equal oral doses and a single dose (1 closest results to the synthetic diuretic in the doses of 200, 400 and 800 mg) topically to ear swelling technique. mg/kg of weight. Results: For oil tested doses showed topical and systemic anti- inflammatory activity with a possible dose-dependent behavior, being able to relate this property with the possible inhibition of cyclooxygenase and lipoxygenase, as well as a possible blockade of histamine H1 receptors. Conclusions: The vegetable oil at doses of 2, 4 and 8 mL/kg has acute anti-inflammatory effect by showing a significant inhibition of inflammation of plantar as well as ear edema, topically and systemically.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S221
LATINFARMA 2013 Resúmenes/Abstracts
PPN 045: TOPICAL ANTI-INFLAMMATORY ACTIVITY OF FIVE PPN 046: PRECLINICAL VALIDATION OF THE TRADITIONAL FRACTIONS OF FRESH AERIAL PARTS OF Phania USE OF Cordia martinicesis matricarioides (CHAMOMILE LAND) Martínez I, Victoria MC, Brito G, Morón F, Duménigo A, Morejón Z, García AI, Martínez I, Domínguez A, Cabrera H, López M, Boucourt E, Nossin E. Acosta L, Morón FJ. Laboratorio Central de Farmacología, Facultad de Ciencias Médicas. "Dr. Salvador Laboratorio Central de Farmacología, Facultad de Ciencias Médicas. "Dr. Salvador Allende”. Carvajal e/ Agua Dulce y A, Cerro, Habana, CP 12000, Cuba. E-mail: Allende”. Carvajal e/ Agua Dulce y A, Cerro, Habana, CP 12000, Cuba. E-mail: [email protected] [email protected]
Introduction: Through ethnobotanical survey as part of Program of Introduction: Recent preclinical pharmacological studies of analgesic, Applied to Popular Medicine in the Caribbean (TRAMIL), leaves anti-inflammatory and anti-diarrhea, as well as toxicological decoction decoction of Cordia martinicensis (Jacq.) shows a significant traditional of fresh aerial parts of Phania matricarioides (Spreng.) Griseb used in local populations for thoracic pain and fever relieve. Our aim (chamomile land) have validated its traditional use for digestive was to determinate the analgesic, anti-inflammatory and antipyretic disorders and dermatological. Our objective was to evaluate the topical activity of leaves decoction of C. martinicensis. anti-inflammatory activity of five fractions of fresh aerial parts of Material and methods: Activity was assayed using a nociception Phania matricarioides (chamomile land). models, writhing test (acid acetic 0.75%, 0.1 mL/10 g, i.p.) and tail flick Material and methods: Collection of fresh aerial parts of P. test (water at 55°C). Model of inflammation was ear edema test, matricarioides, botanical identification and assembly of voucher applying 20 µL of Croton oil (75 µg/ear). All these models were herbarium specimens were carried out. Five fractions were obtained conducted in male OF-1 mice (20–25 g). Finally, antipyretic activity from plant material; PhAF1 (precipitate); PhAF2 (aqueous); PhAF3 was tested inducing pyrexia with brewer's yeast (15% in water; 1 (butanol); PhAF5 (supernatant butanol), that were assayed for its anti- mL/100 g, sc.) in male Wistar rats (180-200 g). inflammatory effect by using ear edema induced by croton oil topically Results: C. martinicensis decoctions doesn’t produced a significant applied to OF-1 (20-25g) male mice. Fractions were assayed (20 µL) at anti-nociceptive in response to thermal stimulus compared to control doses of 2, 1, 0.5 and 0.25 mg, except fraction PhAF4 (precipitate group. However, doses of 5 g/kg decrease the number of abdominal butanol) that assayed at doses 1, 0.5, 0.25 and 0.125 mg). stretching with 44.4% of inhibition. Anti-inflammatory activity of oral Results: Inhibition of inflammation in the ear edema (55.1%, 53.5%, administrations of C. martinicensis showed a significant inhibition at 10 35.5% and 33%) induced by Croton oil was obtained for PhAF2 and 5 g/kg, with percentage of inhibition 60.9 and 56.9%, respectively. fraction (aqueous) whereas no anti-inflammatory effect was obtained Topic administrations at 6 mg/ear had a 62.9% of inhibition. C. by the others. martinicensis showed a significant antipyretic activity similar to paracetamol, after the 1st hour to 4 hours of administration. Conclusions: Of the five fractions of fresh aerial parts of P. matricarioides evaluated, only the fraction PhAF2 (aqueous) showed Conclusions: These results validate the traditional use of herbal topical anti-inflammatory activity. preparations in the study.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S222
LATINFARMA 2013 Resúmenes/Abstracts
PPN 047: EVALUATION OF ANTI-INFLAMMATORY AND PPN 048: PRECLINICAL VALIDATION OF ANTI- ANALGESIC PROPERTIES OF AN ORGANIC EXTRACT OF INFLAMMATORY EFFECT OF Hibiscus rosa sinensis RED SEAWEED Galaxaura rugosa (Marpacífico) Duménigo A, Frías AI, García N, Ramentol RM, Cabrera HR, Suárez AM. Brito G, Martínez I, Morón F, Victoria MC, Duménigo A, Morejón Z, Nossin E. Laboratorio Central de Farmacología, Facultad de Ciencias Médicas. "Dr. Salvador Allende”. Carvajal e/ Agua Dulce y A, Cerro, Habana, CP 12000, Cuba. E-mail: Laboratorio Central de Farmacología, Facultad de Ciencias Médicas. "Dr. Salvador [email protected] Allende”. Carvajal e/ Agua Dulce y A, Cerro, Habana, CP 12000, Cuba. E-mail: [email protected]
Introduction: Inflammation is a local response that tends to restore the imbalanced homeostasis in the organism. However, sometimes is Introduction: In Cuba and Caribbean countries Hibiscus rosa sinensis undoing of an excessive and inappropriate manner, giving place to are very common in garden. Reports of traditional use are related with different pathological process that require of treatment. Galaxaura conjunctivitis, fever, headache, flu and cough. rugosa is one of the most abundant species of red algae in the Cuban coral reef, nevertheless, a few is known about of their pharmacological Our aim was to determinate preclinical anti-inflammatory effect of activities. In this work was realized the chemical characterization and decoction of leaves and flowers of Hibiscus rosa sinensis. was evaluated the anti-inflammatory and analgesic activities of the Material and methods: Activity was assayed on acute inflammation extract obtained by dichloromethane extraction. model (ear edema test), applying 20 µL Croton oil (0.4%). Different Material and methods: The seaweed was collected in Havana´s north doses of decoctions 30% of flowers and leaves were evaluated topically littoral in April 2011. For the extract preparation, the sample was and orally. Ten µl of decoctions were applied at each side of the treated subject to a Soxhlet extraction with dichloromethane. The topic anti- ears. Model was conducted in male OF-1 mice (20–25 g), 6 animals inflammatory activity of the extract was evaluated in the ear edema each group. Dexamethasone (0.5 mg/ear) and indomethacin (15 test induced by Croton oil. Besides, was evaluated the analgesic activity mg/kg) were used as reference drugs. of the extract by i.p. way in the writhing test (acid acetic 0.8%, i.p.). Results: The extracts from leaves and flowers (30%) applied topically Both models were conducted in male mice OF-1 (25-30 g). inhibited inflammation on 54.7% and 30.9% respectively. Oral Results: The dichloromethane extract of G. rugosa shows a potent anti- administrations do not show a significantly anti-inflammatory activity inflammatory activity since the dose of 0.125 mg/ear (higher than in both extracts. 40%). The extract get reduce the pain sensation in more than 75% Conclusions: Results validated traditional use of leaves of Hibiscus rosa since the dose of 6 mg/kg. sinensis in inflammation process. Conclusions: The effects demonstrated in the present study of red seaweed G. rugosa, constitute new pharmacological properties, which open new perspectives to the possible therapeutic use of this algae so abundant in our country.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S223
LATINFARMA 2013 Resúmenes/Abstracts
PPN 049: ANTIPYRETIC ACTIVITY OF A WATERY EXTRACT PPN 050: EVALUATION OF THE HYPOGLYCEMIC ACTIVITY OF Cecropia peltata L. IN RATS OF THE WISTAR SPECIES OF EXTRACTS FROM Boldoa purpurascens CAV. EXPERIMENTAL MODEL González D, Hernández Y, By B, Vicet L, SaucedoY, Pieters L, Appers S. Hernández Río M, Pizarro Espín A, González Madariaga Y, Ruiz Perez Universidad Marta Abreu, Carretera a Camajuaní km 5 1/2, 50400 Santa Clara, R, Machado García D. Cuba. E-mail: [email protected] Universidad de Ciencias Médicas de Villa Clara. “Dr. Serafín Ruiz De Zárate Ruiz”. Facultad de Medicina. Centro de Toxicología, Villa Clara, Cuba. E-mail: [email protected]. Introduction: Boldoa purpuracens, Cav, a plant belonging to Nyctaginaceae family, is traditionally used for its diuretic effect comparable to furosemide. In the species described the presence of Introduction: The Cecropia peltata L. species is a plant greatly used by several flavonoid compounds widely used for its diversity of actions the population. The use of this plant has been mentioned in affections among which is the hypoglycemic. that involve asthmatic or catarrhal episodes. The present study is carried out with the objective of checking experimentally, for the first Material and methods: The phytochemical analysis by 1H and 13C time, the antipyretic effect attributable to the watery extract of NMR spectroscopy allowed the presence of D-pinitol in the ethanol Cecropia peltata L., in rats. extract from the leaves of the plant. The aimed of the investigation was checking the hypoglycemic effect of aqueous and alcoholic extracts Material and methods: An experimental study was developed, of obtained from Boldoa purpurascens at doses of 50, 100 and 200 mg/kg preclinical rehearsal to randomized blind double, by means of the using insulin 5 UI/kg as a positive control and NaCl 0.9% as negative intraperitoneal injection of a watery suspension of 20% brewer’s yeast control. Another experiment was performed similar but dried aqueous in chloride of sodium to 0.9% as exogenous pyrogen in 4 groups of 8 extract was used at doses of 50, 100 and 200 mg/kg; using metformin animals each one; in the Toxicology’s Center (CENTOX.) of the Medical at dose of 50 mg/kg as a positive control and keeping the 0.9% NaCl as University of Villa Clara in February of the 2013. Three groups were a negative control. The statistical analysis was carried out by the test of created and received doses of 200, 400 and 800 mg/kg of the extract Kruskal Wallis with an interval of trust of 99%. and 1 group positive control with ibuprofen (100 mg/kg). It were applied as descriptive statisticians the stocking and the standard Results and conclusion: The species possesses hypoglycemic activity deviation. The comparison among the groups was carried out by at all doses tested in both extracts, being the reduction greater for the means of the application of not parametric technical, using the test of ethanol extract (40%), comparable to insulin. Kruskal-Wallis and Mann-Whitney for independent samples, with a trust interval of 95%. Results: The antipyretic effect of the extract of Cecropia peltata L. was proven through the described technique, to the doses of 200, 400 and 800 mg/kg, with similar final temperatures to those of the group used positive control. Conclusions: The aqueous extract of Cecropia peltata L. presented a considerable antipyretic activity to the dose of 400 mg/kg of weight when comparing with the reference medication.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S224
LATINFARMA 2013 Resúmenes/Abstracts
PPN 051: ANTIVIRAL ACTIVITY EVALUATION OF Laurencia PPN 052: CLINICAL TRIAL PHASE IV WITH SURFACEN IN obtusa AGAINST HERPES SIMPLEX VIRUS AND DENGUE NEONATE POPULATION VIRUS Barrese Y, Díaz E, Avila Y, Morilla A, Uranga R, Fernández O. Rojas L, Álvarez M, Morier L, Pérez O, Torres Y, Valdés O, del Barrio G. Centro Nacional Coordinador de Ensayos Clínicos (CENCEC). Ave 200 esq. at 21, Departamento de Microbiología y Virología. Facultad de Biología. Universidad de Atabey, Playa, Habana, Cuba. E-mail: [email protected] La Habana, Cuba. E-mail: [email protected]
Introduction: SURFACEN has a sanitary registration emitted by the Introduction: Herpes and dengue virus are important human Center for the Control of the Medications, Devices and Medical pathogens with high levels of morbidity and mortality. Failure in the Equipment (CECMED) from 1995 for substitution therapy under development of vaccines, along with the absence of antiviral conditions of dysfunction of the surfactant system lung, as respiratory compounds and the emergence of viral variants resistant to antiviral distress syndrome (RDS) in the newly born with intubation drugs currently used highlights the need for new antiviral drugs. Algae endotracheal and mechanical ventilation. The objective of this clinical remain an interesting alternative in this regard, due to the diversity of trial is to evaluate the use of SURFACEN in neonate population. compounds with biological activity founded in these organisms. In this work we evaluated the antiviral activity of Laurencia obtusa aqueous Material and methods: Design and conduction of a phase IV clinical extract against Herpes simplex virus in Vero cells and Dengue virus in trial, multicenter, national, not randomized, not controlled, open and C6/36HT cells. with only one treatment group, SURFACEN + conventional therapy, in neonate population with less than two hours of born, gestational age Material and methods: The cytotoxicity of the algae (CC50) was between 26 and 36 weeks, use approach early of SURFACEN and RDS determined in both cells lines using the MTT reduction assay. Antiviral tried in neonatal units of intensive cares (NUIC). It was administered a activity (EC50) was calculated by means of cytopathic effect inhibition dose of SURFACEN at least, 100 mg, by means of a endotracheal in cells, then the selective index (SI) =CC50/EC50 was calculated. probe and, later on, positive continuous pressure was applied in the air nasal road or another ventilator modality to the investigator's Results: The seaweed was non-cytotoxic at concentrations evaluated approach. For the evaluation were considered clinical, gasometrical, (0-5000 µg/mL). Laurencia obtusa inhibited Herpes simplex virus-1 ventilators and imagenologic variables; as well as the detection and and Herpes simplex virus-2 replication in Vero cells with SI values control of adverse events for safety evaluation. higher than 29 and 42, respectively. On the other hand there was no inhibition of Dengue virus replication in C6/36HT cells at Results and conclusions: In phase IV clinical trial 225 patients were concentrations evaluated (0-5000 µg/mL). included. The increment of the number of doses of SURFACEN was associated with the appearance of complications; however 141 patients Conclusions: Given these results, this red seaweed appear as good (62.67%) alone it required of a dose of the surfactant (p <0.000). The candidate for further studies on its mechanism of action and its stocking of the days of stay in NUIC was of 22.7 days, while the potential for inhibition of herpes virus in vitro, and in vivo. This is the ventilation requirement was of 5.7 days; not being necessary the first report of Laurencia obtusa antiviral activity against Herpes simplex ventilation prolonged in 76.00% of the patients and was evidenced the virus and Dengue virus. absence of ventilators complications in the 83.33% (p <0.000). The improvement was appreciated in the oxygenation index and in the relationship PaO2/FiO2. The treatment with SURFACEN was tolerable and safe.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S225
LATINFARMA 2013 Resúmenes/Abstracts
PPN 053: THE IMPACT OF PHARMACEUTICAL SCIENCE PPN 054: TOPICAL TREATMENT FOR MYCOTIC VAGINITIS LOOKING THROUGH TECHNOLOGY: WEB PAGE OF WITH GARLIC EXTRACT EXPERIMENTAL STATION OF MEDICINAL PLANTS "DR. Izquierdo M, Avilés L. JUAN TOMAS ROIG" Facultad de Ciencias Médicas de Mayabeque, Güines, Cuba. E-mail: Elizagaray-Fernández B, Fernández-Fernández Y, Castro-Armas R. [email protected] Centro de Investigación y Desarrollo de Medicamentos. (CIDEM). AVE 26, No. 1605 e/ Boyeros y Puentes Grandes, La Habana, Cuba. E-mail: [email protected] Introduction: The vaginal mycotic sepsis constitutes more than a 70% of the cases who attend the Gynecological consultation, being Candida albicans the etiologic agent which can be found in an 80-90% of these Introduction: A website today is the global media excellence to the cases. There have been a great deal of antimitotic medications which needs required for people who surf the Internet and their companies. have been used during many years, but with the improvement of the The general objective to this work is design and implementation of the pharmaceutical industry, they have been used with lower or higher web page of the Experimental Station of Medicinal Plants "Dr. Juan level of effectiveness and with their corresponding adverse reactions. Tomás Roig” belongs to the Center for Research and Drug There have been different studies which treat aspects related to Development. The specific objectives are: Achieve high-impact alternative therapies using phyto drugs such as Allium sativum L. corporate visibility nationally and internationally in the Medicinal Material and methods: An experimental study was performed with Plants and Natural Products pharmaceutical area: Provide detailed 37 patients of the Cervical Pathology consultation at “Manuel Fajardo” information on the characteristics of the entity: Facilitate access to R & Maternity Hospital from Güines with results of altered organic cytology D information (articles, processes, projects, etc) online non-profit: and with symptoms and signs of acute vulvovaginitis by Candida Rescue potential and real customers to exchange and/or confirmed by wet mount and microbiological study. With the objective commercialize of products and technologies. of assessing the effectiveness of the use of garlic in this disease and Material and methods: Visual design information to be edited; performing a formulation of the topical use and its possible adverse definition of structure and hierarchical relationship of the web site reactions in the period between August 2010 to December 2011; a pages through the navigation chart; identification and implementation collecting information form was performed and statistical procedures of software to use (Wordpress) and definition and organization of of X2 and Duncan test were applied with the information found as a relevant content to add on the website. result of the investigation in this aspect. Results: Was set the web page of the Experimental Station of Results and conclusions: The elimination of Candida was determined Medicinal Plants "Dr. Juan Tomás Roig" where can view online in an 83% of the patients and the symptoms were relieved in more than information about the general characteristics of the center and one 75% of the cases, with very few adverse reactions and none of them that allows scientific cooperation for the research area in question. By serious. The elaboration of the phyto-drug with the proposed implementing is viable the virtual approach of real users and potential pharmaceutical technic: garlic ovule of 100 mg during three days clients on real-time to the entity. showed to be an alternative in the pharmacological treatments prescribed for this pathology and it represented an economic saving of Conclusions: According to the above elements concludes that there has all the affected ones. been a positive step forward for the institution because its visibility in the web environment, which is an indispensable element for corporate performance in the world today.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S226
LATINFARMA 2013 Resúmenes/Abstracts
PPN 055: BACH FLORAL THERAPY IN TYPE 2 DIABETIC PPN 056: EFFECTIVENESS OF OZONIZED SUNFLOWER OIL PATIENTS AND ITS EFFECT ON T LYMPHOCYTE FUNCTION (ORAL OLEOZON®) COMBINED WITH GIARDINUM IN THE TREATMENT OF GIARDIASIS Mahía M, Díaz A, Garcia M, Hernández J, Ramos E, Alonso C. Marcel Llovet A, Rodríguez Delgado N, Izquierdo Estrada M. Instituto Nacional de Angiología y Cirugía Vascular, 1551 Calzada del Cerro, Habana, Cuba. E-mail: [email protected] Centro Provincial de Medicina Natural y Tradicional. Calle José Martí No. 55. Bayamo, Granma, Cuba. E-mail: [email protected]
Introduction: Floral therapy is considered a useful tool for psychological harmony by influencing on neurological, endocrine and Introduction: Giardiasis is one of the most common pathogenic immunological function of human beings. The evidence suggests that intestinal protozoal infections worldwide and is a very important there is a relationship among stress, circulating cortisol and immunity health problem. Global statistics report prevalence rates of 2 - 30%, system. depending on the countries’ development level and geographic location. In Cuba, the rates are 7 - 15%. The symptomatology can be an Objective: This research was aimed to assess the effect of Bach floral acute phase with diarrhea alternating to constipation, abdominal pain, therapy on the immunological capacity of T lymphocytes of type 2 flatulence and urticaria. In the chronic phase, diarrhea can be steady, diabetic patients with immunodepression. with a severe weight loss, producing a disordered or inadequate Methods: Two hundred type 2 diabetic patients non hospitalized absorption of nutrients. The adverse effects and treatment failures to within vascular complications, both sexes and aged from 40 to 80 years some of the currently recommended drugs for Giardia lamblia infection old were included in this study in a randomized double-blind versus have given rise to the need for alternative antigiardiasis agents. placebo experimental design. Psychological tests, T lymphocytes Method: A prospective and descriptive study with the objective of function by delayed hypersensitivity test (in vivo), and serum levels of evaluate the effectiveness of oral Oleozon combined with the glycaemic and cortisol by blood sample were performed to each homeopathic remedy Giardinum in the treatment of giardiasis was patient before and after a two-month period with floral essences or carry up in patients resistant to the conventional treatment referred by placebo. We obtained ethics-committee approval. The statistical different gastroenterology services from Bayamo municipality to the significance of the data included the comparison of values of these Provincial Traditional Medicine Clinic (March 2010 -Nov 2012). The variables and was determined by T student and chi-square tests. P diagnosis of giardiasis was confirmed by fecal heces complementary values less than 0.05 were taken as significant. and the biliary drainage. To solve the objective stated variables were Results: Significative difference was found in delayed hypersensitivity selected: age, sex, symptoms, complementary results and treatment test. A decrease in serum levels of glycaemic and cortisol after response. Oral Oleozon and Giardinum were indicated in the treatment by oral flower essences administration was evidenced. In recommended doses for ten days, in both cases were oriented to rest a addition, favourable changes in the emotional levels after floral week and to repeat the same cycle. All the patients were evaluated treatment in comparison with placebo were observed. clinically taking into consideration the symptoms persistent or not at the beginning of the consultation and the results of the biliary drainage Conclusion: Our finding implicated that Bach floral therapy might be and fecal heces in the 3rd, 5th and 7th day after finishing the treatment. useful to enhance the immune, psychological, endocrine and glycaemic levels status in these patients. Results: 109 patients whit giardiasis diagnose were attended in ages between 5 and 55 years, the male sex was predominant 68 (62.3%) in ages between 5 and 15 years (11.0%). The main symptoms were: abdominal pain (71.5%), cutaneous injuries (66.0%), rash (55.9%), flatulences (54.1%) and slow digestions (44.0%). All the patients finished the treatment as it was indicated and a referral of symptoms were seen in 89.9% (98/109) of the cases, in 86.2% (94/109) of them the parasite was eliminated and it was corroborated by means of fecal heces and biliary drainage. Patients cured after treatment with Oral Oleozon and Giardinum, were checked again after 3 and 6 months, and only 6 cases of 94 were reinfected, according to the lab test (6.3%). Conclusion: The oral Oleozon combined with Giardinum is effective in the treatment of Giardiasis.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S227
LATINFARMA 2013 Resúmenes/Abstracts
PPN 057: EFFECT OF A NATURAL SOLUTION OF THE PPN 058: USE OF VIDATOX® 30CH IN INFLAMMATORY, Rhopalurus junceus SCORPION VENOM IN PATIENTS WITH ONCOLOGICAL AND AUTOIMMUNES DISEASES BRAINSTEM GLIOMA. CASE´S REPORT Casamayor Z, Guevara M, González S. Cruz N, Ríos M. Grupo Empresarial de Producciones Biofarmacéuticas y Químicas. LABIOFAM. Grupo Empresarial de Producciones Biofarmacéuticas y Químicas. LABIOFAM. Calle Corrales Nº 105 entre Cardenas and Cienfuegos. Habana Vieja. La Habana, Habana. Cuba. Edif. 23-A, apto 23. Guiteras, Habana del Este, La Habana, Cuba. E- Cuba. E-mail: [email protected] mail: [email protected]
Introduction: VIDATOX® 30CH is a homeopathic product from the Introduction: The brainstems gliomas are considered among the most venom of the Rhopalurus junceus scorpion. aggressive in the pediatric population with bad prognosis; these Objective: To describe the clinical evolution of the patients treated tumors are heterogeneous, ranging from low-grade tumors that need with VIDATOX® 30CH. little treatment to high-grade lesions that are rapidly fatal despite aggressive therapy. The natural solution of the Rhopalurus junceus (RJ) Material and methods: It was performed an observational and scorpion venom has been studied for more than 10 years in different descriptive study of patients attended on the medical services of kinds of tumours, showing a decrease of the viability of tumour cells by LABIOFAM treated with VIDATOX® 30CH during the period of 2011- apoptotic and necrosis mechanisms. In other preclinical studies 2012. 2541 patients were included. Symptoms consultation reason, analgesic, anti-inflammatory and no toxic effects were found. That`s frequency of administration of VIDATOX® 30CH and the moment in why, this venom would be an alternative therapy for patients with which they began to improve symptoms were the main variables. The cerebral tumors. Chi-square of Pearson test was used to compare the clinical evolution and the improvement of the symptoms was tested by Analysis of the Objective: To evaluate the use of a natural solution of the scorpion Variances (ANOVA). venom in a patient with brainstem glioma. Results: The patients with oncoproliferative diseases prevailed (2261; Material and methods: It was designed a prospective and 88.98%) and the degenerative ones were in second place (132, 5.19%). observational study with two patients with brainstem glioma, a patient The pain was the most referred symptom (1431; 56.32). The majority with brainstem glioma with exophytic growth that includes left of the patients were prescribed VIDATOX® 30CH three times daily thalamus and other patient with a diffuse brainstem glioma; both (1389; 54.7%). 96.92% of the patients that were prescribed VIDATOX® patients received as only treatment the natural solution of the RJ 30CH three times daily improved the pain scorpion venom. The evaluated indicators were life´s quality according to the Lansky and Karnosfky scale, size of the tumour lesion by Nuclear Conclusions: The homeopathic product VIDATOX® 30CH is a Magnetic Resonance as well as the appearance of adverse reactions therapeutic reliable option in the symptomatic treatment of patients referred to the treatment. with oncological, inflammatory, autoimmune and degenerative disorders. Results: The 100% of patients showed improvements in the life´s quality, it was also observed a tumor size reduction and adverse reactions were not reported.
Conclusions: The use of a solution of the RJ scorpion venom improves the quality of life of patients with brainstem glioma and it diminishes the tumoral size without secondary effects in the ones that consumed it.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S228
LATINFARMA 2013 Resúmenes/Abstracts
PPN 059: ETNOMEDICAL USE OF A NATURAL SOLUTION OF PPN 060: EFFICACY OF BACH´S FLORAL THERAPY IN THE Rhopalurus junceus SCORPION VENOM IN COLORECTAL TREATMENT OF ACADEMIC STRESS CANCER PATIENTS Maceo O, Ramos K, Maceo A, Morales I, Maceo M. Morales C, Cruz N, Bermudez MI, Espronceda M, Guevara M, Filial de Ciencias Médicas Dr. Efraín Benítez Popa Bayamo, Granma, Cuba. E-mail: Fernández, Casamayor Z, González S. [email protected] Grupo Empresarial de Producciones Biofarmacéuticas y Químicas. LABIOFAM. Departamento de Investigaciones Clínicas. Ave 1ra y B, Vedado, Habana, Cuba. E- mail: [email protected] Introduction: Academic stress is frequent in the university students because of the high responsibility and all the knowedge they should get in short time in orders to take care of human being. In our country Introduction: Jointly with the lung, prostate and breast cancer, the more than a 70% of university students suffer from academic stress. colorectal cancer is considered one of the most frequent carcinomas in Any effort to reduce the level of academic stress would help them with the world, as well as one of the main causes of death. Enterprise Group their academic results and health. LABIOFAM specialists have carried out several investigations on the pharmacological activity of Rhopalurus junceus scorpion venom Material and methods: An experimental double blind controlled, solutions, especially on the originally epithelial tumor cells. study was carried out to evaluate the efficacy of Bach's Floral Therapy in the treatment of academic stress in first-year dentistry students at Material and methods: An observational descriptive study was made the Medical Sciences Brand of Bayamo, from September 2010 to June in patients with colorectal cancer in order to evaluate the effects and 2011. The universe was conformed by 60 students were tested and security of a natural solution of Rhopalurus junceus scorpion venom. proved to be stressed once applied the Inventory of Academic Stress. Registers of 144 histological confirmed colorectal cancer patients were Two groups were created; one received 3 daily doses for 30 days at a analyzed whose were treated in LABIOFAM Enterprise Group Medical rate of 4 drops sublingually of the flower mixture and the other Service, since February 2003 to November 2011. It was evaluated well- received a placebo. known time in treatment as survival indirect variable. The quality of life was evaluated through scales of pain evolution and incorporation Results and conclusions: The Statistical analysis to determine the to daily activities. association among the groups (Chi-square test of Friedman) showed a significant difference (p <0.05). These results support the hypothesis Results: There was a survival media of 3 years, a pain relief was that floral therapy is effective in the treatment of academic stress. reported in 84% of patients and they were incorporated to daily activities 36.8% of them. Severe side effects were not reported. Conclusions: This natural solution of Rhopalurus junceus scorpion venom is safety and effective for adjuvant treatment of colorectal cancer patients.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S229
LATINFARMA 2013 Resúmenes/Abstracts
PPN 061: AURICULAR MICROSYSTEM THERAPY AND FLORAL PPN 062: BACH FLOWER THERAPY IN THE TREATMENT OF THERAPY COMBINATION IN THE TREATMENT OF FEMALE CLIMACTERIC SYNDROME ESSENCIAL HYPERTENSION. BAYAMO 2011- 2012 López Suárez JC, Cepero Franco S, Del Toro Mosquera G, Corrales Ramos K, Aguilar M, Ortiz Y, Rodríguez N, Díaz J. Zamora Y, Cepero Carballo N.
Universidad Médica de Bayamo. Carretera vía Santiago de Cuba Km 1 ½, Bayamo, Universidad Médica de Ciego de Ávila. Facultad de Ciencias Médicas Morón, Ciego Granma, Cuba. E-mail: [email protected] de Ávila, Cuba. E-mail: [email protected]
Introduction: The grade I essential arterial hypertension, regarding A prospective longitudinal study was carried out from January 2011 to Natural and Traditional Medicine is a syndrome mainly caused by liver February 2013, in order to demonstrate the effectiveness of Bach heat (Kan Yol Zung) or empty kidney (Sim Um Jo zung). Thus, the Flower Therapy to treat menopause symptoms. The sample comprised treatment is to energy balance by sedating the liver yang or toning up 60 patients who met the inclusion criteria. They were divided into two the kidney yin. According to Dr. Bach, the use of his floral remedies is groups: perimenopausal and postmenopausal women, which was aimed at relieving psycho-emotional. Thus, the general objective of this applied Bach Flower Therapy. The heat or hot flashes predominated in work was to evaluate the effectiveness of the auricular microsystem 88.9% of perimenopausal women, asthenia was more common in therapy and floral therapy combination to diminish the levels of postmenopausal women by 87.9%.The psychic manifestations that arterial tension. occurred more frequently in perimenopausal women were irritability and insomnia, for 66.7% and 59.2% respectively. In sexual sphere Material and methods: A quasi-experimental study was carried out to dominated vaginal dryness (75.5%) and libido decreased (51.5%). evaluate the effectiveness of the auricular therapy and floral therapy After administration of treatment it was found that clinical and combination to reduce blood pressure levels in risk A group patients psychological symptoms achieved a rapid resolution. It was concluded with grade I essential arterial hypertension previously diagnosed that vasomotor and psychological disorders were more common in during the January, 2011–January, 2012 period at the Provincial perimenopausal women, whereas sexual and general sphere Natural and Traditional Medicine Center in Granma. Eighty patients predominated in postmenopausal women. There was a significant who met the inclusion criteria were evaluated. The variables studied improvement of clinical symptoms present in patients to the extent were age, sex, blood pressure levels, time of response to treatment, and that they received treatment with Bach Flower Therapy. adverse events. The patients were evaluated on weekly basis during the first month and then at 3, 6, and 9 months.
Results: Female patients over 65 years of age predominated in the study and at the end of the first month of treatment 70 of them were stable, 9 had improved and 1 was not stable, at 6 months of treatment 73 patients were stable, and 3 months after treatment, all of the 80 patients remained stable. Conclusions: Our study demonstrated that the combination of auricular therapy with the stimulation of hypertensive and sedative loci with floral remedies 1, 18, and 21 is effective for the reduction of arterial blood pressure levels in grade I essential hypertensive patients, without serious adverse effects or the need of other medications.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S230
LATINFARMA 2013 Resúmenes/Abstracts
PPN 063: Cymbopogon citratus FRACTIONS, PROTECTIVE PPN 064: PROGRESS OF ELDERLY WITH ANEAMIA DUE TO ACTIVITY AGAINST UVC LIGHT IN Caulobacter crecentus NUTRITIONAL DEFICIT TREATED WITH APIASMIN Fuentes-León F, García F, Aguilera K, González-Pumariega M, Sánchez- Morfi R, Suárez D, Beyris R, Jimenez I, Bouza F, Cañadilla M. Lamar A. Centro de Investigaciones Apícolas CIAPI. Carretera de El Cano al Chico, Departamento de Biología Vegetal, Facultad de Biología, UH. Calle 25 #445 e/I y J. Artemisa, Cuba. E-mail: [email protected] Vedado, Plaza de la Revolución, La Habana, Cuba. E-mail: [email protected]
Introduction: Anaemia for inappropriate consumption of protein, Ozone layers hole entails the increase in ultraviolet radiation of some vitamin, iron, copper and other heavy metals is call nutritional. sunlight on the earth surface, raising the risk of skin diseases, even Apitherapy study’s well cared of human health by means of application cancer, in exposed individuals. The use of vegetal compounds is a new of beehive products. Honey has a high nutritional value, the pollen that strategy to protect against UV damage by overexposure. Substances gather all essential amino acid even those that our organism can’t obtained from natural sources are less hazardous than synthetic synthesize is the most complete food on nature whereas propolis rise products. They also have a huge molecular diversity and biological up the immunological level. When those products are mixed is function. For that reason, evaluation of toxic and genotoxic capacity of obtained a nutritional supplement very useful treatment for anaemia, these compounds is required before the use of its beneficial properties. called Apiasmin. Objective: To administer Apiasmin to treat nutritional Cymbopogon citratus (DC) Stapf, also known as Caña Santa, is consumed aneamia on elderly as national nutritional supplement. as a popular decoction and has several medicinal properties such as: anti-inflammatory, analgesic, antispasmodic, hypotensor, anxiolytic, Material and method: It was made a case study on the old people’s expectorant and antiasthmatic. Other studies have also shown home Alfredo Gomez Gendra with a universe of 63 elderly and a anticancer, antitumor and antimutagenic properties. A lot of these sample of 17 fragile elderly with nutritional aneamia from January to studies were assayed in total extract, less in fractioned extract. In this March of 2013. The used methods were the historical, the work, we tested the cytotoxicity, genotoxicity and the ability to protect documentary, the analysis and the synthesis. The checking of the against UVC light of two fractions obtained from Cymbopogon citratus diagnosis and cure of patients was made through full blood test. The (butanolic and essential oils fractions). For this, SOS Chromotest and treatment consists of two daily spoonful of Apiasmin. It was respected Survival test were used in the experimental model of Caulobacter the informed consent of the elderly and relatives. crecentus (NA 1000 p3213 lac z). Increasing concentrations of these Result: The 82% of the elderly (14) healed or make them feel better fractions (0.1, 0.5, 1, 2 and 4 mg/mL) were applied continuously: and only the 18% (3) do not healed considering that they present before, during and after UVC exposure (100 J/m2). Results showed that infections on many occasions which make their evolution difficult. both fractions were cytotoxic at the highest concentration tested (4 mg/mL) and don´t possess genotoxic properties at concentrations Conclusion: Apiasmin is a new natural by-product of the beehive lower than 2 mg/mL. These fractions increase the survival of products useful on the treatment of nutritional aneamia on elderly. Caulobacter and the induction of SOS phenomenon. Finally, butanolic and essential oils fractions don´t possess DNA protective activity against UVC light, even when they protect cells from radiation.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S231
LATINFARMA 2013 Resúmenes/Abstracts
PPN 065: PHYTOCHEMISTRY DETERMINATION OF TWO PPN 066: BIOACTIVE COMPOUNDS AND PHARMACOLOGICAL SPECIES OF ALGAE GROWN UP IN CUBAN COAST PROPERTIES OF A HYDROSOLUBLE CRUDE EXTRACT OF Pleurotus SPP. MYCELIUM Cabrera H, Frías Ana I, Dumeningo A, Rementol Rosmery, Romero A, Cuellar A. Morris H, Alcántara M, Llaurado G, Lebeque Y, Fontaine R.
Universidad de Ciencias Médicas “Dr. Salvador Allende” Carvajal s/n y Agua Centro de Estudios de Biotecnología Industrial (CEBI), Universidad de Oriente, dulce, Cerro, La Habana, Cuba. E-mail: [email protected] Santiago de Cuba, Cuba.
Introduction: Marines products are an important source of drugs. Introduction: The study of bioactive components and the Among them, algae are a big source of new metabolites with potential pharmacological properties of a hydrosoluble extract obtained from uses for treatment several illnesses. Thereby this research work aim the decoction of Pleurotus spp. mycelium was developed in this work. was to explain the relationship between the chemical composition and the anti-inflammatory properties of two red seaweed; Dichotomaria Objectives: To obtain by heat treatment of an aqueous extract of obtusata and Galazaura rugosa that grow in Cuban cost. mycelia of Pleurotus spp. using submerged culture. Determine the major macromolecular components and phytochemicals and evaluate Material and methods: Red seaweeds were collected in Jaimanitas the in vitro activity of the extract on the alternative pathway of Beach to west of Havana City. To evaluate the anti-inflammatory complement and cytotoxic activity on human leukemia NB4 cells. activity a classic pharmacological test in mice was used (ear edema induced by croton oil). Samples (fractions of methanolic extracts) were Methods: Data collection and immunopharmacological evaluation obtained using organic solvents as, dichloromethane, n-hexane and activity in vitro. buthanol and they were assayed given topical dose of 1 mg/kg/ear. Results: The composition of the extract was mainly characterized by Chemical composition was analyzed through qualitative tests, thin the presence of carbohydrates and proteins, with values of 70.4% and layer chromatographic (TLC) and HPLC. 15.0%, respectively. The spectroscopical analysis showed the existence Results: In red seaweed the organic fraction with dichloromethane in carbohydrates of β-D-glucans molecular structures. The solvent showed the best anti-inflammatory; 61.3% of inhibitory effect phytochemical screening reflected the presence of different for D. obtusata and 84% for G. rugosa, in correspondence with the metabolites with immunomodulating activity, like tannins, flavonoids presence of lactones and fatty compounds in both cases. and phenols. The mycelia extract exerted in vitro immunopharmacological actions at the level of the activation of the Conclusions: They were identified some groups of metabolites with alternative pathway of complement system, depending on anti-inflammatory properties presents in red seaweed. concentration and incubation time; as well as, an anti-tumor cell-cycle dependent effect on NB4 human leukaemic cells, presumably related with apoptosis induction. Conclusions: The submerged culture allows obtaining immunoceutic biopreparations of Pleurotus spp. The phytochemical screening showed the presence of flavonoids, tannins and phenols. Spectroscopic analysis showed the existence of β-D-glucan type structures. The mycelia extract exerted in vitro immunopharmacological actions by the concentration-dependent activation and incubation time of the alternative complement pathway and an antitumor effect on cell cycle dependent NB4 human leukemia cell, related to the induction of apoptosis. In view of these findings, the extract could be considered as an immunomodulating preparation, which would support its potential applications in immunotherapy.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S232
LATINFARMA 2013 Resúmenes/Abstracts
PPN 067: ASSESSMENT OF ANTI-INFLAMMATORY ACTIVITY PPN 068: USE OF VIDATOX® 30CH IN PATIENTS WITH OF Agave brittoniana POLAR FRACTION IN ULCERATIVE ADVANCED TUMORS COLITIS EXPERIMENTAL MODEL González S, Casamayor Z, Guevara M, Morales C, Cruz N, Domínguez M, González Y, Suárez S, Santiesteban D, Llerena T, Guerra de León JO, Espronceda M, Fernández J. Nieto L. Group of Biopharmaceutical and Chemical Productions. LABIOFAM. Havana, Toxicology Center. University of Medicine “Serafín Ruiz de Zárate Ruiz”, Santa Cuba. E-mail: [email protected] Clara, Cuba. E-mail: [email protected] Introduction: Cancer constitutes one of the first causes of death worldwide. Our country has the same situation, that’s why, the Introduction: The plants of Agave genus are rich in steroidals importance of modifying the life’s quality in this kind of patients. saponins, compounds that could be used in medicine due to their anti- inflammatory properties. Agave brittoniana Trel. Spp. Brachypus, is an Objective: To describe the behavior of the functional capacity of endemic specie of Cuba central region. We are acquainted with patient with advanced tumors treated with a homeopathic formulation ® procedures for extracting and fractioning polar extracts. In this study, of the Rhopalurus junceus scorpion venom (VIDATOX 30CH) and to we proved the effect of polar extract of Agave leaves that contain high describe the reliability of this product. saponins levels, in a model of acute ulcerative colitis with Spragüe Material and methods: It was performed an observational and Dawley rats. prospective study by the Medical Services of LABIOFAM. 2261 patients Material and methods: This model is based on the rectal instillation were included with confirmed histological diagnosis. of 2.5% acetic acid and on an oral supply, for 48 hours, of the agave Results: Prevailed masculine sex and epithelial tumors. More than extract to a 600 mg/kg dose, according to total solid determination. 70% of the patients had a favorable evolution with the improvement of Four experimental groups of eight animals each were created. The first functional capacity and pain relief. The best answer was obtained with group was instilled with acetic acid without subsequent medical the frequency of administration of VIDATOX® 30CH three times a day. treatment. The second one was given prednisolone (10 mg/kg) after Severe adverse events were not reported. the colitis induction. A third group or negative control group, received ClNa 0.9% via rectum and no treatment at all and the last one was the Conclusions: The use of VIDATOX® 30CH was effective and safe in the agave group. The reduction of intestinal damage, through macroscopic improvement of the functional capacity of the patients with advanced damage index and histopathology analysis, was evaluated. The values stage tumors. of myeloperoxidase (MPO), as an inflammation indicator, and malonyldialdehide (MDA), which is used to evaluate the lipidic lipoperoxidation grade, were determined. Results: The macroscopic results showed lower intestinal damage index in Agave group compare to both no treatment group and prednisolone group. This finding is supported by histopathology analysis, where the least leucocytary infiltration grade and damage epithelial were exposed. The MPO and MDA values were lower than control group, with or without treatment, and very similar to no colitis induction group. Conclusions: The hydroalcoholic extract of Agave leaves has anti- inflammatory properties in a model of ulcerative colitis in rats.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S233
LATINFARMA 2013 Resúmenes/Abstracts
PPN 069: DIURETIC EFFECT OF THE PEPEROMIA PELLUCIDA PPN 070: HEPATOPROTECTIVE EFFECTS OF AN AQUEOUS IN RATS WISTAR ETHANOLIC EXTRACT FROM Thalassia testudinum IN THE DAMAGE CCL4-INDUCED IN RATS Dranguet Y, Soler D, Silva J. Rodeiro I1, Coballase-Urrutia E2, Hernández-Ojeda S3, Espinosa- University of Medical Sciences, Guantánamo, Cuba. E-mail: 3 [email protected] Aguirre JJ.
1 Departamento de Farmacología, Centro de Bioproductos Marinos, CEBIMAR, Loma y 39, Nuevo Vedado, Plaza de la Revolución, La Habana, Cuba. E-mail: Introduction: The Traditional and Natural Medicine is the humanity's [email protected]. 2Laboratorio de Neuroquímica, Instituto Nacional cultural important part of the scathing one. The Peperomia pellucid is a de Pediatría, México. C.P. 04530. E-mail: [email protected]. 3Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de small herb that grows in the humid places, in the garden gavels and Investigaciones Biomédicas. Universidad Nacional Autónoma de México, C.P. shady walls. Empirically the plant was an employee as diuretic, against 70228, 04510 D.F., México. E-mail: [email protected]. the inflammations of the rectum and illnesses of the heart. However, preclinical reports to determine the diuretic effects don’t exist. The nephrons of the rats are similar histologically to those of the man and Introduction: Reactive oxygen species (ROS) are products of cellular their filtrate glomerular possesses the same physical properties and metabolism. ROS induce oxidative damage to several biomolecules chemical composition. Thus, the aim of this work was to evaluate the involved in the development of several human diseases. Thalassia possible diuretic properties of the decoction of Peperomia pellucid. testidunim (T.t) extract have been recognized by the beneficial effects Methods: Wistar rats were used. To evaluate the diuretic effects doses as antioxidant, hepatoprotector, skin regenerating, antibiotic, and HIV of 200 and 400 mg/kg of body weight were used. A positive control integrase inhibitor. group administered with furosemide (20 mg/kg) was used whereas Material and methods: Wistar rats (200–250 g) were used to induce negative control was administered with saline. The urinary excretion liver damage with administration of CCl4 and corn oil mixture. Group 1: of Na+, K+, Cl- and Ca2+ and P were also determined. received corn oil (0.1 mL/kg; v.o.), Group 2: administered CCl4/corn oil Results: The dose of 200 mg/kg demonstrated highest diuretic effect (1.5 mL/kg; i.p.), Group 3: received T. testudinum extract (BM-21) (40 when compared with 400 mg/kg. When comparing with the mg/kg; v.o.), in combination with CCl4 (1.5 mL/kg; i.p.), Group 4: furosemide it was observed that the excretion of potassium in urine administered with BM-21 (100 mg/kg; v.o.), in combination with CCl4, diminishes, which suggests a diuretic action acting as thrifty of and Group 5: received BM-21 (400 mg/kg; v.o.), in combination with potassium. CCl4. The groups 2, 3, 4 and 5 were treated in the last 3 days with CCl4. The liver was dissected and homogenate for the analysis of antioxidant Conclusions: Our results demonstrated the diuretic action of the enzymes and lipoperoxidation. Date are analyzed by ANOVA, followed decoction of the plant and support the empiric used of Peperomia by Dunett´s multiple test. pellucid as diuretic agent in traditional medicine. Results: The determination of the antioxidant enzymes activity, showed that CCl4 administration produced decrease (p<0.01), in the levels of all antioxidant enzymes, compared with the controls (Group 1), the groups treated with different doses of the extract enhanced antioxidant enzymatic activity. The lipoperoxidation levels are increased in the CCl4 group, however the groups treated with 40, 100 and 400 mg of BM-21 extract, showed less damage in a manner of dose-response (p<0.01). Conclusions: Thalassia testidunim extract contains free radical scavengers that showed an effective protection against oxidative damage induced by CCl4 in the liver. The product inhibited detoxifying enzymes CAT, GR, GPx, SOD and the GST oxidation and prevented to lipoperoxidation.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S234
LATINFARMA 2013 Resúmenes/Abstracts
PPN 071: Tilia americana VAR. MEXICANA: A SPECIES WITH PPN 072: ETHNOPHARMACOLOGY OF Moringa oleifera Lam: HIGH ANTIOXIDANT POTENTIAL DEVELOPMENT OF A NEW TABLET FORMULATION
Coballase-Urrutia E1, González-Trujano ME2, Cárdenas-Rodríguez N1, Lemus Z, Chong A. Huerta-Gertrudis B1, Montesinos-Correa H1, Carmona-Aparicio L.1 Empresa Laboratorio Farmacéutico “Oriente”, Calle 5. S/N Rpto. 30 de 1National Institute of Pediatrics, Mexico City, Mexico. Noviembre, Santiago de Cuba, Cuba. E-mail: [email protected] 2National Institute of Psychiatry, Mexico City, Mexico. E-mail: [email protected] The medicinal plant Moringa oleifera L., commonly named moringa or paraíso francés in Cuba, horse-radish tree in Florida (USA) and ben Introduction: Infusions of Tilia species are used widely in Europe and olifère in Haití, is an small tree native from Northwest India, where is Latin America, due to its properties in traditional medicine as an cultivated since prehistorical times. Nowadays it grows in tropical anxiolytic and sedative. In different regions of Mexico inflorescences of regions in the entire world. According to the Indian medical texts, this Tilia americana L. var. mexicana (Schltdl.) Hardin (Tiliaceae) are often plant has more medicinal properties than any other, its medicinal parts used by people for their therapeutic effects. Although it has been being leaves, barks, nuts and roots, which have numerous uses in reported the effects of Tilia on the central nervous system, the traditional medicine. In this work several ethnopharmacological mechanisms of action involved in its therapeutic properties are still references were revised and the ethnopharmacological profile of the unknown. The aim of this study was determine its ability as scavenger plant is presented. This plant is mainly used in folk medicine as of reactive species that participate in the oxidative state. analgesic, antibacterial, anti-inflammatory, antispasmodic, cardiotonic, diuretic, emetic, hypotensive, laxative, stimulant and vermifuge. Material and methods: Inflorescences and leaves of Tilia were Additionally, results regarding the technological development of a new collected in Puebla, Mexico in 2010 (voucher No. 131613, Herbarium tablet formulation from leaves are also discussed. Several combinations of the Faculty of Sciences of National Autonomous University of of the disintegrant (sodium starch glycolate and croscarmellose Mexico), and prepare in different extracts, by using maceration with sodium) were used in the external and the inner phases or in both of solvents in increasing polarity (hexane, ethyl acetate and methanol). them in order to obtain the best disaggregation of the tablet, which is a The solvent-free crude extracts were tested through critical parameter in this compressed form. Physical qualification of the spectrophotometric techniques to determine their antioxidant capacity ●- tablet demonstrated that the formulation is suitable for its future against the reactive species superoxide radical anion (O2 ), commercialization. Indeed, this formulation is currently under hypochlorous acid (HOCl), hydrogen peroxide (H2O2) and oxygen 1 evaluation for its quality control and stability in order to obtain its singlet ( O2). approval as a new herbal product.
Results: IC50 (µg/mL) in all the extracts of Tilia suggesting their ability to trap the reactive species studied. However, only the ethyl acetate extract from inflorescences and leaves (IC50: 0.037 ± 0.001 and 0.48 ± 0.012 µg/mL, respectively), and methanol extract from leaves (IC50: 0.80 ± .001 µg/mL) were statistically significant compared with the reference compound, GSH (IC50: 7.58 ± 0.25 µg/mL). The results obtained suggested that the different extracts of Tilia have a high potential as an antioxidant.
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LATINFARMA 2013 Resúmenes/Abstracts
PPN 073: HARVEST, POSTHARVEST AND LAB QUALITY PPN 074: MAIN ITEMS IN THE PRODUCTION OF NATURAL CONTROL MONITORING SYSTEM FOR AROMATIC MEDICINES IN PINAR DEL RIO, 1990-2009 ESSENTIAL OILS Callava C, Rivera N, Olivera L. Abuín A, Rodríguez Y, Boan M, Torrientes D, Gonzáles R, Bacallao M, Programa Medicina Natural y Tradicional, Dirección Provincial Pinar del Río, Pensado L, Moreno E. Cuba. E-mail: [email protected] Matanzas Medical Science University, Km 101 Carr. Central, Matanzas, Cuba. E- mail: [email protected] Introduction: The techniques of Traditional and Natural Medicine
occupy since several years ago, an important place in the national and Introduction: The monitoring of eco-climatic, agricultural, international health. It is a reality the effectiveness of a great quantity technological and formulation making variables are utmost importance of natural products in the treatment of diferent illnesses as in Medicine to determine if a pharmaceutical product derived of medicinal plants as in Odontology, although there are problems due to do the low he fulfills specificities for which it was conceived. scientific knowledge of those products, together with other problems of organization in the process of plannig and production. Material and methods: We make a file that contains a “Good Practices” focus in Agriculture and Recollection (GPAR), in Lab (GPL ) Methods: Because of these problems a descriptive study was carried and Making Formulation (GPM) show critical points control of the full out to describe the main items in the production of natural medicines life cycle, from his genetic origin, planting, cultural attentions, harvest, in Pinar del Río, since 1990 until 2009, in which we analyzed in details, postsharvest, secondary processing to final formulation. Around 14 using the methods of the scientific investigation, the increase of the items with 108 monitored variables were identified, getting registered volume of production, the decrease of the variety of the products, the the factors that can influence quality and quantity of active relationships between flask per habitants, the pharmacological groups phytocomplex. For validation in situ our system, we proceeded to more represented and the most phytomedicines produced. Matricaria's recutita production in “Agroecologic Transition” Results: The plans of production show a tendency to the farmstead according to Cuban Standard NC 500-2010. accomplishment being 2000 the best year. There exist a progress in The characteristic essential oil was obtained by steam distillation of relation to flask habitant, indicator of the stability, access and equity dry flowers. Convenient sample runing in Thin Layer Chromatography for the population. There was a decrease the variety of the products (TLC) plates movable phase in a mixture of Toluene and Ethyl Acetate. from 370 in 1993 to 56 in 2009, looking for a better relation to quality. The selected biomarker for our system of monitoring was Camazulene. The more produced natural medicine was corresponding to A calibration curve in increasing concentrations of essential oil we pharmacological groups according to breath, skin, and digestives. The runed and read by optic density (D.O.), using a Cuban LASER optic great quantity of natural medicines was corresponding to the derived Densitometer “DENSYSTEM LD 02” that detect and quantify a blue of the aloe products, with the Imefasma as the most produced. chamazulene visible spot of the chromatographic plate in every application. The position, height and surface area of every peak were determined and the data of chamazulene peaks were processed in acceptable linearity of optic density in relation to concentration. We got a lineal correlation equation Y([Chamazulene])= F([D.O.]) Results: The system of complete cycle quality monitoring production of these products guarantees the record and traceability of critical points and his intervals of tolerance, which determine the measurement of the quality of aromatic therapeutic essential oils.
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LATINFARMA 2013 Resúmenes/Abstracts
PPN 075: ACUTE TOXICOLOGICAL EVALUATION OF TWO PPN 076: ANALGESIC ACTIVITY OF A WATERY EXTRACT OF EXTRACTS OBTAINED FROM LEAVES OF GUANÁBANA Matricaria recutita L. USING TWO ALGESIC MODEL IN (Annona muricata L.) IN MICE SPRAGUE DAWLEY RATS Isidrón M, Hernández I, Hernández Y, González K, Rodríguez D, Valido Díaz A, Pizarro Espín A, Hernández Río M, Ruiz Perez R, Herrera L, Martínez D, Del Vallin T, Rodeiro I. Machado García D, Aparicio Morales AI.
Universidad Agraria de la Habana (UNAH), Autopista Nacional km. 23, San José Universidad de Ciencias Médicas de Villa Clara. “Dr. Serafín Ruiz De Zárate de las Las Lajas, Mayabeque, Cuba. E-mail: [email protected] Ruiz”.Facultad de Medicina. Centro de Toxicología, Villa Clara, Cuba. E-mail: [email protected]
Annona muricata belong to the family Annonaceae (Guanábana). The medicinal and nutritional uses have been exploited by the native Introduction: The Matricaria recutita L. species is a plant greatly used Indians before the discovery of this continent. In America and tropical by the population, the use of this plant has been mentioned in areas of the Caribbean Island, these fruit have been preserved by affections that involve painful or inflammatory episodes. The present tradition, but are still unknown as crop plants. Anonaceae are a study is carried out with the objective of checking experimentally, for productive promising resource of a group of compounds called the first time, the analgesic effect of an aqueous extract of this plant in acetogenines which nave antineoplastic, as well as antibiotic rats. properties, they also have antihelmintic and antiparasitary effects. Material and methods: An experimental study was developed, of However, up to date, there are none reports in our country about if preclinical rehearsal to randomized blind double, through two products obtained from leaves of Guanabana tree (Annona muricata L.) experimental techniques: contortion‘s induction with acetic acid in 5 have the potentiality of inducing toxic effects to man. A preliminary groups of 8 animals each one and the hot plate proves with 5 groups of acute toxicological evaluation of two extracts prepared from is reported 6 animals each one. The study was carried out in the Toxicology’s at this work. Acute toxicity of both extracts was evaluated in mice of Center (CENTOX.) of the Medical University of Villa Clara, in November both sexes by oral administration. Under these experimental of 2011. In each test, 3 groups were created and received dose of 200, conditions, it showed no lethality at the limit doses of 2 000 mg/kg 400 and 800 mg/kg of the extract of Matricaria recutita L. and 2 body weight and only transient clinical symptoms during the first hour controls groups; negative with placebo and positive with acetil salicylic after administration were observed. That is to say, according to the acid and morphine’s sulfate, respectively. It were applied as classification of the OECD it is located in the category “without descriptive statisticians the stocking and the standard deviation. classification”, thus being considered potentially non toxic for humans. Our results showed that extract is not toxic product on these Results and conclusion: The analgesic effect of the extract of the experimental conditions. Matricaria recutita L. was proven by means of the pattern of contortions, to the doses of 400 and 800 mg/kg, with moderate inhibition percents but superiors to the used negative control. In the test of the hot plate the plant showed activity to the dose of 800 mg/kg. Concluding, the aqueous extract of Matricaria recutita L. presented a moderate analgesic activity to dose of 800 mg/kg of weight when comparing with the reference medication.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S237
LATINFARMA 2013 Resúmenes/Abstracts
PPN 077: ANTI-DIABETIC, ANTIOXIDANT AND ANTI- PPN 078: SYNTHESIS OF TRITERPENOID URSOLIC ACID INFLAMMATORY EFFECTS OF A Momordica charantia L. DERIVATIVES PLANT EXTRACT Alonso MM1, Aguilera SL1, Marrero JG1, Osegueda MS1, Rico M1, Medina Menéndez R, Lagarto A, Bellma A, Núñez Y, Nguyen Hang PT, Phoung FG1, Campos ML1, Herrera L1, Ortega A2, Maldonado E.2 NT, Martínez D. 1National Polytechnic Institute (IPN). Engineering Interdisciplinary Drug Research and Development Center. CIDEM. 17 No. 6208 e/ 62 y 64, Playa, Professional Unit. Campus Guanajuato (UPIIG). 200 Mineral Valenciana La Habana, Cuba. E-mail: [email protected] Avenue. Industrial Park Puerto Interior, Zip Code: 36275. Silao de la Victoria, Gto, Mexico. E-mail: [email protected] 2Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, Coyoacán, México, D.F. 04510, México. Introduction: Among the many plants that are recognized with antihyperglycemic effect, Momordica charantia L is one of the most documented. Its fruits, leaves and roots have been shown to exhibit Usolic acid (AU), a naturally occurring pentacyclic triterpene acid antidiabetic action in experimental models and human. This study was widely distributed in food and medicinal plants, is one of the most undertaken to evaluatethe M. charantia L. foliage extract obtained in popularly studied pentacyclic triterpenes. Its biological functions our center by spray dryer, for its anti-hyperglycemic, antioxidant and include anti-inflammation, anti-HIV, antioxidation, antidiabetes, anti-inflammatory effect. hepatoprotection, and anticancer effects. Material and methods: The antihyperglycemic effect was determined UA is constituted by a rigid pentacyclic skeleton, which is highly by using normal rats, glucose tolerance test in normal healthy rats and hydrophobic and makes UA poorly water-soluble. As part of our alloxan-induced diabetic mice. All were assessed by glucose efforts in developing pentacyclic triterpenes as therapeutic agents, determination in serum and by comparison with glibenclamide as we were in pursuit of novel bioactive compounds based on UA, positive control. Radical trapping properties in vitro were assayed which enhance physical-chemical and pharmacokinetic- ●+ ●+ ● -● against DPPH , ABTS , R-OO and O2 and the anti-inflammatory pharmacodynamic properties. It is expected that incorporation of effects were studied by using cotton pellet in mice and carrageenan- polar moiety onto the C-3 position might improve the water induced pleuresy in rats. In both, classical drugs were used as positive solubility and thus clinical utility. controls and the extract was administered at doses effective as antidiabetic agent. In this study, the synthesis of a series of novel UA derivatives with distinct amines on C-3 position is reported. Results: Significant decrease in blood glucose (15 min - 2 h) was seen in normal rats after acute oral administration (50 and 150 mg/kg) with The compounds were prepared as followed: Esterification of UA with a maximum fall of 74 and 68%, respectively. In the oral glucose chloroacetyl chloride produced the corresponding chloroacetic acid tolerance test, pre-treatment with the extract (25, 50 and 100 mg/kg) ester. Subsequent treatment of ester with different amines, afforded decreased blood glucose between 15 min and 1 h in the manner similar the corresponding derivatives. than glibenclamide (10 mg/kg). A maximun decrease of 63.3% was observed (50 mg/kg). In alloxan-administered mice oral administration of the extract (25, 50 and 100 mg/kg) significantly reduced serum glucose by 21.6, 44.5 and 58.7%, respectively, whereas glibenclamide by 53.4%. The plant extract (400 µg/mL) scavenged in ●+ ●+ ●- -● vitro DPPH (40%) and ABTS , R-OO and O2 (IC50 12.83; 58.3 and 20.58 µg/mL, respectively). Oral administration (25–100 mg/kg) to mice significantly reduced granuloma dry weight towards the value of dexamethasone and when administered to rats at 50 and 100 mg/kg the extract reduced leukocyte migration and reduced the formation of exudate induced by carrageenan. Conclusions: These results suggest that the M. charantia foliage powder possesses antihyperglycemic effects. Our results also suggest that the antioxidant/anti-inflammatory action of the extract may contribute, at least in part, to this pharmacological action.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S238
LATINFARMA 2013 Resúmenes/Abstracts
PPN 079: SAFETY ASSESSMENT OF A MEDICINAL EXTRACT PPN 080: Vernonanthura patens’ LEAVES AND STEMS’ FROM Caesalpinia paraguariensis BARK IN A SUB-CHRONIC CHEMICAL - BIOLOGICAL CHARACTE-RIZATION OF ORAL TOXICITY STUDY IN RODENTS OBTAINED ETHANOL EXTRACTS. PRELIMINARY STUDIES
Sgariglia M1,4, Honoré S3,4, Soberón R1,4, Sánchez S3,4, Vattuone M.1,4 Manzano Santana P1, Orellana T1, García Parra M1, Monzote Fidalgo L2, Miranda M3, Peralta E1. 1LABIFITO, Facultad de Bioquímica, Química y Farmacia (UNT), Ayacucho 471; 3INSIBIO (UNT), Chacabuco 461; 4CONICET. San Miguel de Tucumán 1Escuela Superior Politécnica del Litoral del Ecuador (ESPOL) Km. 30.5 Vía (4000).Tucumán. Argentina. E-mail: [email protected] Perimetral, Campus Prosperina, Apartado: 09-01-5863. Fax: (593-4) 2 854629. Guayaquil, Ecuador. 2Instituto de Medicina Tropical “Pedro Kourí” .Habana, Cuba 3Instituto de Farmacia y alimentos. Universidad de la Habana, Cuba. E-mail: Introduction: Caesalpinia paraguariensis Burk. (Caesalpiniae) bark is [email protected], [email protected] used in Argentine traditional medicine to treat diabetes, atherosclerosis and skin affections. This specie is frequently used in Northern Argentine as “mate” additive. Although the absence of acute toxicity was determined already, nothing is known about adverse Introduction: In this work, it was performed a chemical-biological effects that could result from sustained consumption. study of Vernonanthura patens (Kunth) H. Rob.’s aerial parts, which grows on the Ecuador’s coast. This work begins with the obtaining of Aim: The present investigation was carried out to evaluate the safety extracts, the isolation and purification of leaves and stems’s fractions of the use of bark infusion of C. paraguariensis (CPBI) by toxicity and compounds of the species by extraction with ethanol in soxhlet, determination after sub-chronic oral administration in rodents. chromatography column with increasing polarity’s solvents and TLC. Methodology: The animals used in this study were free zoonosis and Material and methods: Structural identification was performed by mycobacteria. Wistar rats, of both sexes, obtained from Fcen/ICBME- Gaseous chromatography - mass spectrometry and NMR. Anti- HI (Bs. As., Argentina); OECD-408 criteria (repeated dose 90-day oral leishmanial activity and extracts’ cytotoxicity was evaluated against toxicity study) were followed and randomized complete block designs Leishmania amazonensis MHOM/77BR/LTB0016’s strain and mouse applied. Briefly, rats (N=18) at 9 weeks old, weighing 140–207 g, were neuroblastoma Neuro 2 A’s cells line, respectively, by following housed in plastic cages and divided into three blocks defined by weight validated protocols of Tropical Medicine " Pedro Kouri” Parasitology range (G0, G1 and G2). CPBI doses, 9 mg/kg WB (D1) and 45 mg/kg laboratory’s Institute in Havana-Cuba. (D2), were administered individually and daily for 90 days, while control rats (C) received the vehicle only. The behavior, body weight, Results and conclusion: 110 compounds’s structures could be food and water intakes were followed weekly. Haematological, assigned by GC-MS, all ones reported by the first time for the species biochemical and organ parameters were determined at the end of the and only eleven had been reported previously for the genre. Of all of 90-day administration. Some bioactive components (ellagic derivatives compounds, only four were isolated and identified by NMR techniques. and other phenolics) present in CPBI were quantified by RP-HPLC. Among the major chemical groups, it were found: hydrocarbons, free fatty acids and their methyl and ethyl esters , terpenoids (mono, Results: NOAEL of CPBI was D1, and LOAEL was D5. The daily oral sesqui, di and triterpenoids ), phytosterols , sugars, vitamin E, alkaloid administration of CPBI did not result in death or significant changes in and fatty acid amides . Leave’s ethanol extract showed antileishma- body weight, haematological or biochemical parameters; some urinary nial´s selectivity and activity with IC50 of 24.3 µg/mL and IS 12, more parameters were observed altered (P < 0.05) in males at D5. Liver, significantly higher than Pentamidine´s positive control (IC50 1.3 kidney, lung and pancreas histopathology did not reveal morphological µg/mL; IS 9) such as reported for species that grows in other countries. alterations. All samples tested against the mouse neuroblastoma cell line Neuro 2A showed IC50 < 165 µg/mL, not interest considered concentrations to Conclusions: The results showed that CPBI had no toxicity after oral continue with assessments “In vivo". Investigation´s results are sub-chronic low dose administration (D1) and indicate that the plant reported for the first time for the species. could be considered safe for oral medication. This work is part of research to validate and protect ancestral laritaco use in Southern Ecuador.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S239
LATINFARMA 2013 Resúmenes/Abstracts
PPN 081: CLINICAL TRIAL PHASE III WITH SURFACEN IN emitted by the Center for the Control of the Medications, Devices and PEDIATRIC POPULATION Medical Equipment (CECMED) from 1995 for the substitution therapy under conditions of dysfunction of the surfactant system lung, as ARD Barrese Y1, Díaz E2, Avila Y1, Rodríguez V3, Uranga R1, Blanco O2, in the newly born with endotracheal intubation and mechanical Clinical investigators' group and co-investigators of the institutions ventilation. Objective: To evaluate the use of SURFACEN in pediatric and coordinators of trials clinical4. population. 1National Coordinator Center of Clinical Trials (CENCEC). E-mail: Material and methods: Design and conduction of a phase III clinical [email protected] trial, randomized, multicenter, controlled, open and with two 2National Center of Agropecuary Sanity. San José, Mayabeque, Cuba. 3Pediatric Hospital "Eduardo Agramonte", Camagüey, Cuba. treatment groups, A: conventional (oxygenation and ventilation 4Pediatric units of intensive cares of hospitals and superior institutes of medical mechanics) therapy and B: SURFACEN + conventional therapy, in sciences. pediatric population with ARDS tried in UIC. SURFACEN 100 mg was instilled by means of a probe endotracheal, every 8 hours for three days. For the evaluation were considered clinical, gasometrical, Introduction: The acute respiratory distress syndrome (ARDS) is ventilators and imagenologic variables; as well as the detection and caused by the increase of the permeability from the alveolus-capillary control of adverse events. and secondary barrier to lung acute damage, being a frequent problem Results and conclusions: In phase III clinical trial 23 pediatric in the intensive care units (UIC); it is heterogeneous in its etiology and patients were included, 11 in the group A and 12 in group B. The use of physiopathology, and it can be lung or extra-lung. Recent studies locate SURFACEN®, combined with the conventional therapy, contributed to their incidence among the one 1.6% and the one the patients' 7.7% the satisfactory evolution of the patients, it improved hospital entered in units of critical, and between 8% and the one the patients' indicators, and it was tolerable and safe. 19.7% that require ventilation mechanics. SURFACEN it is a natural surfactant of swinish origin produced by the National Center of Agropecuary Sanity of Cuba (CENSA), which has a sanitary registration
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S240
LATINFARMA 2013 Resúmenes/Abstracts
Neuroinmunomodulación / Neuroimmunomodulation
PNF 001: NEUROPROTECTIVE EFFECT OF JM-20 ON PNF 002: EFFECTS OF JM-20 ON RATS BRAIN EXPERIMENTAL STROKE MODELS INVOLVES MITOCHONDRIA AND SYNAPTOSOMES. UNCOVERING ITS MITOCHONDRIAL STABILIZATION AND REDUCTION OF NEUROPROTECTIVE MECHANISM (PART I) EXTRACELLULAR EAA LEVELS Núñez Y, Pardo-Andreu GL, Ramirez J, Pastoris A, Ochoa E, Verdecia Ramírez-Sánchez J, Núñez-Figueredo Y, Hansel G, Pires E, Merino N, Y, Delgado R, Valmor L, Souzac DO. Valdes O, Delgado-Hernández R, Porto-Verdecia M, Ochoa-Rodríguez E, Centro de Investigación y Desarrollo de Medicamentos (CIDEM), Cuba. E-mail:
Verdecia-Reyes Y, Salbego C, Souza DO, Pardo-Andreu GL. [email protected] Centro de Investigación y Desarrollo de Medicamentos, Ave 26, No. 1605 Boyeros y Puentes Grandes, CP 10600, La Habana, Cuba. E-mail: [email protected] Introduction: There is an increasing interest in the identification of
new classes of compounds that simultaneously target several toxic Introduction: We previously showed that JM-20, a novel 1,5- processes in ischemic neuronal cells, including at the mitochondrial benzodiazepine fused to a dihydropyridine moiety, possess similar level. Recently, we obtained a new family of 1,5-benzodiazepines, anxiolytic profile that diazepam and cytoprotective activity in structurally different from the currently available 1,5-benzodiazepines dissociated cells cultures subjected to different neurotoxic insults. due to the presence of a 1,4 dihydropyridine moiety fused to the Here we investigate whether JM-20 protects against neuronal damaged benzodiazepine ring. JM-20 (3-ethoxycarbonyl-2-methyl-4-(2- induced by ischemia/reperfusion in vitro and in vivo. nitrophenyl)-4,11-dihydro-1H-pyrido[2,3-b][1,5]benzodiazepine) is a member of this family of compounds with an anxiolytic profile similar Methods: The effect of JM-20 on hippocampal slices subjected to to that of diazepam. Its dihydropyridine moiety does not appear to oxygen and glucose deprivation (OGD) was evaluated. For in vivo interfere with the GABAergic activity associated to its benzodiazepine studies, Wistar rats underwent 90 min of middle cerebral artery portion, but could confer Ca2+ channels blocking properties, pointing occlusion (MCAO). JM-20 (2, 4 or 8 mg/kg) was orally administrated 1 out JM-20 as a potential neuroprotectant. Moreover, mitoprotection is hour following reperfusion. After 24 hours, neurological deficit was another potential mechanism involved in the neuroprotective effect of scored and infarct quantification, histological, mitochondrial or JM-20, since it has been reported that Diazepam and Nimodipine, both biochemical analysis were conducted. JM-20 (8 mg/kg) was exhibiting structural features of JM-20, protected neuronal cells in administrated at different times of post-reperfusion to establish a brain ischemia models throughout mitochondrial mechanisms. therapeutic window. Material and methods: Thus in this study we evaluated the in vitro Results: In vitro, JM-20 (1 and 10 µM) added during reperfusion effect of JM-20 on isolated rats brain mitochondria (RBM) and reduced cellular death in 31 and 51%, respectively as compared to synaptosomes (RBS) to find some clues about its potential cultures exposed to OGD alone. In vivo, treatment with JM-20 (4 and 8 neuroprotective action. mg/kg) reduced total infarct volume in 89 and 98%, respectively. The treatment also diminished pathological manifestations including Results and conclusions: Mitochondrial membrane potential neurological deficit, mitochondrial disruption and histological dissipation, reactive oxygen species generation, and permeability alterations in hippocampus, striatum and cortex. JM-20 (8 mg/kg) transition pores occurrence due to Ca2+ accumulation into reduced glutamate and aspartate content in cerebrospinal fluid with mitochondria are all events implicated in neuronal cell death mediated respect to untreated rats and the cerebral damage even when therapy by the intrinsic pathways in the ischemia/reperfusion brain damage. was delayed up to 8 hours after blood flow restoration. We have observed here that JM-20 has strong antioxidant activity in RBM and RBS. This effect can be explained by its ability to accept Conclusions: Present results suggest that JM-20 is a robust electrons conferred by its low redox potential (-700 mV). Thus, JM-20 neuroprotective agent against ischemia/reperfusion injury with a wide can compete with oxygen for the electrons “slipped” from the therapeutic window in rats. mitochondrial electron transport chain (at complex I and III), avoiding superoxide and consequently H2O2 formation. This molecule also inhibits mitochondrial calcium uptake, an effect that probably explains its ability to prevent Ca2+ -mediated mitochondrial permeability transition, well known mediator of mitochondrial impairment. Others mitochondrial events associated with neuronal cell injury in ischemic + brain damage, such as ATP-dependent K channels opening and the hydrolytic activity of mitochondrial F1F0 ATP synthase, were also inhibited by JM-20 in the low micromolar range. Together, these results suggest that JM-20 mitoprotection could be an important clue as to one of its primary/direct mechanisms of neuroprotection.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S241
LATINFARMA 2013 Resúmenes/Abstracts
PNF 003: THE EFFECTS OF JM-20 ON [3H] GLUTAMATE PNF 004: SCREENING OF A NOVEL SERIES OF SYNTHETIC UPTAKE BY SYNAPTIC VESICLES, SYNAPTOSOMES, AND ANTI-GLUTAMATERGIC STEROIDS AS CYTOPROTECTIVE ASTROCYTES FROM RAT BRAIN. UNCOVERING ITS AND MODULATORS OF IN VITRO INFLAMMATORY CELLULAR MECHANISMS OF NEUROPROTECTION (PART II) RESPONSES Núñez Y, Pardo GL, Ramirez J, Loureiro SO, Ganzella M, Ochoa E, García-Pupo L, Núñez Figueredo Y, Tacoronte Morales JE, Delgado Verdecia Y, Delgado R, Souzac DO. Hernández R.
Centro de Investigación y Desarrollo de Medicamentos (CIDEM), Cuba. E-mail: Centro de Investigación y Desarrollo de Medicamentos (CIDEM), Cuba. E-mail: [email protected] [email protected]
Introduction: Although being a physiologically important excitatory Cerebrovascular diseases represent the third Cuban cause of death in neurotransmitter, glutamate plays a pivotal role in various the last decade, in which cerebral ischemia occupies the first places. neurological disorders including ischemic neurological diseases. Its Molecular mechanisms involved in the ischemic event include level is increased during cerebral ischemia with excessive neurological glutamatergic excytotoxic signaling, oxidative and ionic imbalance and stimulation causing the glutamate-induced neuronal toxicity, inflammatory response. Therefore, design and characterization of new excytotoxicity, and this is considered the triggering spark in the steroid compounds which retains its anti-inflammatory potential with ischemic neuronal damage. Glutamate transmission involves its neuroprotective activity and decreased adverse effects is of vital accumulation into secretory vesicles and the subsequent exocytosis to importance. In our study we show the screening of a novel series of the extracellular space. Accumulation of glutamate in secretory synthetic anti-glutamatergic steroid compounds as cytoprotective and vesicles is mediated by vesicular glutamate transporters (VGLUTs). modulators of inflammatory responses in vitro. Cultures of This process is driven by an electrochemical gradient of H+ established undifferentiated PC12 cells exposed to glucose deprivation and cyanide by V-ATPase. We have recently observed that JM-20, given 1h after were used as an in vitro model of ischemia and mitochondrial damage, reperfusion at the neuroprotective dose of 8 mg/kg, significantly to test the cytoprotective potential of the steroid compounds. In reduced the MCAo-induced increase in glutamate concentration in addition we setup up a primary culture of microglia from adult rat cerebrospinal fluid, compared to vehicle-treated. On the other side, we brains, to evaluate the inhibitory activity of the cytoprotective steroids also identified the ability of this molecule to selectively inhibit the in the production of nitric oxide and IL-1β induced by LPS and IFNγ hydrolytic activity of mitochondrial F1F0 ATP synthase, at very low stimulus. The majority of molecules increased the survival of PC12 cells micromolar concentrations. Since V-ATPases have similar structure exposed to glucose deprivation and mitochondrial damage, while just a and mechanism of action that F-ATPase (Nelson N, Harvey WR. few of those molecules inhibited the IL-1β and nitric oxide productions, Vacuolar and plasma membrane proton-adenosinetriphosphatases. in the stimulated primary microglia. Our results suggest a critical Physiol Rev. 1999 Apr;79(2):361-85.), we hypothesized that the in vivo influence of the chemical structural characteristics of each synthetic anti-excytotoxic effect of JM-20 could be mediated by the inhibition of steroid in its biological in vitro activity. Moreover, the combination of V-ATPase. cytoprotective and inhibition of pro-inflammatory mediators’ activities, two critical mechanisms involved in the etiology of cerebral ischemia, Material and methods: To prove (or not) the above mentioned converts these molecular entities in attractive therapeutic candidates hypothesis we evaluated the in vitro effects of JM-20 on: (i) rats brain for neurological diseases. synaptic vesicles (3H-glutamate uptake, proton gradient built-up , and V-ATPase hydrolytic activity), (ii) rats brain synaptosomes (3H- glutamate uptake) and (iii) primary culture of rats astrocytes and astrocytes-cortical neurons co-culure (3H-glutamate uptake). Results and conclusions: We observed here that JM-20 impairs the H+-ATPase activity and consequently the vesicular glutamate uptake. This molecule also inhibits Ca2+-dependent glutamate release from brain synaptosomes and markedly increases glutamate uptake by co- cultured neurons and astrocytes. This impairment of vesicular glutamate uptake by inhibition of the H+-ATPase, caused by JM-20, could decrease the amount of the transmitter stored in the synaptic vesicles, could increase the cytosolic levels of glutamate, and will thus downregulate the transmitter release. All these effects contribute to explain the anti-excytotoxic effect of JM-20 observed in vivo.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S242
LATINFARMA 2013 Resúmenes/Abstracts
PNF 005: PHYCOCYANOBILIN INDUCES A PROTECTIVE GENE PNF 006: C-PHYCOCYANIN AND INTERFERON BETA: EXPRESSION PROFILE AND RESTORES THE REDOX MOLECULAR MECHANISMS ASSOCIATED TO A NEW BALANCE IN A MODEL OF ACUTE CEREBRAL COMBINED THERAPY FOR MULTIPLE SCLEROSIS IN THE HYPOPERFUSION IN WISTAR RATS EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS MODEL Marín-Prida J, Pavón-Fuentes N, Llópiz-Arzuaga A, Fernández-Massó JR, Delgado-Roche L, Cruz-Ramírez A, Valenzuela-Silva C, Nazábal- Nazabal-Gálvez M, Pentón-Rol G, Cervantes-Llanos M, Lagumersindez- Gálvez M, Cintado-Benítez A, Pardo-Andreu GL, Polentarutti N, Riva F, Denis N, Llópiz Arzuaga A, Falcón-Cama V, Cintado- Benítez, Pentón-Arias E, Pentón-Rol G. Fernández-Masso JR, Cabrera-Gómez JA, Pentón-Arias E.
Center for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba. E-mail: Center for Genetic Engineering and Biotechnology (CIGB). Ave 31 e/ 158 y 190, [email protected] Cubanacan, Playa, Havana City PO Box 6162, Havana 10600, Cuba. E-mail: [email protected]
Introduction: Ischemic penumbra rescue is the main objective of acute stroke interventions, but they have shown low translational Introduction: Beta IFN (IFN-b) was the first agent to show clinical success. More thorough studies on the penumbra physiology would efficacy for Multiple Sclerosis (MS) treatment. In neurodegenerative help foster the development of effective treatments. However, a diseases, neuronal and axonal loss is mediated by oxidative stress and common practical problem for its accurate dissection is the variability cytotoxicity which constitute a final common toxic pathway. C- of the ischemic lesion size in focal models. The permanent bilateral Phycocyanin (C-Pc) is a natural product and a main component of occlusion of the common carotid arteries (BCCAo) in rats produces a Spirulina platensis algae with antioxidant effect. global acute drop of the cerebral blood flow similar to the penumbra after a focal stroke. Here we used the acute BCCAo in rats as a model of Objectives: To study the gene expression profile in this model in ischemic penumbra to evaluate the effects of Phycocyanobilin (PCB), response to both treatments in order to find the molecular the C-Phycocyanin linked tetrapyrrole, on gene expression and mechanisms involved in the effect of a new combined therapy: IFN-b oxidative status. plus C-Phycocyanin (C-Pc) in MS. Methods: After the BCCAo, Wistar rats were treated with saline or two Methods: The effect of C-Pc and interferon beta was tested in chronic- different doses of PCB, taking samples at 24h post-surgery. Global gene progressive EAE model in C57BL6 mice. Finally, we compared the expression was analyzed with GeneChip Rat Gene ST 1.1 from mRNA expression profile using Illumina bead-array platform in brain Affymetrix, and for particular genes was used the Fast SYBR Green Real tissue of the EAE- mouse strain C57BL/6. The differential expression Time PCR Master Mix method. Redox markers (MDA, PP, CAT, SOD) analysis was conducted using Bioconductor and Cytoscape plugin were evaluated spectrophotometrically. BINGO for Gene Ontology categories statistically overrepresented. Results: PCB differentially modulated 190 genes (93 up- and 97 down- Results: Both groups of animals have a positive response to the regulated) in the anterior cerebral cortex, mainly related with the treatment. The C-Phycocyanin treatment significantly altered the inflammatory response and the biosynthetic pathways in metabolism. expression of 681 unique genes in comparison with the IFN-b. Those PCB also positively modulated the expression of 6 particular genes genes were mainly related to neurological and immunological tissues. involved in cerebroprotective processes such as remyelination, Interestingly, a larger number processes related to regulation of energetic metabolism, anti-apoptosis, synaptic plasticity and neuronal apoptosis, glial cell development and REDOX were involved angiogenesis. Our results revealed a significant rise in the in C-Pc response in comparison to IFN-b. But, the processes and the set susceptibility to lipid peroxidation (LPO) with a concomitant reduction of genes associated with regulation of immune system were favored in of CAT and SOD activities in the brain and serum of hypoperfused rats. IFN-b treatment. The comparison of both treatments showed that PCB reduced LPO and induced SOD without any effect on CAT, there are a number of shared processes that have different set of genes suggesting powerful antioxidant capabilities. involved. There are also several unique biological processes and genes that characterize each response. Conclusions: Altogether, our results provide evidence that may justify the application of PCB as a new acute disease modifying drug against Conclusions: The mechanism of response involves same biological ischemic stroke, for which further studies are needed. process but a different set of genes. Our results support a combination IFN-b/C-Pc as strong therapeutic candidate for the treatment of MS.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S243
LATINFARMA 2013 Resúmenes/Abstracts
PNF 007: MULTIPLE SCLEROSIS PATIENT’S TREG CELLS PNF 008: EGF AND GHRP6 CO-ADMINISTRATION FOR MARKERS ARE UP-REGULATED IN-VITRO AFTER IFN-γ CEREBRAL ISCHEMIA: DOSE RESPONSE AND THERAPEUTIC AND C-PHYCOCYANIN STIMULATION TIME WINDOW STUDIES
Cervantes-Llanos M, Alonso-Ramírez R, Martínez-Sánchez G, Cabrera Subirós-Martínez N, Perez Saad H, Coro- Antich RM, Berlanga Acosta J, Gómez JA, Valenzuela-Silva C, Llópiz Arzuaga A, Milian Jordan A, López- García del Barco D. Saura P, Pentón-Rol G. Center for Genetic Engineering and Biotechnology. La Habana, Cuba. E-mail: Center for Genetic Engineering and Biotechnology (CIGB). Ave 31 e/ 158 y 190, [email protected] Cubanacan, Playa, Havana City PO Box 6162, Havana 10600, Cuba. E-mail: [email protected] Introduction: Epidermic Growth Factor (EGF) and Growth Hormone Releasing Peptide-6 (GHRP6) have been shown to exert Nowadays there is a growing knowledge of the pathogenic process that neuroprotective and neurorestorative properties in a variety of CNS takes place in Multiple Sclerosis (MS) characterized either by signs of injury models. Both molecules are endowed of cytoprotective effects autoimmunity, inflammation and demyelination or primary which block excytotoxicity, oxidative stress, mitochondrial dysfunction oligodendrocyte loss. Reactive oxygen species (ROS) have been and apoptosis. The aim of this work was to study the dose response implicated as mediators of demyelination and axonal damage in MS. relationship and the therapeutic time window for the co- administration of GHRP6 and EGF in a model of global brain ischemia. Interferon-beta is an approved therapy for MS, due to the immunomodulatory, antiviral and stimulation of neurotrophic Material and methods: Transient global ischemia was achieved by a substances and endogenous opioids properties. 15-minute occlusion of the two common carotid arteries. Several doses of the combination therapy and of the separated peptides were C-Phycocyanin is the principal phycobiliprotein of the Spirulina administered intraperitoneally during 3 days, starting at 0 hours after platensis, a blue - green alga, with several reports documenting its reperfusion. For the therapeutic time window study, the treatments pharmacological properties as strongly antioxidant and anti- were applied at 0, 2, 4, 6, 8 or 24 hours after the ischemic insult. inflammatory. Survival, neurobehavioural outcome and infarct volume were After performing the molecular characterization of cellular immune examined. response (TNF-α, IFN-γ, IL-10, MMP-9, TIMP-1) and oxidative stress Results: The co-administration of EGF+GHRP6 showed a parameters (MDA, AOPP, Peroxidation Potential, SOD, Catalase, Total neuroprotective effect in the experimental model of global brain Hydroperoxides) we found a profound oxidative stress state and a ischemia, evidenced by a reduction in mortality, in neurological deficit significant down-regulation in serum levels of the regulatory cytokine, and in infarct volume, respect to the groups receiving vehicle, EGF or IL-10, in MS patients when compared to controls. GHRP6. The neuroprotective effects of EGF+GHRP6 were observed Furthermore, in-vitro stimulation of peripheral blood mononuclear even when administered 4 hours after the ischemic insult. cells from MS patients with IFN-γ or c-Phycocyanin, significantly up- Conclusions: These results suggest that the combined therapy with regulated mRNA as well as surface markers of Regulatory T cells. EGF and GHRP6 might be a good therapeutic strategy for the treatment Most MS approved therapies point only toward the inflammatory and of stroke. immunological components. Still, there is an increasing need of approaches in response to the more complex physiopathological phenomenon of the disease. Antioxidant and anti-inflammatory properties of c-Phycocyanin suggest it might be used in the treatment of neurodegenerative diseases like Alzheimer, Parkinson and also MS. Moreover, in MS, our results support the combination of IFN-γ and c-Phycocyanin for a wider spectrum and likely more effective treatment for the disease.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S244
LATINFARMA 2013 Resúmenes/Abstracts
PNF 009: THERAPEUTIC EFFECT OF ZINC AND NEURO EPO IN PNF 010: PROLONGED ORAL ADMINISTRATION OF BM-21, TRANSGENIC MICE WITH ATAXIA TYPE 2 AN AQUEOUS-ETHANOLIC EXTRACT OF THE MARINE PLANT Thalassia testudinum, ENHANCES REFERENCE González Triana C, García Rodríguez JC, Rodríguez Cruz Y, Arteaga Pérez ME, Sosa Testé I, Jay Pérez D, Batista Castro Z, Garayburu de la SPATIAL MEMORY PERFORMANCES IN MICE Fuente G, San Jorge Y, Díaz Rivero BL, Forte Miranda C, Mengana García T, Morales RA, Palmero A, García N, Laguna A, Valdés O, Tamos Y, Fuentes Morales D, Mantilla Gattorno N, García–Somines Menéndez R. García J, Cruz Portales Y, Matos Díaz D. Centro de Bioproductos Marinos, Agencia de Medio Ambiente, Ministerio de Centro Nacional para la Producción de Animales de Laboratorio (CENPALAB), Ciencia, Tecnología y Medio Ambiente, La Habana, Cuba. E-mail: Habana, Cuba. E-mail: [email protected] [email protected]
Introduction: The spinocerebellar ataxia type 2 (SCA2) it is the most Introduction: BM-21 the extract from the marine plant Thalassia frequent form in Cuba, with the regions of more prevalence and world testudinum standardized to thalassiolin B content (5.8 ± 0.9%) possess concentration of sick and families in risk of suffering it which doesn't antioxidant, anti-inflammatory and neuroprotective properties. The present an effective therapy that modifies the course of the of the present study investigates the effects of BM-21 on spatial learning and disease. One of the developed therapeutic strategies is the memory in mice. administration of erythropoietin recombinant human EPO (rHu-EPO) of low sialic acid (Neuro-EPO) another treatment effective is the supply Material and methods: Young and aged (17-19 month) OF-1 mice and of zinc (Zn) it has been demonstrated that both as neuroprotector and Al-intoxicated Balb/c mice (50 mg/kg/day, 3 months) were used. After neuromodulator of the central nervous system (CNS). The objective of examining general motor activity by open field and rota rod test, this work was to demonstrate the therapeutic effectiveness of the reference spatial memory performance was assessed by Morris Water administration of both medications individually and combined Maze. Latency to find the escape platform (escape latency, EL) during (intranasal and oral) in animals model (transgenic mouse SCA2) as the training sessions, time in the target quadrant in the probe trial and neuroprotective agents to modify the course of the illness, evaluating the number of crossing were measured as indicators of water maze its effects in clinical nutritional and neurological parameters. performance. Also oxidative stress parameters in brain were determined. Material and methods: 5 groups experimental group 1 (ataxic control), group 2 (Neuro-EPO treated), group 3 (Zn treated), group 4 Results: In young animals (8 weeks) both, control and BM-21 treated (Neuro EPO + Zn combined treaty) and group 5 (control). The clinical (400 mg/kg daily, 1 month), gradually reduced EL; however the course was evaluated for three parameters: age of beginning of the statistical significance was higher for BM-21 treated animals (P < 0.05 ataxic manifestations, clinical square and survival; and realized tests of vs P< 0.01). Further experiments were conducted using lower doses neurological expression of motor and of the equilibrium coordination: and increasing administration period (100 mg/kg/day, 3 months) in Clasping, Sticker, Foot printing and Rota-Rod. aged mice and AlCl3-exposed young Balb/c mice. Our experiments confirmed that Al-exposed and aged mice showed more difficulties in Results and conclusion: The results showed retard in the beginning learning the task when compared non-Al exposed and young mice, age and smaller frequency and graveness of the ataxic symptoms and respectively. However, administration of BM-21 significantly enhanced increment of survival neurologically they manifested significant motor cognitive performance by decreasing EL and by increasing the time and of the equilibrium in the individual treatments, not being this way spent in the target quadrant and the number of platform crossing. Al- for the combined treatment. The combined treatment (Neuro-EPO + exposed and aged mice also showed significant raising of Zn), it didn't show positive results, while the individual treatments malondialdehyde (MDA) and a decrease of reduced glutathione (GSH) showed positive results as therapeutic alternative to modify the clinical and superoxide dismutase activity (SOD). However, BM-21 course of the SCA2. significantly modified them towards the normal values of controls. Also, the increase of AChE activity observed in Al-exposed group was reverted to normal by BM-21 administration. Conclusions: Our results showed that BM-21 (400 mg/kg) has cognition-enhancing abilities in young mice after 4 weeks of exposure. Besides its sub-chronic administration at lower doses (100 mg/kg) can block age-dependent and Al-induced declined in spatial cognition with a simultaneous improvement of oxidative stress in brain suggesting the involvement of antioxidant mechanism.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S245
LATINFARMA 2013 Resúmenes/Abstracts
PNF 011: NEUROPROTECTION IN A MODEL OF QUINOLINIC PNF 012: BRAIN INSULIN RESISTANCE AND COGNITIVE ACID TRANSPLANTED WITH BONE MARROW CELLS FUNCTION IN AGING RATS: NEUROMODULATORY AND NEUROTROPHIC EFFECTS OF INSULIN ADMINISTRATION Serrano-Sánchez T, Alberti-Amador E, Pavón-Fuentes N, Lorigados- Pedre L, Diaz-Armesto I, Robinson-Agramonte MA, Bergado-Rosado J. Haas CB, Kalinine E, Zimmer ER, Brochier AW, Hansel G, Portela LV, Sousa DO, Muller AP. Centro Internacional de Restauración Neurológica (CIREN), La Habana, Cuba. E- mail: [email protected] Departamento de Bioquímica, ICBS, UFRGS. Programa de Pós- Graduação em Ciências Biológicas - Bioquímica. Rua Ramiro Barcelos, 2600 anexo, CEP 90035- 003, Porto Alegre, RS, Brazil. E-mail: [email protected]. Fone number: Introduction: The growth derived neurotrophic (BDNF) it is a protein (55)(51)33085557 that promotes the growth and neural development. It has been reported that the lesion brain with quinolinic acid reproduces some of the characteristics of Huntington disease. At the same time, the use of Introduction: Aging is a risk factor for the development of brain bone marrow cells (CMO) it constitutes a therapeutic alternative that neurodegenerative disorders. The hippocampus neurodegeneration contributes to improve the alterations associated to this model. The along with the disruption of neural systems has been implicated in the BDNF constitutes an element of value to evidence the mechanisms by cognitive decline associated with aging. Moreover, impaired brain means of which the transplanted cells induce its modulatory effect. insulin signaling is involved in aging cognitive dysfunction. The main goal of this study was to assess the effects of intracerebroventricular Material and methods: The following work was guided to determine (i.c.v.) insulin on spatial memory, using the Morris Water Maze (MWM) the concentrations of BDNF in cerebral areas in an animal model of task, and neural and mitochondrial plasticity in aging. rats injured with quinolinic acid, false transplanted and transplanted with CMO, using an ELISA kit for BDNF. Each experimental group was Material and methods: Wistar male young (4 months old) and aged integrated by 10 animals. (22 months old) rats were i.c.v. injected with insulin (20 mU) or vehicle during five days. Results and conclusion: The lesion reached a significantly reduction of BDNF concentration in comparison with the controls. The animals Results and conclusion: The neural plasticity and neurogenesis were transplanted with the DMEM used for the maintenance of the cells, increased by treatment just in aged rats. However, insulin improved didn't alter this concentration. However, the animals transplanted with spatial memory in the MWM and hippocampal BDNF levels only in CMO showed significant increase in the detected concentrations (post young animals. Furthermore, insulin i.c.v. increased the extracellular hoc Turkey HSD test, p = 0.000017). The transplanted cells modulated fluid lactate levels in the hippocampus of young but not in aged rats. the detected levels of BDNF in the studied areas, and arguing the paper Mitochondrial H2O2 production induced by succinate was decreased in of this protein in the recovery of brain neuroprotection in an animal aged-insulin group relative to other groups. Also, the immunocontent of model of Huntington disease. mitochondrial PGC1-α, a biogenesis-stimulate protein, was increased by insulin administration in young animals. In summary, insulin administration presents positive effects on neural plasticity, neurogenesis and H2O2 production on hippocampus in aged animals.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S246
LATINFARMA 2013 Resúmenes/Abstracts
PNF 013: NEUROPROTECTIVE EFFECT OF BERBERINE ON PNF 014: A LOW DOSE OF DIAZEPAM REDUCES ANXIETY- BRAIN ISCHEMIA IN VITRO MODEL: INVOLVMENT OF LIKE BEHAVIOR IN WEANLING RATS IN THE ELEVATED SURVIVAL AND APOPTOSIS PATHWAY PLUS-MAZE TEST
Simões Pires E, Frozza R, Hoppe J, Menezes B, Salbego C. Guillén-Ruiz Ga, Bernal-Morales Ba, Cueto-Escobedo Ja, Rodríguez- Landa JFa, Contreras CM.a,b Biochemistry Department. Basic Health Science Institute. Federal University of Rio Grande do Sul (UFRGS), Brazil. E-mail: [email protected] aLaboratorio de Neurofarmacología, Instituto de Neuroetología, Universidad Veracruzana.Av. Dr. Luis Castelazo s/n Col. Industrial Las Ánimas, Xalapa 91190, Veracruz, México. E-mail: [email protected], [email protected], [email protected], [email protected], [email protected]. Introduction: Brain ischemia is one of the leading causes of death on bUnidad Periférica Xalapa. Instituto de Investigaciones Biomédicas, Universidad industrialized countries. Berberine is an alkaloid derived from herb Nacional Autónoma de México. Av. Dr. Luis Castelazo s/n Col. Industrial Las Berberis sp. and has long use on Oriental medicine. Studies among the Ánimas, Xalapa 91190, Veracruz, México. years have demonstrated its beneficial effect in various neurodegenerative and neuropsychiatric disorders. The subject of this study was to evaluate whether Berberine protects against delayed Introduction: Although clinical and experimental evidences have neuronal cell death on organotypic hippocampal culture (OHC) shown anxiety indicators in very young subjects, most of the studies exposed to oxygen and glucose deprivation (OGD) and the cell aiming to identify the pharmacological properties of substances with signaling mechanism related to its effect. anxiolytic effects use adult subjects. Additionally, the effect of anxiolytics in infants has been scarcely studied. The aim of this study Material and methods: Hippocampal slices were obtained from 6-8- was to identify the lowest effective anxiolytic dose of diazepam in post- days-old male Wistar rat and cultured for 14 days. Following, the weaning rats. cultures were exposed to 1 hour of OGD and then treated with Berberine (10 and 20 µM). Material and methods: Five experimental groups of 21 days aged Wistar rats included a control group (VEH: 0.9% NaCl, 0.3 mL/rat, Results and conclusion: After 24 h recovery, propidium iodide (PI) n=15) and other groups received different doses of diazepam (DZP): uptake was analyzed and it was observed a decrease on PI uptake on 0.1 mg/kg (n=11), 0.5 mg/kg (n=12), 1.0 mg/kg (n=12) and 5.0 mg/kg OGD Ber-treated culture, which means a decrease on cellular death. (n=9). These range of doses included lower and higher doses than 1.0 Western blot analysis showed that proteins Akt, GSK3β and JNK appear mg/kg, considered it the most used anxiolytic dose in adult rats. to play a role on Ber-mediated neuroprotection. Furthermore, capase-3 Treatments were subcutaneously injected in a volume 0.3 mL/rat. One activity of OGD Ber-treated culture was diminished by control level on hour after administration, the rats were evaluated in the plus maze and a fluorimetry assay. These findings suggest that Berberine-mediated open field tests. All procedures were performed during the light period neuroprotection after ischemia involves Akt/GSK3β survival/apoptotic between 11:00 a.m. and 3:00 p.m. signaling pathway as well as JNK and caspase-3 activity inhibition. Results: All doses exert any anxiolytic action, but a dose of 0.5 mg/kg resulted the minimal effective, producing the largest number of entries and time spent in the open arm in the plus maze test as compared to vehicle, without actions on spontaneous locomotor activity. Conclusion: We conclude that infant rats require lower doses of diazepam than an adult, which is relevant and may be considered in future studies evaluating the effect of substances with anxiolytic effect in this age.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S247
LATINFARMA 2013 Resúmenes/Abstracts
PNF 015: GUANOSINE IMPROVES FUNCTIONAL RECOVERY PNF 016: CHARACTERIZATION OF L TYPE CA2+ CHANNELS IN AND DECREASES BRAIN OXIDATIVE STRESS AFTER SPONTANEOUS DIFFERENTIATED OLFACTORY NEURONS SENSORIMOTOR CORTICAL ISCHEMIA IN RATS IN CULTURE, OBTAINED FROM BIPOLAR DISEASE AND SCHIZOPHRENIA PATIENTS Hansel G, Ramos DB, Delgado CA, Souza DG, Almeida RF, Portela LV, Quincozes-Santos A, Souza DO. Solís-Chagoyán H1, Calixto E2, Benítez-King GA.1
Departamento de Bioquímica. Instituto de Ciências Básicas da Saúde. 1Departamento de Neurofarmacología, 2Dirección de Investigaciones en Universidade Federal do Rio Grande do Sul. Porto Alegre, RS, Brazil. E-mail: E- Neurociencias del Instituto Nacional de Psiquiatría “Ramón de la Fuente Muñiz”. mail: [email protected] Calz. México-Xochimilco No.101, Col. San Lorenzo Huipulco, C.P. 14370, México, D.F. E-mails: GABK: [email protected], HSCh: [email protected].
Introduction: Ischemic stroke is a devastating disease with a complex pathophysiology. The sudden reduction in blood flow leads to a Introduction: In schizophrenia and bipolar disorder patients, decrease in oxygen and glucose supply to the corresponding ischemic impairments in odor detection and in olfactory receptor neuron brain area, resulting in cellular bioenergetics failure, tissue damage response to odor stimulation have been detected. L-type Ca2+ channels and loss of neurological function. Oxidative stress plays an important are involved in the chemical to electrical transduction occurred in role in ischemia/reperfusion injury, which has a direct negative impact olfactory neurons. Olfactory neuroepithelial cells in culture have been on ischemic cerebral tissue. proposed as a model to study the physiopathology of psychiatric disorders and characterization of biomarkers for diagnosis. In this Material and methods: Animals: Wistar male adult rats (90–100 days regard, we recently developed a method to obtain viable olfactory old). Permanent focal ischemia: Ischemic lesion was induced by neuroepithelial cells by nasal exfoliation from ambulatory patients and thermocoagulation (+ 2 to − 6 mm A.P. from bregma). Experimental culture conditions that promote olfactory precursors proliferation and groups: Sham Saline, Sham Guanosine (GUO), Ischemia Saline and their spontaneous differentiation into olfactory sensory neurons. The Ischemia GUO. Treatment: GUO (60 mg/kg diluted in saline) or saline, 1 aim of this work was the characterization of the L-type Ca2+ current in mL/kg i.p. administration of the drugs immediately, 1 h, 3 h and 6 h spontaneous differentiated olfactory sensory neurons in culture, after surgery. Cylinder test: animals were placed into cylinder and 20 obtained from patients with the paranoid type of schizophrenia (SZ) touches were counted. Infarct volume lesion: TTCstating assay. and bipolar disorder type I (BD). Oxidative stress assay: ROS/NOS levels, neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) expression, lipid Mateial and methods: L-type current recording was performed by peroxidation, and the activity/levels of antioxidants non-enzymatic whole-cell patch-clamp technique, employing Ba2+ to replace Ca2+ and (GSH, vitamin C) and enzymatic defenses (SOD, CAT, GPx, GS) in the superfusing cells with nifedipine (10 microM). L-type channels CNS. expression in olfactory sensory neurons was evaluated by double immunofluorescence with a specific anti-L-type alpha subunit antibody Results: Twenty-four hours after injury, GUO significantly reduced and with an anti-olfactory marker protein (OMP) antibody. tissue damage and restored function of the impaired forelimb (maintained up to 15 days). GUO decreased lipid peroxidation and did Results and conclusion: Amplitude of L-type current in neurons of BD not modulate GS activity. GUO strongly prevented an increase in patient was 60% of the total amplitude of Ca2+ voltage-activated ROS/RNS production in the ischemic area, modulating the enzymatic currents; this level of the nifedipine- sensitive current was similar to (SOD, CAT and GPx) and non-enzymatic (GSH and vitamin C) that in neurons of healthy subjects. In contrast, this Ca2+ current in SZ antioxidant defenses against cellular damage.GUO prevented a was 30% of the total Ca2+ voltage-activated currents. 100% of the cells decrease of nNOS and did not modulate iNOS. immunostained with the anti-L-type channels antibody were also positive to anti-OMP antibody, which suggest that L-type channels are Conclusion: GUO proved to be neuroprotective against ischemia, expressed only in mature olfactory sensory neurons. This reduction in restored function of the impaired forelimb. The neuroprotection effect L-type current in SZ is a potential biomarker that may differentiates SZ seems to be linked by the modulation of important antioxidant and BD. defenses in the SNC.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S248
LATINFARMA 2013 Resúmenes/Abstracts
PNF 017: ACTION OF FATTY ACIDS ON GABAA RECEPTORS: PNF 018: METHYLPHENIDATE AMPLIFIES LONG-TERM IMPLICATIONS FOR THEIR ANXIOLYTIC-LIKE EFFECTS IN POTENTIATION IN THE HIPPOCAMPUS THROUGH β- WISTAR RATS ADRENERGIC AND D1/D5 RECEPTORS
Rodríguez-Landa JF1, García-Ríos RI1, Cueto-Escobedo J1, Bernal- Carreño M1 , Contreras D1, Zeise M2, Morales B.1 Morales B1, Contreras CM.1,2 1Depto. de Biología, Fac. Química y Biología, 2Escuela de Psicología, Fac de 1Laboratorio de Neurofarmacología, Instituto de Neuroetología, Universidad Humanidades, Universidad de Santiago de Chile, Santiago, Chile. Veracruzana, Xalapa 91190, Veracruz, México. E-mail: [email protected] 2Unidad Periférica Xalapa, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Xalapa 91190, Veracruz, México. Emails: [email protected], [email protected] Introduction: Methylphenidate (MPH) is a psychostimulant used widely in the therapy of the Attention Deficit/Hyperactivity Disorder and recently has become also a drug of abuse. Our and other laboratories have demonstrated that MPH modifies synaptic plasticity Introduction: A mixture of eight fatty acids (FAT-M) identified in in the hippocampus. However, the cellular and molecular mechanisms human amniotic fluid (C12:0, lauric acid, 0.9 g%; C14:0, myristic acid, involved are still unknown. We investigated the effects of MPH on LTP 6.9 g%; C16:0, palmitic acid, 35.3 g%; C16:1, palmitoleic acid, 16.4 in hippocampus slices. g%; C18:0, stearic acid, 8.5 g%; C18:1cis, oleic acid, 18.4 g%; C18:1trans, elaidic acid, 3.5 g%; C18:2, linoleic acid, 10.1 g%) Material and methods: 3-4 weeks old Sprague-Dawley rats were produce anxiolytic-like effects comparable to diazepam in Wistar rats, decapitated under halothane anesthesia, and hippocampus slices (400 μm thick) were prepared. LTP was induced and recorded in CA1 by suggesting the possible involvement of GABAA receptors, a possibility not yet explored. Therefore, the present study explored the applying theta burst stimulation (TBS, 5 trains, 100 Hz) at the Schaeffer collaterals. participation of GABAA receptors in the anxiolytic-like effects of the FAT-M. Results: Superfusion of hippocampal slices during 20 min with MPH, Material and methods: Male Wistar rats were subjected to the increased in a dose-dependent manner the magnitude of LTP from defensive burying test, elevated plus maze, and open field test. In 134.6 ± 1.2% (controls) to 137.5 ± 2.8 7% (3 nM; n=3, 3; p>0.05), 163.4 ± 10.4% (50 nM; n=5, 7; p<0.05), 194.3 ± 5.8 (5 μM; n=6, 8, p<0.01), different groups of rats, three GABAA receptor antagonists were and 196.4 ± 4.2% (50 μM; n=4, 4; p<0.01). The paired-pulse curves administered 30 min before the FAT-M, including the competitive remained unchanged after perfusion with MPH, suggesting that the GABA binding antagonist bicuculline (1 mg/kg), GABAA benzodiazepine antagonist flumazenil (5 mg/kg), and noncompetitive effect of MPH does not involve modifications of presynaptic components. The increase induced by MPH was inhibited by 5 μM GABAA chloride channel antagonist picrotoxin (1 mg/kg). timolol, β-adrenergic blocker, from 194.3 ± 5.8% (TBS + 5 μM MPH) to Results: The FAT-M exerted anxiolytic-like effects in the defensive 152.7 ± 1.66% (TBS+ 5 μM MPH + timolol); n=4, 4; p<0.01). burying test and elevated plus maze, without affecting locomotor Interestingly, LTP increase was also inhibited by 5 μM of SCH23390, activity in the open field test. Administration of the GABAA antagonists D1/D5 blocker, from 192 ± 7% (TBS + 5 μM MPH) to 151.3 ± 0.9% alone did not produce significant changes in the behavioral tests. (TBS + MPH + SCH23390; n=3, 3; p<0.01). Both effects probably are Picrotoxin, but neither bicuculline nor flumazenil, blocked the postsynaptic because the paired-pulse curves remain unchanged. anxiolytic-like effect produced by the FAT-M. Conclusions: These results suggest that MPH increases LTP in a dose- Conclusion: The FAT-M exerted its anxiolytic-like actions through dependent manner involving β-noradrenergic and D1/D5 receptors GABAA receptor chloride channels in Wistar rats. through a polysynaptic mechanism.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S249
LATINFARMA 2013 Resúmenes/Abstracts
PNF 019: HEPTANOIC ACID INCREASES ACTIVE BEHAVIOR IN PNF 020: COMPARISON BETWEEN TRICAINE AND THE FORCED SWIM TEST IN WISTAR MALE RATS BENZOCAINE IN THE BEHAVIORAL PROFILE OF EPILEPTIC SEIZURE CAUSED BY ADMINISTRATION OF KAINIC ACID IN Saldivar-Lara M1, Gutiérrez-García AG1,2, Contreras CM1,3, Guillén-Ruiz G1, Molina-Jiménez T.1 ZEBRAFISH ADULT
1Laboratorio de Neurofarmacología, Instituto de Neuroetología, Universidad Rico EP, Baggio S, Mussulini BH,Rosemberg DB, Oliveira DL, Souza DO. Veracruzana. Av. Dr. Luis Castelazo s/n Col. Industrial Las Ánimas, Xalapa 91190, Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Veracruz, México. E-mails: [email protected], [email protected], Saúde, Departamento de Bioquímica. Rua Ramiro Barcelos 2600 – Anexo Bairro [email protected]. [email protected], [email protected] Santa Cecília Porto Alegre – RS, Brasil. E-mail: [email protected] 2Facultad de Psicología, Universidad Veracruzana. Manantial de San Cristóbal s/n. Col. Xalapa 2000. Xalapa, Veracruz, México. 3Unidad Periférica Xalapa. Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México. Av. Dr. Luis Castelazo s/n Col. Industrial Las Introduction: Kainic acid (KA) is a convulsant agent used for the study Ánimas, Xalapa 91190, Veracruz, México. of seizures and for the development of anticonvulsant drugs. Zebrafish has been proposed as model to evaluate the status epilepticus (SE) in both young and adult individuals. Here, we studied the influence of Introduction: Amineptine and tianeptine are clinically effective tricaine (TRI) and benzocaine (BZC) pre-treatment on behavioral antidepressants; both contain heptanoic acid in their chemical seizure-stage induced by KA in zebrafish. structure. The aim of this study consisted in explore the possible anti- despair effects of the heptanoic acid in the forced swim test. Material and methods: The experiments was performed using 72 animals (n = 12 per group), which KA were injected intraperitoneally Material and methods: We included 40 male Wistar rats aged 3 with 4, 5, 6 mg/kg and evaluated the seizure behavior and mortality months and weighing 250-300 g, assigned to 4 groups: one control- during 7 days after exposure. The frequency of animals to achieve each vehicle group (n=10), two groups receiving different doses ofheptanoic stages was measured (median and interquartile range) which the acid (1 mg/kg n=10; and 10 mg/kg n=10) and one active control group latency analyzed using one-way ANOVA followed by Bonferroni post- received fluoxetine 1 mg/kg (n=10). Treatments were long-term test and the mortality by chi-square. The stages was quantified administered for 21 days and then were evaluated in the open field test according the scale previously described (Alfaro et al., 2011) (5 min) and forced swim test (5 min). considering stage V and VI, whole-body clonus-like convulsions and spasms. Results: No significant differences attributable to treatments were detected in the open field test. In the forced swim test we found that Results: Our results express the seizure along time for each the heptanoic acid and the fluoxetine yielded less immobility episodes concentration, which it was observed that the scores progress rapidly (P<0.05) without affecting the total immobility time. The heptanoic in the first 10 min, with the predominance of V and VI scores between acid (10 mg/kg) group obtained the longer total time and number of 10 and 20 min. Pre-treatment with BZN showed lower latency to episodes of climbing (P<0.05). seizure stages compared to TRI when submitted to KA. Lower dose of KA (4 mg/kg) for both anesthetics tested showed highest latency to Conclusion: We conclude that the 10 mg/kg dose of heptanoic acid stages V compared to other doses tested. Groups KA 6 mg/kg showed a increases active behaviors in the forced swim test. shorter latency to the stages V when pre-treated with BZN compared with pre-treatment with TRI. The mortality was verified showing for BNZ 30%, 100% and 100% and TRI 10, 20 and 90% at doses of 4, 5, and 6 mg/kg, respectively. Therefore, BZN and TRI have different responses to SE. Conclusion: Our results allow us to better understand the strategies regarding the use of anesthetics to induction of SE in zebrafish and for studies related to excytotoxicity.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S250
LATINFARMA 2013 Resúmenes/Abstracts
PNF 021: CYTOCHROME P450 2J3 AND 2C11 REGULATION IN PNF 022: IN VITRO MODEL OF MILD A LPS-INDUCED MODEL OF NEUROINFLAMMATION IN HYPERHOMOCYSTEINEMIA CAUSES MODULATION IN ASTROCYTES REDOX STATE IN CEREBRAL CORTEX AND HEART
Navarro-Mabarak C, Espinosa-Aguirre J. Longoni A1, Koling J1, Siebert C1, dos Santos TM1, Turcatel E1, Herpich T1, Grunewald M1, da Silva EL1, de Assis AM1,2, Wyse AT.1,2 Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), Distrito Federal, DF, Mexico. E-mail: 1Programa de Pós graduação em Bioquímica, 2Departamento de Bioquímica, [email protected] Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, 90035-003, Brazil. E-mail: [email protected]
Introduction: Cytochromes P450 (CYP) is a wide family of enzymes characterized by carrying out the oxidation of organic compounds. In Introduction: High homocysteine level is a risk factor for addition to mediate the metabolism of xenobiotics, CYPs also cerebrovascular and cardiovascular diseases. Some studies have metabolize many endogenous substrates such as cholesterol, steroids, shown a direct link between the accumulation of homocysteine and hormones and fatty acids to biologically active intermediates. CYP 2C oxidative stress. and 2J isoforms, which have epoxygenase activity, are the main responsible of the arachidonic acid oxidative metabolism to Material and methods: Adult male Wistar rats (PND 60) were epoxyeicosatrienoic acids (EETs). Among their diverse biological sacrificed by decapitation and heart and cerebral cortex were isolated, properties, EETs have anti-inflammatory actions. CYP epoxygenases weighed and chopped: on a tissue chopper to 300 μm and incubated at and its metabolites have been proposed as a good therapeutic target to 37°C in 24 wells plate with Dubbeco buffer pH 7.3 containing different treat both systemic and organ specific inflammatory processes, even in doses (0 uM, 15 μM, 30 μM and 50 μM) of homocysteine at different the CNS. However, little has been described about the regulation of times (30 min, 1 h and 3 h) of incubation. After incubation, the slices these enzymes during inflammation, an important issue considering were washed with cold buffer Dubbeco, the slices were homogenized that it has been reported that the expression of some CYPs can be in 20 mM PBS with 140 mM KCl for subsequent analysis of oxidative modified with changes in the levels of pro-inflammatory cytokines stress (TBARS, DCFH oxidation, sulfhydryl groups, carbonyl content, such as IL-6, IL-1b and TNF-a. We are interested in elucidate whether SOD and GPx). an inflammatory process in the CNS can modify CYP 2J expression and Results: In cerebral cortex, we observed that the different the mechanism by which this process is carried out. concentrations of homocysteine increased lipid peroxidation, DCFH Material and methods: We examined the effect of 100 ng/mL LPS on oxidation and SOD activity (p<0.05) in all times studied, however, the CYP 2J3 RNA and protein expression in isolated astrocytes obtained concentration of 50 μM of homocysteine seems to increase carbonyl from the cortex of newborn rats. content after 1 h of incubation. In cerebral cortex, GPx activity was decreased at all concentrations and times studied in a concentration- Results: The addition of LPS to astrocyte cultures caused a decrease in dependent manner. In heart, homocysteine in the concentration of 30 the RNA and protein expression of the CYP2J3. and 50 μM increased lipid peroxidation and decreased the sulfhydryl content (p<0.05) after 1 h of incubation. In addition, we observed that Conclusions: The inflammatory process triggered by the addition of SOD activity was increased by homocysteine (30 and 50 μM) when LPS to astrocytes cultures is able to modulate CYP2J3 expression, incubated for 30 min, but its activity was decreased with 1 h of transcriptional and in the protein levels of the enzyme, suggesting that incubation (p<0.05). inflammatory mediators such as cytokines or ROS may play an important role in mediating the regulation of this cytochrome in the Conclusion: These results showed that this model mimics the effects of CNS. the redox state promoted by hyperhomocysteinemia in vivo, demonstrating the potential of this model to be used for screening of different therapeutic substances, although more studies are necessary.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S251
LATINFARMA 2013 Resúmenes/Abstracts
Miércoles 23 / Wednesday 23rd
TALLERES Y SIMPOSIOS / WORKSHOPS AND SYMPOSIA
Ensayos Clínicos / Clinical Trials
Farmacoepidemiología / Pharmacoepidemiology
Farmacología del Dolor / Pharmacology of Pain
Farmacoeconomía / Pharmacoeconomy
Farmacovigilancia / Pharmacovigilance
Cronobiofarmacología / Chronobiopharmacology
Enseñanza de la Farmacología / Teaching of Pharmacology
Productos Genéricos / Generic Drugs
Farmacología Básica / Basic Pharmacology
Pharmacogenética / Pharmacogenetics
Otros / Others
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S252
LATINFARMA 2013 Resúmenes/Abstracts
Ensayos Clínicos / Clinical Trials
PEC 001: CONTROLLED CLINICAL TRIALS: AN ACTIVITY IN PEC 002: SAFETY OF ANTI-IDIOTYPIC 1E10/ALUMIN INCREASE IN VILLA CLARA VACCINE. RESULTS OF 6 FASE II CLINICAL TRIALS Rodríguez M, Méndez R, Marrero R, Castañedo Z, Arboláez M, Sánchez García E, Mendoza I, Ills D, Guerra PP, Viada C, Macías A. P, Herrera L. Centro Nacional Coordinador de Ensayos Clínicos (CENCEC). Calle 200 esq. 21 University of Medical Sciences Dr Serafín Ruiz de Zárate. Carretera Acueducto y Atabey. Playa. La Habana, Cuba. E-mail: [email protected] Ci.rcunvalación. Santa Clara. Villa Clara, Cuba. E-mail: [email protected]
Introduction: The anti-idiotipic 1E10/Alumin vaccine is an antibody Introduction: The clinical trials constitute the most rigorous monoclonal (AcM) highly specific against the AcM P3 that inhibits the investigations in the sphere of the health and let allow the evaluation union from the ganglioside NGcGM3, present in certain tumors. To of the effectiveness and the security of drugs, equipments and describe the safety profile of this vaccine, it was continued with the procedures. In Villa Clara this activity began to develop in the year chronic use and in combination with the conventional treatment of 1992 starting from the creation of the Provincial Subcenter of Clinical chemotherapy and radiotherapy. The objective was to evaluate the Trials. Since that year, the number of professionals involved, the safety of the anti-idiotypic vaccine in the different executed clinical specialities, and the evaluated products, have being increased. trials. Material and Method: It was carried out a documental revision and Material and methods: Four studies phase II were designed interviews to directive and professionals related with the activity for (controlled and not controlled) and two compassionate drug use the summary of the information. studies, in oncological services of the whole country, in the indications of breast, colon and no small/small cells lung cancer. Results: It have been carried out 54 clinical trials in the territory, mainly with the Center of Molecular Immunology and directed to the Results: 316 patients were included and received the vaccine. All therapy of the cancer. The lung localizations and breast cancer have patients received the product by intradermal route, dose of 1 mg/mL been the most favored with treatment options in clinical trials. An every 14 days the first 5 administrations (induction stage) and every increment was evidenced in the number of professionals, medical 28 days the remaining ones (maintenance stage). The intensity of the specialties and participant institutions. We could appreciate the adverse events was evaluated by the Common Terminology Criteria for correspondence between the health´s situation of the territory and the Adverse Events (CTCAE) version 3.0 and the causality was evaluated developed clinical investigations. too. The most frequent adverse events presented in these studies were of local type: pain and reaction in the injection, local eritema, while the Conclusions: Villa Clara has experienced a growing development in the systemic ones were fever and chills. The biggest percentage of events activity of clinical trials achieving an increment of the scientific activity according to intensity was between light and moderate. directed to the improvement of the medical care and the quality of the patients' life. Conclusion: The immunization with the anti-idiotypic 1E10/alumin vaccine demonstrated to be safe and of low toxicity.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S253
LATINFARMA 2013 Resúmenes/Abstracts
PEC 003: RESULTS OF CLINICAL TRIALS WITH PEC 004: EVALUATION OF THE ACCEPTABILITY OF RECOMBINANT HUMAN ERYTHROPOIETIN IN CUBA METERED DOSE INHALATOR SALBUTAMOL HFA, 100 MICROGRAMS IN THE TREATMENT OF PRESISTENT Vargas A, Mendoza I, Pérez-Oliva JF, Sijó A, Piedra P, Saurez G, Román Y, Robaina M, Uranga R. BRONCHIAL ASTHMA
National Coordinating Center of Clinical Trials. 200 and 21. Atabey, Havana, Cuba. Bermudez Y, Ávila Y, Cívico H, Uranga R, Ronquillo M, Valdés S, E-mail: [email protected] Oramas M, Toledo L, González I, Vázquez DN, Nápoles NA, Filiu J, Castillo A, Gómez M, Tasé R, Martínez R, Pérez M. Introduction: Recombinant Human Erythropoietin (Rh-EPO) is an National Coordinating Center of Clinical Trials. 200 and 21. Atabey, Havana, Cuba. erythropoiesis stimulating agent used as antianemic in diseases E-mail: [email protected] involving absolute or relative deficit of erythropoietin. Ior®EPOCIM produced by the Center of Molecular Immunology has shown benefits in correcting anemia and reduction of transfusion requirements. We Introduction: Asthma is a serious public health problem throughout performed a compilation of studies with ior®EPOCIM which evaluated the world, affecting people of all ages. The impact of the efficacy and safety of this drug. Hematological response was chlorofluorocarbons (CFC) on the environment has lead to apply a evaluated, adverse events (AE) and quality of life in some of them. replacing strategy of CFC; hydrofluoroalkanes (HFA) which are evaluated are those that do not hurt the stratospheric ozone and that Material and methods: Were conducted four phase IV clinical trials have been assessed in clinical trials with success as solvents and with ior® EPOCIM in anemia secondary to chemotherapy in cancer metered dose inhalers propellant. This study evaluated the patients, anemia in patients with Chronic Kidney Disease (CKD) in acceptability of Salbutamol HFA 100 µg in the treatment of bronchial dialysis and anemia of prematurity in preterm new born. asthma, the respiratory airways functioning, the clinical evolution and Results: Four Clinical Trials were performed: two clinical trials in safety of Salbutamol HFA. anemia in cancer patients, adults (326 patients) and pediatric (157 Material and methods: An exploratory non comparative, non patients), one clinical trial in patients with CKD in dialysis (617 randomized multicentric and open label study was performed. Cuban patients) and one clinical trial in neonates (72 patients). patients between 18 and 65 years with informed consent given were In oncology, the recovery of anemia was achieved in 8 weeks in 68.8% included. Patients with another bronchodilator, with severe psychiatric in children and 77.9% in adults, adverse events in adults occurred in disorders, diabetics, with arterial hypertension, cardiac diseases 97 patients (28.7%) and children in 46 patients (29.3%). In dialysis among others, pregnant women and nursery period were excluded. was achieved maintaining the hematocrit and hemoglobin above 30% Only one therapeutic scheme was evaluated in out patients according and 100 g/L in 54.4% and adverse events occurred in 54.9%. Regard to to recommended doses for Salbutamol HFA, during four weeks. quality of life improvement, was achieved only in the dimension Results: From 108 patients included, 93 (86.11%) accepted General Health. In the phase III neonatal clinical trial, the 90.3% did Salbutamol HFA. The bronchodilator effect was evaluated in 26 not require transfusion. Adverse events occurred in 18 patients (25%). included patients form hospital located in Havana, it was observed that They are currently enrolling patients two phase IV clinical trials, in 11 (42.31%) of them a significative response of the variation of FEV1 predialysis patients in CKD and preterm new born. and FVC. Clinical evaluation showed a significative decrease of clinical Conclusions: Ior®EPOCIM shown to be effective and safe in approved signs and symptoms. 136 adverse events were reported in 50 doses and frequencies used in medical practice. (46.30%) subjects. Conclusions: Salbutamol HFA, substituting Salbutamol CFC, is accepted by patients; enhance the respiratory airways and the clinical status and it is safe for asthma treatment.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S254
LATINFARMA 2013 Resúmenes/Abstracts
PEC 005: EFFICACY AND SECURITY OF CRANIOPUNCTURE PEC 006: EXPERIENCES IN THE CONDUCTION OF A CLINICAL VERSUS BACLOFEN IN PATIENTS WITH SPASTICITY TRIAL IN PRIMARY ATTENTION IN VILLA CLARA, CUBA Saumell Y, Herrera MB, López Peña R. Lorenzo G, Ortiz RA, Rodriguez C, Norvel M, Rodriguez M, García MC, Artiles M, De la Barca NC, Alonso M, Castañeda Z, Mendez R Center of Molecular Immunology 15 Esq. 216, Siboney, Playa, Havana City, Cuba. E-mail: [email protected] Center of Molecular Immunology (CIM Delegation Villa Clara), Cuba. E-mail: [email protected]
Introduction: Spasticity is an exaggerated answer to the partial or total loss of the supra spinal inhibitory control on the spinal marrow. Introduction: In 2010, the Center of Molecular Immunology, extended The modulation of spasticity in a consistent way is a problem of health clinical trials to the primary attention health level by means of the that is not solved with the conventional drugs. That is why it´s evaluation of the therapeutic vaccine CIMAvax EGF, registered for the necessary to search other alternative that present less secondary treatment of late lung tumors. The objective of this investigation is to reactions for patients in a longer period of use. show the experiences in the conduction of a clinical trial with CIMAvax EGF vaccine in the primary attention health level in Villa Clara. Material and methods: It was carried out a controlled and randomized clinical trial, with the purpose to evaluate the efficacy and Material and methods: A Good Clinical Practices and Oncology security of craniopuncture versus baclofen in patients with spasticity, training program was designed. There were selected the investigation in the Polyclinic Ramón López Peña of Santiago de Cuba. A sample of sites using checking lists according to the requirements of 60 patients was obtained, and randomized in two treatment groups International Conference of Harmonization (ICH) and Regulation No. with 30 patients each one, selected according to diagnostic and 165:2000 from Cuban Regulatory Agency (CECMED). The coordinating inclusion criteria. The control group was treated with kinesiology and clinical trial team and the elements or actions of integrality in patient’s baclofen, and the study group with kinesiology and craniopuncture. To attention in his locality were identified. The roles for the conduction of evaluate the clinical improvement were used 5 scales of the American a clinical trial in this scenario were also defined and there were Neurological Association. The information was processed in the SPSS coordinated the diagnostic test execution and the distribution of the program version 11.5. It was used the percentage as a summary vaccine. measure, and the non parametric test of Pearson with a P< 0.05 as significant. Results: There were trained medical doctors, pharmacists, nurses and clinical laboratory specialists. 6 polyclinics of Santa Clara were selected Results: It was obtained as a main result a significant improvement to to participate in the study. 162 patients were included in the study the 6 months of treatment with regard to the group who received which reached a survival average and median of 10.66 and 8.06 baclofen. 19 adverse events of mild and moderate intensity were months respectively. There were no important adverse effects after the reported, all of them with very probable causality: 2 for the administration of the vaccine. It was reached an increase in the quality craniopuncture in the study group, and 17 for the baclofen in the of life of the patients. control group. Conclusions: Primary attention health level has the conditions which Conclusion: It concluded that the craniopuncture turned out to be allow an adequate conduction of clinical trials which are intended to effective and sure in relation to baclofen in patient with spasticity, ameliorate the quality of medical assistance and benefit the quality of being recommended the use of the same one as complementary life of patients. treatment by the physiotherapeutic personal, and the continuation of the studies for a longer period of use.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S255
LATINFARMA 2013 Resúmenes/Abstracts
PEC 007: PERFORMANCE EVALUATION OF GOOD CLINICS PEC 008: INTEGRATION OF MONITORING BASED ON RISK IN PRACTICE AT THE CLINIC PREVISORA OF CAMAGUEY THE MANAGEMENT OF BIOLOGICAL SAMPLES IN LABORATORY Infante E, Valls AR, Morales K, Ramirez M, Margenat A, Hernández J. Bueno E. Universidad Médica de Camagüey. CPEC, Cuba. E-mails: [email protected] , [email protected] Centro de Inmunología Molecular Calle 216, Atabey-Playa, La Habana, Cuba. E- mail: [email protected]
Introduction: In Camagüey developing a Phase IV clinical trial to evaluate the safety and effectiveness of CIMAvax EGF therapeutic Introduction: Monitoring Based on Risk (MBR) is one of the most vaccine in patients with tumors of non-small cell lung cancer treated at accepted by the control agencies and the pharmaceutical industries. the Primary Health Care, sponsored by the Center of Molecular The biological samples taken from the patients related to clinical trials Immunology. Regulatory authorities require that the execution of the are the basis of scientific research, but they are not always adequately study is conducted in compliance with Good Clinical Practice standards monitored. The objective of this work is to propose a MBR for the in order to ensure the protection of research participants and the management of biological samples. quality and integrity of the data obtained. Therefore this study was aimed to assess compliance with GCP in four of the services involved in Material and methods: The study was made during a period of 8 the study at the Polyclinic Previsora. months, 844 samples were analyzed in the CIM Laboratory. The Operation Normalized Procedure (PNO)-2366 and the schema of Material and methods: We developed a checklist to measure traceability were used, and 2 notes of arrival and departure of the qualification of personnel, conditions of service and the status of the samples of the laboratory. The MBR design was adapted to the study documentation. The sum of all items reached a maximum of 100 infrastructure of the inventories. points. It was considered appropriate compliance with GCP if the score ranged from 70 to 100 points and unsuitable when the values were Results and conclusion: A Security and Data Monitoring Plan (DSMP) lower than 70 points. was arranged in order to optimize the Laboratory work, a PNO, a report, a check list with a distribution of 10 chapters and 61 items, a Results: In each service has a single investigator trained for this CAPA, a critical guideline and traceability tables were prepared. The activity. There were adequate for research conditions but notes that incorporation of the MBR in the process of checking of samples was the thermometer is not calibrated, do not have the crash cart in the successful. This investigation was made in order to improve the quality room to administer the PI and the lab does not have the certificate of of the work in the laboratory and we recommend that this kind of accreditation. All services have the required documents are current but monitoring was spread for scientific research. have difficulty with Operational SOPs.
Conclusions: An adequate compliance with Good Clinical Practices during the execution of the clinical trial.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S256
LATINFARMA 2013 Resúmenes/Abstracts
PEC 009: AUDITS OF GOOD CLINICAL PRACTICE: TOOL TO PEC 010: CLINICAL TRIALS: FEASIBILITY´S EVALUATION IMPROVE THE QUALITY OF A CLINICAL TRIAL Rodriguez J.
Alvarez S, González Z, Riquelme I, Saborido L. National Coordinating Center of Clinical Trials. 200 and 21 st, Atabey, Playa. Havana, Cuba. E-mail: [email protected] Centro Nacional Coordinador de Ensayos Clínicos (CENCEC), La Habana, Cuba. E- mail: [email protected] Introduction: The development strategy of a new drug must be Introduction: In the execution of clinical trials errors can be made that composed of parameters that facilitate the analysis of real conditions rebound in not wanted consequences, that’s why is totally necessary to for the completion of each stage. In this sense the evaluation of the work with a maximum of quality, taking this into account the audits are feasibility of a clinical trial is essential to measure the relevance, the an important tool to detect errors in clinical trials since they allow you clinical development of a product. The purpose of this paper is to to detect the difficulties and to trace work strategies to achieve a present the strategy of the National Coordinating Center for Clinical maximum of quality in the development of a clinical trials. The Trials to assess the feasibility of a clinical trial. objective of this work was to design a strategy for the solution of the Material and methods: The strategy consisted in designing a tool for difficulties founded in audits to clinical sites. assessing the feasibility of applications for designing and conducting Methodology: In this investigation we worked with 7 reports of audits clinical research. Its development and content was the result of an carried out between January and December of the 2012 by the National extensive literature search, evaluation by experts on different topics Coordinating Center of Clinical Trials to different clinical site of the related to clinical trials and implementation. Havana, corresponding to 7 trials. Results: The tool for feasibility´s evaluation was composed for 4 Results: The strategy was focused to develop a series of blocks of assessment: Regulatory Aspects, Scientific-Methodological, methodological activities that contribute to better performance of the Epidemiological and Logistics. The application of the tool allowed the clinical investigators in the trial and work on the implementation of evaluation of 63 applications corresponding to 34 new products from advanced technologies with a point of view of the improvement the 13 promoters centers, 24 of which required a designed of strategy for quality in the clinical trials, besides increasing linking professionals in their preclinical and/or clinical development. In all cases the analyzed other fields with the profile of clinical trials. trials reached approval by the regulatory authority and the time required for this purpose decreased. Conclusion: The audit to the clinical trials allowed us to have a working strategy to solve the difficulties and ensure a higher quality of Conclusions: The tool allowed us to detect problems relating to clinical trials. information lack; it has shown that the use of this tool ensures minimal backup information for the clinical trial, speeding up the design and conduction of clinical investigation that will influence on the reduction of time necessary to obtain opportune results.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S257
LATINFARMA 2013 Resúmenes/Abstracts
PEC 011: PLANNING QUALITY IMPROVEMENT REPORT PEC 012: THERAPEUTIC EQUIVALENCE BETWEEN IOR ADVERSE EVENTS IN CLINICAL TRIAL LEUKOCIM, HEBERVITAL AND NEUPOGEN AS Martín Y, Ríos M, Marrero R, Lorenzo G, Crespo JC. TREATMENT OF SEVERE NEUTROPENIA AFTER CHEMOTHERAPY IN PATIENTS WITH ACUTE LEUKEMIA Hospital Universitario “Dr. Celestino Hernández Robau”. Santa Clara. Villa Clara, Cuba. E-mail: [email protected] Mendoza I, Carnot J, Fernández J, Robaina T, Piedra P, Hernández F, Cachimaille Y, Galano E, Robaina M, Valenzuela C, López P, Saurez G.
Centro Nacional Coordinador de Ensayos Clínicos. (CENCEC). Calle 200 esq. 21 Introduction: The report and classification of adverse events (AE) is a Atabey. Playa. La Habana, Cuba. E-mail: [email protected] process likely to be difficult, because often you do not have the knowledge and tools necessary to carry out the required quality for clinical research. Introduction: Use of granulocyte colony-stimulating factors shortens Methodology: An observational, descriptive, prospective research was the time to recuperation from adverse events associated at perform in the September-November period of 2012, with the objetive induction/consolidation in acute leukemia (AL). The objective was of identifying the main weaknesses of the classification process and EA evaluated therapeutic equivalence between ior LeukoCIM, Hebervital report and develops a plan to improve the quality of the University and Neupogen in severe neutropenia in patients receiving dose- Hospital "Dr. Celestino Hernández Robau ". Reported AEs were intensive chemotherapy for AL. evaluated in the clinical records of patients in 6 clinical trials (3 CIM, 3 Methodology: It was phase IV study, multicenter, randomized, IGBC) identified major deficiencies: inadequate classification (23), late controlled, open label, which recruited 93 treatments cycles (36 ior notification and reporting of serious AE (3), no treatment recording AE LeukoCIM, 30 Hebervital and 27 Neupogen), in 61 patients. (12) EA registration is not (5). It was developed a Pareto diagram Treatment G-CSF beginning 72 h after ChT (5 µg/kg). The end point defining as nonconformity main misclassification of AE (failure evaluated was severe neutropenia recuperation, number of doses intensity, causality, time, result). required, febrile neutropenia incidence, infections and adverse events. Results and conclusion: To determine the potential causes of the Results and conclusion: Per protocol analysis, patients treated with problem was used the method that yielded 635 as root causes lack of ior LeukoCIM, recovered severe neutropenia at 84.8%, in Hebervital classification instruments, lack of training of researchers, overwork. A plan of measures was design to resolve nonconformities detected, group 86.7% and in Neupogen group 73.1%. Responses proportion mainly the training of researchers and implementation of tools for the differences ior LeukoCIM vs Neupogen was 11.7% [IC 97%:-1; 9.0] correct classification of the AE. Deficiencies were identified in the (p=0.002), and Hebervital vs Neupogen was 13.6% [IC 97%:-1; 7.3] process of reporting the EA process and were plan the improvement of (p=0.008). Intent to treat analysis showed recovered severe the quality of the process. neutropenia at 85.7% in ior LeukoCIM group, 83.9% in Hebervital and 74.1% in Neupogen. Responses proportion differences ior LeukoCIM vs Neupogen was 11.6%, [IC 97%:-1; 11.0] (p=0.001) and Hebervital vs Neupogen was 9.8% [IC 97%:-1; 11.0] (p=0.003). The median to time to recover neutrophils ≥ 0.5 x 10 9/L was 10.0 days with ior LeukoCIM, 9.0 in Hebervital group and 10.0 in Neupogen group. There not were difference between group to neutropenia incidence (p=0.059) or infection (p=0.558). The most frequents adverse events were fever (89; 14.0%), thrombocytopenia (50; 7.9%) and vomiting (27; 4.2%), similar in all groups. Ior LeukoCIM and Hebervital, was equivalents to Neupogen.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S258
LATINFARMA 2013 Resúmenes/Abstracts
PEC 013: TEACHING PROPOSAL FOR RESEARCHERS IN PEC 014: QUALITY OF LIFE IN PATIENTS WITH NON-SMALL CANCER CLINICAL TRIALS CELL LUNG CARCINOMA TREATED WITH EGF VACCINE Valls AR, Madera J, Pérez K, Torres O. Saborido L, Neninger E, Alvarez S, González Z, Riquelme I.
Centro de Inmunología Molecular, La Habana, Cuba. E-mails: [email protected] , National Coordinating Center of Clinical Trials. 200 and 21 st, Atabey, Playa. [email protected] Havana, Cuba. E-mail: [email protected]
Introduction: Clinical trials have a role in the development of new Introduction: Systemic chemotherapy in lung carcinoma prolongs cancer therapies once the preclinical phase. Are experimental studies survival and improve quality of life. Combinations of two alkylating that require an extremely complex design? The domain, by the agents by one of the "new" drugs include a higher percentage of researchers, the methodology for conducting this type of study antitumor response, longer survival, reduced toxicity and improved facilitates proper execution and obtaining reliable and useful results quality of life. Previous studies have shown that EGF vaccine produced for later use in medical practice. Based on the high training needs by the Molecular Immunology Center complies with the previously presented by researchers and high assistance it difficult for them to proposed so to assess the quality of life of patients participating in the graduate planned assistance with attending classes, we are motivated clinical trial "Evaluation of efficacy in patients with advanced lung to design a distance learning course in oncology clinical trials. tumors non-small cell treated with EGF vaccine compared with conventional supportive treatment" was performed this work in the Material and methods: The study had three phases: a diagnosis Oncology Clinic Surgical Hospital Hermanos Ameijeiras. where a test was applied to 32 researchers involved in Clinical Oncology in Camagüey province and monitoring reports were Methodology: It consisted of an observational study, quantitative and reviewed to identify the topics with more difficulty. Another design of longitudinal where 16 patients were included in the clinical trial the proposal and other ongoing valuation by specialists’ criteria. participants generally apply to all test quality of life at the time of inclusion and then at 3, 6 and 12 months respectively. Questionnaire Results: 94% of researchers examined presented high training needs. was used to assess the quality of life of the European Organization for Then identified the adverse event classification and application of Research and Treatment of Cancer (EORTC QLQ-30). The analysis of RECIST are developed with greater difficulties in performing the the results was processed by the SPSS statistical package with activity. We designed the course in Moodle allowing individualized significance 95% confidence. training, convenient, interactive and free of the constraints of time and space professionals who perform these investigations. Finally, a group Results and conclusion: For both groups (vaccinated and of experts assessed the proposal with 98% acceptance. conventional treatment) were not significant differences. Notwithstanding this improvement is seen for vaccine patients and Conclusions: We developed a distance learning course on Clinical aggravation to those included in the control group. Trials in Oncology will contribute to the training of the researcher who will conduct such clinical research.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S259
LATINFARMA 2013 Resúmenes/Abstracts
PEC 015: CHARACTERIZATION OF DETECTION AND PEC 016: USE OF IMMUNOTHERAPEUTIC PRODUCTS REPORTING OF ADVERSE EVENTS IN CLINICAL TRIALS TREATMENT OF PATIENTS WITH CANCER IN CLINICAL TRIALS PERFORMED IN SANTIAGO OF CUBA Garcés O, Marrero R, Martín Y, Arbolaéz M, Méndez R, Rodríguez M. Griñan D, Saumell Y, Landazuri S, Clape O. Universidad de Ciencias Médicas de Villa Clara. Cátedra Multidisciplinaria de Ensayos Clínicos. E-mail: [email protected] Clinical Trials Center of Santiago de Cuba, Cuba. E-mail: [email protected]
Introduction: Information on the safety of a drug is of vital importance, although there is evidence that reports of adverse event Introduction: During the last three decades the treatment of patients (AE) in Clinical Trials (CT) are sometimes inadequate. With the with cancer has enhanced its possibilities with the incorporation of a objective of characterizing the detection, management and reporting of fourth modality denominated Immunotherapy. This therapy can be adverse events in clinical trials a research in Health Systems and used to complement some of conventional oncospecific treatments. Services was made. The therapeutic vaccines against cancer constitute a new Methodology: An observational descriptive, cross-sectional, analyzed immunotherapeutic strategy that stimulates in the patient the immune the structure and process of the system in the Celestino Hernández response against tumour antigens. Robau Hospital, in the period from February to June 2012, using Methodology: It were realized a descriptive study with a sample of 20 strategic planning as a methodological guide. The sample consisted of clinical trial’s protocols coordinated by the national Center professionals involved in the CT. Coordinator of Clinical Trials that has been executed in this province Results and conclusion: The characterization showed inadequate with the objective of describe the characteristics of clinical trial’s structure to be sufficient documentation with the procedures for conduction. Additionally, the quality of trials in accordance to Good notification of AE, material resources for the notification and reporting, Clinical Practices fulfillment will be evaluated. All the clinical histories and not defined process flowchart. 100% of the professionals were reviewed. The information was processed in the SPSS program expressed high needs of knowledge, lack of familiarity with the version 11.5. It was used the percentage as a summary measure. terminology for the classification of AE and regulation in Cuba for the Results and conclusion: This work summarizes the results obtained report and there are no training courses. The process was considered during 15 years in the management of clinical trials performed with unsuitable because of insufficient medical and nursing evaluation and immunotherapeutic products in Santiago de Cuba. In these years, more inadequacies exist with familiarization and filling models prompt than 500 investigators of 25 medical specialities and 8 institutions of notification and reporting, and being adequate treatment of AE. health have participated in clinical trials. Additionally, we have executed 20 protocols in 8 localizations such as breast, prostate, glyoma, lung, esophagus, colon, ovary, skin by using 6 immunotherapeutic products from the Molecular Immunology and Genetic Engineering Centres, so around more than 200 patients have been beneficiated. Overall, all investigations have been performed respecting the ethical principles and good clinical practices. It concludes that the use of the immunotherapeutics products in oncological clinical trials is very important for the survival and the quality of life´s improvement of these patients.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S260
LATINFARMA 2013 Resúmenes/Abstracts
PEC 017: APPROACH TO THE EPIDEMIC SITUATION OF THE PEC 018: EVALUATION OF NO-INFERIORITY WITH WHOOPING COUGH IN CUBA DURING THE 2010 – 2011 CORRELATED TIME-TO-EVENT OUTCOME. A RANDOMIZED TRIAL OF TREATMENTS IN LEUKEMIA PATIENTS Muñoz Y, Toraño G, Vega D, Menéndez D, Monroy E. Robaina-García M, Arcia Montes de Oca N, Fariñas H, Mendoza I. National Coordinating Center of Clinical Trials. 200 and 21 st, Atabey, Playa. Havana, Cuba. E-mail: [email protected] National Centre of Clinical Trials (CENCEC), Calle 19, entre 198 y 200. Atabey, Playa, Cuba. E-mail: [email protected]
Introduction: Since the 1990s, resurgence in pertussis has been reported in many countries with high vaccine coverage. Despite the Introduction: The methodology for the evaluation of therapeutic non fact that pertussis vaccines are highly effective against pertussis, inferiority has been developed for censored data uncorrelated but such immunity from immunization is known to wane in the decade applications are limited if correlated data are analyzed. following the last pertussis vaccine dose. Outbreaks of pertussis are increasingly being reported, especially among infants. Methods: We present statistical procedures for analysis with this kind of data of a randomized trial performed in patients with acute Methodology: With the aim of confirm the clinical suspicion of the leukemia in intensive QT treatment. The duration of severe occurrence of whooping cough cases and to identify and characterize neutropenia in QT cycle was principal outcome. Several cycles were other bacteria recognized as potential etiologic agents of this evaluated by patient (correlated events) and the interest is non- syndrome, we performed cross-sectional descriptive study, which inferiority evaluation of two experimental products against a standard included 68 children admitted with a diagnosis of pertussis like control using procedures of hypothesis testing and confidence syndrome in the Respiratory service of a pediatric hospital in Havana, intervals. Several multivariate models were assessed to obtain risk between April 2010 and May 2011. functions of the event in the study groups. To calculate the hazard ratios between the compared groups were used the parameter Results: Through the conventional method of bacterial culture, the estimates of the treatment effect from selected model. Since isolated microorganisms were: B. pertussis (27.9%), S. pneumoniae dependence structure was necessary to make modifications to the (14.7%), M. catarrhalis (4.4%), H. influenzae (2.9%), Asperillus niger commonly procedures used to test the null hypothesis that the true and Candida albicans (1.5% each). Between isolates of S. pneumoniae value the ratio of two risk functions (r) is at least equal to a limit were demonstrated serotypes 6B and 23A and non-vaccine serotypes (r0=0.70). isolates. Alone an isolation of H. influenzae type b was identified. For all cases where diagnosed B. pertussis the identification was confirmed by Results: The rationale for using frailty models and shared frailty PCR and tested in vitro susceptibility to antimicrobial treatment models, instead of the Cox models is shown. For our data, the best recommended (erythromycin, azithromycin, clarithromycin and fitted model was the shared frailty model with Gamma distribution for others). Eleven of the 19 pertussis cases occurred in children under frailty and Gompertz distribution for baseline hazard time. We develop one year of age, in nine cases it was known that they had not yet a proposal for the no inferiority hypothesis test in two populations also received the three doses of pertussis vaccine. for the calculation of confidence limits (1-2α), α=0.025. Conclusions: The results demonstrate the need to revitalize the Conclusions: The estimation of hazard ratio starting from shared microbiological diagnosis and surveillance of cases of whooping frailty model made possible to obtain less biased estimates. The effect cough in Cuba. New preventive strategies are required to further of treatment is conditionally independent of time so we suggest take reduce the impact of this infection. the largest interval which corresponds to the minimum time observed like equivalence (non inferiority) limits. In the studied trial, the lower limit of confidence intervals at 97,5% level of hazard ratios of experimental treatment against control, in both comparisons was higher than 0.72, demonstrating non-inferiority of the products studied.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S261
LATINFARMA 2013 Resúmenes/Abstracts
PEC 019: BIOTECHNOLOGICAL PRODUCTS FOR THE PEC 020: BEHAVIOR OF HEMATOLOGICAL VARIABLES WITH TREATMENT OF ADVANCED NON-SMALL-CELL LUNG USE OF FERRICAL IN FEMALE BASKETBALL SPORTSMEN TUMORS IN THE PROVINCE OF LAS TUNAS Espronceda M, Gaínza V. Montes de Oca N, Trista Y, Vázquez M, Santiesteban E, Reyes D, Rúa M. Group of Biopharmaceutical and Chemical Productions. LABIOFAM. Havana. Universidad de Ciencias Médicas Las Tunas, Cuba. E-mail: [email protected] Cuba. E-mail: [email protected]
Introduction: Within the group of malignant neoplasias, lung cancer Introduction: Sportsmen energetic demands don’t make clinical constitutes the first cause of cancer and the first cause of cancer normal hemoglobin levels be optimum to achieve their purpose. It is mortality. been shown the tendency in athletes to present below normal levels of hemoglobin, that is reinforced with sport practice time, and it’s define Objective: To assess the use of the vaccine EGF and the monoclonal as sport anemia; that is the hemoglobin levels are lower than the antibody CIMAher in patients with advanced non-small-cell lung optimal for the amounts of oxygen need. tumors in the period from 2009 to 2012 in Las Tunas. Objective: To evaluate the behavior of hematologic variables with the Material and methods: A random open clinical trial was carried out in use of Ferrical in sportsmen of National Pre-selection of Basketball patients with diagnostic criteria who gave their informed consent to during 2012 micro cycle. participation with the following treatment scheme Vaccine EGF. Pre- treatment with cyclophosphamide: Day 1 (200 mg/m2), 1st Material and methods: An experimental, open and prospective study immunization: DAY 4, 2nd immunization: DAY 18, 3rd immunization: was made in 16 athletes that integrate the National Pre-selection of DAY 32, 4th immunization: DAY 46, 5th immunization: DAY 76. Re- female Basketball team, that have received supplementation with immunization: monthly from the third month using the same dose and Ferrical in a dose of 17.9 mg of heme iron daily, during 45 days. At the the monoclonal antibody CIMAher. 200 mg: once a week during 12 beginning, of the 21 and 45 days of treatment with Ferrical, were been weeks. Maintenance: 200 mg, once every 14 days. Survival and the quantified clinical, and lab tests variables: hemoglobin, hematocrit, incidence of adverse effects were assessed. reticulocytes, serum iron, ferritin, saturation index transferrin and corpuscular constants. Also adverse effects were identified during the Results: The patients with the monoclonal antibody CIMAher achieved study. an average of 13 doses, while those with the vaccine EGF got 4 doses, showing a survival in months of 10.25 with the monoclonal antibody Results: Hemoglobin increase in a 100% was obtained in athletes that AcM CIMAher and of 5 months with the vaccine EGF. Only slight and took part in the study, in relation with the initials values. The same moderate adverse effects appeared. results were obtained with the rest of the hematological variables studied. Conclusions: The use of these biotechnological products constitutes a therapeutic option for patients with advanced lung tumors. Conclusion: the supplementation with Ferrical was obtained the increase of hemoglobin levels in sportsmen and the tendency of normal behavior of the rest of studied hematological parameters. Adverse effects weren’t significant.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S262
LATINFARMA 2013 Resúmenes/Abstracts
PEC 021: IMPLANTATION AND EVALUATION OF A PEC 022: SIDE EFFECTS ASSOCIATED TO THE EGF VACCINE LOGISTICAL SYSTEM FOR THE INVESTIGATIONAL IN PATIENTS WITH NON-SMALL CELLS LUNG CANCER PRODUCT IN CLINICAL TRIAL Peacok Aldana S, Griñán Semaná D, Landazuri Llago S, Navarro Martínez L, Hernández R, Viada C, Torres O, Wilkinson B, Troche M. Alemán R, Fuentes Gómez Y, Torres Santiago J
Centro de Inmunología Molecular. 216 esq. a 15, Atabey, Playa, La Habana, Cuba. Universidad de Ciencias Médicas de Santiago de Cuba Avenida de las Américas E-mail: [email protected]; [email protected] S/N entre Calle E y Calle I, Cuba. E-mail: [email protected]
Introduction: The supply chain management of investigational Introduction: Cancer has increased with a great rate and mortality in product (IP) in clinical trials has particular relevance, inherent our country. Lung cancer is one of the most frequent affections that difficulties and growing challenges. The objectives of this work were: have been seen in both sexes. The therapeutic to treat oncological 1) to implant a logistical system for the IP, which is delivered to patients has been enriched by the use of immunotherapy as a way to hospitals for the subjects’ treatment and; 2) to evaluate the quality of complete the conventional treatment. their service. Methodology: A study was done to characterize the side effects Material and methods: Implantation was carried out in two periods: associated with the administration of EGF (epidermic grow factor) Preparation and Establishment. For the Evaluation, a methodology vaccine in patients with non-small cells lung cancer, stages III and IV, with indicators was created and 21 sites were assessed. The quality of the patients are attended in the service of pneumology in “Juan Bruno service was equal to average of the quality punctuation for each stage Zayas” hospital. The study was motivated due to the need of assessing (Distribution, Storage and Use); and the agreed acceptability criteria the security of this new product. To obtain the necessary information was 80 points. The quality punctuation was the summation of seven clinical charts of patients with lung cancer were reviewed. pondered means of deficiencies indicators obtained. To analyze Results and conclusion: 13 side effects were observed and most of potential significant relationships, the sites were grouped in Projects them were related to the appearance of pain in the site of injection and Regions and also were correlated with variables such as audits (57.31%) and wet cough (42.8%), the side effects were classified as impact, trials duration, sites attention frequency and IP handling mild or moderate and they were not considered a strong reason to complexity. interrupt the treatment. The most frequent relation degree of causality Results: Implantation had an organizational emphasis and the in these side effects was the possible (45.8%), followed by the pharmacist's protagonism was evidenced. The quality of service was conditional and the definitive, category in which pain in the site of 81.14 points. There was better acting in Use stage. The major injection was included. The medication was considered of an adequate weaknesses were associated with the cool chain in Distribution and security in the doses, administration via, and indication use. Storage; and the capital reached better results. There were low percentages of delays, errors, losses and outside temperature values. Audits and attention impacted positively, but duration and complexity didn't influence favorably. Conclusion: The implanted system conferred an acceptable quality of service, according to the defined objectives.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S263
LATINFARMA 2013 Resúmenes/Abstracts
PEC 023: QUALITY LIFE OF PATIENTS WITH CANCER PEC 024: RECURRENT SQUAMOUS CARCINOMA OF INCLUDED IN CLINICAL OF TRIALS CONJUNCTIVE IN PATIENTS WITH AIDS AND NEW MODALITY OF THERAPEUTIC CONTROL. PRELIMINAR Viada C, Ballesteros J, Luace P, Sánchez L, Fors M, Robaina M, Wilkinson B, Martínez P, Troche M, Fernández A, Frías A, Álvarez M, RESULTS Santiesteban Ya, Santiesteban Yu, Sánchez Y, Montes A. Carnesoltas Lázaro D, Melgares Ramos MA.
Center of Molecular Immunology (CIM), 216 y 15, La Habana, Cuba. E-mail: Oftalmology Services, National Institute of Oncology and Radiobiology, Havana, [email protected] Cuba. E-mail: [email protected]
Introduction: The Center of Molecular Immunology (CIM) is dedicated Squamous carcinoma of conjunctive (SCC) is a rare tumor with to research, development, production and marketing of human different geographic regional frequency of 0.02/100.000 inhab. in the biotechnology. CIMAvaxEGF vaccine is a receptor that recognizes the high latitude and 3.5/100.000 inhab. in low latitude. The etiology of this epidermal growth factor receptor with high affinity for the treatment pathology is multifactorial and the causes are high exposition to UV and of cancer. The aim was to develop a one-dimensional version of the also systematic infections like HPV and HIV. Those tumors have low quality of life questionnaires QLQ-C30 and QLQ-LC13 by applying the potential of malignity, but in it natural evolution, this type of cancer are theory of item response. capable to provoke local recurrence and distant metastasis and finally Material and methods: The quality of life responses QLQ-C30 and the death of patients. For this neoplasia, we have different ways of QLQ-LC13 of 331 lung cancer patients including three clinical trials the treatment like surgery, radiotherapy and local antineoplasic and following distribution: Phase II (65 patients), Phase III QVV (240 immunomodulator agents. Today, the treatment of SCC is not patients) and Phase VQV III (26 patients), became nonparametric standardized. For this reason, and with the aim to decrease the Mokken analysis to determine the underlying dimensional structure incidence and recurrence, we apply diverse adjuvant therapies. In this and obtain a reduced-dimensional version, the Samejima graded work, we report three HIV-infected patients with SCC recurrent response model to evaluate the characteristics of the items in the short diagnosis. They have a positive diagnosis of this kind of tumor and they version, and factor analysis confirmatory to confirm the dimensionality have been treated in the Ophtalmology Services of the National of the reduced version and evaluate the quality of the items for the Institute of Oncology and Radiobiology, in Havana Cuba. The patients latent variable. have a conservative surgery and superficial radiotherapy at the beginning of the treatment, later they develop recurrence and the new Results: The Mokken analysis resulted in two dimensional scales treatment was chemotherapy and cytostatic drops, with a minimal of comprising 17 items related to the functionality and 13 items related adverse reactions and interactions of standardized of antiretroviral to symptoms. All items showed higher scalability 0.30. The agents, after five years of following the evolution was favorable and the unrestricted model Samejima graded response was an appropriate prognosis have been good. way, and most of the items on the reduction of 12 relevant items having difficulty and discrimination parameters. The results of confirmatory factor analysis of the items showed two dimensional latent structures. Conclusions: The 17-reduced items for functionality and reduced to 13 items symptoms latent variables adjust to two-dimensional quality. Other studies of response to items are equivalent for different populations, sensitivity to change and a minimal important difference guaranteed.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S264
LATINFARMA 2013 Resúmenes/Abstracts
PEC 025: CIMvaxEGF VACCINES IN PATIENTS WITH NON– PEC 026: CLINICAL TRIALS REGISTRY, WHO ARE SMALL CELL LUNG CANCER TREATED IN THE PRIMARY RESPONSIBLE FOR COMPLIANCE? HEALTH CARE IN CIENFUEGOS Jiménez G. Fernández D, Basante M, Lara G, Hermida R, Hidalgo M, Rodríguez M, National Coordinating Center of Clinical Trials, 200 at 21 Ave, Atabey, Playa, Cuevas O. Havana City, Cuba. E-mail: [email protected] Universidad de Ciencias Médicas, Dirección Municipal de Palmira, 51 final, entre Ave 5 de Septiembre, Cienfuegos, Cuba. E-mail: [email protected] Introduction: The registration of a clinical trial on a public database
before recruiting the first subject (prospective registration) is an Introduction: A number of therapeutic modalities are being developed ethical requirement established in the amended Helsinki Declaration in to improve unacceptably poor outcomes in lung cancer. Cimavax-EGF 2008 and, a condition for the publication of trials results established in is a Cuban therapeutic vaccines, it was registered for a treatment of 2005 by the International Committee of Medical Journal Editors. In non small cell lung cancer by the Centre of Molecular Immunology. 2007 the World Health Organization (WHO) launched the International Clinical Trials Registry Platform web site. However, the challenge in Methodology: In Cienfuegos, since March 2011 to December 2012, 32 this field is compliance. Who are responsible and what can they do? patients were included in the clinical assay phase IV developed in the Primary Attention of Health and they were treated with this product. Material and methods: A full search strategy of documents published In this study we proposed characterize these patients as for age, sex, from 2009-2011 was performed using key terms related to clinical trial scale of ECOG, initial stage and describe the adverse events happened registries. The retrieved articles were reviewed for identifying during the clinical assay. As part of the study the medical records were different parties involved in assure compliance with WHO standards. consulted and the notebooks of collection of data and made a database The International Standards for Clinical Trial Registries was identified with the study variables. Adverse events were classified by the as the main document. Its review allowed the analysis and description Common Terminology Criteria for Adverse Events version 4.0 for the of those actors playing an important role in assuring compliance. U.S. National Cancer Institute. Results: The sponsors (Responsible Registrants) are responsible of Results and conclusion: The result showed that the patients included register all clinical trials, keep the information up-to-date, and in this study were between 60-69 years old, male sex; 50% had a grade guarantee the quality of data. The registries are responsible to ensure 1of ECOG and 65.4% were in IV stage. The more frequently adverse compliance with all of the international standards and they can to events reported were injection site reaction (pain), fever, headache, develop educational initiatives for other stakeholders. However they tremble, chills, hypotension, muscle and articulation pain and it had are not the only. Journal editors, ethics committees, regulatory mild and moderate severity. Cimavax EGF is a new option in patients authorities and funding agencies can play a role in ensuring with non small cell lung cancer in our country. compliance. The Editors of Medical journals are responsible for guaranteeing the precondition for publication (some Journals do not require registration or accept retrospective registration). The Ethics Committees can establish the trial registration like a precondition of approval or demand the registration number in the progress report. The Regulatory authorities can establish mechanisms at a national level and, the funding agencies can demand the registration before give the funds to a specific project. Conclusions: Every actor plays an important role for assure compliance.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S265
LATINFARMA 2013 Resúmenes/Abstracts
PEC 027: A BAYESIAN APPROACH TO OVERCOME SMALL PEC 028: CLINICAL EVOLUTION OF PATIENTS WITH SAMPLE SIZE IN AN EXPLORATORY CLINICAL TRIAL DIABETIC FOOT ULCER TREATED WITH HEBERPROT-P®
Uranga R, Valles R, Rodríguez R. Álvarez Crespo A, Alonso Carbonell L, Yera Alós I, García Milián A, Marrero Miragaya MA. National Coordinating Center for Clinical Trials (CENCEC). Address: 200 and 21, Atabey, Playa, La Habana, Cuba. E-mail: [email protected] Centro Coordinador Nacional de Ensayos Clínicos, La Habana, Cuba. E-mail:
Introduction The frequentist theory of hypothesis testing, commonly used in clinical trials, does not allow conclusions when the sample size Introduction: The Heberprot-P® prescribed for the treatment of the is small. The Bayesian approach is an alternative that offers greater ulcer of the diabetic foot (UPD) it has evidenced to contribute to the re- flexibility and can be advantageous. establishment of the granulation fabric favoring their healing action. Methods This was an exploratory study with fixed sample size. We Objective: Characteristic of the clinical evolution of the patients with compared the results of the application of frequentist and Bayesian ulcer of the foot diabetic treaties with Heberprot-P®. methods in the analysis of the effect of creatine in patients with Ataxia. A concurrent control group was included. The primary endpoint was Method: Study prospective, multicenter, of pursuit post- increased muscle mass after three months of treatment. Probability commercialization of Heberprot-P® among the month of June of 2007 intervals (PI) at the 95% level were calculated for this variable, per to March of 2010 in the City of Havana. group and for the difference between groups, and Bayesian factors Results: 53.1% of the patients belonged to the feminine sex and the were presented in favor and against the posterior probability of a age average was 62.66 ± 11.758 years. The hypertension arterial was greater increase in average muscle mass for the study group as the pathology that more he/she associated to the patients with UPD in compared to the control group. This analysis was supplemented with 65.0%. In 75.2% of the patients treaties with the product complete the fitting of a bivariate linear model, which considered as independent granulation was observed. The diabetic patients type II presented with variables the study group, time, and group-by-time interaction. more frequency UPD, in 66.1% and the same ones were Wagner's in Results The IP for the control group was, in kilograms, (0.00, 2.50); for stadia 3 and 4 with 39.5 and 27.7% respectively. The 81.9% of the the creatine group, (0.42, 3.51); and for the difference between groups, patients used dose of 75 µg. Prevailed patients of the feminine sex and (-0.51, 2.14). The Bayesian factor in favor was 8.22, which describes older than 60 years. the degree of evidence as "substantial", and the posterior probability Conclusions: Most of the cases with UPD were diabetic type 2. was 90%. The fit of a linear model detected no significant influence of Complete granulation was achieved in around the fourth three parts of the group variable. the treaties, existing association between the same one and the Conclusions The classical linear model does not lead to any presented type of the diabetic mellitus. conclusions because of the small sample size; however the Bayesian method detects substantial influence. The study is a clear example of the negative influence of the small sample size in the conclusions when applying the frequentist method.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S266
LATINFARMA 2013 Resúmenes/Abstracts
PEC 029: SAFETY AND EFFICACY OF GRANULOCYTE COLONY- PEC 030: CLINICAL EVALUATION DEVELOPMENT STRATEGY STIMULATING FACTOR (IOR®-LEUKOCIM) IN ONCOHE- OF RECOMBINANT STREPTOKINASE IN CUBA MATOLOGY PATIENTS. PHASE IV Marrero Miragaya MA, Lopez Saura P, Tirado Marrero M. Cachimaille Y, Mendoza I, García E, Wilford M, Menéndez A, Fernández National Coordinating Center of Clinical Trials. 200 and 21 st, Atabey, Playa. JD, Vázquez E, Robaina M, Piedra P, Sáurez G. Havana, Cuba
th National Coordinating Center of Clinical Trials (CENCEC). 200 and 21 , Atabey. Playa, Havana, Cuba. E-mail: [email protected] Introduction: Once the Recombinant streptokinase production in
Cuba finished it was prepared and carried out its clinical development Introduction: Neutropenia does not in itself cause symptoms, but it strategy. predisposes patients to infection, especially if the neutrophil count falls Objective: To register and introduce into medical practice, this below 0.5 x 109/L and persists longer than 10 to 14 days. In patients product and to contribute to the modernization of the management of receiving chemotherapy, the administration of G-CSF can lessen the thrombotic diseases in the country, including acute myocardial incidence and severity of neutropenia. infarction. Material and methods: This is a multicenter phase IV study in Results: The strategy began to demonstrate therapeutic equivalence oncohematology patients under chemotherapy and/or radiotherapy with a drug-like, international market leader, with a very high cost and treatment evaluating ior®LeukoCIM, a Cuban granulocyte colony- it was proceed with the demonstration of its impact on the mortality stimulating factor. Nine hundred three episodes received from these diseases and pharmacovigilance to establish the safety ior®LeukoCIM (300 µg/kg) as primary, secondary prophylaxis or profile of this new drug. Additionally we demonstrated the product's neutropenia treatment, to recovery the neutrophil count (1.5 x 109/L) efficacy in other indications such as thrombosis of heart valve and were assessed for safety and efficacy. Ior®LeukoCIM was prostheses, hemodialysis and deep vein fistulas. administered subcutaneous, in prophylaxis beginning 24-72 hours after chemotherapy and/or radiotherapy, and as treatment from Conclusions: All trials followed the methodology established for each neutropenia diagnosis. development phase including the ethical aspects of the protocols approved by the relevant ethics committees and the informed consent Results: The 48.2% of adverse events were evaluated as drug-related of the subjects. adverse events. The most frequently were leucocytosis (14.9%; 161 episodes), neutrophilia (13.1%; 142 episodes) and bone pain (10.5%; 114 episodes). Others adverse events were fever (7.4%), thrombocytopenia (7.0%) and headache (5.2%). Ior®LeukoCIM was safe with no serious adverse events. The 94.6% (819 episodes) finished treatment with neutrophil count ≥ 1.5 x 109/L. Conclusions: Ior®LeukoCIM showed safety and efficacy as primary, secondary prophylaxis or neutropenia treatment in oncohematology patients under chemotherapy and/or radiotherapy treatment.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S267
LATINFARMA 2013 Resúmenes/Abstracts
PEC 031: THE ETHITCS IN THE DESIGN, THE CONDUCTION PEC 032: VQV CLINICAL EVALUATION SCHEME WITH EGF IN AND THE MONITORING OF CLINICAL TRIALS IN THE THE TREATMENT OF PATIENTS WITH PROSTATE CANCER CUBAN UNITS OF INTENSIVE CARES Ills D, Mendoza I, Guerra P, González J, Amador RM, Santiesteban E, Avila Y, Barrese Y, Díaz E, Morilla A, Rodríguez V, Fernández O, Blanco Crombet T, Rodríguez C, Viada C. O. National Coordinator Center Clinical Trials. 200 esq. 21, Atabey, Playa. Havana, National Coordinator Center of Clinical Trials (CENCEC). 200 and 21, Atabey, Cuba. E-mail: [email protected] Playa, Havana, Cuba. E-mail: [email protected]
Introduction: Malignant tumors are the leading cause of death in our Introduction: National Coordinator Center of Clinical Trials and country. Prostate cancer is reported as the second cause of death in National Center of Agropecuary Sanity in Cuba, among 2004 and 2012, this disease, with the rate of 43.3 per 100 000 population. We has worked in the design, conduction and monitoring of clinical trials evaluated the effect and safety of the vaccine CIMAvaxEGF in prostate that evaluate the SURFACEN®. cancer patients with hormone-refractory. Objective: To describe practical considerations contemplated in the Methodology: A phase II, controlled, multicenter, randomized, open, design, conduction and monitoring, and to determine the internal and with two groups: 1. CIMAvax scheme EGF vaccine-chemotherapy- external validity of these clinical trials. vaccine and 2. Chemotherapy only. Chemotherapy with mitoxantrone 12 mg/m2 every 21 days and prednisone 10 mg daily for 10 cycles. We Material and methods: Clinical trials phase II, III and IV, multicenters evaluated the survival of patients and the incidence of adverse and opens, in three different groups of population: neonate, children reactions during treatment. with age > 28 days and 18 years and adult, in the Cuban units of intensive cares (UIC). Results: The intention to treat survival rate was 26.59% vs. 17.44% (24 months) and 22.79% and 13.95 (36 months), with median control Results and conclusions: During the planning you proceeded with the group vaccinated vs 17.10 vs. 10.73 months. Survival for patients with selection of hospitals, unification of approaches and basic courses of at least 6 doses of EGF CIMAvax and 4 months of survival for the clinical trials. To begin the execution it was developed conferences and control group, showed rates for the vaccinated group vs. 81.99%. visits of beginning, and during the execution they were carried out 57.04% (12 months), 8.77% vs 17.94% (24 months) and 38.77% and monitoring and conferences of upgrade. The internal validity was 17.94% (36 months), with medians that differ for the vaccinated group endorsed by a design and conduction that contemplated three of the (19.37 vs. 13.5 months). The most common adverse event in both basic pillars: objectivity in the observation, recurrent comparison and groups was bone pain with 26.8% in the vaccine group and 47.9% in aleatory assignment of the treatments, for the planning and execution the control, with 47.3% mild. according to that promulgated in the Code of Nuremberg, the Declaration of Helsinki, the Guide of BPC of ICH and the Guide of BPC of Conclusion: The vaccine proved to be safe with trend to benefit in Cuba; as well as for the standardization in the hospitals of the survival proportions for the vaccine group. diagnostic approaches of respiratory distress syndrome/acute respiratory distress syndrome settled down in the American-European Conference of Consent in 1994, and the decrease of the days of stay in the UIC and of requirement of invasive procedures like the endotracheal intubation and ventilation mechanics. The external validity was appreciated in the enrichment of SURFACEN® dossier, emission of a new version of its handout, and its readiness in the pharmaceutical Cuban market. The design, conduction and monitoring of clinical trials with SURFACEN® it considered and it executed ethical basic principles for the clinical investigation.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S268
LATINFARMA 2013 Resúmenes/Abstracts
PEC 033: THERAPEUTIC DRUG MONITORING IN CUBAN PEC 034: ANALYSIS OF HEMATOLOGY AND BLOOD PATIENTS WITH ANTI-RETROVIRAL THERAPY CHEMISTRY’S ADVERSE EVENTS DOCUMENTED IN SPONSOR’S DATABASES Tarinas A, Tápanes RD, Gil L, Gravier R, Caro R, Bermudez Y Wilkinson B, Neninger E, Crombet T, Viada C, Martínez L, Troche M, Clinical Pharmacology, Institute of Tropical Medicine, Autopista del Mediodia Km 6½, La Lisa, Cuba. E-mail: [email protected] Torres O. Centro de Inmunología Molecular. 216 y 15, Atabey, Playa, La Habana, Cuba. E- mail: [email protected] Introduction: The anti-retroviral therapy is generally recommended for patients with plasma HIV RNA viral loads greater than 55 000 copies/mL, CD4+ counts below 350/µL, or symptomatic disease. Introduction: Compliance with Good Clinical Practice (GCP) on safety Treatment failure is indicated by increases in viral load, declining CD4+ data is important for the knowledge of the toxicity profile of a product. count, or clinical progression. Before changing or adjusting therapy, All adverse events (AEs) including abnormal laboratory findings however, the physician must determine if the treatment failure is due should be documented, sorted, and analyzed to ensure the protection to viral resistance or inadequate drug concentrations reaching site of of patients. The main objective of this work was to identify and classify viral replication. Therapeutic drug monitoring (TDM) for blood the hematological and blood chemistry data not documented as AEs in concentrations of antiretroviral agents have been proposed as possible sponsor's adverse event and clinical laboratory databases of five test that could prove helpful when deciding between these two clinical trials. possibilities. We aimed to view the relationship between plasma antiretroviral drug concentration and progression markers of AIDS in Methodology and results: From 458 screened laboratory parameters, 40 HIV-infected patients undergoing TDM. 450 were unidentified as AEs and eight of them were documented as AEs in the adverse event database. The abnormal clinical laboratory Methods: All TDM of protease inhibitors, nucleoside and non- parameters found in these databases were identified and classified as nucleoside reverse transcriptase inhibitors were determined for high- AEs, using the table of toxicity indicated in each protocol. Most of the performance liquid chromatography methods for determination of events were found mild and moderate; while only three of them were zidovudine, lamivudine, nevirapine and indinavir in human plasma. life threatening. The most frequent AEs were anemia and increased Statistical methods was used to evaluate associations of drug levels of alkaline phosphatase. concentration with HIV-viral load and CD4+ T lymphocytes count in 40 patients with ART combination (AZT-3TC-NVP). Conclusions: These results show that there are deficiencies in the recognition and classification of data as AEs by clinical investigators, Results: In patients with concentration inadequate of antiretroviral causing underreporting in safety data. therapy (under optimal Cmin) the HIV-viral load was great and CD4+ T lymphocytes count was depleted. In patients with concentration over optimal Cmax the both progression markers of HIV evolution haven’t variation. Zidovudine was the antiretroviral drug of more available measurements. CONCLUSIONS: Physicians report that 30-60% of patients who fail treatment, when pressed, admit that they have resisted taking the antiretroviral medication. For this reason the TDM are an important tool for determinate to treatment failure is or not truly or an adherence problem.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S269
LATINFARMA 2013 Resúmenes/Abstracts
PEC 035: TREATMENT PEGYLATED INTERFERON (PEG-IFN) PEC 036: SAFETY OF NIMOTUZUMAB IN THE TREATMENT AND RIBAVIRIN FOR THE TF CHRONIC HEPATITIS C (CHC). OF HEAD AND NECK TUMORS IN ADVANCED STAGES FROM A CASE REPORT OCTOBER, 2012 THROUGH APRIL, 2013
Hernandez E, Martinez L. Del Toro Rúa M.
Hospital Carlos J Finlay, 114 y 31 Marianao Habana, Cuba. E-mail: Hospital Ernesto Guevara, Las Tunas, Cuba. E-mail: [email protected] [email protected]
Introduction: The head and neck tumor is the seventh cause of death Introduction: Chronic hepatitis C virus (VHC) is a health problem by cancer in the world. The monoclonal antibody Nimotuzumab is a worldwide. The World Health Organization estimates that near 180 drug of recent introduction, registered for its use in patients with millions of people, around 3% of the world population is infected by malignant head and neck tumors of epithelial origin in advanced VHC. It is considered that from 3 to 4 millions of people get infected stages, by the Center for the Control of Drugs, Devices and Medical yearly. At present is the most frequent cause of hepatic cirrhosis, Equipments (CECMED). hepatocarcinoma and liver transplantation. The only clearly effective treatment for attenuating or inverting hepatic fibrosis caused by VHC Objective: To assess the safety of Nimotuzumab in the treatment of is the elimination of the causal agent. Currently, a combination therapy head and neck tumors in advanced stages at the chemotherapy ward of with pegylated interferon (PEG-IFN and ribavirin is being widely used “Dr. Ernesto Guevara” Hospital from October, 2012 through April, for the treatment of CHC. 2013. Material and methods. A case report is presented of a 50 years old Material and methods: A transversal descriptive study was carried male healthy patient who came for a volunteer blood donation. When out using the method of drug surveillance and intensive supervision of biosafety tests were carried out, he proved positive to infection by the inpatients of the chemotherapy ward. The sample was made up by the hepatitis C virus as well as for a qualitative polymerase chain reaction patients diagnosed with malignant head and neck tumors of epithelial (PCR) The patient denied the use of intravenous drugs, blood origin in advanced stages treated with Nimotuzumab, admitted at the transfusions and referred protected sexual relationships. He was chemotherapy ward of “Dr. Ernesto Guevara” Hospital during the study treated with pegylated interferon (PEG-IFN) 180 µg weekly and 1200 period. The following variables were studied: patient age; location; mg of ribavarin daily during 6 months. During this period the only adverse events taking into account intensity: degree 1 slight, degree 2 adverse reactions observed were asthenia and leucopenia which were moderate, degree 3 severe, degree 4 life-threatening, degree 5 death- treated with hebervital. causing; according to its consequence: seriously ill and non-seriously ill, expected and unexpected; and according to causality: definite, very Results: The hepatic biopsy showed chronic hepatitis with moderate probable, probable, possible, non-related and unknown. activity. Thyroid function was normal and also the functional hepatic tests. Abdominal ultrasound corroborated a normal size liver, with a Results: 26 patients were included (7 males and 19 females) with an slight increase of the ecogenecity. The rest of the organs of the upper average age of 57 years old. The location at esophagus level prevailed. hemiabdomen were without alterations. After six weeks of the The reported adverse events were mostly degree 1, only 2 patients treatment the viral marker was negative. developed moderate reactions (degree 2); with a probable causality; there was no evidence of serious and unexpected toxicity. Conclusions: The combination of pegylated interferon and ribavirin during a period ranging from 24-72 weeks is the choice treatment in Conclusions: The treatment with Nimotuzumab showed a wide safety chronic hepatitis due to C virus. profile, considering it as a well-tolerated treatment.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S270
LATINFARMA 2013 Resúmenes/Abstracts
PEC 037: SAFETY, EFFICACY AND PHARMACOKINETIC PEC 038: CLINICAL STUDY RESULTS FROM A RANDOMIZED EVALUATION OF INTRAVENOUS CIGB-300 IN PATIENTS CONTROLLED TRIAL OF THERAPEUTIC CLINICAL WITH SOLID TUMORS, REFRACTORY TO ONCOSPECIFIC EVALUATION OF THE Plectranthus amboinicus LOUR TREATMENTS SPRENG (FRENCH OREGANO) TABLETS IN PATIENT WITH COMMON COLD González L. Jimenez D, Rodríguez J, Rodríguez Y, Glacial M, Festary T. Center for Genetic Engineering and Biotechnology. Havana, Cuba. E-mail: [email protected] Drug Research and Development Center, CIDEM, La Habana, Cuba.
Introduction: CIGB-300 is a novel synthetic peptide that induces Introduction: A phase I II double blinded against placebo clinical trial apoptosis in malignant cells and elicits antitumor activity in cancer research was carried out with 90 patients to evaluate the efficacy and animal models. Based on CIGB-300 could represent a candidate drug safety of different French Oregano doses in patients with common cold. for cancer therapy, we investigated its tolerability, efficacy and pharmacokinetics in patients with solid tumors, resistant to previous Method: We analyze the individual responses in each study groups oncotherapy. classified as placebo (G1 group), 300 mgs daily doses (G2 group) and 600 mgs daily doses (G3 group). The statistics indicator used was Chi Material and methods: An open-label, sequential, dose-scaling Phase square and the variables evaluated were the frequency and intensity of I clinical trial was carried out. Doses of 0.2, 0.4, 0.8 or 1.6 mg/kg of the cough and the expectoration to 3, 7 and 15 days of treatment. CIGB-300 were administered intravenously through infusion pumps, once per day, during five consecutive days. This cycle was repeated in Results and conclusions: The response at 7 days of treatment had alternate weeks to complete 3 cycles. In order to mitigate expected significance differences (p less than 0.05) in cough variable but no CIGB-300-induced allergic reactions, premedication with intravenous significance differences were found in G1 and G2 group. We found diphenhydramine and hydrocortisone was applied. Therapeutic significance differences at expectoration symptoms variable in G3 response was mainly defined by the overall survival. Pharmacokinetics group too. G1 and G2 groups no had significance differences. Five drug of plasmatic CIGB-300 was developed in four patients, using a adverse reactions were reported. They were classified as light intensity validated ELISA. Blood samples were taken immediately, 5, 15, 30 and only none had causal relationship with the drug used. minutes and several times until 24 hours after first and fifth infusions in the first cycle.
Results: Sixteen patients were included, lung cancer prevailed (10 patients), followed by breast cancer (3 patients). The most frequent adverse events were those related with the allergic syndrome, but these were mostly mild (70.7%), none serious. Most of these events occurred with the higher dose (175 mg). Nine patients remaining as alive for more than 6 months; one of them, with lung cancer, is alive 2 years after treatment. Concerning pharmacokinetics, intravenous profiles were as expected for this class of peptides, low half-life (30 minutes), fixed better to mono-compartmental model, and low volume of distribution (< 5L). This behavior is considering ideal for CIGB-300 actions over circulating tumor cells, which lead to metastases and patient death. Conclusions: Intravenous CIGB-300 had a satisfactory tolerability at high doses, using concomitant anti-histaminic drugs. Efficacy and pharmacokinetic data show that non-responder patients with solid tumors could obtain benefits from its use.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S271
LATINFARMA 2013 Resúmenes/Abstracts
PEC 039: NIMOTUZUMAB, IN THE TREATMENT OF TUMORS PEC 040: MANAGEMENT SYSTEM FOR BIOLOGICAL SAMPLES OF EPITHELIAL ORIGIN: NEW KNOWLEDGE OF PATIENTS INCLUDED IN MULTICENTER CLINICAL TRIALS Ramos Suzarte M. Troche M, Wilkinson B, Martinez L, Fernandez A, Viada C, Lorenzo Centro de Inmunología Molecular, 216 y 15. Reparto Atabey. Playa, La Habana, Cuba.Teléfono 2143146 o 45 o 44. Fax: 2040644. E-mail: [email protected] Luaces P, Mazorra Z. Centro de Inmunología Molecular (CIM), La Habana, Cuba. Calle 216, esq. 15, Atabey, Playa, Cuba. E-mail: [email protected]
Introduction: The epidermal growth factor (EGFr) is one of the most frequent targets evaluated in the past 20 years to treat cancer of epithelial origin. Since 1995, the Center of Molecular Immunology Introduction: Clinical trials (CT) are human subjects research aimed (CIM) has developed a humanized monoclonal antibody (Mab) at discovering the pharmacological or other pharmacodynamic effects nimotuzumab, anti EGFr, which has antiangiogenic and apoptotic of the investigational product. Given the scale and greater demands capacity, inhibiting cell proliferation in vitro and in vivo. required to perform Multicenter Clinical Trials (MTC) Phase II or III with vaccines and monoclonal antibodies produced in the Center of Results: During more than 10 years many clinical trials have been Molecular Immunology (CIM) where the main objective is the effect of development in Cuba and outside it, Nimotuzumab was approved for the investigational product, the collection biological samples is of great the treatment of head and neck tumors in combination with chemo- importance in the clinical evaluation of patients in multicenter clinical radiotherapy, brain and esophagus tumors. With this product has trials of Oncology. The objective of this work was the design and pursued a strategy of differentiation of clinical trials in several implementation of a Logistical System of biological samples from indications: locally advanced breast cancer, hepatocellular carcinoma patients in MCT ensuring that data are credible and shall conform to (HCC), esophageal tumors, cervical and lung tumors in non-small cell in the protocol. order to know an optimal biological evaluation concerning to a dose and safety profile. 200 mg dose was selected at different phase I Methodology and results: We identified system processes, clinical trials completed as an optimal biological doses, for each of responsible for conducting the actions of each one the documents that these indications in the induction dose weekly for the duration of flowed through the entire system. It was applied in a pilot 6 chemotherapy or radiotherapy - chemotherapy and maintenance dose multicenter clinical trials, which were developed in 12 research sites every 14 days even after progression while performance status has distributed in the country's capital and other six provinces. Three demonstrated acceptable and manageable toxicity have been records and two Standard Operating Procedures (SOP) located in established therapeutic criteria, demonstrating in all cases a suitable clinical laboratories of different research sites were prepared, also two profile of safety and increased survival of the treated patients Records and six PNO located in the Clinical Immunology Laboratory of compared to the control groups. Sponsor Center CIM. Logistics Application contributed in the improvement of the system design in a practical, specifically in Conclusion: It is found that nimotuzumab becomes a therapeutic detecting that flows, the critical path and traceability of biological alternative for the treatment of various tumors of epithelial origin. samples.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S272
LATINFARMA 2013 Resúmenes/Abstracts
PEC 041: THE THERAPEUTIC PSYCHOPHARMACOLOGY OF PEC 042: CLINICAL TRIAL RESULTS OF THE RECOMBINANT THE DEPRESSION: CHALLENGES AND CONFLICTS STREPTOKINASE IN THE HEMORRHOIDAL DISEASE IN CUBA Zarragoitia Alonso I. Pelaez Y, Bernal F, Lopez P, Valenzuela C. Hospital C. Q. Hermanos Ameijeiras, San Lázaro 701 Centro Habana. Cuba. E-mail: [email protected] Tropical Medicine Institute “Pedro Kourí”, La Habana, Cuba. E-mail: [email protected]
Introduction: The depression constitutes a chronic illness that bears a great invalidity and it considered that the year 2020 second cause Introduction: Hemorrhoidal disease is a health problem where would become of disability. medical treatment could be beneficial before turning to invasive procedures. Recombinant streptokinase (SKr) has shown favorable Although the one and only is not form of treatment, the results in animal models and human rectal inflammation. antidepressants constitutes an important arsenal for the handling of this upset. Material and methods: We performed a Phase II clinical trial-III, multicenter, randomized, double-blind, placebo-controlled, in order to Development: A brief historic review of the antidepressants that do determine the efficacy and safety of the streptokinase in the treatment relevant this disease, the importance of the treatment of depression of patients with acute hemorrhoidal disease. We included 80 patients and epidemiologic elements and the motives will be exposed in the older than 18 years who consented to participate in the study, which lecture. were randomly assigned to 4 treatment groups: I) Placebo, II) Sodium In addition, they will examine the different utilized pharmaceutical and salicylate, III) SK 100 000 IU and IV) SK 200 000 IU, which were the more updated investigations that are coming true for part of the administered the test product rectally as a suppository every 6 hours pharmaceutical industry in the production of new molecules that they to complete four administrations (at 24 hours). Patients were mitigate to you symptoms of the aforementioned disease. hospitalized for 24 hours and evaluations were done at 24 hours and 3, 5 and 20 days after inclusion. Adaptive design was made from a An exposition and analysis of the position of different currents in the sequential Bayesian analysis. The primary endpoint was healing use of the aforementioned pharmaceutical will be accomplished. response after 5 days into the study, and as secondary endpoints of Another subject matter will be the risk of the utilization of response to treatment at each assessment, the development of pain, edema, lesion size, the need for surgery and the appearance early antidepressants in children and teens. relapse. Adverse events were recorded during the test performance. Finally, the area under discussion will develop having like base the Results: The efficacy of SK suppository (200 000 IU) in the healing of challenges that come into question for to confront the aforementioned acute hemorrhoidal disease on the 5th day (37% significant difference disease and the problems that have been up for the establishment of from placebo), the cure rate was significantly higher in group IV (SK - consent upon indicating a pharmacologic specific therapy and his level 200 000 IU) compared to other groups, with a median estimated within of efficacy and effectiveness. 5 days (elsewhere median of 10 to 11 days). Also, evaluation of the Conclusions The need of the integral boarding for part of the scientific response to the 5th day showed the superiority of SK suppository (200 community in the resolution of the complications that he bears this 000 IU) with statistically significant differences with respect to placebo upset will be described in detail, being the worst of wholes suicide. groups, salicylate and SK - 100 000 IU. In internal hemorrhoids and mixed grades III and IV, the highest dose of SK healing showed superiority over placebo (68% point difference) and overall response superiority over placebo and salicylate (specific differences of 52 and 40%, respectively). In terms of security we can argue that recombinant streptokinase suppository is safe and tolerable.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S273
LATINFARMA 2013 Resúmenes/Abstracts
Farmacoepidemiología / Pharmacoepidemiology
PFep 001: EVALUATION OF DRUGS AUTHORIZED OUTSIDE PFep 002: LOW FREQUENCY OF PROPHYLAXIS VADEMECUM IN A FIRST LEVEL CARE PUBLIC HEALTH PRESCRIPTION FOR OSTEOPOROSIS IN PATIENTS PROVIDER OF URUGUAY RECEIVING CHRONIC TREATMENT WITH CORTICOS- TEROIDS IN COLOMBIA Santurio A, Moreale J, Iglesias V, Bonet C. Machado-Alba J, Alzate-Carvajal V , Mondragón-Cardona A, Jiménez- Primary Care Network (PCN), Administration of State Health Services (ASHS). Address: Cerro Largo 1726 bis. Tel: (598) 24001896. Montevideo, Uruguay. E- Canizales CE. mail: [email protected] Universidad Tecnológica de Pereira - Pereira, Vereda La Julita, Risaralda, Colombia. E-mail: [email protected] Introduction: PCN is an ASHS executing unit that manages the primary care, covering 500,000 users. PCN has a Vademecum and drug Introduction: Chronic ingestion of corticosteroids can cause applications exist outside of it, which are analyzed by the Pharmacy osteoporosis, which leads to increase the risk of fractures (hip, femur and Therapeutics Committee (PTC) that meets criteria for rational and and spine), more hospitalizations, disability and lost of work time, for efficient. It has seen an increase in requests for what is necessary to this reason is important to administrate adequate prophylaxis. conduct this study as a diagnosis of the situation. Material and methods: Cross-sectional study. Information about Objectives: 1) Know the pharmacological groups requested. 2) people affiliated to the General Social Health Security System of Analyze the resolutions of applications. 3) Calculate the spending and Colombia (3.7 million) was used. This study included men and women saving of authorized and unauthorized medicines, and its economic of all ages who were prescribed any glucocorticoid from August 1 to impact. November 30, 2011. Sociodemographic variables and the Methodology: Observational, descriptive and retrospective study. We characteristics of of the glucocorticoid prescription and CIO reviewed PTC resolutions, ranging from January to December 2012. prophylaxis drugs in a defined daily dose (DDD) were identified. Applications were investigated: age and sex; principle active by generic Results: A database of 255,568 prescriptions of glucocorticoids was name, trademark and ATC classification, concentration, pharmaceutical obtained, with a total of 1,837 patients receiving some glucocorticoid form, dosage, indication, foundation and applicant. Were analyzed as chronically. The majority of participants were females (60.2%), with "authorized" and "unauthorized". The latter was sub classified: "lack an average age of 55.2 ± 16.9 years distributed in 65 cities of the justification and/or data" and "use drug available in Vademecum". The country. Prednisolone was the most commonly used glucocorticoid latter, was indicated the pharmaceutical alternative. We used absolute (1,546 patients, 84.1%), whereas the most prescribed prophylaxis and relative frequency percentage. For the calculation of cost prices drug used was calcitriol (67.1%). Despite the need to receive used UCA "CALL No. 30/2009", and was performed according to the prophylaxis, 994 cases (54.2%) were not receiving it. indicated dose for 6 months. Conclusions: There is a poor utilization of CIO prophylaxis. The Results: 192 applications were reviewed in 2012. 12% of the requests implementation of drug surveillance actions that allow the had no age, 68% were older than 19 years. 17% had no generic name, identification of problems related to these drugs in order to prevent and were requested by trademark. Of the remaining 83% we mention adverse events and optimize resources is recommended, thus the 3 most common generic names: Clopidogrel, Oxcarbazepine and anticipating the emergence of complications in the patients. Escitalopram. Classified by ATC: Group A 18% (73% A16), Group B 20% (60% B01), Group C 16%, Group N 31% (46% 3N03 and 35% N06). 1/3 of the applications lacked concentration and dosage form. 90% had an indication and support of the application. 63% of applications were approved. From the "unauthorized", 32% were rejected for lack of justification and 30% indicated use the Vademecum. Drug spending was US$ 4,364 for authorized, and was saved by unauthorized US$ 6,240. Conclusions: It highlights the lack of data, being cause for various applications "unauthorized". There was high percentage of applications by trademark, which could be the result of pharmaceutical promotion. It is striking the high percentage of absence of the concentration and dosage form of medication requested, as there is more than one pharmaceutical presentation available. The rejection of several requests, with the suggestion of pharmaceutical alternative included in the Vademecum, could be interpreted as a lack of knowledge by physicians. The cost of the acquisition of authorized medicinal products poses no economic impact on annual spending PCN drugs. On the other hand, saving for drugs "unauthorized", though, is one and a half spending mentioned above, also has no discernible impact on the PCN budget.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S274
LATINFARMA 2013 Resúmenes/Abstracts
PFep 003: UTILIZATION OF ERGOTAMINE ¿DO PHYSICIANS PFep 004: ANTIPSYCHOTIC PRESCRIPTION PATTERNS IN KNOW IN COLOMBIA AS PRESCRIBE? PATIENTS AFFILIATED TO THE SOCIAL SEGURITY SYSTEM IN HEALTH OF COLOMBIA Morales-Plaza C, Machado-Alba J. Morales-Plaza C, Machado-Alba J. Universidad Tecnológica de Pereira, Colombia. E-mail: [email protected], [email protected] Universidad Tecnológica de Pereira, Colombia. E-mail: [email protected], [email protected]
Introduction: Ergot derivatives are drugs designed to abort migraine attacks, with vasoconstrictor effects. To determine how ergotamine Introduction: Schizophrenia alters individual perception, thought, derivatives are being prescribed by physicians in Colombia and affect and behavior. Drug therapy can improve these manifestations. variables associated with inappropriate prescribing and their potential interactions in patients in 2012. Objective: Determine the prescribing patterns of antipsychotic drugs in a group of patients with the Social Security System in Health of Methods: It reviewed 86,411 formulations made during April 2012. Colombia. We identified the drug, dose, interval, time of use and indication. We interviewed 288 randomly selected patients in whom also sought to Materiales y methods: Descriptive studies on database of 6.2 million concomitant use of: a) antihypertensive, b) ischemic heart disease people were selected 3,075 patients medicated with antipsychotics, of medications, c) antiretrovirals, d) other antimigraine, and e) both sexes, of all ages, with continuous treatment from March to June macrolides, because of their interactions. 2012 and resident in 57 Colombian cities. We designed a database on drug consumption, obtained by the company that distributes the drugs Results: We obtained 801 prescriptions in 27 cities with mean age: to patients. 35.1 ± 14.1 years, 82.5% of prescriptions in women, 96.5% held by the primary care physician; (n=524, 65.4%) cases for migraine, were found Results: A total of 3075 patients were studied, with mean age 56.3 ± 26 different prescription forms and 797 incorrect prescriptions 21.5 years; 50.3% of the participants were women. Of all patients, regarding improper usage recommendations (99.5%). Inappropriate 81.9% were receiving monotherapy and 18.1% two or more prescribing was significantly associated with health service (p=0.005). antipsychotics. The prescription order was: 77.1% atypical and classic In patients who were contacted by telephone (n=266, 92.4%) took it 31.9%. Drugs most frequently used were: quetiapine (30.3% of the according to the incorrect indication. We found 54 (6.7%) patients patients), clozapine (23.7%), levomepropamize (18.4%), and taking antihypertensive drugs, 24 (2.9%) patients with macrolides, five risperidone (14.9%). The most common combinations were: more other antimigraine drugs. haloperidol + levomepromazine (n= 67, 12.1%), clozapine + pipotiazine (n= 54, 9.7%) clozapine + risperidone (n= 45, 8.1%), Most patients are receiving improperly ergotamine, plus possible quetiapine + levomepromazine (n= 40, 7.2%). The most prescribed co- interactions that increase the risk of health problems such as ergotism medications were: antidepressants (n= 998, 32.5%), anxiolytic (n= and coronary events. Assessment measures should be implemented, 799, 26.0%), statins (n= 672, 21.9%); antiparkinsonian (341, 11.1%) updating and training for physicians. and anti-diabetics drugs (n= 327, 10.6%). Conclusions: The practice of prescribing medicines with a high therapeutic value predominates mainly in antipsychotic monotherapy. Most agents were used in higher doses than recommended. This raises the need to design educational strategies to address these prescribing habits and research evaluating the effectiveness of treatment.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S275
LATINFARMA 2013 Resúmenes/Abstracts
PFep 005: THE ESTABLISHMENT OF A STRATEGY FOR THE PFep 006: PHARMACEUTICAL ORIENTATION AT THE TIME RATIONAL USE OF INJECTABLE OMEPRAZOLE OF HOSPITAL DISCHARGE: STRENGTHENING ADHERENCE AND PROVIDING CONTINUITY OF CARE Moreira Da Costa J, Diniz Silva L, Fonte Freitas L, Moraes Santos C. Pedroso L, Martins J, Reis A, Moreira Da Costa J, Castro M. Hospital Risoleta Tolentino Neves, Universidade Federal de Minas Gerais, Brazil. E-mail: [email protected]; [email protected] Hospital Risoleta Tolentino Neves, Universidade Federal de Minas Gerais, Brazil. E-mail: [email protected]; [email protected]
Aim: To describe actions taken and results attained during the establishment of the Injectable Omeprazole Use Qualification Program Introduction: The transitional process of care is presented as a critical (IOUQP) at a teaching hospital in Brazil. moment to the patient’s safety. Among them, hospital discharge is a situation which breaks the pharmacotherapeutical care process, Method: This three-stage study was conducted at an Emergency including changes in medication and lack of information exchanged Medical Services belonging to the city of Belo Horizonte, Minas Gerais among health professionals from other attention levels. When this State. The first stage comprised the identification of all prescriptions problem was detected, the reorientation of pharmaceutical service has recommending the use of Injectable Omeprazole (IO) issued at the occurred at the time of being discharged from the hospital, in the hospital. During the second stage, a protocol with directions on IO use context of multi-professional internship for the health of the elderly. was devised and distributed among the clinical staff. Finally, the third Patients are accompanied during the whole hospitalization, when their stage comprised a new analysis of prescriptions recommending the use demands and necessities, in what refers to domiciliary medical of IO, followed by pharmaceutical interventions according to needs. treatment, are identified. At the time of hospital discharge, they receive Results: During the first stage, all prescriptions recommending IO (n = orientation to new medication prescription, posology, administration 353) and 129 medical records were analyzed. Among the main reasons and access. for IO prescription, upper digestive hemorrhage (17; 27.9%) was the Methodology: According to each patient's profile, adherent adjunct primary one. The third stage comprised the analysis of 82 methods were built, as an organizer box and adjunct record of prescriptions, the observation of 75 patients, and the performance of medication usage. Besides, the elaboration of “pharmacotherapeutical 14 pharmaceutical procedures. care transition protocol” was proposed, which was sent to primary Conclusion: One notices the importance of studies promoting a attention professionals. From March 2012 to February 2013, a total of reasonable use of anti-secretory drugs within a hospital environment. 96 patients - average age is 74 years old - received pharmaceutical orientations as they were discharged. Results: Out of these patients, 58% left the hospital with a higher number of prescribed medicines, when compared to their before regress use. In average, the number of medicines used per patient was 4 before being hospitalized and 6 after they were discharged. As for the medication administration, 41.67% of the patients needed family care before admission. This number increased to 50% when they were discharged, showing the fragility caused by hospitalization. In relation to pharmaceutical interventions, 100% of the patients received a dosage orientation record, 64.58% were oriented in relation to access, and medicine-organizer boxes were made to 20% of the patients in order to avoid administration mistakes and improve adherence. Of the oriented patients, 81.25% were referred to primary attention to keep treatment. Conclusions: In this process, the pharmacotherapeutical orientation service, after discharging patients, brought benefits and contributed to a better understanding of adherence to drug-therapy as well as to a better referencing quality.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S276
LATINFARMA 2013 Resúmenes/Abstracts
PFep 007: PRELIMINARY RESULTS BENZODIAZEPINES PFep 008: DRUG PRESCRIBING IN INTERNAL MEDICINE AT A PRESCRIPTION UNIVERSITY HOSPITAL Martínez E, Speranza N, Telechea H, Ormaechea G, Pagano E, Mendez G, Arredondo G, López M, Viroga S, Speranza N, Ormaechea G, Artagaveytia P, Boccino S, Tamosiunas G. Tamosiunas G.
Department of Pharmacology and Therapeutics. School of Medicine. University of Department of Pharmacology and Therapeutics. School of Medicine. University of the Republic, Uruguay. E-mail: [email protected] the Republic, Uruguay.
Introduction: Is estimated that 2.5% of the world population uses Introduction: One of the measures suggested by the World Health Benzodiazepines (BZD). This widespread use increases the risk of Organization (WHO) to help promote rational drug use (RDU) is the irrational use. The most frequent problems linked to irrational use of creation of a list of essential medicines (LEM). BZD are: prescription and lack of monitoring of adverse effects. These problems are not fully characterized in our country. In 2009, at the Clinical University Hospital [Hospital de Clínicas Dr. Manuel Quintela, (HC)] evidence was gathered that 38% of the drugs Objective: The aim of the study was to conduct a nationwide approach prescribed were not included in the LEM, a fact that determined its to BZD prescribing profile by internist and psychiatrists. updating during 2010 and 2011. Methods: A cross sectional drug utilization study was conducted in Objective: To evaluate the adjustment of the prescriptions to the LEM 2012 in Montevideo. Data was collected through an anonymous survey in Internal Medicine floors. Assess the quality of the prescription. developed by the authors. Surveys were conducted by mail and in person. Method: Observational, cross-sectional study performed in Medicine Departments at the HC during 8/31/2012. The clinical records of Results: 148 surveys were conducted (50 psychiatrists and 98 patients hospitalized in medical floors were revised. They were internist). Among psychiatrist BZD were the second most prescribed classified as “LEM yes” if the prescription included active substance, psychotropic drugs (38%). 28% of psychiatrists reported prescribing safety dosage, and pharmaceutical form available in the LEM. They by trade name. The reasons for this were: more efficacy (56%), were classified as “Complete Prescription” if they included generic drug availability in their workplace (19%), fewer adverse effects (12.5%). name, dosage, route of administration and dosing interval. Anxiety was the most frequent indication (60%). 88% considered BZD dependence as a major problem. Only 9.5% answered that they not Results: There were 736 prescriptions in 97 hospitalized patients. A prescribe BZD for more than 4 months. While 90% of physicians tried total of 127 drugs were prescribed, of which 21 were not in the LEM to discontinue BZD treatment at some point, only 26% were able to (16%). accomplish it successfully. Among internist BZD were the first most In terms of quality of the prescriptions, 74% were complete. Of the prescribed psychotropic drugs (85%). 10% reported prescribing by incomplete prescriptions, 68% did not specify dosage, 7% dosing trade name. The reasons for this were: more efficacy (39%), interval and 23% the route of administration. availability in their workplace (38%). Anxiety was the most frequent indication (72%). 75% considered BZD dependence as a major The most prescribed drugs were Omeprazole (8.7%) and Fraxaparine problem. Only 9% answered that they not prescribe BZD for more than (6.7%). 4 months. 92% of internist tried to discontinue BZD treatment, only Conclusions: Updating the LEM improved prescriptions’ adjustment, 31% were able to accomplish it successfully. The most frequent side although not quite significantly, since in 2009 22% of the prescribed effects were cognitive disorders (31%) and sleepiness (47%). drugs in Medicine floors were not included in the LEM. It is essential to Conclusions: Strategies to promote a rational use of benzodiazepines know the causes to this poor adjustment to the LEM in order to are needed in order to improve prescription. permanently be able to evaluate and establish strategies that promote RDU. Even though most of the prescriptions were complete, it is necessary to improve them.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S277
LATINFARMA 2013 Resúmenes/Abstracts
PFep 009: PRELIMINARY RESULTS OF AN ANALGESIC PFep 010: COMPARISON OF NON-PHARMACOLOGICAL UTILIZATION STUDY IN A HOSPITAL IN HIDALGO, MEXICO TREATMENT GUIDELINES OF ADULT HIV/AIDS PATIENTS IN GUYANA AND JAMAICA TO THAT OF BRITISH Reynoso-Vázquez J, Velázquez-Alvarado P, Chehue-Romero A, López- Martínez S, Betanzos-Palmeros Z, Camacho-Gómez R, De la O- GUIDELINES Arciniega M. Moncreiffe S, Nraine S, Pererra S, Rambarran S, Siebs S.
Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, School of Pharmacy, UTech, Jamaica. México. E-mail: [email protected]
Introduction: Non-pharmacological treatment and support services Introduction: Pain is a public health problem that affects a large such as emotional needs support through counseling services, and number of Mexicans. It is one of the main reasons of outpatient clinic provision of palliative care, psychological, spiritual and nutritional and its prevalence is high in the hospital service. Drugs Utilization guidance as well as education and empowerment of patients are Studies have demonstrated to be very useful to contribute to Rational important in the provision of holistic care in the treatment of Use of Drugs. The aim of this study was to analyze the prescription of HIV/AIDS. analgesics in the Hospital General “B” Pachuca in Pachuca, Hidalgo, Mexico. Methodology: The project was a qualitative, comparison of the non- pharmacological treatments offered to HIV positive adults in Guyana, Material and methods: A prospective drug utilization study was and Jamaica; compared to the British HIV Association’s Standard for performed; it was of prescription-indication. The information was HIV Clinical Care (BHIVA). The research was carried out over a six (6) collected from medical records of patients with analgesic prescription months period. according to inclusion criteria; therefore this sampling was not probabilistic. In the first part of this study a descriptive analysis was Results: The British gold standard outlined many areas of non- performed to characterize people studied and bivariate to analyze the pharmacological care such as monitoring of patients with the use of variables associated with the prescription using the Statistical Package laboratory investigations, counseling, public health and sex education, for the Social Sciences (SPSS); measures of central tendency and and services to prisoners, commercial sex workers and other dispersion as well as ratios and proportions were estimated. vulnerable groups. The Jamaican guidelines focused on nutrition, social care, laboratory monitoring and management of patients with Results: 411 clinical records were included, of whom 64.2% were carcinomas; Guyana on the other hand focused on counseling and female. The mean of age was 59.97 ± 17.36 years. The main diagnoses laboratory monitoring. were bone fractures, cholecystectomy, diabetic complications and venous thrombosis, among others. The most common comorbidities Conclusions: It was also observed that Jamaica did not emphasize were hypertension, diabetes and associations of them. The intensity of public education and specialist services; while Guyana needed to pain was reported only in 13% of sample, prevalence of pain was include nutrition, public health and sex education and specialist 57.7% for females. The analgesics more prescribed were ketorolac, services for prisoners, commercial sex workers and vulnerable groups, diclofenac, lysine clonixinate, and metamizole. as well as obstetric and gynecological services. Recommendations were made to address these deficits in order to facilitate improvement of Conclusions: Non-steroidal anti-inflammatory drugs (NSAID) were the health care delivery for HIV positive adults in the three countries: main analgesics prescribed to treat different kind of pain. For treating England, Guyana and Jamaica. pain adequately is recommended to know the treatment schedule proposed by the World Health Organization (WHO). An effective pain management improves the patient's general condition.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S278
LATINFARMA 2013 Resúmenes/Abstracts
PFep 011: PHARMACOEPIDEMIOLOGY OF PSYCHOACTIVE PFep 014: WORKING SYSTEM AND EVALUATION OF MEDICATION IN ADULT PATIENTS IN THE PSYCHIATRIC PHARMACOTHERAPEUTIC COMMITTEES. CUBA 2012 DEPARTMENT OF DURANGO, MEXICO GENERAL HOSPITAL Calvo D, Broche L, Lara. C, Jiménez G, Alfonso I, López M. Cano-Torres E, Loera-Castañeda V, Lares-Asseff, Sosa-Macías M, Departamento de Farmacoepidemiología, MINSAP, Cuba. E-mail: Salas-Hernández C, Allegre-Alonso A, Galaviz-Hernández C, Lares- [email protected] López A.
Centro Interdisciplinario de Investigación para el Desarrollo Integral Regional, CIIDIR-IPN Unidad Durango, México. Introduction: As an effective alternative to try to alleviate the unfavorable trends related to the improper use of drugs, the World
Health Organization, from the 80s adopted among its strategies for Introduction: Psychiatric diseases have become a public health achieving a rational use of drugs, the establishment of therapeutic problem owing to their increased prevalence. An option for their committees (PTC). Cuba as part of Pharmacoepidemiology strategy has treatment is psychoactive medications, which are associated with worked to strengthen the committees, and is a work objective Area multiple adverse effects. Medical Assistance. This research aimed to design a working system for the PTC of the country, assess the performance and effectiveness of Objective: The purpose of this study was to determine the the PTC in the country and identify the main problems related to its pharmacoepidemiology of psychoactive medication and the prevalence operation. of psychiatric disease in adult patients seen at the Psychiatry Department at Durango General Hospital. Material and methods: This is a descriptive study; the unit of analysis was the PTC of the country, in 2012. A sample was of the same Material and methods: Clinical histories of the patients were amounting to 161 Committees, 135 from 25 areas of health and reviewed for patients over 18 years of age that were seen at the hospital committees. As part of the work were conducted educational outpatient clinic of the Psychiatry Department at Durango General and managerial interventions in addition to the preparation and Hospital that were diagnosed at this hospital with psychiatric implementation of an assessment instrument, with its guide and a conditions requiring psychoactive medication for their treatment. The database for the compilation of results. study was conducted between January 2009 and February 2010. Results: was installed the working and the effectiveness system of Results: The most commonly diagnosed conditions were the neurotic evaluation PTC, performed 3 PCT quarterly assessments. The disorders, stress related disorders, and somatization disorders evaluating system of effectiveness was implemented and made three (42.9%), with the most common sub-classification being major quarterly assessments PTC. Overall evaluation Committees of the depression with anxiety (26.3%). Seventy six percent of patients institutions visited reported that 70% were evaluated as well, the 20% received more than one medication for their treatment. The most is assessed regularly and between a 10% malfunction. The average commonly prescribed medications were the selective serotonin rate as guide points for the PTC of the country was 79.6. reuptake inhibitors, with fluoxetine being the most prescribed medication (42.2%). Anxiolytics were the second most prescribed Conclusions: We succeeded in implementing the system of group, with clonazepam being the most prescribed medication within pharmacoepidemiology working with PTC, over 60% of the PTC was this group (67.8% of patients). evaluated as well and this strategy has identified the main problems they face. Conclusions: Contrasting with the clinical practice guidelines, in which single drug therapy is recommended for most of the psychiatric diseases, only 23.24% of the patients received single drug therapy. The age group with most prescriptions was between 30 and 59 years of age.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S279
LATINFARMA 2013 Resúmenes/Abstracts
PFep 015: PRESCRIBING BEHAVIOR OF NPH INSULIN IN PFep 016: ANTIMICROBIALS PRESCRIPTION IN ADMITTED PATIENTS WITH DIABETES MELLITUS. CUBA 2012 PATIENTS WITH BACTERIAL PNEUMONIA Broche Villarreal L, Calvo Barbado D, Alfonso Orta I. Legón Pérez T.
Departamento de Farmacoepidemiología, MINSAP, La Habana, Cuba. E-mail: Hospital Universitario Clínico Quirúrgico Miguel Enríquez, La Habana, Cuba. E- [email protected] mail: [email protected]
Introduction: Diabetes mellitus is a common disease in our country, Introduction: The irrational use of the antibiotics has world reach. with a prevalence of (513 405 patients, according to statistical The bacterial pneumonia is the infectious illness of more incidence in yearbook 2011) for a rate of 45.7 per thousand inhabitants. In Cuba the the hospital Miguel Enriquez and one of the first causes of death; there drugs available (slow NPH insulin, Actrapid insulin, glibenclamide, has been detected that the protocols of treatments are not up-to-date, metformin and tolbutamide) are prescribed by medical certificate and the commission of antibiotics doesn't work regularly, a few use of the dispensed through control card. This way of working also includes microbiology and high consumption of antibiotics of last generation; monthly record number of prescriptions nationwide, the which in the then we suspected an inadequate use of antibiotics. The aim was assess first half of 2012 showed an increase in NPH insulin prescribing, but it the use of antibiotics in the treatment of the bacterial pneumonia in is not known which are the causes for this increase, so what is decided admitted patients. to perform this study, in order to identify demographic and clinical characteristics of patients enrolled with NPH insulin in the country Method: A study descriptive was conducted in 65 admitted patients from January to July 2012, evaluate the prescribed doses of insulin with diagnosis of bacterial pneumonia from medicine services at slowly and identify key combinations used. Miguel Enriquez hospital, between January and March 2012. We got demographic and clinical characteristics of patients, type of drug Methods: An observational, descriptive research type of prescription prescribed, doses, duration of treatment, if microbiological studies drug utilization indication therapeutic elements, being the universe of were done, evaluation of antimicrobial prescription and time of the study all certificates of insulin during the period January to July hospitalization. 2012, identifying variables such as age, type of diabetes, prescribed dose, other medications associated and vials to dispense each month. Results: Most of patients had more than 75 years (47.7%), women (50.8%) and smokers (50.8%); 47.7% of them had hypertension and Results: We reviewed a total of 52 447 medical certificates from a total 27.7% illness lung obstructive chronicle. Pneumonia acquired in the of 114 485 entries that exist in Cuba at the end of August constituting community was the most frequent type of pneumonia, 96.9%. Only in 45.8%, no information was available or was incomplete from three 9.2% of them were indicated microbiological studies. Cephalosporins provinces. The study provided that the predominant population was were antibiotics more prescribed, ceftriaxone was the drug more used over 60 years, but in terms of the prevalence by age group the largest (50.8%), it was combined with azithromycin in 81.8% of them. The number of patients with insulin is in the group under 15 years, duration of the treatment oscillated from the 3 until the 7 days and the followed by the age group 16 to 59 years; depending on the types of time of hospitalization varied from 2 to 30 days. The prescription was Diabetes 7.5% of patients with type 2 diabetes used insulin slowly. The inappropriate in 60% of patients. most common dose is given 1 to 33und day to 56.4% and 70% prescribed in combination with other drugs such as insulin Actrapid Conclusions: The antibiotics prescription in the treatment of the and glibenclamide. The 58% of patients who are prescribed insulin bacterial pneumonia in the observed patients was inadequate. It is dispenses them one monthly vial. necessary educational and organizational interventions for improving their use. Conclusions: The rate of insulin therapy is acceptable for the international trend than as indicator of better prognosis and better therapeutic approach in diabetic patients, however it is appreciates misclassification of disease that make not possible the relationship with dispensarization and evaluation of quality of treatment. It is suggested actions in order to improve the diagnosis and treatment of diabetic patients with good metabolic control and prevent complications.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S280
LATINFARMA 2013 Resúmenes/Abstracts
PFep 017: DETECTION OF POTENTIAL DRUG-DRUG AND PFep 018: CONSUMER PHARMACEUTICAL MARKET DRUG-DISEASE INTERACTIONS ON PRESCRIBED SEGMENTATION OF DRUGS IN CUBA MEDICATIONS FOR ELDERLY PATIENTS IN A COMMUNITY García Milián AJ, Alonso Carbonell L, López Puig P. Peña C, Yodú N. Escuela Nacional de Salud Pública, La Habana, Cuba. E-mail: 10 de Octubre Medical School, Medical University of Havana, Cuba. E-mail: [email protected] [email protected]
Introduction: The measurement process of the pharmaceutical Introduction: The extraordinary technical and scientific development market is a fundamental aspect of market research and in the process experienced in the health field and the social progresses during the last of providing meaningful information for decision-making. decades have enabled to improve the way of treating diseases, to Objectives: Segment the drug user population in Cuba and to establish achieve healthier lifestyles and to increase the life expectation of the their consumption patterns. population. In Cuba, 17.8% of population is 60 years or older. Along with the increase in the proportion of elderly people, the prevalence of Method: The same was carried out through a process that consisted of chronic diseases and the use of medications have also risen. three stages: study, analysis and patterns. To collect information Prescription of drugs in elderly people is a very complex issue. With regarding the first stage, we designed a questionnaire validated by the goal of identifying potential drug-drug and/or drug-disease experts and a pilot study. The population is segmented demographic, interactions in elderly patients a cross-sectional descriptive study was geographic, socioeconomic and behavioral. Finally, we included four conducted in two primary care clinics located at the Municipality of population segments that describe the consumption pattern (profiles). Centro Habana from September 2011 to February 2012. Results: Analysis of drug consumption by the Cuban adult population Material and methods: 140 charts were revised and the prescribed can draw the outline epidemiological drug use by establishing some medications by the primary physician during the last consultation common characteristics of these groups from the practices identified were analyzed. Chose variables in our study were: patient’s age, sex, and segmented in several levels prescribed drugs, and diagnosis. The National Formulary of Medications was used to identify drug interactions. The clinical Conclusions: The pattern provides viewing parameters identified relevance of the drug-drug interactions was assessed using the socio-demographic and other consumer fundamentals. To decrease the classification system of the Department of Pharmacology of the pharmaceutical market imperfection, can develop social marketing Huddinge Hospital in Stockholm, Sweden and for the drug-disease strategies based on the profiles obtained by optimizing the potential interactions Beers and STOPP criteria was applied. benefit of therapeutic arsenal available through a rational consumption. Results: 84 drug interactions were detected (68.9%); the majority was pharmacodynamics (82.2%) that increased adverse effects (53.6%). The main drugs found were psychoactive (26.1%) and beta-blocker drugs (23.8%).In the clinical relevance predominated type C (86.9%). The most common association type D found was enalapril/spironolactone (3.6%).There was 74.2% of drug-disease interactions; 13.5% identified according to criteria of Beers and 60.7% according to criteria STOPP. Conclusions: We conclude that the inadequate prescription of medications in elderly patients attended in the community is frequent, so it would be appropriate to find ways to solve this health problem.
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LATINFARMA 2013 Resúmenes/Abstracts
PFep 019: DRUG CONSUMPTION IN SELECTED CITIES OF PFep 020: PHARMACO-EPIDEMIOLOGICAL STRATEGIES FOR CUBA THE IMPROVEMENT OF THE CONTINOUS MEDICAL PRESCRIPTION, GENERAL HOSPITAL “JUAN BRUNO ZAYAS García Milian AJ, Alonso Carbonell L, López Puig P. ALFONSO” National Coordinating Center for Clinical Trials, Havana, Cuba. E-mail: [email protected] Acosta E, Dupuig R, León Y, Navarro M Hospital General Dr. Juan Bruno Zayas Alfonso, Santiago de Cuba, Cuba. E-mail: [email protected] Introduction: Scientific journals play an important role in the scientific communication process. Objective: To characterize the scientific publications on drug consumption in Cuban medical journals Introduction: To promote the rational use of drugs, modified habits of indexed in SCIELO in the period January 2000 to December 2012. malpractice medical prescriptions, to achieve the safety of the drugs, to Methods: A descriptive bibliometric Cuban medical journals indexed study the economical implications in using them, are some of the in SCIELO. The choice of units of analysis was performed taking into contributions of the pharmacy-epidemiology. account the term drug consumption. Variables were studied number of Methodology: Thus, this scientific research was designed to assess the articles by year of publication, number of publications by author, indicators of safety and the impact well-established by pharmacy- article distribution by number of authors, institutions conducting epidemiology at Dr. Juan Bruno Zayas Alfonso, General Hospital in research, institutional productivity, number of references per Santiago de Cuba from January 2011 to December 2012, related to the publication and subject. quality of the medical prescriptions, control medical certificate, Results: Of the period analyzed, 2009-2012 was the highest scientific medical prescriptions, and the prescriptions of records in patients production, 42.8%. Most of the authors were bystanders 91.7%. admitted in the hospital, that in the year 2011 had a percentage of Institutions that conduct drug consumption were the Centre for error over 5%, the goal is to maintain it under 5% and it was achieved development of pharmacoepidemiology six (28.6%), followed by in 2012. medical schools and Calixto Garcia Enrique Cabrera with 2 (9.5%). Results: The suspicious report of adverse reactions to a drug was Magazines and books were reference types that were used most another point that since may 2011 was fulfilled over 12 month reports. frequently. The Journal of Pharmacy 42.8%, with 19.0% of Family The evaluation of adherence to therapeutic protocols such as acquired Medicine and Medicinal Plants 9.5% were in the most commonly pneumonia in the community also showed positive results as the first identified articles on the subject. The 69.3% of the institutions were line of treatment of this disease with cephalexine corresponding with classified as small producers. the use of anti-microbial and not using ceftriaxone. The preservation of Conclusions: The scientific literature on drug consumption while cephazoline for surgical prophylaxis was another effective result and agreeing with most consumed drug groups is low and is characterized also the decrease of consumption of ciprophloxacine bulb during 2012 by authors in articles passers high rate of shared authorship. where the consumption was 279 bulb less than in the year 2011, representing $18 720,90 less used of the drug budgets so it seem that systematic interventions and the multidisciplinary work of pharmacy - epidemiology in the hospital as well as the pharmacy-therapeutic committee that allow the improvement of the quality of medical prescription, useful and rational use of antimicrobials in this hospitality centre.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S282
LATINFARMA 2013 Resúmenes/Abstracts
PFep 021: DRUG USE IN THE HOSPITAL PHARMACY PFep 022: CHARACTERIZATION OF THE ANTMICROBIANS SERVICES AND EVALUATION THROUGH QUALITY COMSUMPTION IN TWO CONSECUTIVE YEARS IN THE INDICATORS HOSPITAL MANUEL FAJARDO Cuba MM. Peña A, Duro E, Pacheco F, Monteagudo L.
Universidad de La Habana, Instituto de Farmacia y Alimentos, Cuba. E-mail: Facultad de Ciencias Médicas Manuel Fajardo, La Habana, Cuba. E-mail: [email protected] [email protected]
The Pharmaceutical Services within the healthcare environment is a Introduction: The pharmacoeconomic study of antimicrobial major player in the chain of actions needed to achieve a Rational Drug consumption in a health institution becomes an important indicator of Use. It is a set of processes that converge toward achieving the former efficiency and feedback to the physicians of the possible implications of goal. Of all these, patient-oriented processes, allow preventive and its use. evaluative functions of drug use. Assessing the quality of this subset of processes allows decision making for continuous improvement. Objective: To characterize the levels of antimicrobial use in our environment as an indicator of rational use of medicines by health A set of 25 quality indicators were applied on a sample of Cuban professionals with prescriptive authority. Pharmaceutical Hospital Services of four provinces, selected on the basis of having pharmacists trained in the use of these tools. It was Material and methods: We conducted an observational, descriptive, possible to apply approximately 80% of the indicators. They, as a retrospective, longitudinal study at Hospital "Manuel Fajardo" in group, showed extreme behavior according to the evaluative scale Havana, during the years 2010 and 2011. The universe was used. Some reached the standard level and others the unacceptable determined by all antimicrobials that were prescribed by physicians at one. Its application allowed taking corrective actions to continuously the hospital during this period (N = 16). The data was obtained from improve these processes. the hospital pharmacy. No exclusion criteria were used. Results: Cefuroxime was the most used antimicrobial (34867 units). 3rd and 4th generation cephalosporins were used in 22.6% compared to other antimicrobials. The seven most commonly used drugs represented a cost of approximately two million pesos. Conclusions: The most used antimicrobial during the years of the study were cefuroxime, metronidazole and co-trimoxazole and 3rd and 4th generation cephalosporins. The ciprofloxacin was the one wich generated the most economic cost.
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LATINFARMA 2013 Resúmenes/Abstracts
PFep 023: BIBLIOMETRIC CHARACTERIZATION OF PFep 024: ANTIHYPERTENSIVE DRUG UTILIZATION STUDY SCIENTIFIC PUBLICATIONS STUDY DRUG USE IN PRIMARY HEALTH CARE García Milian AJ, Blanco Hernández N, Alonso Carbonell L, López Puig Arias Gallardo AI, Zayas González M, Moré Hernández N, Alfonso P. Hidalgo A, Hernández Parets M, Jiménez Fernández L.
Facultad de Ciencias Médicas Enrique Cabrera, Universidad Médica de La Universidad Médica “Dr. Serafín Ruíz de Zárate Ruíz” Villa Clara. Cuba. E-mail: Habana, Cuba [email protected]
Introduction: The usefulness of the analysis of the literature on drug Introduction: Hypertension is a chronic disease with high prevalence, utilization study gives insight into the research activity in this type of which can successfully be treated with antihypertensive drugs. pharmacoepidemiological design. Nevertheless existing hypertension treatment guidelines are not fully implemented in practice. Drug utilization studies give an overview of Objective: To characterize the scientific publications on drug patterns of utilization of drugs. utilization studies in medical journals indexed in SciELO Cuba in the period January 2000 to December 2012. Aims: The aim of this research is to describe the prescription patterns of antihypertensive drugs in primary health care and to evaluate the Methods: A descriptive bibliometric. A review of scientific studies conformity with the Cuban Guideline to Diagnose and Treat regarding drug use during the period between January 2003 and Hypertension. December 2012 from Cuban medical journals indexed in SCIELO. Variables were studied number of articles by year of publication, Material and methods: An indication prescription study was number of publications by author, article distribution by number of conducted in Villa Clara province, Cuba, from January 2012 to March authors, institutions conducting research, institutional productivity, 2013. Five municipalities were included in the study, under the criteria number of references per publication and subject. of having a large number of inhabitants. The Data were collected from medical certificate indicating drug treatment. Those certificates were Results: We identified 26 articles involving 78 authors from 21 consulted in 22 pharmacies of the territory. A sample of 9 857 patients institutions. The years 2009 to 2012 were the most productive. The was included. Information about age, gender, classification of Journal of Pharmacy and General Medicine was the most widely hypertension, comorbidities, drugs and doses was considered. published. Most of the authors was classified as transient, the group of three to six authors per article and institutions as small producers. Results: 78% of the patients were in range from 40 to 60 years old. Indication prescription designs and descriptive statistics were released Prevalence of hypertension was slightly higher in female gender. Type more frequently. The medical records and surveys were the sources of II hypertension is the most frequent classification. Angiotensin data used most often. Psychotropic drugs and antimicrobials were the converting enzyme inhibitors (ACEI) (62.8%) along with diuretics most investigated. The number of citations per article was mostly (38.3%) were the most commonly used hypertensive drugs, either as between 11 and 20, being the most used type magazines and books. monotherapy or in combination with other agents. About 30% of the patients were receiving 2 drugs; only 12% received 3 drugs. The most Conclusions: The authors conclude if there is a low number of common errors of prescription were dose related or mistaken drug scientific productions on EUM in Cuban medical journals in general are selection taking into account comorbidities presented by the patients. growing in recent years. Conclusions: Treatment of hypertensive patients is suboptimal. Prescription habits with no regard for Cuban guidelines to treat hypertension have been detected.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S284
LATINFARMA 2013 Resúmenes/Abstracts
PFep 025: ANTIMICROBIAL DRUG UTILIZATION STUDIES IN PFep 026: RECURRENT APHTHOUS STOMATITIS. HOMEO- PATIENTS WITH PNEUMONIA IN THE INTERNAL MEDICINE PATHIC TREATMENT PATIENTS AT GASTROENTEROLOGY SERVICE INSTITUTE Arias Gallardo A, García Pérez A, Moré Hernández N, Zayas Gonzáles Quintero M. M, Martínez Fernández F, Nguyen Trong V. Instituto de Gastroenterología, La Habana, Cuba. E-mail: [email protected] Universidad Médica “Dr. Serafín Ruíz de Zárate Ruíz” Villa Clara. Cuba. E-mail: [email protected] Introduction: Aphthous stomatitis is the most common oral mucosal disease in human with a high prevalence and recurrence rates. As its Introduction: The growing trends in bacterial resistance in etiology is unknown there are so many local or systematic treatments. community and intra hospital acquire infections are related to the Homeopathy is a philosophic and scientific doctrine based mainly in inappropriate use of antibacterial agents. Drug utilization studies are the Law of Similars and it is very effective in acute as well as in chronic designed to diagnose the mistakes in drug prescription. Often, empiric diseases. antibiotic regimens are not as correct as expected. Material and method: A detailed homeopathic history was made to all Objective: To assess the prescription of antimicrobial drug in the outpatients diagnosed as Recurrent aphthous stomatitis (RAS) treatment of community acquired pneumonia. emphasizing to determine the prevailing miasm (miasm is the tendency of suffering diseases in a certain way that we bring at birth) Material and methods: A transversal descriptive study was in their pathological background. The homeopathic remedies, performed at Arnaldo Milián Hospital, an urban teaching hospital in individually chosen, were given usually at 200 CH potency. A monthly Santa Clara, from January 2011 to March 2012. An intentional sample follow-up was made during 6 to 12 months. of 124 patients was taken. Data like age, sex, diagnosis, bacterial agent, results of bacterial culture and antimicrobial treatment, were Results: 22 patients concluded the assay. The prevailing miasm in the abstracted from the patients´ clinical history. family hereditary background of the patients was the syphilis miasm, as well as in the attributed miasma series of the remedies given. The Results: The most affected patients were those males (53.2%) and results obtained at the beginning of the treatment and during the those over 60 years old (72.6%). Ceftriaxone had a 79.3% of use and follow-up were very positive: aphthous lesions improved with regard third generation cephalosporins had 84.6% of total use. They were the to size, duration and frequency. The percentage of permanent most common treatment indicated. Pneumonia due to pneumococci symptoms-free patients after 2 months of treatment was 59% and was the first diagnosed type of pneumonia (94.3%). The combination 100% at ten months. Three patients who delayed its healing had an of ceftriaxone and azithromycin was the most employed. The most extra 6 months follow-up, without relapse. frequent mistakes in prescriptions were associated with the indication of ceftriaxone, aminoglycosides, ciprofloxacin, metronidazol in The prevailing syphilitic miasm in the family hereditary background pneumococci´s treatment. Azithromycin 1 g per day during 8 days and and in the homeopathic remedies medicated give us an overall view gentamycin 80 mg per day are examples of inadequate doses that this is the miasm that has to be priority treated (RAS is a identified. destructive disease with regard to the oral mucosa). This theory is corroborated in this work by the positive results obtained. Conclusions: Third generation cephalosporins were overused in the treatment of pneumococci pneumonia. The most common mistakes in Conclusions: We consider that in RAS patients, the homeopathic prescription were the use of antimicrobial drugs in the treatment of individual treatment taking into account the miasmatic focus was very microorganisms not included in their bacterial spectrum. Overdoses effective. and sub doses were also diagnosed.
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LATINFARMA 2013 Resúmenes/Abstracts
PFep 027: ANTIBIOTICS CONSUMPTION IN THE ARTEMISA PFep 028: ANTIMICROBIAL RESISTANCE AGAINST Shigella PROVINCE HOSPITALS, 2012 SPP. IN THE PROVINCE OF CAMAGUEY Cabrera Cepero JR, Tenreiro Hernández X, Hernández Pizarro M, Ferrándiz D, Valdovinos N, Barreto G. Sánchez Hernández P, Ortega Salud A, Suárez Martínez Y. Universidad de Camaguey, Cuba. E-mail: [email protected], Drugs Commerce and Delivery Enterprise, BioCubaFarma, Artemisa, Cuba. E- [email protected] mail: [email protected]
Introduction: Antibiotic resistance is the capacity a microorganism Introduction: The Pharmacoepidemiology has been developed in has against antibiotics. Shigellosis is a self-limited disease without Cuba since the 90´s, with the purpose of obtaining a correct use of severe complications. Today, the main problem related to shigellosis is drugs. The antibiotics are situated among the most frequently used treatment. As antimicrobial treatment is recommended for infections, drugs which have carried about a serious global problem of bacterial it favors a decline in the duration and severity of diarrhea. It reduces resistance. the transmission time of the microorganism and the potential complications. Objective: To characterize the antibiotics consumption in the Artemisa Hospitals in 2012. Methodology: A study carried out in the province of Camaguey (2003- 2006) to measure Shigella spp. antimicrobial reaction, showed Methods: Drugs utilization research descriptive, transversal. The resistance to nalidixic acid and other antimicrobials used. information has been taken from hospitals dispensation records. The Consequently, this study continued (2007-2009) to analyze Shigella methodology ATC/DDD and the calculation of DDD x 100 bed/day antibiotic resistance. A retrospective descriptive study, including 293 (ABC calc 3.1 program) were used for data analyses. isolates from the feces of the same number of patients with diarrhea, Results: In the Artemisa Hospitals, the major antibiotics consumption was developed. Duncan multiple comparison test was used to process corresponded to the Cephalosporins with 33.2338 DDD x 100 bed/day; the results, with resistance as the independent variable. Simple followed by Penicillins with 15.3841 and the Aminoglicosides (7.4288). regression was applied to obtain a linear model describing the The Monobactams, Carbapenems and Fosfomycin all together antibiotic-resistance ratio. represented 1.2075. Finally, the Vancomicina consumption was 0.6562. Results: The resistance percentage to different antibiotics was shown, The Ceftriaxone with 12.7134 DDD x 100 bed/day, was the most used with the highest peaks for ampicillin, tetracycline, nalidixic acid, sulfa among to the Cephalosporinics, followed by the Cefuroxime 9.2810 and and streptomycin. The figures analyzed in nalidixic acid resistance Cephazoline 4.5627 (a chosen drug for surgical prophylaxis). The were shocking. Shigella had a remarkable resistance to first-choice consumption of the antibiotics above mentioned in Artemisa Hospitals antibiotics. Several studies showed that ciprofloxacin has some was the following: at the “José Ramón Martínez” (53.3607), “Ciro advantages in the treatment. Thir-generation cephalosporin also kept Redondo” (58.2824), “Ivan Portuondo” (58.3745) and in the very active against Shigella. However, they are generally reserved for “Comandante Pinares” 76.1525. The last one had the major antibiotics severe and systemic infections, or severe cases of shigellosis, as new consumption. resistant strains have appeared. Conclusions: The results indicate that antibiotic resistance is high; hence, surveillance actions must be implemented to detect and control the appearance of new resistant strains, as well as the implementation of new epidemiological typification techniques.
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LATINFARMA 2013 Resúmenes/Abstracts
PFep 029: KNOWLEDGE MANAGEMENT STUDY OF THE DRUG PFep 030: INAPPROPRIATE MEDICATIONS IN OLDER IN NURSING. SERVICE OF RESUSCITATION. GYNECOLO- ADULTS PATIENTS GICAL AND OBSTETRIC HOSPITAL IN GUANABACOA 2011 Ortega IL, Luna Y, Aldana A, Mederos C, Pérez D, Pérez C, Rodríguez L, Montero Vizcaíno Y, Couto Ramos MJ, Vizcaíno Alonso MC, Quiñones Diaz Abner W, Fernández Z. J. Pharmacy Department, Orient University. Santiago of Cuba City, Cuba. E-mail: Hospital Ginecobstétrico de Guanabacoa, La Habana, Cuba. E-mail: [email protected] [email protected]
Introduction: In the world population there has been a progressive Introduction: The period of birth of the newborn is a stage, where increase in the number and proportion of individuals older than 65 they are very vulnerable to changes, in some occasions is imperative in years and approximately 60% of the medicines consumed are intended the use of drugs for stabilization. Objective: To evaluate the degree of for them. Inappropriate prescribing of drugs is a common problem in preparation of the nurse that attends births on the use of drugs. these patients, which contributes to the increased risk of adverse drug reactions and the consequent deterioration of the quality of life. Material and method: A descriptive and retrospective study was Several tools have been developed to detect potentially inappropriate conducted by applying previously validated survey to the nurses who prescribing, being Beers criteria the most used around the world. were working in the center and attended the births of January - December 2011 in the Gynecological and Obstetric Hospital in Material and methods: Was performed a study to determine the Guanabacoa. prevalence of potentially inappropriate prescriptions for patients older than 60 years, developing a prospective observational study through a Universe: consisting of 24 nurses who attended births in the analyzed standard operating procedure, which included patients admitted to the period and the actual reanimation service. geriatric and internal medicine service at a hospital and patients who Sample: Composed of 19 nurses who are working in the center in the received outpatient treatment. Pharmacotherapeutic profile was same period and place. prepared for each patient and identified the inappropriate medications according to Beers’ criteria, 2012. Statistics: Variables were analyzed: related to conditions associated with the management of drugs, as well as medications used in the Results: A sample of 86 patients was included, registering 6.98 service investigated, adverse effects and management thereof. Was prescriptions per patient, detecting 102 inappropriate medications used as a measure of descriptive summary the number and percent of affecting the 72.09% of this sample. Also were found 46 drug which were presented in the tables, for its better understanding and interactions involving these inappropriate medications, 38 of them analysis. (82.60%) were associated with increased risk of adverse drug events and 8 (17.39%) to ineffective therapy. The drugs that were involved to Results: A significant number of nurses does not associate the a greater extent were: nifedipine, digoxin, diphenhydramine and respiratory alterations to the possibility of administration of drugs, as chlordiazepoxide. well as a high percent known drugs used in the service investigated, not the adverse effects that can cause, however the majority dominates Conclusions: Educational interventions are needed to improve the the dose of hardcover. quality of prescribing in elderly patients with polypharmacy and thus increase more life to years and not years to life. Conclusions: There is a lack of significant changes in breathing patterns to the use of drugs and adverse effects of drugs administered in the service of Neonatal Resuscitation that could be given for use in first option of oxygen to the stabilization of this condition and the need to strengthen the ongoing formative training
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LATINFARMA 2013 Resúmenes/Abstracts
PFep 031: DETECTED ERRORS IN MEDICAL PRESCRIPTIONS PFep 032: STUDY ABOUT THE USE OF ANTIMICROBIALS IN IN ST. ANN’S BAY HOSPITAL PHARMACY, JAMAICA CRITICALLY ILL PEDIATRIC PATIENTS WITH LOWER RESPIRATORY INFECTIONS Barroso A, Rico O, Peñate M. Hernández Núñez A, Tasé Martínez MJ, Del Pino Glez D, Pereira Relis Sectorial Municipal de Salud, Pinar del Río, Cuba. E-mail: [email protected] E. Hospital Angel A Aballí, La Habana, Cuba. E-mail: [email protected] Introduction: Pharmacists in all practice settings have been encouraged to provide pharmaceutical care, to identify, prevent and Methodology: We performed a retrospective, descriptive study of the resolve drug-related problems and reduce negative medication use of such indication-prescription medicines, which analyzed 50 outcomes. Pharmaceutical care has been defined as the responsible patients with lower respiratory tract infections admitted to the provision of drug therapy for the purpose of achieving defined Intensive Care Unit AAAballí Maternity Hospital from November 2012 outcomes that improve a patient’s quality of life. to April 2013 with the aim of knowing the antimicrobials used to treat Methodology: A retrospective and descriptive study was done in St. such infections and if their treatments have microbiological support. Ann’s Bay Hospital Jamaica to determine the total of drugs prescribed Results and conclusions: In 85% of patients had begun empiric during the period August – October. Our objectives were: identify the antimicrobial treatment, which may be given by the fact that critically therapeutic categories that were most frequently dispensed, determine ill pediatric patients, in which we could not wait to start a the frequency of medication errors in accordance to age and detect the microbiological treatment, in 15% of antimicrobial therapy was incidence of errors in prescriptions. The population included out- supported by microbiological studies, which correspond to patients patients that came to the pharmacy. The main variables were the from service respiratory hospital itself. The most used antimicrobials number of prescriptions and prescription errors. The prescription were: Cephalosporin 3rd generation by 82%, vancomycin 30%, 12% errors were defined as errors of dosage, dosage strength, duration and Trifamox. In most cases (98%) groups of antimicrobials used to treat others. The source of data came from prescriptions in the hospital these infections coincide with those reported in the literature with the pharmacy. highest levels of recommendations, although 93% were used in broad Results and conclusion: The pharmacy received 9809 patient from spectrum antimicrobials being able to use a narrower, perhaps this is August to October 2007. The doctor prescribed 27872 drugs in this due to the lack of support microbiological increase microbiology period. The pharmacy dispensed 20848 drugs and 7022 were not studies contribute to more rational use of antimicrobials. dispensed due to unavailability. The most frequent dispensed were Cardiovascular (30.3%), Infections (21.5%), CNS (19.1%) and Endocrine (13.6%). The medication errors were more frequent in pediatric patients (41%) than adults (59%). The prescriptions with errors represent a 2.3%. The most frequent medication error was drug overdose (60%). This mistake can increase the side effects of the drugs. This medication error was frequents in pediatric age. The number of errors in the prescriptions was low and statistically not significant. However, this does not make the errors less important, because these errors, though few compromise the health of the patient and may seriously endanger their lives.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S288
LATINFARMA 2013 Resúmenes/Abstracts
PFep 033: STRATEGY FOR THE IMPLEMENTATION OF THE PFep 034: PSYCHOTROPIC MEDICATION CONSUMPTION IN PHARMACEUTICAL CARE IN SANTIAGO OF CUBA PATIENTS BELONGING TO THE FAMILY DOCTOR’S HOSPITALS CONSULTATION #16 FROM “JULIO ANTONIO MELLA” UNIVERSITY POLYCLINIC Reyes I, Bermúdez I, Storpirtis S. Serrano Y, Miranda T, Miranda M. Departamento de Farmacia, Universidad de Oriente, Santiago de Cuba, Cuba. E- mail: [email protected] Universidad Médica Carlos J Finlay, Camagüey, Cuba. E-mail: [email protected]
Introduction: In Cuba, it is not the pharmaceutical professional's social object that works in the hospitals, the practice of Pharmaceutical Introduction: Psychotropic drugs as natural or artificial elements used Care because in spite of existing an approach to the conception of these therapeutically to modify psychic reactions. functions, the Cuban pharmacists carry out administrative functions mostly, of address, management and dispensation. The need to develop Objective: To characterize the use of psychotropic drugs in patients the practice of Pharmaceutical Care Hospital, adapted to the reality of belonging to the family doctor’s consultation #16 from Julio Antonio the Cuban health system, with a standardized working philosophy, Mella university polyclinic in Camagüey, from February 2012 to systematic and continuous was verified through an assessment January 2013. conducted in hospitals in the province of Santiago de Cuba city, using Material and methods: an observational, descriptive, transversal indicators of structure, process and results, in addition to the study was carried out with a universe of 153 patients. The sample technique of Ishikawa and weighted voting. involved 97 patients after a simple randomized study and according to Methodology: From this diagnosis, it was designed a systems with inclusion and exclusion criteria. Variables such as age, sex, race, systemic approach, which integrated the components identified as educational level, toxic habits, psychotropic drugs used, how and why essential to implement the practice of pharmaceutical care, which also they were used and how the patients had access to these drugs were allowed to guide the design of a Standard Operating Procedure (SOP) included. Descriptive statistical methods were used. Results were for pharmacotherapy follow up . We performed the procedure given presented in tables and graphs. criteria the Third Granada Consensus related to pharmaceutical care. Results: The female sex and the white race prevailed, representing The evaluation was conducted through Delphi methodology and using 78.5% and 60.5% respectively. The 49-58 age group also prevailed. indicators to determinate the efficacy of the procedure in the practice. 55.8% of patients used psychotropic drugs for hypertension. The most Expert’s suggestions (Kendall coefficient 0.8) were considered to widely used psychotropic drug was meprobamate (54.5%). 49% of the improve the procedure. individuals took one of these medications every night. They obtained Results: The application in five hospitals, reached a performance index the medications with illegal sellers. of more than 80 points, in all institutions. The procedure can be used Conclusions: The female sex, the white race and the 49-58 age group as a tool to provide in inpatients a Pharmacotherapy follow up service, prevailed. Most of the individuals who took psychotropic drugs used to due to, the acceptable Kendall index value (expert’s evaluation) and drink coffee. The principal causes for the use of psychotropic drugs efficacy in the practice. The system was implemented in four service were to decrease blood pressure. The most widely used psychotropic hospitals in the province of Santiago de Cuba, using the SOP developed, drug was meprobamate. Many of the patients used these drugs without allowing the activity deployed evenly and with scientific rigor, avoiding medical advice. the spontaneity and voluntariness of actions professionals.
Conclusions: It also found that the effectiveness of the Pharmacotherapy follow up is greater when working with SOP.
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LATINFARMA 2013 Resúmenes/Abstracts
PFep 035: BEHAVIOR OF THE CONSUMPTION OF PFep 036: ANTIMICROBIAL RESISTANCE OF Staphylococcus PARENTERAL ANTIMICROBIAL DRUGS IN “HERMANOS AND GRAMNEGATIVE GERMS IN THE INTENSIVE CARE CORDOVÉ “PEDIATRIC HOSPITAL FROM MARCH TO UNIT. GUANTÁNAMO, 2011 AUGUST, 2012 Cazull I, Romero K, Díaz E, Hernández R, Planche E, Velázquez T. Arceo Naranjo R. Dr. Agostinho Neto Hospital, Guantánamo, Cuba. E-mail: Hospital Pediátrico Provincial “Hermanos Cordové” Manzanillo, Granma, Cuba. E- [email protected] mail: [email protected]
Introduction: Severe sepsis and septic shock are major healthcare Introduction: The economic evaluation in medicine has gained problems, affecting millions of people around the world each year, substantial importance in the last few years as it has allowed making killing one in four, and increasing in incidence. The administration of rational and coherent decisions for more efficient strategies in effective antimicrobials within the first hour of recognition of septic healthcare. At present, antimicrobial drugs are irrationally exploited, shock and severe sepsis without septic shock should be the goal of causing high consumptions within the assistance units. therapy. Staphylococcus and gramnegative germs are the most common pathogens that cause sepsis in hospitalized patients. Methodology: In order to evaluate the behavior of the consumption of antimicrobial drugs of parenteral use in "Hermanos Cordové" Methodology: It was made a correlational, retrospective and Provincial Pediatric Hospital of Manzanillo, it was organized an transverse study with the objective to evaluate the antimicrobial observational descriptive retrospective study in order to evaluate the resistance of staphylococcus and gramnegative germs in the intensive handling of the antimicrobial drugs in each service and the lines more care unit of Dr. Agostinho Neto Hospital in Guantánamo during the broadly exploited in the period from March to August, 2012. The year 2011. The accessible population was 27 patients according to the orders, as well as the medical prescriptions made by each ward were inclusion criteria. It was utilized contingence coefficient and case study used. The totals consumed by every line in each month were multiplied methods. Klebsiella was the most frequent germ in the discharged and by their respective economic prices. In order to process the data, and dead patients, and also in the nosocomial or community sepsis to build the charts and the graphics, Microsoft Excel was used. together with the Enterobacter. The resources of the microbiologic laboratory were insufficient for the purpose of the diagnosis and Results: A high consumption of parenteral antimicrobial drugs was treatment protocol. It was not possible to determinate the resistance evidenced within the hospital, representing over 50% of the total levels of ceftriaxone, and so it was not certificated the empirical expenses for the purchase of medications per month. There are a high progressive resistance of this drugs. number of interventions with antibiotics in the patients admitted. These results are higher than those reported by some authors. The Conclusions: There were very high resistance levels of all isolated most antibiotic-consuming services were Respiratory Disease Service microorganisms for the majority antimicrobials. The resistance in vitro one (Ward E), Pediatric Intensive Care Unit (PICU), Infectious Disease of Escherichia coli was absolute for ceftazidime and Enterobacter for Service one, and Surgery (Ward A), possibly due to the high morbidity cefotaxime. The same occurred with Acinetobacter for meropenem, of these services and the characteristics of the patients admitted in ciprofloxacin and aztreonam. The third part of the culture of them. The most widely used antimicrobials were cephotaxime 1g, staphylococcus resistant to oxacillin was also resistant to vancomicin. ciprofloxacin 200 mg, ceftriaxone 1 g, and amikacin 500 mg. The total Aztreonam, having a restrict use in the hospital, shows high resistance consumption of these medications reached $ 140,821.2 in the period levels for frequent germs in the microbial map. under analysis.
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LATINFARMA 2013 Resúmenes/Abstracts
PFep 037: IMPACT OF POST GRADUATE COURSE IN THE PFep 038: PROFICIENCY OF THE DRUG INFORMATION SELECTION AND MANAGEMENT WITH ANTIMICROBIALS IN SERVICE OF CEDIMED – VC. RESPIRATORY AND URINARY INFECTIONS González N, Bermúdez del Sol A, San Gabino Y., Jaramillo L., Canto M., Fernández D, Acedo G, Quiros M, Cruz N, Valdés Y, Quintana J, Hernández E. Calderón K. Centro de Estudios, Documentación e Información de Medicamentos de Villa Universidad de Ciencias Médicas, Cienfuegos, Cuba. E-mail: Clara, Cuba. E-mail: [email protected] [email protected]
Introduction: The evaluation of the quality and patient satisfaction is Introduction: The antimicrobial constitutes one of the currently one of the points of interest in the evaluation of drug pharmacological groups of more prescription and use in the primary information services as a strategy for continuous improvement of the health care for their evident effectiveness in the treatment and quality of care to users. prevention of multiple infections but exist many studies that show the irrational use of it in this level of attention. The municipality of Palmira Objective: To evaluate the quality of Drug Information Services (MIS) is part of this problem, for this reason we proposed evaluate the of the Center for Documentation and Information on Drugs of Villa impact of a post graduate course about selection and management with Clara (CEDIMED-VC). antimicrobials in respiratory and urinary infections, in the doctors of Methods: A retrospective study from January to December 2012 was this place. conducted. The annual reports of the SIM that collect the total Methodology: We take like sample 20 doctors of the municipality that pharmaceutical inquiries received were analyzed; moreover, indicators represent 52.3% of the total of the universe. The level of knowledge of Structure and Process focused on efficiency and productivity were was diagnosed for the application of a questionnaire of knowledge and evaluated. As a technique for data collection and processing of the the correspondence of the antimicrobials was evaluated for the check results was used Microsoft Excel template. of the prescriptions emitted by the doctors. Everything was carried out Results: With regard to the structure, there is a suitable, easily before and after the realization of the post graduate course. We use accessible office of exclusive use with sufficient capacity for operation. methods of the descriptive statistic to allow the results in table of There is access to medical libraries, both physical and digital places relationship of variables, expressed by number and percent. The through electronic services (INTERNET) and external hotline. differences between both moments it was determine using the Professionals show skills in search, selection and management of statistical package Microstat, the procedure chi-square (χ²) and the information sources, they have experience in publishing and critical difference among proportions for samples of oneself group were analysis of information. Among the indicators related to passive applied. information 311 inquiries were received and the responses were given Results and conclusion: The impact of the course was positive 24-72 hours to 296 consultants, resulting Timely service. 100% of the because after receiving it, among 85-100% of the doctors had an models forms were correctly filled, and written suitable responses acceptable level of knowledge about this topic and among 62.5-86.5% were given in each case. 100% of the queries were answered of the prescription had an excellent correspondence of the satisfactorily, so the service indicator was relevant resoluteness. antimicrobial prescribed with the recommended in the clinical practice Regarding the active information Publications Produced and guidelines established for the management of these pathologies. Opportunity indicators were Adequate and Opportune respectively. Conclusions: Information Service Drug CEDIMED-VC has quality.
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LATINFARMA 2013 Resúmenes/Abstracts
PFep 039: RISK OF ENVIRONMENTAL DAMAGE DUE TO PFep 040: USE OF ACAMPROSATE IN THE TREATMENT OF ANTIBIOTIC RESIDUES IN THE BELICO RIVER AREA IN ALCOHOL DEPENDENCE DISORDER SANTA CLARA, CUBA Galán L, Martínez G, Flores I. Hernández E, Martinez B, Carrazana D, Águila E, Marrero O, Alonso G, Facultad de Ciencias Médicas 10 de octubre, Universidad de Ciencias Médicas de Seijo M, Serrano H, Morales A La Habana, Cuba. E-mail: [email protected] Centro de Estudios, Documentación e Información de Medicamentos de Villa Clara, Cuba. E-mail: [email protected] Introduction: Alcohol dependence is a major public health problem
and the fourth leading cause of disability worldwide. Three drugs are Introduction: In recent years there is growing concern about the approved by the US Food and Drug Administration for treating effects of drug waste in the environment. The objective of this research alcoholism: disulfiram, naltrexone and acamprosate. In our country is was to determine the risk of environmental damage from antibiotic frequent the use of disulfiram in the treatment of alcoholism, it is an residues in an area of a river that runs through a very urbanized area aversive agent, but it has significant adverse effects and compliance of the city of Santa Clara. difficulties with no clear evidence that it increases abstinence rates, decreases relapse rates, or reduces cravings. In contrast, acamprosate, Methodology: In order to achieve the aim of this work the possible an anticraving agent and glutamate antagonist, reduces short-term and residues of antibiotics estimated by means of a consumption study for long-term (more than six months) relapse rates and cravings in a year at a hospital, and concentrations in river water were predicted patients with alcohol dependence when combined with psychosocial using a mathematical model and its ecotoxicological risk was treatments and increases abstinence rates. The relapses are the major determined. problem in the treatment of this disorder and the introduction of Results and conclusion: In the study period 22 antibiotics were used, anticraving drugs is necessary for the treatment of alcoholism and the the ceftriaxone reached the highest consumption and the amphotericin goal of this work was to value the evolution of alcoholism with B reached lowest one. Among the antibiotics used: cefazolin, acamprosate treatment. ceftriaxone, cefuroxime, cefotaxime, cefepime, vancomycin, trifamox, Material and methods: A Drug Use Study was made. It was meropenem and sulfaprim constitute a risk to the environment. There descriptive, observational and retrospective with elements of practical was no inhibition of germination seed Lactuca sativa L. and sulfaprim consequences of use of acamprosate in patient with alcoholism presented the highest inhibition of the root elongation. Ceftazidime and diagnosis. sulfaprim are slightly toxic to Eisenia foetida, due to their LC50 values of 3.33 and 4.99 g/kg, respectively. Cefazolin and cefepime caused the Results: Of 94 patients valued, the 90.9% did not have any relapse, greatest mortality to Physa cubensis (53.33% and 86.66%) at the only 4 patients had relapse. Only 9% had cravings for consume alcohol. concentration of 1000 mg/L (pure product) and the ones that induced One patient had intranquility as adverse effect. The autovaluation of all the lowest mortality were ceftazidime and trifamox with 20% each. In patients was positive after treatment with acamprosate. The evolution the trial of Artemia salina very low mortality was observed and no of 68.8% of patients was excellent. Other studies with acamprosate mortality was shown in Poecilia reticulate no although some changes in have reported similar results. the behavior of these organisms could be observed. That is why the Conclusions: These results demonstrated that the treatment with dumping of antibiotic residues may, therefore, constitute a pollution acamprosate is one of the best choices for prevention of relapse and risk for some species that live in the aquatic ecosystem studied or the reduce craving in alcoholism. like.
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LATINFARMA 2013 Resúmenes/Abstracts
PFep 041: ERECTILE SEXUAL DYSFUNCTION AND RESPONSE PFep 042: SEXUAL DYSFUNCTION IN PATIENTS UNDER TO SILDENAFIL IN HYPERTENSIVE PATIENTS HYPOTENSIVE DRUG THERAPY Brito Ferrer Y, González Caballero Y, Arias Gallardo AI, Armada Armada Esmores Z, Arias Gallardo A, Jiménez Fernández L, Brito Esmore Z, Jiménez Fernández L. Ferrer Y, González Caballero Y, Chala Tandrón JM.
Universidad Médica “Dr. Serafín Ruíz de Zárate Ruíz” Villa Clara, Cuba. E-mail: Universidad Médica “Dr. Serafín Ruíz de Zárate Ruíz”, Villa Clara, Cuba. E-mail: [email protected] [email protected]
Introduction: Sexual dysfunction is currently considered a serious Introduction: Sexual dysfunctions have multifactorial causes. They are quality-of-life-related health problem, more prevalent in hypertensive associated with organic and psychic problems. Organic dysfunctions patients. Several mechanisms have been implicated in the include the use of drugs like antihypertensive drugs. pathogenesis of sexual dysfunction in hypertensive patients, and major determinants include severity and duration of hypertension, age, and Objective: To describe the behavior of sexual dysfunction in patients anti-hypertensive therapy. under hypotensive treatment. Objective: To determine the influence of anti-hypertensive drugs in Methods: A descriptive pharmaco epidemiological transverse study erectile dysfunction (DE) and the response to treatment with sildenafil. was achieved .The universe was formed by 285 male patients, taking into consideration the screening results on hypertensive persons. A Material and methods: A cross sectional study was achieved in randomized sample of 100 individuals was collected. This represents a hypertensive patients attending the Sexual dysfunction medical 30% of the whale universe with inclusion criteria. An anonymous consult. Inclusion criteria were age from 20 to 60 years old and they inquiry was also applied after the patients personal consents were should be taking sildenafil. Variables like previous medical history, confirmed socio demographic factors, toxic habits, previous history, antihypertensive therapy, severity of DE (measured by International drug therapy, dysfunction during erection and ejaculation are orgasms Index of Erectile Function IIFE-5), and effectiveness of sildenafil were were used as variables in this study. taken into consideration. Results: A 75% of patients taking hydrochlorothiazide had sexual Results: Diuretics, mainly thiazidic diuretics (hydrochlorothiazide dysfunction. Other drugs didn’t have significant results, the (p<0.01) and β-blockers exerted negative results in etiology and combination of captopril and hydrochlorothiazide showed a 73.18% of severity of erectile function. The number of patient and severity of DE dysfunction in the sample. Lack of orgasm alone was the chief increased after 6 years of antihypertensive treatment. The majority of complaint of 41% of patients. Individuals of 51 to 60 years old had the patients (86%) had a good response to sildenafil. more probabilities to suffer from sexual dysfunctions; divorced, diabetic patients suffering from psychiatric problems also had big Conclusions: Thiazidic diuretics in monotherapy or combined with β- percentages of sexual disorders. blockers influenced sexual activity. The first phosphodiesterase type 5 inhibitor (sildenafil) was effective for treatment of sexual dysfunction Conclusions: The administration of dyazide diuretics in the treatment regardless etiology, severity and anti-hypertensive medication. of hypertension is associated with the presence of sexual dysfunction. A combination of captopril and hydrochlorothiazide increases the risk of suffering from these undesirable effects. Sexual dysfunction in the hypertensive patients under study is manifested in different ways, especially by a combination of orgasmic disorders with erection and ejaculation disorders. Elderly and diabetic persons, psychiatric disorders, consensual marital status and divorce are some contributing factors in the presence of sexual dysfunction smoking habit and alcohol consumption could not be related to these disorders.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S293
LATINFARMA 2013 Resúmenes/Abstracts
PFep 043: FEMALE SEXUAL DYSFUNCTION IN HYPERTENSIVE PFep 044: DRUG USE IN THE ADULT FEMALE POPULATION PATIENTS OF CUBA González Caballero Y, Brito Ferrer Y, Arias Gallardo A I, Perdomo García Milian AJ, Alonso Carbonell L, López Puig P Barber H, Armada Esmore Z. Escuela Nacional de Salud Pública, La Habana, Cuba. E-mail: [email protected] Universidad Médica “Dr. Serafín Ruíz de Zárate Ruíz” Villa Clara, Cuba. E-mail: [email protected] Introduction: The need to adopt a gender approach in addressing health problems is to try to visualize precisely the multiple ways in Introduction: Female sexual dysfunction is more prevalent in which gender constructions iniquity situations occur that affect health. hypertensive patients than normotensive individuals and more This approach to health taking gender differences into perspective, frequent than its male counterpart. It remains largely under- contribute to greater achievements in their field and the design of recognized, and from the other hand, there is scarcity of studies about public health interventions appropriate to satisfy the requirements of this subject in our country. men and women on an equitable. Objective: To describe the Female sexual dysfunction behavior in Objective: To characterize the use of medications in the adult female patients under anti-hypertensive treatment. population of Cuba. Material and methods: A cross sectional study was achieved in two Method: It performs this cross-sectional descriptive study to Family doctors’s attending room, involving female hypertensive characterize the drug consumption from the perspective of gender in patients under pharmacological treatment lasting for at least 3 months. adult females of Cuba in 2007. For the collection of information a A randomized sample of 100 patients aged from 18 to 60 years old was questionnaire was designed "drug consumption", validated by an selected. An anonymous questionnaire to assess sexual behavior was expert panel and a pilot study. Items were fabricated in the form of given to them. Diagnosis of sexual dysfunction was made taking into seven statements that cover the categories that make up the account the answers to the questions and in regard to DSM IV criterion. operational definition considers the use of medications. Previous medical history, lifestyle habits, anti hypertensive therapy and sexual behavior were inquired. Results: More than half of respondents taking drugs, being the retired with the most consuming 88.8%, while the students (33.3%) were the Results: 71% of the studied patients suffered from at least one least. The highest percentage, 66.4%, reports that always keeps drug category of sexual dysfunction. Symptoms began after receiving treatments as it was prescribed by your doctor. antihypertensive treatment. Older antihypertensive drugs (diuretics, β-blockers) exerted negative influence on sexual symptoms, especially Conclusions: Drug use increases with age, low educational levels and hydrochlorothiazide (51.4%). The majority of the patients (69.01%) retired, still use drugs for cardiovascular, anti-inflammatory, analgesic suffered orgasmic disorders and 59.15% of them also complained from and antipyretic, and psychotropic drug groups most consumed by late sexual arousal. The group of psychiatric patients showed Cuban women. significant differences between patients with sexual dysfunctions and patient without sexual disorders.
Conclusions: Thiazide diuretics impaired fully satisfactory sexual activity. Alcohol consumption, cigarette smoking, coffee ingestion were not factors that precipitate the apparition of sexual disturbances.
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LATINFARMA 2013 Resúmenes/Abstracts
PFep 045: CHARACTERIZATION OF SCIENTIFIC PFep 046: CHARACTERIZATION OF ANTIMICROBIAL PUBLICATIONS DRUG CONSUMPTION PRESCRIBING IN THE INSTITUTE OF CARDIOLOGY AND CARDIOVASCULAR SURGERY, 2012 García Milian AJ, Alonso Carbonell L, López Puig P, León Cabrera P. Pavón J, Figueroa A. Escuela Nacional de Salud Pública, La Habana, Cuba. E-mail: [email protected] Universidad de La Habana, Instituto de Farmacia y Alimentos, Cuba. E-mail: [email protected]
Introduction: Scientific journals play an important role in the scientific communication process. Introduction: Antibiotics are one of the most effective drugs that are Objective: To characterize the scientific publications on drug available and may be those who have contributed to the health and consumption in Cuban medical journals indexed in SCIELO in the welfare of the population during the last half century. The data on period January 2000 to December 2012. global patterns of antibiotic use in hospitals have shown that a third of the hospitalized population received antibiotics and this has resulted Methods: A descriptive bibliometric Cuban medical journals indexed in the selection of bacteria resistant to antibiotics administered. The in SCIELO. The choice of units of analysis was performed taking into excessive and uncontrolled use of antibiotics exerts selective pressure account the term drug consumption. Variables were studied number of on bacteria and encourages them to create mechanisms of resistance. articles by year of publication, number of publications by author, The Institute of Cardiology and Cardiovascular Surgery was subjected article distribution by number of authors, institutions conducting to a process of capital repairs for several years and not until 2010 that research, institutional productivity, number of references per returned to service. It is for this reason that does not yet have a policy publication and subject. of current antimicrobials. Therefore in this paper, the characterization Results: Of the period analyzed, 2009-2012 was the highest scientific of antimicrobial prescribing in the hospital during 2012 was made. production, 42.8%. Most of the authors were bystanders 91.7%. Material and methods: To complete the work we reviewed all Institutions that conduct drug consumption were the Centre for prescriptions issued during the month sunder study. Those who had development of pharmacoepidemiology six (28.6%), followed by used prescription of antibiotics and they were legible. A model of data medical schools and Calixto Garcia Enrique Cabrera with 2 (9.5%). collection which included the following variables: antibiotic Magazines and books were reference types that were used most prescribed, dose and indication. frequently. The Journal of Pharmacy 42.8%, with 19.0% of Family Medicine and Medicinal Plants 9.5% were in the most commonly Results: The results showed a high number of prescriptions for identified articles on the subject. The 69.3% of the institutions were antimicrobials, associated with a variety of indications and doses used. classified as small producers. The most frequently prescribed antimicrobials were ceftriaxone, cefazolin, gentamicin and vancomycin. Conclusions: The scientific literature on drug consumption while agreeing with most consumed drug groups is low and is characterized Conclusions: The wide variety of antimicrobials used in the Cuban by authors in articles passers high rate of shared authorship. Institute of Cardiovascular Surgery, and the differences in indications and dosage can be given by the absence of antibiotic policy to date.
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LATINFARMA 2013 Resúmenes/Abstracts
PFep 047: CLIMATIC CHANGE AND MEDICATIONS PFep 048: RESEARCH METHODOLOGY IN HEALTH SYSTEMS AND SERVICES FOR ASSESSING QUALITY OF PRESCRIPTION López Aguilera AF, Furones Mourelle JA Cruz Barrios MA, Bravo Palma PP. DRUG
Facultad de Ciencias Médicas “JulioTrigo López”; La Habana, Cuba. E-mail: Gross Fernandez C, Alvarez Glez R, Pajarin Fdez L, Casas Gross S. [email protected] Universidad de Ciencias Médicas de Santiago de Cuba Avenida de las Américas S/N entre Calle E y Calle I, Santiago de Cuba, Cuba. E-mail: [email protected] The Climatic change will exert great influence on the increase of transmissible diseases as well as chronic non-transmissible ones, but Introduction: The Research in Health Systems and Services is the the exact consequences continue to be uncertain. application of scientific method to the study of the relationships It is not clear yet what the medication consumption will be like in between people and the system for health care since the introduction order to face these problems. On the order hand, it is not clear either of Pharmacoepidemiology in our country. how the disposal of expired medications will affect ecosystems and the Objective: Implement Systems Research Methodology and Health environment in general as well as the effects on bacteria which could Services to evaluate the quality of prescriptions of drugs. become drug resistant. It is an emergency to build up enough knowledge about how health will be affected by the climatic change, Methodology: The methodology proposed by the National School of especially in vulnerable populations characterized by poor Public Health in Cuba for the evaluation of the quality of services environmental, socio-economic conditions. considering its three dimensions: structure, process and outcomes. For each dimension, were elaborated criteria or sub-criteria, indicators, In order to cope with these problems we must strengthen our health and standards or reference values. We considered each sub criteria care system in order to face up the oncoming climatic changes which adequate when the indicator result equaled or exceeded the standard are to consider the greatest threat mankind has crossed. predetermined by the group of experts and Inadequate when the indicator result did not reach the standard. Each criterion was considered adequate when the sum of the appropriate sub-criteria was bigger than 70% and Inadequate when were lower than 70%. To implement this methodology we evaluate the quality of prescription of many drugs frequently utilized shush as nifedipine, propranolol, digoxin, amitriptyline, meprobamate, chlorodiazepoxide Results: The structure was adequate in all assessments during the process. The knowledge of prescribers were inadequate with meprobamate and digoxin, also drug interactions predominated with amitriptyline and the propranololol in at least all of kind of indications. Conclusions: The methodology given to evaluate the quality of prescribing of nifedipine, propranolol, digoxin, amitriptyline, meprobamate, chlorodiazepoxide was effective and allowed to find misconceptions in the prescribing process. Educational intervention has been necessary in order to improve the competence of prescribers and customer satisfaction healthcare.
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LATINFARMA 2013 Resúmenes/Abstracts
PFep 049: EVALUATION OF THE SATISFACTION LEVEL OF PFep 050: STRATEGY OF INTERVENTION FOR THE AD- THE MEMBERS OF THE MAILING LIST FARMEPI-L, 2012- DICTIONS PREVENTION IN AN UNIVERSITY COMMUNITY 2013 Pupo Perera E. López M, Calvo D. Universidad de Oriente, Facultad de Ciencias Naturales, Departamento de Pharmacoepidemiology Department of Public Health Ministry, La Habana, Cuba. Farmacia. E-mail: [email protected] E-mail: [email protected]
This investigation was carried out to design a strategy for the Introduction: The mailing list is a way to disseminate and share prevention of the undue use of substances psychotropic’s in an information, with minimal effort and cost among users. The university community, based on an appropriate work of Sanitary Department of Pharmacoepidemiology MINSAP since 2003 has a Education, keeping in mind the indicators of diagnostic and the carried distribution list called Farmepi-l grows substantially. out intervention, which were carried out in university students belonging to the careers of Right, Telecommunications and Electronics, Objectives: To characterize user’s mailing list, determine the level of Pharmaceutical Sciences, and Sociology, of the University of East in satisfaction and describe the information needs of its members. Santiago from Cuba. The investigation was developed during the Method: We performed an observational, descriptive, cross- understood period of five months of January to May of 2012. For the interpretive approach and qualitative and quantitative. The sample design of the strategy of prevention, they were defined the vision, the consisted of 445 users in the list and the sample by 96 survey objectives and the prospective results. Later on was carried out the respondents, the same group contained 10 questions, 8 closed, atmosphere analysis by means of the study of the field of external multiple choices and 2 open. Was circulated through the list requesting forces and you intern of the population's prevention in question, to voluntarily respond. identify those aspects of the atmosphere that can influence in the achievement of the objectives, for this analysis was carried out a rain or Results: 67.4% of users are medical specialist MGI, followed by storm of ideas firstly with the actors involved in the investigation, it pharmacists. The 40% have a scientific degree. The attention paid was proceeded to the observation and heap of experience for the 37.5% APS, 21% in hospitals, 34.4% work at other levels. The 61.5% identification of the action forces being proceeded starting from the classified items you receive as excellent and 32.3% as very good. There obtained results of the implementation of the intervention developed in were no fair or poor assessments, 86.5% claim to use the information these careers, as well as of the program of sanitary education for personal growth. The 38.5% of users want to receive the elaborated previously, taking like base the obtained initial results of the information sent, 36.5% demand information about drugs and courses 2008 - 2009, 2009 - 2010 and 2011 - 2012. Achieving the therapeutics. They suggest sending small items. design of strategy to prevent the addictions of substances psychotropic’s in this community. Conclusions: The level of satisfaction of users of the list is high and conforms to the type of information received, mostly from APS physicians and hospitals.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S297
LATINFARMA 2013 Resúmenes/Abstracts
PFep 051: IMPACT OF EDUCATION SERVICE TO DIABETIC PFep 052: CHARACTERIZATION OF THE PEPTIC ULCER IN PATIENTS THE HOSPITAL MANUEL FAJARDO IN THE YEAR 2011 Bermúdez I, Reynaldo G, Moreno S, Almuiña Y, Mena L, Robaina R. Tawfiq M, Pacheco F, Peña A, Duro E.
Pharmacy and Food Institute. University of Havana. Ave. 23 no. 21425 214 Y 222 Facultad de Ciencias Médicas Manuel Fajardo. E-mail: La Coronela, La Lisa. Havana CP 13600. Cuba. E-mail: [email protected] [email protected]
Diabetes mellitus constitutes a chronic illness that requires of the Introduction: The peptic ulcer constitutes a problem of health for its continuous care and it affects 350,000 Cubans. An epidemiology study raised incidence and complications. It is between first fatal causes in carried out in Artemisa reported that this illness is suffered by 20 177 Cuba. patients, 3 035 belong to Güira de Melena and they need to improve the knowledge of their illness, the adherence to medication and the Objective: Characterizing the behavior of the peptic ulcer in the metabolic control of this pathology. The educational needs identified Hospital Manuel Fajardo in January and February. 2012. allowed to design the service with 12 activities, 1 for month that Material and Method: It was a descriptive, transverse and contemplated the educational talk, the video debate, the discussion of observational study at Medicine Internal’s living rooms of the Hospital group, narration of anecdotes, the role game, the dramatization, the Fajardo, in the period of January and February 2012 rain of ideas and the delivery of educational materials. The service was implemented in the Main Municipal Pharmacy of this territory in the Universe: 63 patients with diagnosis of peptic ulcer that entered at period of July from the 2011 to June of the 2012 in 52 diabetic patients Medicine Internal’s living room of the Hospital. There wasn´t a sign. (26 received the education: Group A and 26 didn't receive it: Group B). A questionnaire of 20 questions measured the knowledge of the illness. The used variables went: Sex, age, diagnostic method, the ulcer's The adherence to medication was determined applying the location, infection for Helicobacter pylori and presented complications. questionnaire Morisky-Green. As indicators of the metabolic control it Results: 61.90% of the patients studied were coming from masculine was glycemic, cholesterol, triglycerides, corporal mass index (CMI) and sex, and 42.86%, from among 63 and 77 years. 44.44% of the ulcers arterial pressure. We observed a increment of the knowledge on illness were diagnosed by endoscopy, 82.54% were duodenal. 52 patients in 93.3% and the adherence to medications in 84.2% of the sample with were detected with an infection for Helicobacter, there were the offered education. The glycemic levels, triglycerides and cholesterol complications in 30.16% of the patients, 19.05% of that number was showed a tendency to the decrease, with reduction of CMI and an due digestive high bloody. effective control of the arterial pressure, these changes were not observed in the group B. This study demonstrates the positive impact Conclusions: The peptic ulcer is a problem of health that affects more of education service because modified the habits and behaviors of the patients of legal age and masculine sex. For the diagnosis the patients that participated, the metabolic control of its illness and your endoscopy was utilized fundamentally, and this is the recommended satisfaction. method. The duodenal ulcer proved to be more frequent than the gastric. Great part of the patients with peptic ulcer was infected with Helicobacter pylori, and this finding confirms the relation among both factors. The principal complication that turned up was digestive high hemorrhage.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S298
LATINFARMA 2013 Resúmenes/Abstracts
PFep 053: INTERVENTION STRATEGY ABOUT CLOPIDOGREL PFD 001: EFFECT OF METFORMINA ON MICE NOCICEPTION PRESCRIBING IN A CARDIOLOGY SERVICE ACCORDING TO ABDOMINAL CONTORTION TEST AND IMMERSION OF THE TAIL Ramos Hernández L, Ramos Medina J, Gálvez Martí L, Roldan Casas R, Casas Gross S. Salazar Granara A, Pante Medina C, Castañeda B.
Universidad de Ciencias Médica de Santiago de Cuba. Avenida Las Américas S/N Instituto de Investigación, CIMTFAR, FMH-USMP, Perú. E-mail: Santiago de Cuba. Teléfono 654697 E-mail [email protected] [email protected]
Objective: To explore the effect of metformin on mice nociception. Introduction: Ischemic diseases are serious health problem, this joined with the inexperience of use that we have with novel drugs such Material and method: We used 160 albino male mice with average as clopidogrel, motivated us to perform this work will weight of 25 g. we determine the pain threshold with two technics: abdominal contortions (negative control group with distilled water, Objective: To evaluate an intervention strategy to improve the tramadol 10 mg/kg, diclofenac 10 mg/kg and metformin 50, 100, 150, requirements of clopidogrel in the cardiology department of Saturnino 200 y 250 mg/kg), and the test of immersion of the tail (negative Lora Hospital of Santiago de Cuba from August 2011 to March 2012 control group that received distilled water, morphine 10 mg/kg, and Methodology: We conducted a drugs utilization study that according metformin 50, 100, 150, 200 and 250 mg/kg). We applied the ANOVA to their classification corresponds to one intervention, with test of one tail, Tukey and Pearson correlation. prescription – indication and therapeutic regimens elements. The Results: The inhibition of pain in the different groups was: 0%, universe was consisted of 33 doctors; and we choose a sample of 24 of 77.69%, 55.10%, 34.90%, 76.51%, 75.84%, 88.26%, and 92.62% them. The research was conducted in three stages: diagnosis, respectively. The ANOVA test was p<0.05. The Tukey test indicated intervention and evaluation. Was considerate the evaluation of p<0.05 between the control group and metformin group. We found prescribers as a main variable variation of the metformin effect in relation to the doses (r=0.6897 y Results: The evaluation of prescribers showed that before R=0.4756, p<0.0001).The pain threshold with the immersion of the tail intervention assessments were inadequate 54.16%, while 95.83% had test after one hour was: 4.41, 14.85, 7.80, 11.50, 14.27, 8.47, and 10.74 after appropriate assessments. It was seen that predominated correct minutes. The ANOVA test was p<0.05. The correlation test showed a prescriptions and instructions both before and after the intervention. low dependence in relation to the dose (r=0.1051 y R=0.0110, p>0.05). We found a ratio of approximately 5 combination of drug by patients Conclusion: We found analgesic effect of metformin directly related to before and after the intervention, drugs that had risky of associations the doses. with clopidogrel were cimetidine 90.90% and omeprazole 9.09%.
Conclusions: The intervention strategy was effective in improving the prescriptions of clopidogrel to achieve reverse were the difficulty associated with it to clopidogrel with omeprazole and cimetidine.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S299
LATINFARMA 2013 Resúmenes/Abstracts
PFD 002: ANALGESIC ACTIVITY OF Renealmia alpinia ibuprofen, a reference analgesic drug at doses of 75 mg/kg and with a (ROTTB.) MAAS, IN EXPERIMENTAL ANIMALS negative control (vehicle). Díaz Henao GP, Chica Rincón LE, Benjumea D. The manifestations of pain were measured by counting the number of writhes or abdominal constrictions in each animal. The results are Universidad de Antioquía, Colombia expressed for the percentage of pain inhibition. Results: The results show that the extract of R. alpinia, at doses of 300 Introduction: Renealmia alpinia is a vegetal species that has been used mg/kg, has a percentage of pain inhibition than presented ibuprofen by the traditional medicine of Colombia against snake bite; was statistically significant compared to the control group. furthermore as analgesic and febrifuge. Conclusion: These results justify the use of R. alpinia as analgesic agent Methodology: In this study, it was determined the analgesic activity of by the traditional medicine. R. alpinia extract, in experimental animals by a nociception test in which induces 1.1% acetic acid, intraperitoneally. Previously, the animals were treated with the extract of R. alpinia, orally, at doses of 100, 200 and 300 mg/kg. These groups were compared with
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S300
LATINFARMA 2013 Resúmenes/Abstracts
Farmacoeconomía / Pharmacoeconomy
PFEc 001: ECONOMIC EVALUATION OF THE ANTIBIOTICS PFEc 002: ESTABLISHMENT OF QUALITY IMPROVEMENT TREATMENT IN HYSTERECTOMISED PATIENT FOR SYSTEM FOR RECEPTION PROCESS IN THE DRUG UTERINE MIOMA. HOSPITAL "DR. AGOSTINHO NETO", MARKETING AND DISTRIBUTION COMPANY OF HOLGUIN GUANTANAMO Walton CT. Romero K, Cazull I, González L. Empresa Comercializadora y Distribuidora de Medicamentos Holguín
Hospital General Docente “Dr. Agostinho Neto”, Carretera El Salvador. Km 11/2, (EMCOMED), Cuba. E-mail: [email protected], [email protected] Guantánamo, Cuba. E-mail: [email protected]
This work was carried out at the storage areas of the Drug Marketing Introduction: Recently the sanitary sector has shown a growing and Distribution Company of Holguin to know the causes and interest for the economy of health, demonstrating the importance conditions that affect the process of receiving and contributing to granted to the objective interrelation of concepts like health and incorporate non-compliant medications in the inventory. For this economy. The marked increase of the costs of medical technology and purpose were designed measurement instruments validated by a panel the growing pressure to diminish the budgets dedicated to the health of experts using the Delphi method. It was found that the personal from have made necessary to apply the economic evaluation of the storage areas, which are the internal customers of reception staff, was medications, defined as the process of determining the efficiency of a satisfied with the work of receiving, although on an individual basis pharmacological treatment compared with other options, to selecting they were not satisfied with the technical quality of the products that the one that has the most favorable cost/effects relationship. Because were received in the area; technological faults were the ones detected of the irrational use of the medications and the lack adherence of the in larger amounts. It was shown that the reception staff should be performance protocols, it was decided to investigate about the most trained in their area operations for better performance, in turn they efficient clinical alternative among the ones that; to reach sanitary reported several difficulties in working conditions that influence on the desirable objective in the hysterectomized patient with the diagnosis efficiency entry checking. As part of the continuous improvement of of uterine mioma. quality was created an action plan involving several areas to solve nonconformities and were created indicators to measure the Methodology: A retrospective study was carried out at the General effectiveness of the reception process, this became part of the Teaching Hospital "Dr. Agostinho Neto" in Guantanamo from April to continued improvement program to provide excellent service to May 2012 with the objective of carrying out an economic evaluation of customers. the used treatment. The clinical histories of these patients were revised in the gynecology service, the age of each one was determined, type of surgery, used antibiotics and duration of the treatment.
Results and conclusion: 61.64% of the patients was between 41 and 50 years of age; 81.62% of the surgeries was classified as clean- polluted; the most used antibiotics was cephazoline as monotherapy representing 51.28%; 84.62% of the patients received treatment during 2 days; 100% of the prescriptions was inadequate; the global cost for antibiotics concept was of 3242.65% pesos in national currency. If the performance protocols were well applied, it could be obtained save of 728.80 pesos in national currency.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S301
LATINFARMA 2013 Resúmenes/Abstracts
PFEc 003: IBUPROFEN IN THE TREATMENT OF THE PFEc 004: COST-CONSEQUENCES EVALUATION PROPHY- ARTERIAL PERMEABLE DUCTUS, HOSPITAL “RAMON LACTIC ANTIBIOTIC USED IN ONCOLO-GICAL HOSPITAL OF GONZALEZ CORO”, 2010-2012 SANTIAGO DE CUBA Duro E, Peña A, Monteagudo L, Pacheco F. Perrand M, Tamayo V, Osorio Y, López H.
Facultad de Ciencias Médicas Manuel Fajardo, Calle Zapata esquina D, Vedado, La Universidad de Ciencias Médicas Santiago de Cuba, Cuba. E-mail: Habana, Cuba. E-mail: [email protected] [email protected]
Introduction: Prostaglandins I2 and E2 are involved in ductus Methodology: A descriptive - prospective study and a cost- arteriosus patency of Botal. In the case of the Newborn with Arteriosus consequence economic evaluation, was carried out to determine and Ductus Permeable (DAP), inhibitors of prostaglandins synthesis can be evaluate the results of a prophylactic antibiotic used in surgically used, mainly indomethacin and ibuprofen which would avoid the need intervened hospitalized patients at the Oncological Hospital of Santiago for surgical closure of the duct. de Cuba, during the period of February- April of 2012. The sample was made up of 47 patients that complied with the established criteria for Objective: To describe Newborns with DAP treated with Ibuprofen in de investigation, and were characterized according to clinical and the Hospital Ramón González Coro between January 2010 and biosocial variables. December 2012. Results and conclusion: The age range with most impact was from 36 Material and methods: A descriptive, observational and cross- to 50 years being 40.42%, meanwhile females were the most affected sectional study of newborns with Patent Ductus Arteriosus treated with (80.9%).Cervix cancer appears as the main pathology (36.18%). with ibuprofen was made between January 2010 and December 2012. For 59.57% of the patients, the clean surgical option was the most used The data were obtained from the medical records of patients in the and Ceporán (1 g)/metronidazole (0.5 g) was the antibiotic Neonatal Special Care Unit. combination most applied in 36.17 of the patients. Arterial Results: In almost all cases, drug closure was achieved with two or hypertension (48.9%) appeared as the pathological antecedent with fewer doses. It was only necessary to use a third dose in one patient more incidences in the sample. The most frequent hospital infections due to a reopening on the fourth day after the second dose was and the responsible germs were determined. The wound infections delivered. prevailed with 8 patients (66.66%), the results of the antibiotic therapy was measured by the % of sepsis avoided (68.42%). Of the Conclusions: In all the infants studied, drug closure was achieved with germs cultivated E. coli prevailed with 25%. Medication cost was the use of ibuprofen, most of them with the administration of two or $1980.02; meanwhile the total cost was $ 3145.59. The mean cost of fewer doses, presenting a minimum number of complications due to medicine for each patient was $ 66.92. this treatment.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S302
LATINFARMA 2013 Resúmenes/Abstracts
PFEc 005: COST EFFECTIVENESS OF TWO STRATEGIES FOR PFEc 006: TRACEABILITY OF PLANNING, ARRIVAL AND ANESTHESIA IN PATIENTS WITH TUMOR SURGERY AT THE DISTRIBUTION OF REAGENTS. CUBA 2013 INSTITUTE OF NEUROLOGY AND NEUROSURGERY IN Garriga Rodríguez Y. HAVANA Ministerio de Salud Pública (MINSAP), La Habana, Cuba. Turro Fuentes M, García Fariñas A.
Escuela Nacional de Salud Pública (ENSAP), Ministerio de Salud Pública (MINSAP), La Habana, Cuba. E-mail: [email protected] Introduction: Cuba has a total of 750 laboratories, divided in clinical chemistry, microbiology, and blood banks. During April and May of the
present year, the planning of diagnostic means for the period covering Objective: To assess which strategy is more efficient for anesthesia of from January 2014 to February 2015 was carried out. This planning is patients with cranial tumor surgery. developed in an upward way and all the labs of the health care units, the heads of national and provincial groups of related programs, as Method: Study cost effectiveness of two alternatives for anesthesia: well as national and provincial departments of medicine analysis and Combined and TIVA. Perspective: NHS. Time horizon: stay in the planning are involved. surgical suite. Each patient was evaluated at the end of surgery regarding anesthesia in B, R and M on the basis of Post-Operative Objectives: Identify the critical points in the process of planning of Complications related to anesthesia and extubation place. For each reagents. alternative we calculated the percentage of patients evaluated in B. We Method: A transversal descriptive observational study was carried out considered only the direct costs of drugs used for premedication, using the results of the surveys taken in the departments of analysis induction and maintenance of anesthesia. Were used official prices for and planning of the whole country. 6 units of national subordination Cuban hospitals? were chosen due to their role in shaping the planning in the period Results: TIVA was used to anesthetize patients and Balanced 41 to 89. from February to April 2013. No patient was evaluated M. The 73% (30 patients) treated with TIVA The survey explored variables like the type of profession and the were scored B while those treated with Balanced only 42% had this working experience of the employees in charge of this task, as well as rating (37pacientes). The total cost for option TIVA was 5484.20 pesos the level of training and their links with other responsibilities. DS (17,10) and the Balanced was 11403.66 pesos DS (16,76). The cost effectiveness of TIVA was 74.95 pesos while balanced had a value of Results: The survey was answered by the 100% of those surveyed. 274.30 pesos per grade B patients after surgery. Critical points of the planning process were identified and will be used to carry out a research to improve the quality of the process. Conclusions: TIVA was the dominant alternative because it had more effect and less cost, is recommended as anesthetic strategy for patients Conclusions: A far-reaching and long lasting research should be with cranial tumor surgery. developed.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S303
LATINFARMA 2013 Resúmenes/Abstracts
Farmacovigilancia / Pharmacovigilance
PFV 001: PATIENTS KNOWLEDGE, ATTITUDES AND PFV 002: PHARMACOVIGILANCE IN CHILDREN. CAMAGUEY, PRACTICES ABOUT REMAINING DRUG DISPOSAL, AN CUBA ECOPHARMACOVIGILANCE APPROACH. BOGOTÁ 2013 Bárzaga Z, Choonara I, Fernández E. Quijano D, Holguín E, Orozco J. Hospital Pediátrico Eduardo Agramonte Piña. Camaguey, Cuba. E-mail: Universidad Nacional de Colombia, Bogotá, Colombia. E-mail: [email protected] [email protected]
Introduction: Adverse drug reactions (ADRs) are a significant Introduction: Drugs reach ecosystems by excretion, inappropriate problem in children throughout the world. Systematic reviews have disposal and others ways. Inadequate practices, like disposing offdrugs shown that almost one in ten children in hospital will experience an like Ordinary Waste (OW), are an understudied problematic; fish ADR. ADRs in children attending outpatients are less frequent (1-2%). feminization by hormones and vulture’s death by diclofenac have been Although many ADRs are mild, a small number are severe and observed. unfortunately some are fatal. Cuba is an active participant in the WHO Programme for International Drug Monitoring. Camagüey Province has There is no information about drug disposal and environmental effects a particular interest in children who experience ADRs. in Colombia; however, a Drugs Return Plan (DRP) exists with “Puntos Azules” to deposit them. This study’s objective is to describe Aim: Our aim was to describe the adverse drug reactions (ADRs) knowledge, attitudes and practices about remaining drugs (RD) and detected following increased education about pharmacovigilance and expired drugs (ED) disposal. drug toxicity in children in Camagüey Province, Cuba. Methods: Over a period of 24 months (January 2009 to December 2010), all reports of Material and method: Descriptive observational study. Pilot test suspected ADRs in children to the Provincial Pharmacovigilance Centre analysis (51 surveys) of a 385 calculated sample. in Camagüey Province were analyzed. ADRs were classified in relation to causality and severity. Results: Participants were 18 to 73 years old, 58.8% (30) claimed they had a total of 48 RD, 74.9% belong to nervous system, cardiovascular Results: There were 533 reports involving suspected ADRs in children system and alimentary tract and metabolism according to Anatomical in the period. Almost one third of the reports received were classified Therapeutic Chemical classification of WHO. as moderate (155.29%) or severe (10.2%). There was one fatality in association with the use of ceftriaxone. Vaccines and antibiotics were 29.4% disposes off RD in OW and 21.6% donate them; 45.1% disposes responsible for most of the ADR reports (392.74%) and for all ten off ED in OW and 13.7% through the drainpipe. severe ADRs. After an intensive educational package, both within the 17.6% of people think RD should be thrown away like OW and 13.7% community and the Children’s Hospital, the number of reports in specialized places.62.7% think ED should be thrown away like OW, increased from 124 in 2008 to 161 in 2009 and 372 in 2010. This was and 9.8% that should be delivered to specialized places. equivalent to a reporting rate of 879 and 2,031 reports per million children per year for 2009 and 2010, respectively. Most think that throwing away drugs is wrong, in the sink 78.4%, toilet 70.6% and OW 58.8%; 43.1% think returning drugs to the pharmacy is Conclusions: The incidence of ADRs in children Camagüey Province, right. Cuba, is greater than previously reported. An educational intervention about pharmacovigilance and drug toxicity in children can improve the 90.2% people don’t know about DRP or “Puntos Azules”; 80.4% don’t reporting of ADRs. know what to do with RD and 94.1% would like information.
80.4% think that throwing away drugs can affect health and, 84.3%, the environment. Conclusions: Most participants dispose off drugs inappropriately; they think it’s wrong and it can damage the environment and health. There’s an interest towards information, which reveals an area of possible work in awareness, information and education, from the perspective of pharmacovigilance, about this subject in benefit of the population- community.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S304
LATINFARMA 2013 Resúmenes/Abstracts
PFV 003: ASSESSMENT OF ADVERSE EVENTS REPORTING. PFV 004: ADVERSE DRUG REACTIONS OF LOW FREQUENCY NATIONAL ONCOLOGY INSTITUTE (INOR). MAY 2011 - OF APPEARANCE IN PREGNANT WOMEN. CUBAN PHARMA- APRIL 2013 COVIGILANCE SYSTEM. 2003 – 2009 Pérez Noya AL, Cuétara Lugo EB, Carnesolta Lazaro D, Rodríguez López L, Furones JA. Duque R. Hospital Dr Angel Arturo Aballí. La Habana, Cuba. E-mail: [email protected] Instituto de Oncología y Radiobiología. La Habana, Cuba. [email protected] Introduction: Cuba reports drugs adverse effects (DAE) to the pharmacovigilance system of the World Health Organization (WHO) Introduction: Antineoplastic chemotherapy is a widespread and since almost 20 years. It has been done many studies in general effective treatment in Oncology; it is often used in combination with population and in specials population groups such as the case of other therapies. Frequently, chemotherapeutic drugs produce pregnant women, which this investigation belong. adverse events which determine clinical conduct. The intervention in Pharmacovigilance performed by the Pharmaco-Therapeutic Material and methods: Our observational, descriptive and transversal Committee, at the Instituto Nacional de Oncología y Radiobiología study was made to distinguish the low frequency of apparition adverse (INOR) in Havana, since 2010, increased the number of reports of effects during pregnancy that were notified to the National adverse events (AE) related to drug´s administration. Current work is Coordinator Pharmacovigilance Unit in 2003 and 2006 to 2009. It was aimed to characterize AE reports since May 2011 to April 2013. based in the spontaneous notification method of suspicion of DAE. The complete reports of the choiced period of time were selected. The Methods: This is a retrospective, observational and descriptive study information was obtained by the national pharmacovigilance database which analyzed the Pharmacovigilance database from INOR. and we apply descriptive statistics. Following parameters were analyzed: number of AE reports; pharmacological group, pharmaceutical drug and scheme of Results: Occasional adverse reactions predominated (37.1%) in treatment associated to the highest number of AE, frequency, comparison to the rare (33.7%) and no described (29.2%). Drugs that causality, severity, type of reaction and most affected system of provoke this DAE more frequently were prenatal tablets (11.2%) (No organs. pregnancy risk categorized), metildopa (6.7%) (B Category), tetanic toxoide (5.6%) (C category) and hierro dextrano (5.6%) (C category), Results: During the analyzed period, 147 probable AE were betametasona (4.5%) (C category), folic acid (4.5%) (A category) and reported; most of them related to antineoplastics. The most reported trofin (4.5%) (A category). The most affected system organs were skin AE were related with the administration of Doxorubicin (27%) and and annexes (21.3%), central nervious system (18.0%), digestive the application of the scheme adryamicin-cyclophosphamide (33%). system (15.7%) and cardiovascular system (14.6%). Moderate DAE Leukopenia was the most reported effect (28.6%) and lympho- predominated (51.7%) and probable (53.9%). hematopoietic the most affected system of organs (63.9%). The majority of the reported AE was of moderate intensity (59.1%); there Conclusions: Relate to the frequency of DAE studied were similar to were classified as possible (82.9%), in relation to causality, and those described in national and international literature. Drugs more frequent (71.4%). reported belong to vitamins and minerals supplements that are use very much for this population group. The most affected organ system Conclusion: The number of AE reports have increased and its quality did not agree with the previous studies in pregnant women of our have substantially ameliorated from May 2011 to present day country. The same occurred with the severity of the DAE. improving Pharmacovigilance system at our Institute.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S305
LATINFARMA 2013 Resúmenes/Abstracts
PFV 005: PHARMACOVIGILANCE WEB SITE ON PRIMARY PFV 006: PREVENTABLE ADVERSE REACTIONS BY THE HEALTH CARE ASSISTANCE CONSUMPTION OF HERBAL MEDICINES. CUBA 2003 - 2010 López M, López S, Méndez JA, Delgado AT, González C, Tejeda Y. Ruiz Salvador K, García Milián AJ, Jiménez López G, Alfonso Orta I, Hernández Pérez B, Morón Rodríguez F. Farmacia Principal de Santo Domingo, Villa Clara, Cuba. E-mail: [email protected] Facultad de Ciencias Médicas General Calixto García, La Habana, Cuba. E-mail: [email protected]
Introduction: The growing interest for drugs safety issues is related to future and progress. Nowadays, together with great benefits that Introduction: The analysis of the preventability of adverse reactions medicine can produce, are also their severe potential injuries to the has revealed that a significant percentage of the harmful effects due to health. For this reason, society is requesting to minimize the risks in errors during the process of using chemical synthetic drugs and therapeutic. On this point, family doctors need to master different natural. aspects related to pharmacovigilance. All information that can be given to family doctors on this issue paves the way for the quality of their Objective: To characterize the preventability of adverse reactions performance. The objective of this work was to design and implement reported by the consumption of herbal medicine in Cuba in the period a Web Site about Pharmacovigilance in Santo Domingo municipality, 2006-2010. Villa Clara. Method: This is an observational, descriptive, retrospective and cross. Method: The Web Site was made in Visual Studio 2005 in the ASP. Net It included the entire report of suspected adverse reactions to herbal 2.0 program language and SQL Server 2000 database manager. medicines produced by the Coordinating Unit National Pharmacovigilance during the period 2003 -2010. Results: It was created a Web Site with different pages for: Pharmacovigilance General Matters; Adverse Drug Reaction (ADR) Results: Of the reports of suspected adverse reactions assessed, 177 Conditional Factors, ADRs Classification, Causality Relationship, were classified as avoidable (19.5%), these occurred more frequently Pharmacological Alerts and Signals; Cuban Pharmacovigilance System with the use of garlic (27.1%) and aloe (23.7%). The 47.5% of the and Pharmacovigilance in Santo Domingo. Information is shown to the preventable reactions occurred in patients from 31 to 60 years and users in a dynamic way. Interaction is guarantee with a registering 37.3% older than 60 years. The most affected body system was the module for ADR data, also with a discussion space, and the Directory of gastrointestinal (40.7%). Most preventable adverse reactions were Research for reporting aspects of interest. It is updated with classified probable (52.5%) and possible (33.3%) according causality bibliographical information of the last 5 years. and minor (72.3%) according to severity. The most frequent cause of preventability was dosing errors (50.8%). Conclusion: The Pharmacovigilance Web Site is a useful tool for health professionals’ performance. Conclusions: This characterization of preventability of adverse reactions caused by herbal medicines is the first nationwide study of this type, allowing analysis includes preventable notifications in the safety profile of herbal medicines.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S306
LATINFARMA 2013 Resúmenes/Abstracts
PFV 007: KNOWLEDGE AND PRACTICES ON PHARMACO- PFV 008: EVALUATION OF THE IMPACT OF VIGILANCE IN DENTISTRY STAFF IMPLEMENTATION OF A DRUG SURVEILANCE SYSTEM IN EMERGENCY SERVICES IN THE QUALITY PHARMACO- Ruiz A, Cruz MA, Furones JA. VIGILANCE SYSTEM. SATURNINO LORA HOSPITAL Policlínico Docente Andrés Ortiz. Guanabacoa. La Habana, Cuba. E-mail: [email protected] Boizant LM, Ramos L, Abreu PM, Farre SM, Pérez CJ. Hospital Provincial Clínico Quirúrgico Docente Saturnino Lora Torres. Santiago de Cuba, Cuba. E-mail: [email protected] Introduction: A voluntary reporting system of adverse drug reactions is fundamental to drug safety surveillance but under-reporting is its major limitation. Among dental practitioners is worse, in Cuba very Introduction: Adverse drug effects are a major cause of hospital few reports are done by these healthcare workers. May be these is admission in many cases increasing the hospitalization and other related with lack of knowledge about pharmacovigilance. representative portion of becoming health expenditures, so we set the objectives: To estimate the incidence of adverse reactions in patients Objective: To identify the level of knowledge and attitude among admitted to the emergency room of our hospital, identify causal dental practitioners in clinical association between drug use and the occurrence of certain disease Method: Descriptive and traverse study. A total of 104 dental states in the population of interest, and evaluate the impact. practitioners working at the dental clinics in Guanabacoa, Havana, Methodology: We conducted a descriptive study on emergency were evaluated with a questionnaire for their knowledge and attitudes department. We interviewed all patients admitted to this service, from to adverse reactions reporting. They were about 70.3% from total April 2012 to May 2013 with: acute bleeding, cardiac arrhythmias, dental workers at the clinic. The questionnaire sought their levels of hypertensive emergency, and fluid and electrolyte imbalance, Stevens - education and training on ADR reporting, years of professional Johnson syndrome. Patients with positive questioning, we filled the experience, knowledge and attitudes to adverse reactions reporting, questionnaire designed for the study. Algorithm was applied (Karsh sources of information about pharmacovigilance. and Lasagna). We filled the ADR reporting model. We calculated the Results: The majority of dental practitioners (65.4%) had more than 5 incidence by dividing the number of patients admitted with diseases years of professional experience; 55.6% of dentist was specialist and caused by drugs among all patients admitted to this service during the only 9.8% was professor, researcher o master degree. They did not study period. We evaluate the impact using quality indicators of Cuban know the concept of drug adverse reaction, although 76% recognized pharmacovigilance system before and after the establishment of the that drugs can cause them; the Cuban official form to report adverse system. reactions was unknown in 94.2% but they recognizes the importance Results: We identified a total of 18 patients with diseases caused by of the pharmacovigilance (92.3%) and if observe a adverse reaction adverse drug reactions. As the incidence rate was 0.75 per 100 inform it (85.6%). They didn't consult correct sources of information patients. The main reason for admission was gastrointestinal bleeding, on adverse reactions (63.5%), they use as mainly source the package followed by arrhythmias of different types and third dehydration, one insert. They had not reported a adverse reactions (90.4%). The patient with Stevens-Johnson syndrome. The quality indicators response of dentist was better than dental technician. improved after implementing the system of pharmacovigilance in Conclusions: It was observed deficient knowledge and practices in emergencies department, through proportion of significant adverse pharmacovigilance on dental practitioners from this community area. reactions since 45.2% in 2011/2012 to 67.3% in 2012/2013 and the This result may have important implications in terms of public health, second one the proportion of low-frequency reactions appearance to if knowledge and practices are viewed as potentially modifiable grew from 31.2% in 2011/212 to 54.8% in the period 2012/2013. factors. Conclusion: We conclude that the implementation of this system in emergency pharmacovigilance improved the quality of our system of pharmacovigilance and allowed detecting a greater number of significant adverse reactions.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S307
LATINFARMA 2013 Resúmenes/Abstracts
PFV 009: A CUBAN NATION-WIDE PHARMACOVIGILANCE PFV 010: ADVERSE DRUG REACTIONS SURVEILLANCE IN A STUDY OF ALLERGEN IMMUNOTHERAPY FOR ASTHMA HOSPITAL LUCÍA IÑIGUEZ. HOLGUÍN 2009 - 2012 USING ALLERGEN VACCINES FROM TROPICAL RELEVANT Rodríguez S, Casas Y, Cruz F. HOUSE-DUST-MITE SPECIES Hospital Clínico Quirúrgico Lucía Iñiguez. Holguín, Cuba. E-mail: Mateo M, Labrada A, Castro RL, Jiménez G, Alfonso I, Reyes MC. [email protected] Centro Nacional de Biopreparados. La Habana, Cuba Introduction: Adverse drugs reactions (ADRs) are causes of hospital Introduction: Efficacy and safety of allergen immunotherapy (AIT) for morbidity and mortality. That's why they must to be search in an asthma, using House Dust Mite (HDM) vaccines has been widely active and permanent way. evaluated in controlled clinical trials. However, relatively few studies Objectives: To describe ADRs report, manifestations, severity, address this problem in routine clinical practice with a large causality, rate and preventability. population sample. The aim of this study was to assess the efficacy and safety of AIT using HDM vaccines by sublingual (SLIT) or subcutaneous Methods: Observational, descriptional Pharmacovigilance´s study route in clinical practice, in Cuba. with the analysis from January 2010 to December 2012 period. Methods: It was a prospective, open, nation-wide, Fase IV, Results: 430 ADRs was reported; this was superior to years before. pharmacovigilance, study of asthmatic patients undergoing AIT with 60% were important according to Cuban Pharmacovigilance National standardized vaccines VALERGEN, BIOCEN, Cuba. The study was System and 84 (19.5%) caused hospitalizations. The most report's carried out in 10 different provinces. Both, adult and infant, asthmatic rate corresponded to open room hospitalization (46.8%) and medical patients were included. Efficacy variables were assessed in 1045 and pharmaceutics professionals were involved. It was reported a patients who completed one year treatment. For adverse reactions, the great number of clinical symptoms (85) such as: skin (48.6%), analysis comprised all included patients totaling 1805. gastrointestinal (16.5%) and general (8.1%) manifestations. Antibiotics, non-steroidal anti-inflammatory drugs, contrast Results: Patients who abandoned the study reached 8.4%. Highly diagnostic agents, peritoneal dialysis solutions, cistostatics and significant improvement (P<0.0001) was reported for all efficacy immunostimulating drugs were the most implicated. Moderate and variables as compared to baseline. In particular, increase of Quality, probable ADRs were predominant but 5.3% were severe and three of decrease of asthma severity by 91.2% and medication intake by 47%, them were mortal. It was identified 24 reactions no described before and increase of symptom-free days by 18.7%. The efficacy was similar and 27 were rare, among these erythema multiforme, toxic epidermal between the two administration routes. Drug consumption was necrolysis and agranulositosis. 44% could be preventable and the significantly (P<0.001) lower in children, particularly by SLIT. The wrong prescription and mistakes in treatment were the principal overall efficacy was similar for the three products. Eighty-seven causes. adverse events were reported, including 60 systemic (Grade I-IV) and 27 local reactions; 4.76% of patients showed adverse events. The Conclusions: Stronger hospital Pharmacovigilance permitted better subcutaneous route predominated in both systemic and local report of ADRs on our professional's duty and to have our own reactions, with a frequency 4 times higher than the sublingual. No reference. The behavior analyses allowed define some areas for future serious systemic events (Grade III-IV) were reported by SLIT. interventions. Conclusions: The efficacy and safety of AIT for asthma, using tropical HDM vaccines was confirmed, in routine clinical practice, with a relatively large and diverse sample of Cuban patients. SLIT showed fewer and less severe adverse reactions. The efficacy of SLIT was similar as compared to subcutaneous route.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S308
LATINFARMA 2013 Resúmenes/Abstracts
PFV 011: PHARMACOVIGILANCE FROM LIORAD PHARMA- PFV 012: BEHAVIOR OF ADVERSE DRUG REACTION CEUTICAL LABORATORY REPORTS AT THE INSTITUTE OF NEUROLOGY AND NEUROSURGERY. 2011 - FIRST QUARTER 2013 Burguet N, Jiménez G. Cordero A. Laboratorios LIORAD. San Agustín La Habana, Cuba. E-mail: [email protected] Instituto de Neurología y Neurocirugía. Plaza de la Revolución, La Habana, Cuba. E-mail: [email protected]
Introduction: Laboratorios Liorad holds a health and medical license for production and commercialization in the line of liquid parenteral Introduction: Adverse drug reactions have important outcomes for and freeze dry products. Information regarding security profile of the individuals as well as for the national health system, and its monitoring products is rendered on a systematic basis. This is a descriptive and allows knowing its behavior in our setting. retrospective study comprising a period of three years on potential adverse reactions received from the National Coordinating Unit of Objectives: To characterize the behavior of adverse drug reaction Pharmacovigilance. reports at the Institute of Neurology and Neurosurgery, during the period 2011- first quarter 2013. Material and methods: Notifications received from and found in the database of the referred pharmacovigilance unit were analyzed and Material and methods: A retrospective observational and descriptive classified into pharmacological group, most notified medication, type, study of 52 adverse drug reaction reports was conducted during the frequency, severity, cause and organs affected. period previously mentioned. With these reports a FarmavigC data base was conformed, which included the variables: age groups Results: Anesthetics rank first with 41 notifications (35%) regarding (children, adults, geriatric), sex, adverse reactions, pharmacologic pharmacological group; the most notified medication was ketamine 50 group, severity of reaction (light, moderate, severe, mortal) and mg (23%) characterized by bronchospasm, tachycardia, hallucination, relation of causality established between the drug and the adverse respiratory depression, allergic reaction, skin rash, erythema, vomits, reaction (definite, probable, possible, conditional, not related). laryngospasms and inspiratory rates; regarding frequency, rare stand out with 42 (35.9%); regarding severity, mild reactions display 70 Results: Data analysis showed that notifications of adverse drug (59.8%), regarding light, serious and life threatening reactions as far as reactions prevailed in female adults. The most frequent were urticaria cause is concerned first come the probable followed by conditional (32.69%), fever (9.61%), and drowsiness, tremor, vomiting (7.69%). (14.5%) and finally possible ones (12%); the most affected organ The drug groups which displayed the greatest reactions were system was the skin. anticonvulsants (30.7%), immunostimulatory drugs (Intacglobin, 25%) and contrast agents (21.15%). Moderate reactions and probable Conclusion: The information obtained in this research work allows us causality predominated. to state that in general the risk-benefit rate of manufactured products in this lab is favorable. Conclusions: The report of adverse drug reactions at the Institute of Neurology and Neurosurgery during the study period has a similar behavior to those reported in the literature taking into account the characteristics of our institution.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S309
LATINFARMA 2013 Resúmenes/Abstracts
PFV 013: QT PROLONGUED SYNDROME IN PFV 014: BEHAVIOR OF ADVERSE REACTIONS AFFECTING OPHTHALMOLOGY THE CENTRAL NERVOUS SYSTEM, NOTIFIED BY THE CUBAN SYSTEM OF DRUG IN 2012 Egaña Arucas M, Otero Alba I, Pérez Pérez M, Montalván Chávez R, Chiang Rodríguez C. Viña Pérez G, Jimenez Lopez G, Calvo Barbado DM, Debesa García F.
Instituto de Oftalmología Ramón Pando Ferrer, La Habana, Cuba. E-mail: Departamento de Farmacoepidemiología. MINSAP, La Habana, Cuba. E-mail: [email protected] [email protected]
Introduction: The Long, acquired QT Syndrome is mainly caused Introduction: Pharmacovigilance Coordinator Unit of the Ministry of because of the use of drugs that prolong ventricular repolarization. Public Health, make an periodical analysis of suspected adverse drug Apart from the antiarrhythmic drugs, this property is shared with the reactions (ADRs) reported in 2012; it was observed that the reactions use of medications of frequent utility in ophthalmology. There are affecting the Central Nervous System (CNS), were among the most numerous no medicational predisposal factors which increase the risk frequent. Given the importance of this system and the implications of of this Syndrome that might be avoided with a correct selection of these reactions to health, it was decided to analize the characteristics patients and an adequate control of the pharmacological therapy of them. Objectives: To determine the presence of Prolonged QT Syndrome in Material and methods: We performed a descriptive, transversal and patients treated with ophthalmological medications retrospective. Research Data were obtained from the database of the Pharmacovigilance Coordinator Unit, for which was evaluated the total Methods: An observational, descriptive study was conducted at the notifications of Cuban pharmacovigilance database in 2012. Adverse OSI “Ramón Pando Ferrer” during the first semester of year 2012, the reactions were classified according to body system affected, choosing sample was obtained from 80 patients that assisted to the Internal to study reactions affecting the CNS. Medicine consultation and had a treatment with ophthalmologic drugs that could cause enlargement of the QT interval, as well as other risk Results: There were 4213 notifications of ADR that affect the CNS, of factors. which the vast majority were classified as moderate, frequent and probable. Among the drug groups most frequently affected this system Outcomes: 55% of the patients were treated with more than one were the antihypertensives, NSAIDs and antibiotics, all widely ophthalmologic drug with the risk to enlarge the QT interval, 75% had consumed in our country, being the captopril, penta vaccine and other other risk factors, mainly being female and having a cardiac drugs more involved. Headache, dizziness and tremors were the most dysfunction for a 60 and a 13.8% respectively. In 12 patients was common reactions. detected a rectified prolonged QT interval. None of them had a case of Torsade de Pointes. Conclusions: With these results we could characterize the behavior of the RAM that affects the CNS, allowing feedback to notify and make Conclusions: The presence of Prolonged QT Syndrome increases when strategies to minimize the health risks of this type of reactions. several ophthalmological medications with this risk are utilized
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S310
LATINFARMA 2013 Resúmenes/Abstracts
PFV 015: USE OF MIDRIATICS IN PEDIATRIC AGE. REPORT PFV 016: CHARACTERIZATION OF THE ADVERSE DRUG OF CASE REACTIONS IN ERNESTO GUEVARA HOSPITAL, 2008 - 2012 Otero Alba I. Gallardo A, Rúa M, Rodríguez L.
Instituto de Oftalmología Ramón Pando Ferrer, La Habana, Cuba. Hospital Ernesto Guevara. Las Tunas, Cuba. E-mail: [email protected]
Introduction: We believe that the use of topical medication in the eye Introduction: Now a day, in the social environment, the medications has no complications and side effects; these can go from cutaneous are the alternative therapeutic more commonly used in public health redness to loss of consciousness and aplastic anemia. There might be system, and it is highly use, is becoming it in an important health side effects in children as long as the systemic absorption is relevant problem. We can't forget the benefits produced by the medications in enough. Children have a high risk of systemic side effects due to the the prevention, healing or diagnosis of a disease but those also have lack of dosage according to weight, in topical medication for the eye adverse effects. and they are especially vulnerable because of the metabolic disorders of the drug, lack of maturity of the haematoencephalic barrier, their Methodology: An observational study of pharmacological surveillance corporal mass index is lower than the one in adults and their optic was carried out using the method of spontaneous report. It consisted in membranes are thinner, which carries an increase of the levels of the the analysis of all the drug reaction adverse suspicions report in medication in plasma. Mydriatics are those medications capable to Ernesto Guevara Hospital during the period January 2008- 2012. The cause a dilatation in pupils. Those are of a frequent use in pediatrics for information was obtained from the database of the institutions. the diagnosis and treatment of ocular diseases, its dosages and cares in Results and conclusion: Regarding the degree of severity, minor administration must be taken in consideration to avoid the appearance reactions represent the 80.7%; the antimicrobial pharmacological of undesirable effects. group 41.3%; regarding causality the probable 53.4% and the most Objective: Review the use of mydriatics in pediatric age. affected organs were the skin 55.5%. In the reports of adverse reactions in the hospital it was found that most of the reactions were Case Presentation: Female patient, 12 years old, with a previous minor. The highest percentage of reports was the antimicrobial background of good health, which after the topical administration of pharmacological group; regarding causality the probable events three drops of 1% ciclopentolate had a sudden loss of consciousness. prevailed and the most affected organs were the skin. After physical examination: drug induced mydriasis, paleness and cold skin. HR: 100 per minute. BP: 110/60. She recovers spontaneously. Complementary exams were negative of any disorder. In Pediatrics consultations we frequently see undesirable effects after the administration of mydriatics; therefore we conducted a revision of the theme.
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LATINFARMA 2013 Resúmenes/Abstracts
PFV 017: ADVERSE REACTIONS RELATED TO CONSUMPTION PFV 018: CHARACTERIZATION OF THE SIDE EFFECTS TO OF CONTRACEPTIVE HORMONE FROM A FAMILY ANTIBIOTICS IN ELDERLY PATIENTS IN A HOSPITAL PLANNING CONSULTATION SERVICE Aguilar M, Olivero M, Reyes I, Zúñiga A, Álvarez H. Echavarría M, García O, Balde M.
Policlínico Docente de Levisa. Mayarí. Holguín, Cuba. E-mail: Instituto de Farmacia y Alimentos (IFAL). La Habana, Cuba. [email protected] [email protected]
Introduction: Elderly patients have more probability of manifestation Introduction: The frequent appearance of undesirable effects that of adverse effects because of factors that differentiate them from other experience women that use hormonal contraceptives, makes necessary population groups, such as, the use of a increased number of drugs and to carry out a systematic pursuit to reach the rational use of these physiological changes related with aging that alter drugs’ medications by the users; the development of this activity starting pharmocokinetic and pharmacodynamic. from the pursuit pharmacotherapeutic is constituted like a robust tool for it. Methods: It is a descriptive and transversal study in the elderly patients with pneumonia diagnosis and treatment antimicrobials at the Objective: The objective of the present study was to detect, to evaluate Calixto García Hospital in 2009-2010, with the objective of determines and to notify the suspicions of adverse reactions to the Hormonal presence of report of adverse effect in a clinic history of this patient. Contraceptives starting from a service of pursuit pharmacotherapeutic. Results: Were evaluated 113 clinics histories and only in a 17 of these, Material and methods: It has been carried out a prospective and were found reported adverse effects. The most frequently effect longitudinal study starting from the service of pursuit adverse found was related with the cephalosporins of second pharmacotherapeutic offered to women users of hormonal generation, the quinolones, and the penicillins represented these contraceptives belonging to the consultation of family planning of the groups for the cefuroxime (29%), the ciprofloxacin (18%) and the polyclinic of Levisa, located in the municipality of Mayarí in Holguín amoxicillin with the 12% of report. The frequent reactions occupied city, in the period among January 2012 to January 2013. For the the major percentage and were report 3 RAM not described in a development of pharmacovigilance activity, the process starts from the National Formulary. The adverse effects more expressed were pharmaceutical tracing, according to a validated standard operating confusion and hypersensitivity reactions. procedure, which facilitated the detection of drug-related problems of the type suspected ADRs, for the prevention and resolution of negative Conclusions: Prudent use of medications and vigilant drug monitoring outcomes associated to medication. are essential to avoid adverse drug reactions. The report of adverse effects provides important data to sanitary system. Results: We bid the service to a total of 21 patients in the period, 55 were detected drug-related Problems of suspected adverse reaction type, 87.7% were detected Defined suspicions. Of the 50 adverse reactions were detected low clinical significance was reached accepted interventions index-resolved reaction suspected 85.6%. All adverse reactions were notified to pharmacy services through the official notification of RAM. Conclusions: The results show that pharmacotherapy monitoring conducted systematically can raise the quality standard of pharmacotherapies prescribed in patients in primary health care, while demonstrating the importance of the pharmacist's clinical work in the team care.
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LATINFARMA 2013 Resúmenes/Abstracts
PFV 019: CHARACTERIZATION OF THE ADVERSE DRUG PFV 020: EPIDEMIOLOGICAL SURVEILLANCE OF DRUGS USE REACTIONS ACCORDING TO THEIR EVITABILITY IN DURING PREGNANCY AND CONGENITAL MALFORMATIONS ELDERLY PATIENTS, GRANMA 2005 - 2012 IN VILLA CLARA Aguilera Aguilera O, Llovet A M, Ramírez Calzadilla Y, Aguilera Herrera Martínez M, Vales Almodóvar M, Fernández Tejera C, Medina O. Martínez Lima MN, Pérez Crispi JM, Noche González G, Noa Machado MD. Dirección Provincial de Salud. Farmacoepidemiología. Granma, Cuba. E-mail: [email protected] Laboratorio de Epidemiología y Genética Clínica. Universidad de Ciencias Médicas. Villa Clara, Cuba. E-mail: [email protected]
Introduction: The population aging is one of the most remarkable changes of modern civilization and its presence determines greater Introduction: The epidemiological surveillance of potentially changes in the design, instrumentation and application of health teratogenic drugs during pregnancy is a task of great importance, policies. One of the main actions to guarantee the health of this which is not free of complexities inherent to the nature of the population group is to identify in a precise way their health situation mechanisms of action, the assurance of the dose and the exposure time and diseases, because aging has been one of the determinant factors to as well as to ethical concerns. increase the prevalence of chronic-degenerative diseases and of course, the increase of medicine consumption, what provokes greater Objective: To contribute to the people's knowledge in relation to the pharmacological interactions and adverse reactions to medicines. potential teratogenic effects of drugs used in early gestation in a sample of pregnant women exposed to these drugs. Objective: To characterize the behavior of adverse reactions to medicines (RAM) in elderly people, reported in Granma province since Methodology: A cohort study was conducted in primary health care 2005 to 2012. taking into account the medical monitoring of gravids and the survey performed about their exposition to these drugs at the beginning of Method: It was performed an observational, descriptive and pregnancy and an assessment of newborns between the second and transverse research of pharmaco-surveillance, applying the fourth month of life in search for congenital malformations and a case- spontaneous method of adverse reactions and the data base of control study taking into account the registration of all malformed pharmaco-surveillance in the province. The universe was represented babies at the neonatal services in this province, with retrospective by 1428 RAM records in 60 year-old patients and older, reported in the investigation of both, case mother/control mother studies, at risk. In province during the period 2005-2012, identifying the both studies the information related to drug exposure, is processed. pharmacological groups and the most related drugs, the classification of adverse reactions according to the severity, the affected organ Results: The cohort study included 355 malformed babies, 230 out of system, the degree of legal responsibility and its preventability. which with major malformations, either in babies born alive, stillborn babies, as interruption products due to genetic causes. We found that Results: The pharmacological group with greater representation was in 9 drugs significant associations between the ingestion and the the antimicrobial one (28.4%), the most frequent drugs were presence of malformations, took place. In the case-control study the aminophillyne, rapilent penicillin and amoxacilline, the moderated overall results and the results for the following groups of specific reactions had the higher percentage as well as the possible reactions, It congenital malformations, were recorded: anencephaly, Down could have been avoided the 54.3% of the studied adverse reactions to Syndrome, reductive defects of members, congenital heart diseases medicines. and cleft lip with or without cleft palate. Conclusion: There was a prevalence of the adverse reactions that can Conclusions: The assessment of the teratogenic risk we found that be avoided in elderly patients due to the use of therapeutic patterns certain drugs, contributes to the provided evidences of other studies and inappropriated indications of medicines. that support the contribution of such drugs together with the genome and the epigenetics in the development of birth defects and it lets a gap to search for primary prevention.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S313
LATINFARMA 2013 Resúmenes/Abstracts
PFV 021: BEHAVIOR OF ADVERSE DRUG REACTIONS PFV 022: CHARACTERIZATION OF THE POLYPHARMACY AT REPORTS AT THE CLINIC DR MARIO MUÑOZ MONROY, THE EMERGENCY ROOM IN THE HOSPITAL MANUEL 2011 FAJARDO, 2011 Sánchez LI, Hernández F F, Pupo NA. Pacheco F, Peña A, Duro E, Kouri A.
Policlínico Docente Dr Mario Muñoz Monroy. Habana del Este, La Habana, Cuba. Facultad de Ciencias Médicas Manuel Fajardo, La Habana, Cuba. E-mail: E-mail: [email protected] [email protected]
Introduction: The adverse reactions to medications are any harmful Introduction: Polypharmacy causes undesirable appearance of Drug effect that happens after the administration from a drug to the normal Interactions, which sometimes cause the death of the sufferer. Having a doses used in the human species, for the prevention, the diagnosis or good knowledge of the subject can significantly reduce their the treatment of an illness or for the modification of some physiologic appearance. function. The Adverse Reactions to Medications constitute a topic forgotten in the current time in which one lives an incessant Objective: To characterize the behavior of polypharmacy in patients production of medications on the part of the industries treated at the emergency room of Comandante Manuel Fajardo pharmaceutical, many times without checking their effectiveness hospital, between January and February, 2011. properly. Material and methods: An epidemiological, cross- sectional and Material and methods: It was carried out a descriptive and traverse descriptive study was made between the months of January and study on the notifications of adverse reactions, in the Area of Health of February 2011 at Comandante Manuel Fajardo Hospital with the Policlínica Dr. Mario Muñoz Monroy, in the period of time located objective to show and assess. 124 patients were interviewed, 87 of between January and December of the 2011. The primary fact was them practiced polypharmacy (70.16%), to wich we applied a obtained of the revision of the municipal statistics. Then it was carried questionnaire prepared reach our objectives. This is an out a survey to a sample of professionals and workers of health of the epidemiological study, a cross-sectional tried to show and assess the center. The investigated variables were: knowledge of the adverse real extent of the practice of polypharmacy and its consequences. reactions; who can report them; if they know or not the existence of a Among the variables used are: Age, Sex and Educational Level. model to make it and that importance confers to these reports. Results and conclusions: We found that more than half of the Results: The Policlínica Dr. Mario Muñoz Monroy ended up occupying respondents practiced polypharmacy patients, detecting the the second place of smaller reports in the municipality, it was also the appearance of potential drug interactions between drugs that were lack of knowledge for the personnel of health of the notification often self-medicated. Females were predominant in the use of multiple possibility from the adverse reactions to medications, as well as of the drugs that can lead to drug interactions, mainly due to self-medication. existence of an official document to carry out these reports, although a The age group with the highest incidence of polypharmacy was high percent of those interviewed recognizes that the topic has a high between 38 and 57 years, mainly middle level of schooling. The most importance. common drug combination was captopril + acetylsalicylic acid. Conclusions: You could verify the subnotification of adverse reactions to medications in the area of health of our center contrasting this with the great population number that they go to their services.
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LATINFARMA 2013 Resúmenes/Abstracts
PFV 023: CONSIDERATIONS ON THE ADVERSE REACTIONS PFV 024: ADVERSE DRUG REACTIONS NOT DESCRIBED IN OF HEBERTRANS® THE CHILDREN. PHARMACO-VIGILANCE SYSTEM. CUBA, 2005-2012 Cruz MA, Furones JA, Broche L. Furones JA, Barbón N, Alfonso I, Jiménez G, Cruz MA, López AF. Escuela Nacional de Salud Pública, ENSAP, La Habana, Cuba. E-mail: [email protected] Escuela Nacional de Salud Pública, ENSAP, La Habana, Cuba. E-mail: [email protected]
Transfer factor is a blood product used in clinical conditions associated with cellular immunodeficiency states such as infectious diseases (viral, Introduction: The main aims pharmacovigilance is to identify adverse bacterial, fungal and parasitic infections), cancer and other diseases; it drug reactions (ADR) were not detected in pre-marketing clinical is a dialyzable leukocyte extract transferring immunity of an immune trials, particularly in high-risk populations such as the children. donor another immune deficient. In Cuba it is registered as a drug and his marketed name is Hebertrans®. The producer is the Center for Objective: To characterize ADR not described in children reported to Genetic Engineering and Biotechnology. For prescription drugs, the Pharmacovigilance system of Cuba from 2005 to 2012. regulatory agency approval process requires evidence of efficacy and Method: Cross-sectional study. The universe was not described ADR, safety for specific clinical situations. The information for this evaluation undesired effect not registered with Cuba Drug Formulary (DF) in gets from results of investigations and reports about safety from patients 15 years and less, in the database of the pharmacovigilance pharmacovigilance centers. This paper reviews available information system. Outcome measures were age, sex, skin color, main RAM, on adverse reactions to this product. We observed that most published imputability, severity, medication, organ system, kind of health researches about Hebertrans® evaluate their effectiveness, not his reporter and source level of the report. Descriptive analysis was adverse reactions. After years in the Cuban pharmaceutical market, the performed information available on the product label says it can cause only erythema at the injection site in 2% of cases. However, we have posted Results: 1102 ADR reported undescribed. Masculine sex information about the safety of transfer factor and the predominated (51.1%) and white skin (73.2%). The more ADR Pharmacovigilance Center of Cuba has several reports of adverse reported were rash (8.6%), vomiting (5.8) and cyanosis (5.3%), which reactions caused by this drug. We can conclude that Hebertrans® affected more the skin as organ system (22.1%). Vaccine pentavalent, causes adverse reactions which are not reflected in the accompanying Heberpenta® (6.7%), dipyrone (5.3%) and sulfate atropine (4.5%) prospectus. The Cuban regulatory agency shall require to the producer were the drugs most associated with undescribed ADR. Conditional for updating the information about safety to ensure rational use. imputability and moderate severity were 75.5% and 59.9%, respectively. The 74.0% of the notifications come from primary health care. The medical professionals (66.2%) were more reported. Conclusions: There is a significant proportion of ADR undescribed in the children, whose main features are similar to ADR already established in Drug Formulary, this does not allow preventing there.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S315
LATINFARMA 2013 Resúmenes/Abstracts
PFV 025: ADVERSE DRUG REACTIONS TO DRUGS IN PFV 026: PHARMACOVIGILANCE STUDY OF HEBERVITAL® CHILDREN OF THE GRANMA PROVINCE. JANUARY 2010 TO TREATMENT TO PREVENT OR CURE NEUTROPENIA. DECEMBER 2012 REPORT OF 250 CYCLES OF TREATMENT Casate ML, Aguilera Aguilera O González T, Verdecia M, Díaz R, Reyes R, Romero GN, Álvarez NP, Echevarría J, Laguna L, Cruz F, Arranz JC, Santiesteban E, Almaguer JA, Departamento Farmacoepidemiología, Granma, Cuba. E-mail: Cedré T, Gil D, Fleites R, Rodríguez Y, Martínez L, López C, Vergara B, [email protected] Ramos I, Arce MA, Núñez R, Carnot J, Muñío JE, Cortés VH, Rich V, Monest AK, López JA, Núñez O, Ramos D, Hernández R, León R, Martínez J, Ortiz E, Bush L, Caballero I, Rivas L, Aguilera I, Águila A, Introduction: The important morbi-mortality caused by adverse Infante E, García I, Álvarez L, García E, Currás T, López P. reactions to medication (ARM) during the last years worldwide has been recognized. Children constitute a risk population. The prevalence Center for Genetic Engineering and Biotechnology, La Habana, Cuba. of this “new disease” in children is scarcely known. It can be assured that children are "orphan of proof". Systematic revisions have evidenced that at least one out of ten children in hospitals have Introduction: Hebervital® is a liquid injection. Each 1 mL vial contains experienced an ARM, with less frequency on those assisted in 0.30 mg Granulocyte Colony Stimulating Factor (G-CSF). ambulatory services (1.2%). Methods: A multicenter prospective pharmacovigilance study was Objective: To identify the adverse reactions to medications informed conducted. Efficacy and adverse events data were reported in a in children less than 18 years at Granma Province from January 2010 designed form for each treatment cycle. to December 2012. Results: Were received 250 reports corresponding with 175 patients Method: An observational, descriptive and transversal study of Drugs treated with Hebervital® to prevent or cure neutropenia. Their age alertness was made, using the spontaneous notification of adverse ranged from 1 to 87 years, and the main patients diagnosis were reactions to medication during January 2010 to December 2012. lymphoproliferative disease or solid tumors (92.1%). The table shows the essential efficacy results. Results: 2098 adverse reactions to medications were detected, 32.49% out of the total of the notifications. 19.0% were considered avoidable. The vaccines were the pharmacological group most Before After P (Wilcoxon) associated to notifications (52.7%). Minor adverse reactions predominated (57.2%), 72.5% of the ARM were classified as probable. White Blood Cell 3.89 3.00 9.12 6.29 N=244 P=0.000 (Leukocytes) (x109xL) Conclusion: The male sex and children under one year old predominated. The most common adverse reaction was fever, and Absolute Neutrophils Count 1.83 2.25 6.29 6.26 N=222 P=0.000 9 vaccines the most reported pharmacological group, with prevalence of (x10 xL) level, frequent and probable ARM. Only 42.5% of patients had adverse events. Burning at site of administration (64 reports) and leukocytosis (23 reports) were the most frequent. Conclusion: Hebervital® has been proven to be both safe and effective.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S316
LATINFARMA 2013 Resúmenes/Abstracts
PFV 027: BEHAVIOR OF ADVERSE DRUG REACTIONS IN PFV 028: TERAZOSIN: AN OPTION FOR THE BENIGN INTERNAL MEDICINE SERVICE FOR 6 MONTHS PROSTATIC HYPERPLASIA IN HYPERTENSIVE PATIENTS Salgado Rodríguez CA, Cabeza Alfonso DM, López Ruíz LG. Acosta C, Mullings R, Camero F, De la Rosa A.
Hospital General Docente “Comandante Pinares”, San Cristobal. Circunvalación Revista 16 de Abril, La Habana, Cuba. E-mail: [email protected] Autopista, reparto “Noel Camaño”, San Cristobal, Pinar del Río, Cuba. E-mail: [email protected] Benign prostatic hyperplasia is characterized to have a high prevalence in advanced ages. The treatment of these entities is varied and the Introduction: A study of all patients admitted at the Internal Medicine selection of the drugs is adjusted in each patient's dependence. The Service of Comandante Pinares General Hospital was carried out from antagonistic alfa-1 adrenergic is an election group and inside these is October 1, 2004 to March 31, 2005, which ascended to a total of 1554 the terazosin. Was carried out a revision of 11 bibliographies with the patients. objective of describing the action mechanism and some Methodology: A sample of 18 patients that showed adverse reactions pharmacological parameters of this drug. Terazosin is an alpha to medications (ARM) within that period of time was extracted. Our blockers of second generation, specific for the alpha-1 adrenergic general objective for the study was to analyze the behavior of this receptor and with smaller activity at level of the alpha-2 adrenergic aspect during that time and specifically to analyze the influence of age, receptor. Also, it blocks the alpha-1 postsinaptic receptors of the sex and race on this problem. It was also determined the severity of the vascular flat muscle producing a decrease of the arterial tension for adverse reactions and the pharmacological medication groups what you/they are of election like antihypertensive in patient with implicated. benign prostatic hyperplasia. Their main adverse effects are drowsiness, orthostatic hypotension, syncope. Results and conclusion: The highest number of ARM occurred in the age group of 61 and above. The average age of the cases studied was 54. The predominant race was the white race with 12 cases, which represents the 66.66% against only 6 cases of black patients, representing the 33.33%. As for the severity of adverse reactions, the mild reactions were predominant, with 8 cases, representing 44.44%. The most frequent cases of ARM were hyper sensibility, idiosyncrasy and side effects. In relation to pharmacological groups, the most implicated groups were antibiotics (8), bronchodilators (3) and prokinetics (2).
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S317
LATINFARMA 2013 Resúmenes/Abstracts
PFV 029: ENDOTHELIN: ITS ROLE IN HYPERTENSION PFV 030: BEHAVIOR OF ADVERSE DRUG REACTIONS MORE Acosta C, Mullings R, Reyes A, Rodríguez R. COMMON IN THE COMMUNITY HEALTH AREAS. Revista 16 de Abril, La Habana, Cuba. E-mail: [email protected] TUMEREMO. VENEZUELA. JANUARY TO OCTOBER 2012 Diaz MA1. Veranes I.2
1 Hypertension is one of the problems more important of the Centro de Diagnóstico Integral “General Domingo Sifontes” República Bolivariana de Venezuela. contemporary medicine. The little clarification of the pathogenesis, in 2Facultad de Enfermería: “Lidia Doce”. MINSAP Nivel Central, La Habana, Cuba. E- the case of the essential hypertension, conditions the failure of the mail: [email protected] therapeutic applied. The theory of the endothelial dysfunction and the list of the endothelin promise to give a good explanation on the pathogenic mechanisms. In the making of the work one investigated in Introduction: In order to make proper use of medicines, Cuba 12 bibliographies with the objective of describing the properties and develops the strategy of Pharmacoepidemiology and Pharmaco- mechanisms of action of the endothelin in the arterial hypertension. vigilance. Research related to the consumption of drugs and adverse The scarce carried out experimental rehearsals although they have not reactions in Tumeremo´s population attending to Mission Barrio provided a clear trial about the therapeutic possibilities, they offer new Adentro I and II, which provide evidence for implementation and perspectives for antihypertensive future therapies. evaluation.
Objective: To characterize the behavior of adverse drug reactions more common in the population to be treated by the Cuban medical mission in Community Health Area of Tumeremo in the period from January to October 2012. Methods: The research use analysis of documents, historical-logical and synthesis. This is a descriptive study from January to October 2012. The source of information was collected by the ASIC statistics and reporting of suspected adverse drug reaction. Results: Could not compare results because there is no history of previous studies in the area, taking this work as a starting point in Tumeremo´s population. The report to antimicrobials was predominated: Quinolones (Ciprofloxacin) and Penicillin (Amoxicillin). Adverse reactions that most affected was skin rash, vomiting, epigastric pain, pruritus; all classified as mild in consider severity of the ADR. Matches with other research which is the female sex which contributes to adverse reactions and is also the route of administration oral the most affected. Conclusions: This characterization of drug suggests the need to design a program to promote the rational use of drugs. A way to identified in practices of consumption validates the ability of people to report adverse reactions and behavior.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S318
LATINFARMA 2013 Resúmenes/Abstracts
Cronobiofarmacología / Chronobiopharmacology
PCB 001: MELATONIN AND MELATONIN-ANALOGUES PCB 002: VARIABILITY OF LIPIDS AND MODIFIABLE RISK FACTORS IN TYPE 2 DIABETIC PATIENTS WITH ACUTE Rosales Mesa Y, Mosqueda C. MYOCARDIAL INFARCTION Hospital Hermanos Ameijeiras. San Lázaro 701. Centro Habana. La Habana, Cuba. E-mail: [email protected] Valle Rodríguez RA. Hospital Hermanos Ameijeiras. San Lázaro 701. Centro Habana. La Habana, Cuba. E-mail: [email protected] Biological functions are regulated according to time-dependent cycles. Human circadian (24 hours) rhythms such as wake-sleep cycle are determined by the alternation of day and night. The pineal gland Patients with diabetes mellitus are at increased risk for cardiovascular produces the hormone melatonin in a rhythmic manner. Melatonin acts disease. This increased risk in diabetics seems to be mediated in part as an endogenous synchronizer that translates the environmental by the increased prevalence of dyslipidemia characterized by low HDL photoperiodic signal in chemical information for the cells. Exogenous cholesterol, triglycerides and LDL cholesterol increased, and the melatonin can entrain the circadian system and promote sleep. In the longevity of the population. past few years there has been growth in the field of melatonin and melatonin analogues. Melatonin exhibits both hypnotic and Clinical research in the field of chronobiological mechanisms of stroke chronobiotic properties, so it has been used for the treatment of has undergone great development in the last decade. The non-uniform insomnia and circadian rhythms of sleep disorders. As disturbances in distribution, circadian, the start time of the different cardiovascular sleep and circadian rhythms are prominent features of depression, diseases suggests that there are triggers the same time show a similar antidepressant drugs that are also effective in alleviating sleep organization. disturbances can be of better therapeutic value in treating depressive This increased risk in diabetics seems to be mediated by the biological disorders. That is the case of the newly introduced melatonergic variability of lipid metabolism, characterized by low HDL cholesterol, antidepressant agomelatine. Taking advantage of its properties, triglycerides, total cholesterol, LDL cholesterol and VLDLc increased, so melatonin and melatonin analogues, are now available for treatment of have an increased risk for cardiovascular disease. Individuals with type these disorders. 2 diabetes associated with myocardial infarction risk factors (smoking, obesity, alcohol consumption and hypertension) show circadian variability in lipid concentrations.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S319
LATINFARMA 2013 Resúmenes/Abstracts
PCB 003: CHRONOTHERAPY VS. CONVENTIONAL THERAPY In it, we characterize the hurt athletes according to: age, topography of IN TREATMENT OF SPORTS INJURIES ON THE NATIONAL the injuries, position at the field and alignment of the athletes, SOCCER TEAM evaluating the efficiency of the treatment considering the evolution of intensity of pain, qualitative evaluation of his relief and length of León Lobeck A. therapeutics. In the investigation were included 14 athletes, 7 in each group of study, couplets according to the kind of present lesion. The Instituto de Medicina del Deporte. Calle 100 y 10. Boyeros. La Habana. Cuba. E- studied injured athletes were mainly regular customers of the juvenile mail: [email protected] preselection. Their most frequent field positions were midfielders and fore. The present injuries were simple and fundamentally of inferior members. Statistical analysis was accomplished intervening Rangos's Soccer is one of the sports where bigger number of injuries are test with Signo of Wilcoxon itself. Both therapeutic variants proved to reported, due to the fact that is a sports of contact, common injuries be efficient in the relief of pain of the sports injuries, but answer in a occur at knees, ankles, spinal column and muscular zones of inferior brief period is obtained by the Chronomassage Tuiná. Also it evidences extremities, due to rough movements, contacts among the players, being the Chronomassage Tuiná more efficacious for the solving of the raised physical loads without the preparation demanded and because injuries, expressed in younger time of necessary treatment to obtain a of overtraining or use. This work aims at evaluating the efficiency of certificate of discharge, than the conventional therapy. applying the Chronotherapy, the Chronomassage Tuiná versus conventional therapy for sports injuries in the National Soccer Team.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S320
LATINFARMA 2013 Resúmenes/Abstracts
Enseñanza de la Farmacología / Teaching of Pharmacology
PEF 002: DETERMINING THE NEEDS AND PROJECTIONS OF PEF 003: SYSTEM OF PROFESSIONAL CONTINUOUS STUDY TEACHERS’ TRAINING FOR PHARMACOLOGY CONTENTS IN OF THE MEDICINE PROFESSOR FOR THE TEACHING OF MEDICINE STUDIES PHARMACOLOGY Milián Vázquez PM, López Rodríguez del Rey MM, Cisneros Nápoles Y, Milián Vázquez PM, López Rodríguez del Rey MM, Cisnero Nápoles Y, Vázquez Montero L, Martín Álvarez C, González Suárez MA Vázquez Montero L, Martín Álvarez C, Lara Díaz L.
University of Medical Sciences. Cienfuegos, Cuba. E-mail: University of Medical Sciences. Cienfuegos, Cuba. E-mail: [email protected] [email protected]
Introduction: Professional training of teachers is a requirement for an Introduction: One of the insufficiencies that are present in the appropriate treatment of Pharmacology contents in medicine studies. education of the General Practitioner is related to the management of the content of Pharmacology in the career of Medicine and the Objective: To identify training needs and educational components to professors’ preparation for facing up this demand from the different be considered in a professional training proposal that would meet subjects and the curriculum itself has been identified amongst the them. many possible causes that have a bearing on it. Method: The study was conducted during 2006-2007 and involved Material and methods: The research was carried out at the University teachers and administrators from the Faculty of Medical Sciences of of Medical Sciences from Cienfuegos. Theoretical, empirical and Cienfuegos and other universities. The methods used included mathematical methods were used in an articulation with the logic of individuals and groups interviews, surveys, observation, documents the practical-theoretical process allowing then to propose a system of analysis, and group discussion. continuous professional study for the medicine professors for an Results: We highlighted that the potentials of pharmacology are not adequate management of the content of Pharmacology which completely exploited in the formation of Medicine Doctors and that no constitutes the aim of this search. training activities are developed in order to meet this purpose. Results: The elaboration of the conditions to hold the continuous Educational components to be considered in order to develop a professional study resulted of the integration of the theoretical professional training proposal for the treatment of pharmacology conceptions about the continuous study of the university professor and contents in Medicine Studies were determined and the potentials of the the searcher’s self experience in the teaching of Pharmacology. These Universities of Medical Sciences in Cuba as to fulfill this purpose were were assumed as a frame for the design of a preliminary proposal that confirmed. once implemented in the practice allowed to determine the bases and Conclusions: Participatory diagnostic assessment process ensured the structure of the system. The dimensions of the system offer a new identification of needs for teachers’ training as well as the didactic quality to the object of the investigation since it widens the implication components that a professional training proposal requires in the of the characteristics of the professors and their responsibilities in the context of Medical Sciences of Cienfuegos for the treatment of curriculum of the career in order to determine the didactic pharmacology contents. components in each sub system. The internal dynamic of the system is hold as well as the possibilities of its insertion in the medical university’s post grade strategies. The sequential assessment of the process through users and expert’s criteria evidences the validity of this proposal. Conclusions: A theoretical and methodological conception of the medical university professor’s continuous study for the management of Pharmacology in the Medicine career is offered in this search, facilitating the design of the professor’s continuous study centered on the psychological, epistemic, didactic, and investigative preparation of the professor.
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LATINFARMA 2013 Resúmenes/Abstracts
PEF 005: LINKING OF THE CONTENTS OF PHARMACOLOGY II PEF 006: ACTION PLAN FOR PEDAGOGICAL FORMATION OF WITH THE WARD ROUND ACTIVITIES OF THE STUDENTS PHARMACOLOGY RESIDENTS IN MEDICAL STUDIES Ortiz Y, Videaux S, Ramos K, Castillo M, Cisneros J, González JM, López Guerra RL, Huguet Blanco Y, Rodríguez Ezcurdia R, López Martínez H. Castellanos D, Quintana Gómez F. University of Medical Sciences of Granma. Bayamo Branch, Cuba. E-mail: Medical College "Dr. Serafín Ruiz de Zárate Ruiz", Villa Clara, Cuba. E-mail: [email protected] [email protected]
Introduction: Pharmacology syllabus is stated taking into account the Introduction: For many years it has been noted that pharmacological functions the specialist must carry out, such as: Teaching, training is sometimes insufficient and that inadequate and irrational Investigation, Welfare and Administrative. Knowing that this prescription of drugs is a very common problem in clinical settings. An professional is highly devoted to teaching the program present some investigation was carried out to design methodological orientations for inadequacies of how to achieve his formative process as a specialty the linking of the contents of the subject Pharmacology II with the teacher; this work is carried out aimed at designing a plan of actions ward round activities of the students in medical studies at Medical that contribute to the pedagogical formation of Pharmacology College "Dr. Serafín Ruiz of Zárate Ruiz", Villa Clara, Cuba during the residents, supported on the teaching improvement system existing in period 2011-2012. our country. Method: The investigation was developed in two fundamental stages: Methods: A qualitative research (research- action) was done, at the Stage I: Diagnostic. Stage II: Design of methodological orientations to Medical Sciences School in Bayamo from January 2011 to December achieve the linking of the contents with the ward round activities of the 2012. It was used the documents revision to know the study students in the 3rd year medical studies. Theoretical, empiric methods curriculum of the specialty, as well as the postgraduate course and statistical procedures were used. Starting from an intentional normative documents; and Structural Functional Systemic Approach sampling a sample was selected that was constituted by the professors method to elaborate the methodological proposal. of Pharmacology and Internal Medicine of the university and some Polyclinics of Santa Clara. Results: With the use of this action plan already developed, there is a high contribution to the development of the residents´ pedagogical Results: The diagnostic of the difficulties of linking were made off. abilities as well as future specialists of Pharmacology. They were related with the contents of the subject Pharmacology II in the ward round activities such as: the planning of the educational tasks This plan also offers the future graduates of this specialty the and insufficient use of the same ones which facilitate the bond of the necessary tools for their teaching work with the individual, family, subject in the ward round activities. Starting from the specified community and undergraduate education. difficulties a proposal of methodological orientations was designed Conclusions: An action plan to contribute to the pedagogical which is distinguished for its linking with the medical practice that formation of Pharmacology residents was successfully prepared. guarantees a developer teaching learning process.
Conclusion: The designed proposal will allow to the future professional to have the necessary scientific elements to make a rational therapy.
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LATINFARMA 2013 Resúmenes/Abstracts
PEF 007: PROFESSIONAL TRAINING OF PHYSICIANS TO PEF 008: METHODOLOGICAL CONSIDERATIONS REGAR- DEVELOP DRUG UTILIZATION RESEARCH DING THE TEACHING OF PHARMACOLOGY DISCIPLINE TO A MULTICULTURAL GROUP OF STUDENTS IN FACULTY OF Cisneros Nápoles Y, Milián Vázquez PM, Quiros Enríquez M. Ramos Cedeño A. Dueñas Pérez Y. Romero Barrios B. MEDICINE "JULIO TRIGO LOPEZ”
University of Medical Sciences. Cienfuegos, Cuba. E-mail: Tasé Martínez MJ, Del Pino González D, Pereira Relis E, Hernández [email protected] Núñez A. Faculty of Medical Sciences ¨Julio Trigo López, La Habana, Cuba. E-mail: [email protected] Introduction: One of the shortcomings presented by physicians in their professional activity is related to the development of drug use studies. Their preparation is one of the causes, since there are a few There are no theoretical framework or methodological in Cuba on the actions in their professional training. teaching of speaking and Pharmacology where non-talking Spanish Objective: which allowed designing a professional training program converge in teaching groups outnumber local deficiency and for physicians oriented to the development of medical drug use technological resources have forced teachers to resort to traditional studies, which was this research objective. forms of teaching. This paper aims to present the experiences of teachers of Pharmacology in the face for the first time for three Method: The research was conducted at the Faculty of Medical courses, a diverse group of students for non-talking Spanish (students Sciences of Cienfuegos during the 2011-2012 academic year, there from the PR China), with Cuban students, with the aim of responding to were used theoretical, empirical and mathematical methods. It is the following questions designed to achieve student-teacher assumed as a theoretical basis of the research a number of conditions communication and student-student in the teaching-learning process such as reflection of practice, identifying training needs and flexible of this course How to make the subject-specific vocabulary in different configuration of the training. The performed diagnosis allowed to subjects is understood by all students, How to set in group identify the regularities, which taken together with the theory allowed relationships that facilitate seminars and tasks?, how to represent the to design the training program. This was structured on the basis of essential content to be internalized by students?. From the above educational components, which were designed from a systemic questions, is plotted as objective: Design a system of means and perspective. resources such as glossaries of terms, concept maps, that balance the difference in the levels of language learners and at the same time, make Results: This program serves as a reference for the design of different more understandable the subject by offering guidelines and guidance ways of training requiring the preparation of Physicians with this to help students in understanding the topics. This research is a novel objective and offers the possibility of applying this in this Medical experience, the disclosure could serve teachers from other educational University. institutions that address similar problems, in which lies its utility. Conclusions: The assessment of the training program, using expert judgment, demonstrates the validity of the proposal.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S323
LATINFARMA 2013 Resúmenes/Abstracts
PEF 009: VIRTUAL COURSE: PROMOTION OF RATIONAL USE PEF 010: SATISFACTION AND RESULT OF STUDENTS WITH OF ANTIMICROBIAL AGENTS IN PRIMARE HEALTH CARE GENERAL PHARMACOLOGY SUBJECT Pereira E, García J, Tasé M, Del Pino D. Álvarez González R, Ramos Hernández L, Pajarin Fernández L, Casas Gross S, Martínez Novellas Y. Faculty of Medical Sciences ¨Julio Trigo López, La Habana, Cuba. E-mail: [email protected] Universidad de Ciencias Médicas de Santiago de Cuba, Cuba, E-mail: [email protected]
Introduction: Actually, many bacteria capable to produced illness are resistant to one or more antibiotics and therapeutics possibilities have Introduction: Taking into consideration the necessity to assess been diminished. This problem has been caused by inappropriate use systematically the formative process in General Pharmacology of antibiotics and can diminish whit diffusion of adequate information discipline, due modifications in the analytic program, we decided to do about rational prescription of antibiotics in health professional trough this paper considering as objective to evaluate satisfaction and result postgraduate education. A great develop of information and of student in it. communication technologies exist and the Health Virtual University (HVU) with the virtual courses are examples of model to learning in Method: A cross-sectional descriptive study was carried out in the first red, very useful actually. For this reason we realize a proposal of semester of 2012 - 2013 course with medical student of 3er year in virtual course: Rational use of antimicrobial agents in primary health Faculty 1 of Medical Sciences University of Santiago de Cuba. The care, with the purpose to increase knowledge to health professionals in evaluation instruments were designed to be anonymously filled out in this topic, make use of possibilities to win with help of technologies, order to get the information referred to satisfaction, for information the geographic, socials and other barriers because, it´s use don´t need referred to result we use the biannual report of pharmacology the presence of traditional model of education. department. Development: To realize this scientific work we need to review Results: Most of the students valued the teaching educative form as themes as learning in distance education courses and the Learning very good being the workshop class the form with less quality. Relative Management System (MOODLE) as technologic didactic support for to motivation and understanding of the different theme received, the distance courses. Them, we define the methodological basis of virtual positive valuations prevailed. Relative to teaching materials received, course (general aspects, didactic structure and course components in most of the students were completely agreed with the different two dimensions (formative and technologic) and finally design a indicators, but dissatisfactions were present because the textbooks virtual course in correspondence of Rational Use of Drugs Program and were not always available, the proportion textbooks - students was not National Drugs Program referents. This course includes 3 topics: 1:1. Most of the students valuate their professor as good in the Introduction of antimicrobial use, Rational use of antimicrobial agents different aspect considered. The administrative aspects of the process and Ways to diminish the irrational use of antimicrobial agents in were considered as very good and the satisfaction with the evaluations primary health care. was majority. The results of quantitative and qualitative promotion were very good. Conclusions: The distance education courses allow development learning in the student and didactic structure of course over MODDLE Conclusions: The student’s satisfaction with the formative process in platform and the association in two dimensions contributes to General Pharmacology discipline was very good mostly, although improvement this modality of education and guarantee high dissatisfactions were presents with some punctual aspects. Promotion understanding, organization, knowledge independent, motivation, results were also valued as good. adequate interaction and adequate evaluation in students.
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LATINFARMA 2013 Resúmenes/Abstracts
PEF 011: IMPLEMENTATION OF THE CURRICULUM PEF 012: INFLUENCE OF THE COURSE CLINICAL EVALUA- STRATEGIES IN PHARMACOLOGY I AND ITS INFLUENCE ON TION OF HERBAL DRGS IN HEALTH PROFESSIONALS THE TEACHING PROCESS AT THE MEDICAL UNIVERSITY OF Castañedo Z, Canto M, Rodriguez M, Méndez R, Marrero R, Arbolaez M. MATANZAS DURING 2011-2013 Cátedra Multidisciplinaría de Ensayos Clínicos. Universidad de Ciencias Médicas Romero MB, Santos L, Hidalgo M, Rodríguez A, Rodríguez W. “Dr. Serafín Ruiz de Zárate Ruiz” de Villa Clara, Cuba. E-mail: [email protected] Universidad de Ciencias Médicas de Matanzas, Cuba. E-mail: [email protected] The Cuban flora is rich in natural products with a high potential for the
treatment of various diseases. Herbal Drug development involves a In medical undergraduate studies, the discipline of Pharmacology and long process in which conducting preclinical and clinical studies to its subjects include in their programs aspects that support the achieve registration and marketing can be distinguished. The objective implementation of essential actions of the curriculum strategies of this study is to evaluate the influence of a postgraduate course proposed for the improvement of the medical professional training aimed at clinical researchers and specialists in Natural and Traditional process. Of these, the most common one turns out to be Natural and Medicine on the development of herbal medicines. A pretest related to Traditional Medicine. This study shows, with an integrated approach, herbal drugs development was applied to diagnose the needs of the implementation experience that has been developing since the knowledge on this theme. Taking into account the results of the pretest 2011-2012 academic year in the subject Pharmacology I at the Medical a graduate course could be designed given: objectives, contents, University of Matanzas, which has led to the strengthening of the methods, means and evaluation, based on the use combination of methodological work of teachers and the improvement of the teaching- lectures, tutorials, workshops and practical theoretical course. It was learning process. composed of 100 hours of face character which covered 5 subjects, where the teaching process included 6 conferences. A series of 3 practical lessons and a workshop where with evaluative character, designed to develop knowledge and skills to the approval and conduct of clinical trials using medicinal plants, are also part of this course. A posttest was applied after completing the course with the same level of complexity, in which the percentage of correct responses was much higher than that of the pretest. It was shown that professionals who attended the course improved their knowledge on herbal drug development.
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LATINFARMA 2013 Resúmenes/Abstracts
PEF 013: FORMATION OF THERAPEUTICAL COMPETENCE PEF 014: METHODOLOGICAL GUIDELINES PROPOSAL FOR THROUGH THE SUBJECT PHARMACOLOGY ON STUDENTS THE INVOLVEMENT OF DRUGS TOPICS IN THE SUBJECT OF OF PHARMACEUTICAL SERVICES MORPHOPHYSIOLOGY III Hernández D, Pérez E, Favier M, Albear F, Estévez M, Carbonell A. Alfonso Hidalgo A, Arias Gallardo Ana I, Orizondo Crespo C.
Filial de Ciencias Médicas Guantánamo, Cuba. E-mail: Medical School of Villa Clara, Cuba. E-mail: [email protected] [email protected]
An investigation of a qualitative development in the field of linking the The competence formation in the universitary institutions constitute subject to the topic Morphophysiology III drug in the undergraduate now days a very discussed issue by many specialists on that topic, its Medical Course in Villa Clara, in order to design interdisciplinary significance remains in the newly graduated performance taking the methodological orientations in different topics of that subject, this successfull labor which look for responsible acting, ethical and creative study was undertaken to facilitate the adequate preparation of according to the real necessities that demanded the laboral contexts. teachers, in order to establish the relationships that allow linking The work that is presented has as a main goal: to elaborate a scientific assume this issue, taking into account the possibilities of the methodology to contribute to the formation of the therapeutical subject and the need to prepare graduates to scientific treatment in competence through Pharmacology. There were applied empirical communities. During the research process, we identified weaknesses methods as the observation and conquest and theoretical methods as for such a link in the teaching-learning process. Developed three stages analysis and synthesis, induction deduction and the fundamentation of in the research: determining the needs and potential of the subject the proposal as well as the actions to apply the methodology and the Morphophysiology III for linking your content to the theme of the drug, specialist criteria that confirmed the significant of the methodology and as a result of practical significance in the second stage was the design their stages which permitted positive results in the formation of the of guidance methodology for this purpose, grounded in scientific competence elevating the quality of the laboral performances of the principles, to foster adequate preparation of teachers, and thus students from the health Technology on the Pharmaceutical Services contribute to the training of future physicians to address this problem confirming on the observation guide to the labor through the in communities. Finally, the proposal was put to the assessment of professional work training or educative work, the quality of the experts, who considered it very relevant and useful. Recommendations examination notes in the principal and integrated subjects and are offered to teachers and administrators to implement the developed Pharmacology, as well as the cycle exams which confirm this option as methodological guidelines. available to the professional formation of the pharmaceutical services technologist.
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LATINFARMA 2013 Resúmenes/Abstracts
PEF 015: METHODOLOGICAL PROPOSITION FOR THE PEF 016: CONSOLIDATION OF LOGICAL ANALYSIS DEVELOPMENT OF CLINICAL PHARMACIST´S GRADUATE IN PROCEDURES IN PHARMACY STUDENTS BY LEARNING THE HOSPITAL’S PHARMACEUTICAL SERVICES IN PINAR DRUGS MECHANISMS OF ACTION IN PHARMACOLOGY DEL RIO, 2013 SUBJECTS Sanchez R, Ramirez F, Martínez H. Hernández M, González I, León OS.
Universitary Clinical Surgical Hospital Dr. Leon Cuervo Rubio, Pinar del Rio, Cuba. Food and Pharmacy Institute, University of Havana, Cuba. E-mail: E-mail: [email protected] [email protected]
Introduction: In the health’s team, the Clinical pharmacist's function is Introduction: Logical analysis procedures are an intellectual to advise the doctor in various aspects of the Pharmacotherapy such operations series that are required for any content assimilation. They as: The regimens’ establishment of dosification, detection and have distinctive characteristics that make possible their formation in prevention of problems once drugs were related to adverse medicinal teaching process of any subject. The operational sequence logically reactions, information to patients and besides related professionals of defined for the procedure can be generalized for any content. In health. The Scientific problem was based on ¿How contributing to the Pharmaceutical Sciences career, the Pharmacology subjects have Perfection of the Clinical Pharmacist´s in the Pharmaceutical hospitals among their objectives the analysis of drugs mechanisms of action. The services and this makes the need of overcoming possible post gradual. aim of this work was to consolidate logical analysis procedures in pharmacy students in teaching/learning process of drugs mechanisms Material and methods: The used Methods were: Logic historic that of action in pharmacology subjects. corresponding with the data gathered on the theme and Empiric, this one based on the revision of documents. The Investigation comes from Material and methods: In the Pharmacology lessons, we defined the Descriptive, and Retrospective type, and it was made in Pinar del Rio logical procedure concept, and describe this process for the analysis of Medicine School in the period of time of 2013 to 2014 with the drug mechanisms of action. In every topic, we explained the procedure objective of Design a Methodological Proposition. for every case, in order to involve the student, consciously, in its own learning process. For that, we start from basal knowledge, from Result: The Program lasts 260 hours to give Seminaries in a year, with previous subjects, and defined the assimilation order for the specific the mode of Conference and other forms of organization like Practical content, in this case we decomposed a drug mechanism in parts. At the Lessons. The subject matters for the modules are itemized in The end of the every topic, we discussed the result with the students. Pharmaceutical´s Attention to the hospitalized patient in the clinical medication distribution for unitary dose, Nourishing parenteral´s and Results: We applied the method in every topic for Pharmacology intravenous mixtures. subjects (2 semesters). Taking into account the previous subjects contribution to logical procedure formation in students, we surveyed Conclusions: Labour of the pharmacist in the Preparation and students and they declared satisfaction with the method, and were Implementation of aspects explained, advantages and disadvantages, conscious of its use. Pharmacosurveillance, Pharmacoepidemiology, Gerency and Hospitality Organization, ethic and Communication, Chemical Conclusions: In Pharmacology subjects for Pharmaceutical Sciences Pharmaceutical, and Physiopathology applied to the adverse students, is possible to consolidate logical analysis procedures, which Pharmaceutical reactions. The Evaluation System is indicated to are crucial for their future competences. culminate the Graduate.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S327
LATINFARMA 2013 Resúmenes/Abstracts
Medicamentos Genéricos / Generic Drugs
PPG 001: DEVELOPMENT AND VALIDATION OF A HIGH PPG 002: VALIDATION OF A CHROMATOGRAPHIC METHOD PERFORMANCE LIQUID CHROMATOGRAPHY METHOD FOR FOR QUANTITATION OF 50 µg/mL LATANOPROST IN A QUANTIFICATION OF DOCETAXEL FOR INYECTION OF 80 CUBAN EYE DROPS MG/BULB García CM, Montes de Oca Y, Martínez V, González A. Izquierdo A, Gato A, Romero J, García C. Centro de Investigación y Desarrollo de Medicamentos, CIDEM, La Habana, Cuba. Centro de Investigación y Desarrollo de Medicamentos, CIDEM, La Habana, Cuba. E-mail: [email protected] E-mail: [email protected]
Introduction: Latanoprost is indicated to treat high intraocular Objective: To develop and validate an analytical high-performance pressure in patients suffering from ocular hypertension or from open liquid chromatography method applicable to quality control and to angle glaucoma. To develop and to validate a high performance liquid stability study of Docetaxel for injection 80 mg/bulb. chromatography-based analytical method for quality control of 50 µg/mL Latanoprost eye drops. Material and methods: To quantify the active principle in the finished product, separation was carried out through a Lichrosorb RP-18 (5 Material and methods: to quantify the active principle of the final µm) (125 x 4 mm) column chromatography with a detector of variable product, the separation was performed through Altima C-18 wave length to 232 nm, a flow rate of 1.5 mL/min and as mobile phase chromatographic column (10 µm) (250 × 4 mm), with ultraviolet Water: Acetonitrile: Methanol: (300:260:440). The quantification of detection at 205 nm, and a mobile phase made up of acetonitryle- this was carried out front to a reference sample using the external phosphate buffer of pH= 4.5 (650:350). The quantification of the standard method. principle against a reference sample was carried out with the external standard method. Results: The equation of the curve of Docetaxel's regression was Y = 1.96848 X – 9. (r = 0.9987) the percents of recovered was 100.23% Results: the results of the evaluated parameters in the validation of with a coefficient of variation lower than 2%. Were not observed the method were found to be within the set limits. statistically significant differences between the determinations Conclusions: the developed and validated high performance liquid realized in the different days by the different analysts. chromatography-based analytical method for the quality control of 50 Conclusions: The analytical method developed was linear, precise, µg/mL Latanoprost eye drops proved to be specific, linear, exact and specific and accurate in the range of studied concentrations .It can be precise within the range of the studied concentrations; therefore, it established for the quality control and stability study of the finished may be safely and reliably used. product since there were not analytical methods designed for these aims.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S328
LATINFARMA 2013 Resúmenes/Abstracts
PPG 003: ADMINISTRATION AND COST DETERMINATION OF PPG 004: DEVELOPMENT AND VALIDATION OF A HIGH AMANTADINA IN “CIREN” PERFORMANCE LIQUID CHROMATOGRAPHY METHOD FOR QUANTIFICATION OF CYCLOSPORINE IN TABLETS OF 20 Díaz AE, Sarria M, Rodríguez A, Ibáñez A. MG Centro Internacional de Restauración Neurológica (CIREN), La Habana, Cuba Romero J, López M, López O, Salomón S, Blanco O.
Centro de Investigación y Desarrollo de Medicamentos, CIDEM, La Habana, Cuba. Introduction: Nervous systems illness are one of the most frequents in E-mail: [email protected] our country (Cuba) and among them, Parkinson is a problem of health care Objective: To develop and validate an analytical high-performance Aim: To explain cost and used of Amantadina in Neurological liquid chromatography method applicable to quality control and to Restoration Center (CIREN). stability study of tablets of Cyclosporine’s nanoparticles, 20mg. Material and methods: To valuate by retrospective study medication Material and methods: To quantify the active principle in the finished treatment with amantadina in 2010, 2011, 2012 and analysis cost and product, separation was carried out through a Luna RP-18 (5 µm) (125 risk in use it. x 4 mm) column chromatography with a detector of variable wave Results: they were showed an increasing of used of this drug related length to 210 nm, using as mobile phase Acetonitrile: Water: Methanol: with one of the first treatment to beginning of Parkinson and cost was Phosphoric Acid: (600:350:50:0.5) and the quantification of this was light increasing, by other way side effect were moderate and it is not carried out front to a reference sample using the external standard represented an important risk its use. method. Conclusion: Amantadina is drugs used at the beginning of treatment of Results: The equation of the curve of Cyclosporine's regression was Y Parkinson and it has increasing use in CIREN but no affect cost. = 0.227995 X - 0.0166 (r = 0.9986) the percents of recovered was 99.86% with a coefficient of variation lower than 2%. Were not observed statistically significant differences between the determinations realized in the different days by the different analysts. Conclusions: The analytical method developed was linear, precise, specific and accurate in the range of studied concentrations .It can be established for the quality control and stability study of the finished product since there were not analytical methods designed for these aims.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S329
LATINFARMA 2013 Resúmenes/Abstracts
PPG 005: SIMPLIFYING AND STREAMLINING THE PPG 006: EVALUATION IN VITRO ACTIVITY OF VITROFURAL MARKETING AUTHORIZATION PROCESS IN CUBA AGAINST PATHOGENIC STRAINS OF Clarias gariepinus Suárez Y, Fernández M, Sánchez C. Morales Y, Medina R, Pozo M, Hernández M, Casanova M, García M.
Centro para el Control Estatal de la Calidad de los Medicamentos, CECMED, La Centro de Bioactivos Químicos, Villa Clara, Cuba. E-mail: [email protected] Habana, Cuba. E-mail: [email protected]
Stress caused by the intensive culture of fish has been identified as a Through Marketing Application process the drug products are selected source of illness in aquatic organisms. Diseases caused by Gram before they get to the market, and labeling, patient information leaflets negative bacteria like Aeromonas spp. and Pseudomonas aeruginosa are and summary on product characteristics, are verified, reviewed and among the most frequent ones. Antibiotic therapy has been used a way approved in order to assure that the information is true, correct and in of control, but marked bacterial resistance has emerged as a result of agreement with the information available in the dossier. The aim of this the indiscriminate use of antimicrobials; hence making the search for work was to assess the impact of Regulation 14 – 2009 on labeling, new therapeutic alternatives necessary. The objective of the present patient information leaflets and summary on product characteristics on work was to estimate the Minimum Inhibitory Concentration (MIC) of human drug products locally manufactured. Comparison between the Vitrofural, a new antimicrobial product, against bacterial strains of current regulation 14 – 2009 and its previous version considering Aeromonas and Pseudomonas. The test product was obtained in the relevant indicators and also the qualitative and quantitative production facility of the Centro de Bioactivos Químicos (CBQ) in Villa characterization of all approved texts during 2010 – April 2012, were Clara, Cuba. Bacterial strains were isolated from pathological lesions of made. The main changes found were related the structure and content, the freshwater fish Clarias gariepinus. Bacterial identification was for example: new statements for special storage conditions, statements performed by Gram stain technique and conventional biochemistry for 63 excipients with risk of adverse reactions, considering the route methods. The Minimum Inhibitory Concentration was determined by of administration, threshold, and statements to declare on warnings the method of macrodilution in broth (M7-A7) as approved by the and precautions are included, new additional requirements on colour Clinical Laboratory Standard Institute. The concentrations of Vitrofural for imprinted parenteral products were added, the summary product tested were in the range of 2-128 µg/mL. The reference strain characteristics (SmPC) was introduced for information for health Pseudomonas aeruginosa ATCC 27853 was used as quality control. professionals, among others. Since the new regulation was Three isolates of Aeromonas hydrophyla, one of Aeromonas sp. and one implemented 2022 labelings, 276 patient information leaflets and 293 of Pseudomonas aeruginosa were obtained, identified and eventually summary product characteristics were uniformly approved. In tested against Vitrofural. MIC values ≤ 32 µg/mL were obtained, being concluding, the new regulation is considered as a permanent powerful the Pseudomons aeruginosa isolate the most sensitive to the test tool for manufacturers and the Cuban Drug regulatory Authority, and product. In conclusion, Vitrofural showed significant antibacterial provides an effective way to promote rational and safety use of drug activity against isolates from relevant pathogenic species commonly product for all distributors, users and Healthcare providers. affecting Clarias gariepinus.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S330
LATINFARMA 2013 Resúmenes/Abstracts
PPG 007: KINETIC OF RELEASE OF CEFALEXINE, PPG 008: PRECLINICAL SAFETY EVALUATION OF ERYTHRO- CIPROFLOXACINE, CEFTAZIDIME, CEFAZOLINE, CEFTRIA- POIETIN WITH LOW SIALIC ACID CONTENT (NEURO EPO) XONE AND MEROPENEM FROM ACRYLIC BONE CEMENTS Lagarto A, Bueno V, Guerra I, Valdés O, Couret M, López R, Vega Y, López M, Duran I, Brizuela N, Ledea O, Delgado JA, Morejón L. Sánchez JA, Barzaga P, Gabilondo T, Beausoleil I, García L, García JC.
Centro de Biomateriales (BIOMAT), Universidad de La Habana, La Habana, Cuba. Centro de Investigación y Desarrollo de Medicamentos, CIDEM, La Habana, Cuba. E-mail: [email protected] E-mail: [email protected]
Acrylic bone cements are materials usually used to fix the artificial Cerebrovascular diseases are one of the principal causes of death and metallic prosthesis to bone structure in total joint replacements. One of incapacity in Cuba. Recombinant human erythropoietin has been the main problems associated with these orthopedic procedures is the shown neuroprotective properties but present side effects such as an periprosthetic wound infections originated from the adhesion of increased incidence of thrombotic vascular effects due to stimulation of bacteria to the biomaterials surfaces. The implant sepsis is a serious erythropoiesis. Erythropoietin with low sialic acid content (Neuro EPO) problem that conduces to multiple surgical interventions or implant can reach neuroprotective concentration in the brain when failures. For these reasons the use of antibiotic loaded bone cements is administered by intranasal route without erythropoiesis stimulation. today a necessary alternative in order to minimize the septic implant The purpose of the present study was the safety evaluation by collapse. In this work was studied the kinetic of release of different preclinical tests of the nasal formulation of Neuro EPO as previous step antibiotics from acrylic bone cements. Cements formulations were to clinical trials. In vitro evaluation in neural cells shown absent of prepared from methyl methacrylate monomer, N,N-dimethyl-p- cytotoxicity. Nasal irritation and acute toxicity assays did not show toluidine and hydroquinone as a components of liquid phase and poly local and systemic toxic effects. Dose repeated evaluation did not show (methyl metacrylate) beads, benzoyl peroxide, barium sulphate and adverse effects, antibody formation and erythropoiesis stimulation. In different antibiotics as a components to solid phase. Cefalexine, normocythaemic mice model neither observed erythropoiesis ciprofloxacine, ceftazidime, cefazoline, ceftriaxone and meropenem stimulation after intranasal repeated doses of Neuro EPO. These results were added to the cements and the kinetic of release was follow by suggest that Neuro EPO could be offered the same neuroprotection as visible spectrophotometry during 30 days. Calibration curves for EPO, without hematological side effects. The absent of significant toxic spectrophotometric method were constructed by plotting absorbance effects of Neuro EPO support the use of nasal formulation for the vs concentration of each antibiotic solution. For sample preparation treatment of stroke. the liquid and the solid phase of the cements (modified with 1.25 wt.% of each antibiotic) were mixed and poured into molds with 6 mm of diameter and 12 mm of height until setting. To liberate the drugs the samples was soaking in 2.5 mL of water and maintained at 37 ± 0.1°C. During the assay the solution was change and analyzed at suitable intervals. The results indicated that ciprofloxacine shows the fastest release kinetics while cefalexine shows the slowest release kinetics. It was detected a large initial antibiotic burst attributable to dissolution of adsorbed particles or to diffusion of antibiotic particles close to the surface that contributes to prevent the risk of infections in the first hours after surgery.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S331
LATINFARMA 2013 Resúmenes/Abstracts
PPG 009: QUALITY CONTROL AND STABILITY STUDY OF 100 photometry used the spectrophotometer SPECTRONIC GENESYS 2, the mg/mL PARACETAMOL ORAL DROPS ideal wavelength was 245 nm since it matches the maximum absorption rate and there is no interference with the excipients. As to García CM, Montes de Oca Y, Martínez V, Salomón S. the stability study of the drops, the on- shelf life method (temperature below 30°C) was used, and for the accelerated stability analysis (40 ± Centro de Investigación y Desarrollo de Medicamentos, CIDEM, La Habana, Cuba. E-mail: [email protected] 2°C) through high performance liquid chromatography. Results: The results of the evaluated parameters in the validation of the methods for the quality control and the stability study were within Introduction: Paracetamol is an effective analgesic and antipyretic the set limits. The results of the stability study, both accelerated and drug of the non-steroidal anti-inflammatory drug group. Paracetamol on- shelf life and reservoir use showed that the final product met the oral drops are indicated for use in infant population aged up to 5 years quality specifications during the study. to relieve fever, headache, toothache and symptomatic relief of common cold. To validate two analytical methods for the quality Conclusions: The analytical methods based on UV spectrophotometry control and the stability study and to study the stability of 100 mg/mL and high performance liquid chromatography are valid for the quality paracetamol oral drops made in Cuba. control and the stability study of 100 mg/mL paracetamol oral drops, since they are linear, precise, accurate and specific. The physical, Material and methods: For quantification of the active principle in the chemical and microbiological stability of the product was proved for 12 final product in order to study stability, a chromatographic column months at a temperature below 30ºC, packed in 15 mL amber glass equipment called Lichrosorb RP-18 was used for separation (5 µm) reservoirs, 18 mm opening and hydrolytic quality III. The product is (250 x 4 mm), with ultraviolet ray detection at 243 nm and a mobile also stable for 30 days after opening the reservoir. phase made up of distilled water: methanol (3:1) and the quantification of this principle against a reference sample by using the external standard method. For the quality control, the spectro-
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S332
LATINFARMA 2013 Resúmenes/Abstracts
Farmacología Básica / Basic Pharmacology
PFB 001: IMAGE ANALYSIS SYSTEM IN THE DETERMINATION PFB 002: USE OF PHYTOTHERAPY IN DERMATOLOGIC OF THE ACTIVITY ANTIDREPANOCYTIC OF O-VANILLIN IN DISEASES HUMAN ERYTHROCYTES Miranda M, Serrano Y, Miranda T. Alonso-Moreno Y, Alonso-Geli Y, Herold S, Marrero P, Fernández A. “Carlos J. Finlay” Medical University Address: Carretera Central Oeste, Camagüey, Centro de Biofísica Médica, Patricio Lumumba s/n, Universidad de Oriente, Cuba. E-mail: [email protected] Santiago de Cuba, Cuba. E-mail: [email protected], [email protected] Introduction: Phytotherapy is the science devoted to the study of medicinal plants and their derivatives with therapeutic use. Sickle cell is a genetic disease which comprises a group of symptomatic disorders associated with mutation of the beta globin gene. In Cuba, it Objective: To describe the results of applying phytotherapy in affects the 3.1% of the population, with a marked impact on the patients with dermatologic diseases at the Natural and Traditional eastern provinces. The main clinical manifestations of this disease are Medicine Clinic in Manuel Ascunce Domenech University Hospital, based on the shape and physical properties of the SS erythrocyte. In from January to December 2010. the search for globally accepted treatments have been studied a series Material and methods: An observational, descriptive, transversal of aromatic aldehydes with antipolymerizing activity. The goal of this study was carried out with a universe of 421 patients. After a simple investigation is to determine the effect of o-vanillin in the morphology randomized study, the sample involved 298 patients. Variables such as of SS erythrocytes. A blood samples were collected from 7 steady-state age, sex, dermatologic diseases, phytotherapy used and the time of patients with homozygous sickle cell disease and regularly attend in response to treatment were included. Data were computer processed. the haematology service from General Juan Bruno Zayas Hospital, Santiago de Cuba. The SS cells were incubated with o-vanillin, at 1:4 Results: The female sex (169 patients), and patients older than 45 and 1:8 molar ratios for 24 hours under deoxygenated conditions. (119) prevailed, representing 56.71% and 39.93% respectively. Morphologic studies of SS cells were carried out using the sickling test Dermatitis had the highest incidence (125 patients), for 41.59%. and a computer-assisted image analysis system, designed at the Dermatitis showed the highest response to the treatment with Faculty of Mathematics and Computer Science at the University of Maticaria Recutita lotion (112 patients, for 37.58%). Between the Oriente, Santiago of Cuba. The results show that o-vanillin inhibits second and the third weeks of treatment those who presented sickle cell formation. In the quantitative analysis the percentage of red dermatitis responded to treatment. blood cells with normal morphology was highest at 1:4 and 1:8 molar Conclusions: Phytotherapy is a therapeutic method that can be used in ratios in 24 and 28% respectively compared to the control, while the the treatment of dermatologic diseases. percentage of echinocytes and sickle were lowest.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S333
LATINFARMA 2013 Resúmenes/Abstracts
PFB 003: VASCULAR INTEGRITY IN AORTIC SAMPLES PFB 004: ANTI-INFLAMMATORY ACTIVITY AND CHEMO- ISOLATED UNDER AIREATION CONDITIONS INFORMATIC ANALYSIS OF NEW POTENT 2-SUBSTITUTED 1-METHYL-5-NITROINDAZOLINONES Hernández E, Ruz V, Ribalta V , Sueiro M, Pérez-Donato JA, Nieto L. Siverio-Mota D, Andújar I, Marrero-Ponce Y, Giner R, Vicet-Muro, Pharmacy Department, Chemistry and Pharmacy Faculty. Central University of Las Villas, Road to Camajuaní km 5 ½. Santa Clara, Villa Clara, Cuba. E-mail: Cordero-Maldonado M, de Witte PAM, Crawford AD, Sylla-Iyarreta- [email protected] Veitía M, Pérez-Jiménez F, Arán VJ. Unit of Computer-Aided Molecular “Biosilico” Discovery and Bioinformatic Research (CAMD-BIR Unit), Faculty of Chemistry-Pharmacy, Universidad Central Introduction: The objective of this study was to evaluate the possible “Marta Abreu” de Las Villas, Cuba. E-mail: [email protected] damage to vascular samples isolated under air-room (non-carbogen) aeration. Introduction: In the present work, new potent analogs of 2-benzyl-1- Methods: Instruments: A PowerLab 4/30 Advanced Adquisition methyl-5-nitroindazolinone (VA5-13l), were investigated as anti- System from ADInstruments® was use in this study. The single inflammatory. chamber organ bath from UGO Basile® was selected for samples incubation. Material and methods: The anti-inflammatory activity was evaluated on leukocyte migration to the injury zone of larvae test using Danio Aeration method: A Diaphragm type pump (ULVAC DTC-21, KIKO Inc.®) rario (Zebrafish) and TPA-induced ear edema in mice. Pro- coupled to pressurized balloon was used to supply the air room with inflammatory cytokine (TNFα ad IL-6) and nitric oxide production, an adequate carbon filter. together with levels of COX-2 and iNOS on LPS-stimulated RAW 264.7 Animals: Male Wistar rats 250-300 g were used in this study. macrophages were developed. SAR analysis, using the concept of an activity landscape with SARANEA software was realized. Isolated conditions: The aortic rings, cut into 5 mm, were suspended in a 10 ml organ bath filled with Krebs-Henseleit solution (pH = 7.4), kept Results: Among the tested compounds in zebrafish, the products 3, 6, at 37 0C, 2 g basal tension, and continuously aerated with air-room. The 8, 9 and 10 showed the lowest values of relative leukocyte migration at vessel solution was changed every 15 min to prevent metabolites 30 µM (0.14, 0.07, 0.10, 0.13 and 0.07, respectively); lower than the interferences. positive control, indomethacin (0.16). All tested compounds significantly inhibited TPA-induced ear edema, showing a significant Isolated tissue studies: Phenylephrine (1 µM) and KCl (60 mM) were reduction in myeloperoxidase activity (except 4 and 16). In the SAR used for elicited contraction, through voltage and/or receptor- study, it is evident that 5-nitro group of indazole ring plays a relevant operated-calcium-channels (VOCCs and ROCCs) activation (Tom, 2010; role in the anti-inflammatory activity. Furthermore, the change of Rattman, 2009). The reproducible contractions in several successive benzyl group (Bn) by other alkyl moieties reduced modestly the cycles were checked until 9 h of maximal incubation time to register activity. A substituted Bn moiety at N-2 (R) is the best substituent (5- any hypoxia effect on contractile capacity. 10); nevertheless, the compounds with halogen substituents on the Bn showed the best results in vivo, (7, R = 4-FBn and 8, 4-ClBn, Several parameters were determinate for both responses. respectively). All compounds, excluding 16, significantly inhibit the Full functional test: Many drugs, with diverse mechanisms of action production of IL-6 at all doses assayed. Nonetheless, the production of over contractile machinery in vascular smooth muscle cells (VSMCs), TNF-α was significantly inhibited only by chemical 16 at a were used as constrictor or relaxant agents to test the total integrity of concentration of 50 µM. Compound 2 was the best inhibitor of iNOS several regulation pathways in VSMCs under aeration conditions. and COX-2 expression. Data Analysis: The LabChartPro®7.3.3 software was used for real-time Conclusions: The inhibition of cytokine release may be one of the analysis of Data and manage Power Lab 4/30 system. mechanisms responsible of this effect for 2-benzyl derivatives while other 2-alkyl derivatives can also inhibit production of NO. Results: The experiments did not show any integrity loss in aortic Furthermore, this chemical prototype could constitute an important rings samples. The vascular response was strong and reproducible. alternative for the search of new anti-inflammatory drugs. Conclusions: These results suggest the possible use of air room flow as aeration method in aorta isolated experiments for Pharmacology Teaching or research purposes with low economic cost.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S334
LATINFARMA 2013 Resúmenes/Abstracts
PFB 005: LUTETIUM-177 RADIOLABELING OF THE PFB 006: MINIMAL STRUCTURAL CHANGES DETERMINE HUMANIZED MONOCLONAL ANTIBODY hR3 USING MACRO- NICOTINIC AGONIST OR ANTAGONIST ACTIVITY FOR NICO- CYCLIC AND ACYCLIC LIGANDS TINIC ANALOGUES
Leyva R, Beckford DR, Beran M, Kropáček M, Melichar M, Tomeš M, Iturriaga-Vásquez P, Farias-Rabelo N, Faundez-Parraguez M, Lažničková A, Lažniček M, Alonso LM, Hernández I, León M. Gonzalez-Gutierrez JP, Guerra-Díaz N, Bermúdez I, Alzate-Morales J.
Isotope Centre, Havana, Cuba. E-mail: [email protected] Laboratorio de Química Biodinámica, Facultad de Ciencias, Universidad de Chile, Chile. E-mail: [email protected]
Introduction: So far, target specific radiopharmaceuticals supply a unique tool for specific delivery of radionuclides to diseased tissues. Neuronal nicotinic acetylcholine receptors (nAChRs), is a ligand gate Humanized anti- EGFR monoclonal antibody hR3 (Nimotuzumab®, ion channel (LGIC) that have been implicated in nicotine addiction, CIMAB) is being studied in many clinical trials for immunotherapy of reward, cognition, pain disorders and depression. The most important various cancers. The aims of this study were to develop simple, fast therapeutic properties of nicotinic ligands have been associated to an and efficient methods for radiolabeling hR3 conjugates with 177Lu for agonist activity, used as a replacement therapy. In the last decade, radioimmunotherapy and compare acyclic and macrocyclic ligands. alosteric antagonism of classical antidepressant drug has opened a new Preliminary biological evaluation was carried out for every conjugate. class of therapy, a nicotinic antagonism, for smoking cessation and depression. Nicotine has been extensively used as a template for the Material and methods: humanized mAb hR3 was conjugated to synthesis of preferring nAChRs. Here, we used the N-methyl- bifunctional ligands in aqueous media (0.1 M phosphate buffer, pyrrolidine moiety of nicotine to design and synthesize novel nicotinic pH=8.5) for 24 hours at 16C using NHS-DOTA, p-SCN-BN-DOTA, p- derivatives, coupling the pyrrolidine moiety to the aromatic group of SCN-Bn-DTPA and CHX-A’’-DTPA (Macrocyclics, Texas). The conjugates nicotine by introducing ether or ester linked functionality. Different were purified by size-exclusion chromatography on PD-10 desalting meta or para-substituted phenolic or benzoic acid derivatives were column (Amersham Biosciences), analyzed using HPLC. The number of used. Binding experiment was performing in human and nAChR clonal conjugated chelates per mAb was determined using an 111In assay. All cell lines and voltage-clamp experiment was recorder for functional conjugates were labeled with 177Lu (produced by neutron irradiation of assays. Molecular docking was performing in the open and close stage 176 isotopically enriched Lu2O3). Labeling yields and radiochemical of the nAChR model in order to understand the agonist or antagonist purity were determined by ITLC and HPLC with radio/UV detection. activity showed by our compounds. Nicotinic derivatives were less Radioimmunoconjugate integrity was also evaluated by HPLC. potent to inhibit binding of [125I]bungarotoxin to human nAChRs. In the Biodistribution was tested in Wistar male rats. other hand, they fully displace [3H]cytisine to human nAChRs at nanomolar concentration. Functional assays showed that the nicotinic- Results: Humanized monoclonal antibody hR3 conjugated with DOTA ether derivatives compounds behave as agonists at nAChRs, whereas, and DTPA derivatives yielded 4 to 14 chelates per mAb molecule. SE- nicotinic-ester derivatives showed antagonist activity. Meta- HPLC showed that no aggregates or fragments were formed during substitution on the aromatic ring of the compounds produced more conjugation reaction. Under optimum conditions the labeling potent compounds than the para-substitution for nAChR. Docking of efficiencies were 95% and 70% for DOTA and DTPA conjugates, the compounds in homology models for agonist and antagonist respectively. The Biodistribution studies showed that the number of conformation to the binding site at the subunit interfaces of nAChRs chelates per protein molecule modified the in vivo behavior of the mAb suggested that the compounds binding with different binding energies radioimmunoconjugates. to agonist or antagonist conformation. Conclusions: The methods for synthesis of hR3-DOTA/DTPA bioconjugates and their labeling with 177Lu have been successfully developed. DOTA-bioconjugates showed better labeling efficiencies than DTPA conjugates.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S335
LATINFARMA 2013 Resúmenes/Abstracts
PFB 007: EFFICACY OF A 2-IMINOTHIAZOLIDIN-4-ONE PFB 008: ACUTE EFFECTS OF SIBUTRAMINE ON LpQM18 AS ANTI-Trypanosoma cruzi AGENT IN INFECTED ADRENERGIC RESPONSE ON YOUNG RAT VAS DEFERENS MICE Souza BP, Dorsa KK, Silva Junior ED, Jurkiewicz A, Jurkiewicz NH. Leite ACL, Oliveira-Filho GBO, Meira CS, Guimarães ET, Soares MBP, Department of Pharmacology – UNIFESP/EPM Rua Três de Maio, 100, 04044- Moreira DRM. 020, São Paulo, Brazil. E-mail: [email protected] Laboratório de Planejamento em Química Medicinal – LpQM, UFPE, Recife – PE, Introduction: Sibutramine affects the sympathetic neurotransmission Brasil. E-mail: [email protected] in adult rat vas deferens. However, the effects of drug treatment show differences between young and adult animals. Thus, this study evaluated the effects of acute treatment with sibutramine on tyramine, The World Health Organization estimates that 510% of Latin America’s noradrenaline and calcium-induced contraction of young rat vas population is afflicted by Chagas disease, which is caused by the deferens. protozoan Trypanosoma cruzi. Current treatment is solely based on benznidazole (Bdz) that is cidal for bloodstream trypomastigotes and Methods: 45-days-old Wistar rats were treated with sibutramine 6 thus efficient in eliminating parasite in circulation during the initial mg/kg (T) or drug-free vehicle as control (C) and sacrificed after 4 stages of infection (acute and asymptomatic chronic). The efficacy of hours. The effects of tyramine (10-4 M, 2-3 min), noradrenaline (10-9 – Bdz for patients with Chagas-related cardiomyopathy is still unknown, 10-4 M) and calcium (10-2 M, 10 min) (in Ca2+-free solution) in absence although a clinical trial aiming to investigate this is expected to be or presence of verapamil (10-8 – 10-5 M) were evaluated in vas deferens concluded in 2013. However, many patients experience drug from both groups. The pharmacological parameters Emax (maximum intolerance and adverse effects for Bdz. Thus, there is a need to look for effect in gram of tension), pD2 (apparent affinity for agonists) and pIC50 other drugs to treat Chagas disease. To identify new trypanocidal (apparent affinity for blockers) were determined. The values were compounds, we performed a structural planning and synthesis of new expressed as Mean ± SEM from at least 6 experiments. 2-Iminothiazolidin-4-ones. We were able to identify one high-efficacy Results: The Emax of tyramine did not show any difference between the trypanocidal compound, 2-minothiazolidin-4-one LpQM18, which groups, but its kinetics was evidently altered showing a slower inhibited the activity of cruzain and the proliferation of epimastigotes contraction. The cumulative concentration-response curves for and was cidal for trypomastigotes but was not toxic for splenocytes. noradrenaline were potentiated in treated group, as described by the Thus, we evaluated the in vivo efficacy of N-phenyl 2-iminothiazolidin- mean values of Emax (C: 1.33 ± 0.08 g; T: 1.80 ± 0.06 g) and pD2 (C: 5.73 4-one LpQM18 to reduce blood parasitemia (acute phase). Starting on ± 0.11; T: 6.31 ± 0.10). The time course response for calcium induces a day 5 postinfection (dpi), compound 18 was orally administered once a biphasic effect, namely phasic response (PR) and tonic response (TR). day at 250 μmol/kg for 5 consecutive days in Balb/c mice infected with The PR was increased by about 48% whereas the TR was decreased by 10 Y strain trypomastigotes. Controls included untreated and Bdz- about 85% in sibutramine pre-treated group. The pIC50 for verapamil treated infected mice. The course of infection was monitored by was augmented for the PR (C: 5.85 ± 0.06; T: 7.0 ± 0.17) and TR (C: 5.6 counting blood parasites in a hemocytometer, and animal survival was ± 0.14; T: 8.02 ± 0.85) in the treated group. followed for one month. Compound LpQM18 was efficient in reducing 89.6% of blood parasitemia when compared to untreated control. No Conclusion: Our data suggest that the acute treatment with signs of toxicity or body weight loss were observed in mice of the sibutramine increases the sensitivity (pD2 and Emax) of the vas deferens treatment groups. to noradrenaline. These effects could be due to failure of neuronal uptake mechanisms and alterations in the calcium influx by L-type voltage calcium channels.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S336
LATINFARMA 2013 Resúmenes/Abstracts
PFB 009: POPULATION PHARMACOKINETICS OF CYCLOS- PFB 010: USE OF FRESHLY ISOLATED RENAL CELLS TO PORINE IN THE EARLY PERIOD OF POST RENAL STUDY RENAL UPTAKE OF SELECTED ANTIVIRALS TRANSPLANT (RT) IN MEXICAN PEDIATRIC RECEPTORS Trejtnar F, Navratilova L, Mandikova J, Kocincova J. Lares-Asseff I, Zaruma Torres F, Saltzman Girshevich S, Urbina Charles University in Prague, Faculty of Pharmacy in Hradec Kralove, Czech Álvarez J, Guillé-Pérez G, Sosa Macías M, Loera Castañeda V, Galaviz Republic. E-mail: [email protected] Hernández C, Toledo López A.
Instituto Politécnico Nacional, CIIDIR-IPN Unidad Durango, México. Administration of antiviral drugs may be in some case associated with severe nephrotoxicity. This effect can be based on active renal Introduction: Cyclosporine (CsA) is an immunosuppressive agent transport and accumulation of the drug in the renal cells. Several used to prevent transplant rejection through selective modification of experimental in vitro methods are available to study the mechanisms the function of T helper lymphocytes. CsA is a therapeutic agent with a responsible for drug uptake in the kidney. The aim of this study was to narrow therapeutic index and large variability in pharmacokinetics. evaluate usefulness of isolated rat renal cells to determine which renal transporters may be involved in transport of selected antivirals into Objectives: To identify differences in the CsA concentrations at steady renal cells. The freshly isolated rat renal cells were prepared by two- state between patients with acceptance or rejection of renal transplant phase collagenase perfusion. The renal uptake of two radiolabeled (RT), and determine the population pharmacokinetic of the drug. antivirals, tenofovir and adefovir, was evaluated to confirm preservation of functions of the renal cellular preparation. To evaluate Material and methods: We included 64 patients 3-18 years enrolled contribution of active and passive transport mechanisms to the renal in RT program of INP, Mexico. Were extracted from one to three uptake, incubation at normal and low temperature was evaluated. To samples per week for each patient, to determine plasma confirm previous information on renal transport, we also determined concentrations of CsA, using polarized immunofluorescence (DX which groups of transporters contributed to the renal accumulation of Abbott). the studied antivirals. For this purpose, we use compounds acting as Results: RT rejection was experienced in 35 patients [13 (37.1%) specific inhibitors of the appropriate transporters. The results males and 22 (62.1%) females] while the remaining 29 accepted the demonstrated that adefovir and tenofovir were transported into the RT [19 (65.5%) males and 10 (34.5%) females]. We monitored 1955 renal rat cells mostly by active transport mechanisms. The most potent concentrations of CsA in accepting [sub-therapeutic 599 (30%), inhibitor of the renal uptake was OAT inhibitor probenecid. Inhibitors therapeutic 178 (8.9%) and toxic 12 (0.6%)] and rejecting [sub- of OCTs and CNTs had a significantly lower effect on the renal therapeutic 809 (40.5%), therapeutic 265 (13.3%) and toxic 86 accumulation. Both antivirals had similar transport characteristics. In (4.3%)] patients p=0.01. The following population pharmacokinetics conclusion, the found results are in accordance with the published data parameters of patients accepting RT were: AUC = 2587.35 on transmembrane transport mechanisms in adefovir and tenofovir. -1 (mcg/mL/h), K10-HL = 2.09 (h) = 0.973 K01-HL (h) alpha (h ) = This fact documents validity of the used method for accumulation study 0.7355; beta = 0.0720 (h-1), alpha-HL = 0.94 (h), beta-HL = 9.61 (h-1), in drugs. from the equation Cp =Aeα.t + Beβ.t, describing a two-compartment model, describing a two compartment model. Conclusions:1) There are significant differences between sub- therapeutic, therapeutic and toxic CsA concentrations within and between the studied groups; those patients rejecting RT showed significantly higher toxic concentrations; 2) Dose should be individualized and based on pharmacokinetic parameters in this population. 3) The new dose of cyclosporine in this population should be calculated on an individual basis, based on the pharmacokinetic parameters of the population studied.
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LATINFARMA 2013 Resúmenes/Abstracts
PFB 011: CHEMICAL COMPOSITION AND PHARMACOLO- PFB 012: CARDIOPROTECTOR EFFECT OF NIFEDIPINE AND GICAL EFFECTS OF MEXICAN PROPOLIS ON RUTHENIUM RED AGAINST CARDIAC ISCHEMIA AND EXPERIMENTAL GASTRIC ULCERS IN RATS REPERFUSION INJURY IN RATS Hernández-Delgadillo GP, Castañeda-Cabral JL, Flores-Morales V, Tavares JGP, Vasques ER, Menezes-Rodrigues FS, Jurkiewicz A, Guerra-Ramírez MA, Trujillo-Saldaña BE, López-Saucedo A. Caricati-Neto A.
Unidad Académica de Ciencias Químicas, Universidad Autónoma de Department of Pharmacology - Escola Paulista de Medicina - Federal University ZacatecasCarr. Zacatecas-Guadalajara Km. 6, Zacatecas, México. E-mail: of São Paulo (UNIFESP), Brazil. E-mail: [email protected] [email protected]
Introduction: In this work, we investigate if blockade of the L-type Propolis is a resinous hive product collected by honeybees from plants, Ca2+ channel by nifedipine (NIF) or inhibition of Ca2+ mitochondrial which has long been used in folk medicine. Chemical composition uniporter by ruthenium red (RR) reduce incidence of ventricular depends on phytogeographical origin, therefore pharmacological arrhythmias (VA), atrioventricular block (AVB) and lethality (LET) properties of propolis vary greatly. In Mexico, information about this caused by cardiac ischemia and reperfusion (I/R) injury in rats. product is very limited. The aim of this study was to identify some chemical compounds and to evaluate an ethanolic extract of Mexican Methods: Male Wistar rats (300 ± 30g) anesthetized (urethane, 1.25 propolis in models of acute gastric lesions induced by ethanol and mg/kg, i.p.) and kept under mechanical ventilation were submitted to indomethacin in rats. Propolis was collected from a semiarid region surgical I/R procedure by means occlusion of left anterior descendent from Zacatecas, where main botanical sources are Opuntia coronary artery by 10 min and reperfusion for 120 min. To evaluate streptacantha, Prosopis laevigata, and Mimosa monancistra. Propolis the effects of NIF and RR on the cardiac activity in I/R injury, the rats ethanolic extract was prepared by maceration at room temperature. were coupled to electrocardiogram system to evaluate incidence of VA, Alcaloids, flavonoids and sugars were identified in a propolis sample by AVB and LET. NIF (1, 10 or 30 mg/kg, i.v.) or RR (1, 3 or 10 mg/kg, i.v.) thin layer chromatography, as soon as 3-hydroxyflavone, 7- were administrated before (pre-I) or after (post-I) ischemia. hydroxyflavone, chrysin and CAPE were determined using reference Results: In rats submitted I/R and treated with saline solution 0.9% compounds. Quantitative analysis of total phenolics compounds, (n=33), a high incidence of VA (85%), AVB (79%) and LET (70%) was flavanones and flavonols contents were determined by spectrometric observed. Pre-I (n=25) treatment with NIF, but not post-I (n=20), analysis, and they were 80.1 ± 4.6 mg/g gallic acid equivalent, 0.56 ± reduced incidence of VA (28 - 62%), AVB (10 - 25%) and LET (14 - 0.02 mg/g naringenin equivalent, and 735 ± 9.4 µg/g quercetin 25%) caused by I/R. Pre-I (n=23) and post-I (n=25) treatment with RR equivalent, respectively. In addition, oxidation index was determined reduced incidence of VA (43%), AVB (25 - 37%) and LET (25 - 30%) by potassium permanganate test (2.5 ± 0.1 s). Pharmacological assays caused by I/R. showed that animals administered with propolis extract (500 and 1000 mg/kg p.o.) showed a significant reduction dose-dependent in lesion Conclusion: These results indicate that agents that attenuate cytosolic index in comparison with control group (P<0.05) in ethanol-induced and mitochondrial Ca2+ overload during ischemia or reperfusion by ulcer model. Propolis extract did not display a significant protection by means blockade L-type Ca2+ channel or inhibition of mitochondrial reducing the evaluated parameters in the gastric ulceration induced by uniporter reduce incidence of cardiac arrhythmia and lethality, indomethacin; however ranitidine as a positive control significantly conferring protection against I/R injury. diminished the lesion index. For histological assessment, stomach tissue was analysed using hematoxylin and eosin staining, and the microscopic evaluation confirmed pharmacological results. These data show that local propolis contents flavonoids which possibly will be responsible of antiulcerogenic activity on ethanol-induced gastric lesions, and this finding contributing for its pharmacological validation.
This work was supported by PROMEP IDCA 8218.
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LATINFARMA 2013 Resúmenes/Abstracts
PFB 013: LUNG EMPHYSEMA: EXPERIMENTAL MODELS PFB 014: EFFECTS OF ETOH INGESTION IN VAS DEFERENS CONTRACTILITY, SPERMATOGENESIS AND CONSEQUENCES Dantas R, Reis E, Campelo N, Alves W, Nunes L. ON THE MALE REPRODUCTIVE SYSTEM IN THE RAT University of Piauí (UFPI), Brazil. E-mail: [email protected] Jurkiewicz NH, Bomfim G H S, Aivazoglou LU, Fabrício VL, Jurkiewicz A, Nichi M, Dalmazzo A, Losano JDA, Barnabe VH. Introduction: According to WHO data, lung diseases represent about Departamento de Farmacologia, Universidade Federal de São Paulo. 8% of all deaths in developed countries and 5% in developing Departamento de Reprodução Animal, Universidade de São Paulo, Brasil. countries. Among these pathologies, the obstructive (such as emphysema) are the most common. In this context, were developed/upgraded two experimental models of emphysema. Introduction: The ingestion of ethyl alcohol (EtOH) is a common and serious condition that has become a public health problem resulting in Methodology: One with passive inhalation of cigarette smoke and one approximately 2.5 million deaths worldwide. EtOH consumption has with tracheal spray of papain. The latter, in an attempt to reduce stress been shown to be involved with the manifestation pathologies such as of team and animals when developing the model with cigarette smoke. metabolic toxic effects on the liver and mainly alterations in After approval by the Ethics Committee (CEP-UESPI 007/2012), were spermatogenesis and male reproductive system. The aim of our study used 30 rats (Rattus norvegicus, Albinus, Wistar rats) with three was to investigate the possible alterations that EtOH consumption months of age and weighing 300 g ± 20 g from UFPI. Were formed entails in the vas deferens (VD) and also changes in spermatogenesis. three groups of 10 animals: control group, group emphysema-papain and group emphysema-cigarette. For the invasive experiments, Methods: Adult male Wistar rats were treated with EtOH by animals were anesthetized with xylazine (6.25 mg/kg) and ketamine intragastric 5g/kg/day v.o (7-days) and control-group received drug- (43.75 mg/kg). For the induction of emphysema with cigarette the free vehicle. In vitro experiments, rat VD were removed for testing animals were placed in an acrilic inhalation chamber for 30 minutes contractility through the following agonists: (a) concentration- twice daily for 45 days (8 filter cigarettes per day). Besides this model, contraction curves for dopamine, phenylephrine, serotonin, barium (b) a new model was tested with spraying of papain powder in the lungs of single dose of tyramine. In the spermatogenesis experiments, animals. Therefore, there were three sprays of papain on days 0, 7 and epididymis sperm samples were collected, resuspended in 1 ml of NaCl 14 (about 3mg in each spray). Spraying was performed by a 0.9% solution and aliquots of the sample were analyzed through the Microspray (Penn-Century®). following parameters: (a) sperm concentration (b) sperm morphology (c) motility and velocity of sperm. Results: Bronchialveolar liquid (BAL) data showed a significant difference (p<0.05) in the number of neutrophils (cells mostly found in Results: The contractility of VD in EtOH treated-group has shown that the BAL of patients with emphysema), comparing the groups pharmacological parameters affinity (pD2) and maximum contraction 6 6 emphysema-cigarette (920 x 10 ) and emphysema-papain (890 x 10 ) induced by agonist (Emax) were decreased for all agonists, except for 6 with control (20 x 10 ). The two experimental groups of emphysema DOP that did not alter pD2. Results on semen samples from EtOH also showed equivalent degrees of hyalinization, congestion and treated-group exhibit sperm alterations in several parameters such as alveolar collapse. decreases in the sperm concentration. Moreover some types of abnormality, motility and velocity of sperm were increased. Conclusion: This shows that the alternative model of emphysema (papain) is an alternative model of emphysema with cigarette. Conclusion: These results may suggest that the vas deferens responsible by moving of sperm the showed contraction decrease. As a consequence of the decrease in contraction of VD, reduction occurs in sperm concentration. In addition EtOH can act directly on sperm and cause increase in abnormality, motility and velocity which decrease spermatogenesis. Therefore, EtOH consumption causes a decrease in EtOH male reproductive system.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S339
LATINFARMA 2013 Resúmenes/Abstracts
PFB 015: ANTI HYPER-GLYCAEMIA EFFECT AND THE SAFETY PFB 016: BIODISTRIBUTION AND PHARMACOKINETICS OF OF THE ZEOLITA: FE2+-CLINOPTI-LOLITA (FZ) IN ANIMAL’S T1H MONOCLONAL ANTIBODY AND ITS ANTI MURINE CD6 EXPERIMENTATION COUNTERPART 10D12 IN HEALTHY ANIMALS AND IN AN ARTHRITIS MODEL Fleitas AS, Rodriguez G. Aldana L, Pérez S, León M, Ayra F, Castro Y, García L, García L, Padrón National Institute of Angiology and Vascular Surgery. 1551 calzada del cerro. Cerro. 12 000, Havana, Cuba. E-mail: [email protected] L, Raymond J, Casacó A, Hernández I. Centro de isótopos, Carretera La Rada km 3.5, San José de las Lajas, Mayabeque, Cuba. E-mail: [email protected] Introduction: The hyper-glycaemia is the main characteristic in the etiopathogenie of diabetic complications, this is a metabolic chronic affection, important morbidity and mortality cause and it is considered Introduction: Biodistribution and pharmacokinetic of two radio a health problem in the world. The metabolic control by means of the labeled monoclonal antibodies was performed with the help of imaging hygienic, dietary and medicinal treatment is essential, from there the techniques. Isotopic labeling was carried out by means of standardized importance of the development new medications that contribute to methods. Pharmacokinetic evaluation was performed using the achieve this objective. population approach and sparse data design. Objective: To evaluate the anti hyper-glycaemia effect and the safety Targeted therapy with monoclonal antibodies (MAb) is an efficient of the Zeolita: Fe2+-Clinoptilolita (FZ) in animal’s experimentation. option for the treatment of rheumatoid arthritis. Th1 is a MAb anti human CD6 developed for the treatment of autoimmune disease and Methods: We worked with the Fe2+-Clinoptilolita (native zeolita 10D12 is its counterpart anti murine CD6 developed as a purified and modified with ions Fe2+). The studies were carried out in: pharmacological tool to get deep into the response mechanisms in Beagles dogs, Chinchilla rabbits, Wistar rats, CENP: SPRD rats, and animals models of rheumatoid arthritis. ENP: NMRI mice. There were realized pharmacological studies (anti hyper-glycaemia effect, dose - response effect and safety). Experiments To investigate the behavior of both antibodies in the assay system, were realized for another possible biological effect. molecules were labeled with 125I to evaluate pharmacokinetic in healthy animals and with 99mTc to evaluate the antibody uptake in Results: There was found a half effective dose of Fe2+-Clinoptilolita. A inflamed area of induced arthritis. decrease in glycaemia was observed in Beagles dogs treated with only dose. Significant differences were no found when compared the anti Material and methods: Antibodies were supplied by the Center of hyper-glycaemia effect of Fe2'+ Clinoptilolita and Acarbosa. It was Molecular immunology. Iodination was performed by the yodogen observed that the treatment with FZ decreased glucose bioavailability method and technetium labeling was carried out by Schwarz method. and the glycaemia post-stimulation. It was demonstrated according to the acute toxicity and genotoxity studies realized to Fe2+-Clinoptilolita Female C57BL6 from CENPALAB were used for experiments. that it is not dangerous for the animal health. Biodistribution and pharmacokinetic was performed by a sparse data design using the population approach. Uptake in region of Conclusion: The anti hyper-glycaemia effect demonstrated, the wide inflammation was quantified by gammagraphy at the same blood availability of material and the economic production, we propose to sampling points. A compartmental model was build to quantify uptake continue another researches to finish the medical register of the kinetic with the help of MONOLIX software version 4.2. pharmacological product. Results: Minor pharmacokinetic differences were found between monoclonal antibodies labeled with 125I and 99mTc. As a humanized antibody, T1h shows a faster clearance than 10D12 and a biodistribution pattern due humanization and non specificity for murine antigen. The arthritis accumulation was not consistent with a targeted mediated uptake. On the other hand, radio labeled 10D12 shows an accumulation profile in arthritis with two peaks of maximum concentration representing an initial transit to inflammatory exudates and a delayed uptake and migration by CD6+ cells.
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LATINFARMA 2013 Resúmenes/Abstracts
PFB 017: COMPARATIVE STUDY OF SEVERAL DOSES OF PFB 018: PREVENTATIVE AND THERAPEUTIC ANTI- PARACETAMOL IN RATS EXPERIMENTAL MODEL ALLERGIC EFFECT OF A NOVEL HOUSE-DUST-MITE VACCINE BASED ON A COMBINATION ADJUVANT Jiménez Martínez MC, Martínez Martín SM, Montero González T, García Sánchez M, Sebazco Pernas C, Maceira Cubiles MA. Ramírez W, Tamargo B, Bourg V, Torralba D, Más A, Infante JF, Sierra G, Pérez O, Labrada A. Hospital “Dr Luis Díaz Soto” Ave Monumental y Carretera Asilo Habana del Este, Cuba. E-mail: [email protected] National Center of Bioproducts, Bejucal, Cuba. E-mail: [email protected]
Introduction: Several chemical substances have been classically used Introduction: Current allergen-specific immunotherapy is based on in rodent models to induce hepatotoxicity, including acetaminophen repeated allergen injections. The adjuvant effect of the outer and carbon tetrachloride. Acetaminophen is considered antipyretic and membrane proteoliposome (PL) of Neisseria meningitides is attractive analgesic secure drugs and of a wide use by adults and children. for designing novel vaccines, with fewer administrations. However, an overdose can cause hepatotoxicity and nephrotoxicity in men and in experimental animals. Aim: To assess the immunomodulatory effect of a novel vaccine based on Dermatophagoides siboney allergens and a combination adjuvant, Objective: To evaluate the level of hepatic affection that is produced containing PL and alum, in prophylactic and therapeutic models of on male Wistar rats after some doses of acetaminophen. respiratory allergy. Material and methods: An experimental study was carried out using Methods: Balb/c or C57/BL6 mice were administered with 3 doses of 600 y 800 mg/kg of acetaminophen dissolved on propilenglicol to 50% the vaccine (2 µg Der s1) by subcutaneous route. In the therapeutic and administered intraperitoneal in only one dose. Four groups of six model, mice were previously sensitized to D. siboney by ip injection animals each one were used in the experiment. The levels of glutamic plus exposure to aerosolized allergen. A challenge test was used after piruvic transaminase were determined (GPT) and oxalacetic glutamic receiving the vaccine in the prophylactic or therapeutic models. (OGT); and the level of hepatic lesion: cellular tumefaction, esteatosis Allergen-specific antibody response was assessed by ELISA, and the and necrosis at 24 and 72 hours. cytokine response, by FACS. Results: An increase of transaminase levels were obtained in the two Results: The vaccine induced IgG2a and IgG1 antibodies in both, naïve times and histopathologic changes which lead to the appearance of and sensitized animals, and prevented the development of systemic necrosis areas with a dosis of 800 mg/kg height at 24 hours which (IgE) and local allergic response in mice subjected to allergen were maintained at 72 hours. challenge, regarding histological signs of lung inflammation. In Conclusions: The humeral and histopathology changes observed after sensitized mice, it was noted a significant increase of the IgG/IgE ratio, the administration of acetaminophen were similar at 24 and 72 hours. and a decrease of blood eosinophils. Moderate levels of IFN-γ were induced in Der s1-stimulated lymphocyte cultures, whereas IL-13 levels decreased as compared to non-treated controls. IL-10 levels showed no significant (p>0.05) differences. Conclusions: The adjuvanted vaccine does not exacerbate the allergic response, nor promote Th1 inflammation, supporting a satisfactory safety profile for further clinical trials. This immunomodulatory effect suggests clinical benefits in cellular and blocking antibody responses for treatment or prevention of respiratory allergy.
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LATINFARMA 2013 Resúmenes/Abstracts
PFB 019: CORRELATION BETWEEN SEROTONIN PFB 020: CHARACTERIZATION OF THE PROTEINS MTL2P CONCENTRATION VARIATIONS AND CLINICAL COURSE IN AND WSC1P LIKE POSSIBLE SENSORS OF THE CELLULAR PATIENTS WITH ALCOHOL WITHDRAWAL SYNDROME WALL IN Schizosaccharomyces pombe TREATED WITH CLOMETIAZOLE Cruz S, Hernández JE, Sánchez Y. Llinás S, Caballero A, Peñalver J, Valdés R. Universidad de Sancti Spíritus, Ave. de los Mártires #360, Sancti Spíritus, Cuba. E- Hospital Hermanos Ameijeiras, Cuba. E-mail: [email protected] mail: [email protected]
Introduction: Alcoholism Withdrawal Syndrome (AWS) is a The cell wall is a vital structure which confers mechanical resistance phenomenon with an unquestionable importance within alcoholic and structural support to the fungal cell. We are interested in the study clinical status. It is a serious condition that can occur when an of the fungus cell wall for two reasons fundamentally: 1) Because is a excessive and prolonged drinking is suddenly halted. The AWS structure in constant change, with a relatively simple composition and biological basis knowledge has demonstrated that alcohol can alter an essential function, which make it to be used as a very good structure and function of a wide group of neurotransmitters such as morphogenetic model at molecular level, and 2) Cell wall is an Serotonin (5-HT). In that sense, we theorized that total 5-HTshould excellent target to develop antifungal agents, since is a structure with significantly increases during treatment of patients with AWS and thus an essential function, and exclusive of the pathogenic agent himself. it could be used as a biological marker of patient classification and The objective of this work consists in characterizing sensors of surface clinical course. and other molecules implicated in detecting and transmitting the status of the cell wall to Rho1p either through of proteins GEF, Rgf1p, Objective: This study sought to correlate total 5-HT concentration Rgf2p and Rgf3p, or by other mechanisms. Some of these sensors have variations with clinical evaluation of 31 patients with AWS at the been characterized in Saccharomyces cerevisiae, but until now, this beginning and at the end of the treatment. kind of sensors has not described on S. pombe. The sensors characterized are transmembrane proteins that have a little Methods: Thirty-one patients diagnosed with AWS according to the cytoplasmatic domain in the extreme of C-terminal, a unique trans- Diagnostic and Statistical Manual of Disorders-IV were included in this membrane domain and a periplasmic ecto-domain rich in serine and study. Patient blood samples were always taken in the morning during threonine. After thorough data base review, in order to find in to S. detoxification period and mixed with 1% EDTA to be centrifuged for pombe similar proteins described to S. cerevisiae sensors (Mid2p and isolating platelet rich plasma. The endogenous and secreted 5-HT Wsc1p), we found two proteins named Mtl2p and Wsc1p respectively, concentrations were always measured by RP-HPLC within 2 h after which have a very similar structure to the S. cerevisiae protein. Mtl2p's blood collections. characterization started and it was proved that when Mtl2p's was Results: Total 5-HT concentration values were statistically different absent, cells were sensitive to caspofungin, which is an antifungal that between days 1 and 10 of treatment (p = 2.00 x 10-5) and there was a interfere the glucans bio-synthesis in to the cell wall, that suggest that strong linear correlation between 5-HT concentration and patient when Mtl2p's is missed there are defects in the cell wall structure, classification at the beginning (R2= 0.9839) and clinical evaluation at while if there is Mtl2p's over-expressing the cell is elongated and wall the end of the treatment (R2= 1.000). is more thin. It was verified that Mtl2p is related to Rgf1p, which is a Rho1p GTPasa's activator that regulates the cell wall synthesis and it Conclusions: We can conclude from this study, that total 5-HT has intervention on the route of cell integrity leaded by the kinase concentration variations can be used as a biological indicator of clinical Pmk1p. course of patients with AWS.
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LATINFARMA 2013 Resúmenes/Abstracts
PFB 021: PROTEOME AND BIOLOGICAL CHARACTERIZA- PFB 022: DISSOLUTION PROFILES OF CAPTOPRIL TION OF Bothrops punctatus VENOM. ISOLATION AND SIMULATING CONDITIONS POST-SURGICAL IN PATIENTS IDENTIFICATION ONE BRADYKININ-POTENTIATING UNDERGOING TO BARIATRIC SURGERY IN "Y" OF ROUX PEPTIDES Alviz A, Mercado J, Martinez J, Utria L, Santos G. Fernández M, Lomonte B, Pereañez JA, Núñez Rangel V. Department of pharmacy, Faculty of Pharmaceutical Sciences, University of Program of Ofidismos y Escorpionismo, Antioquia University, Colombia. E-mail: Cartagena, Colombia. E-mail: [email protected] [email protected]
Introduction: Bariatric Surgeries were increased exponentially at Bothrops punctatus venom is poorly characterized and only one study global level. One approach is widely used in this surgery is“Y” Roux related pharmacological properties has been published. We reported (Padwal, 2008).The post-bariatric patients have comorbidities such as the proteome of this venom, where the proteins masses were in the hypertension, so used drugs that decrease blood pressure type IECAs range of 14 a 90 kDa to both venoms. They belong to 9 different groups as captopril. of toxins where metalloproteinase are the predominant proteins Objective: To determine the dissolution profile in different com- followed by C - type lectin-like (24.4%), D49 PLA2 (8%), mercial presentations of captopril 50 mg tablet, under conditions of Serinproteinase (5%), desintegrin 3.8%, L-aminoacid oxidase 3%, simulating gastrointestinal surgery patients “Y” Roux. endothelial growth factor 1.7%, Cysteine-rich secretory proteins 1%. One PLA2 K49 was also identified (1.3%) and speciality a fraction Method: The dissolution profile of eight brands of captopril, to bradykinin-potentiating peptides (10.7%). By comparing the compare the efficiency in different dissolution matrix, simulating pre- composition of the venoms B. punctatus of Antioquia and Chóco, there operative and post-operative bariatric surgery in "Y" Roux. All is a high similarity. The effects of this venom in both zones showed products were previously validated by Liquid Chromatography. The important proteolytics, but moderate compared to other species of the statistical t-student was applied, accepting significant differences (p family Viperidae. However the activity PLA2 and L-amino acid oxidases <0.05). (LAO) were moderate. The antivenoms were used to show cross- reactivity with B. punctatus venom. In the last decade, the study of the Results: Liquid chromatographic evaluation of different brands, were composition of snake venoms from proteomic analysis has contributed 98.5% and 103% range accepted by the USP35/NF35. The profile of to generate new knowledge of toxic function, formulation of hypotheses dissolution efficiency in both matrix pre-operative and post-operative that integrate biological and biochemical aspects of the production of average was 86.3 ± 5.1 and 83.5 ± 10.5% respectively, for all brands, venom, and a better understanding of ecological and evolutionary noting that two of them showed statistically significant difference (p> species, additionally, the identification and characterization of 0.5).The area under the curve (AUC) of dissolution profile, showed no molecules with activity pharmacology like are bradykining-potentiating significant difference between the means (2588.2 ± 5.8 and 2505.7 ± peptides compounds that gave rise to captopril. 12.6 pre-operative and post-operative, respectively). Conclusion: Significant differences were found between pre-operative and post-operative dissolution profiles in pre-surgical and post-surgical media, for some captopril brands sales in Colombia. So there may be therapeutic failures in patients who consume certain brands that have problems in their dissolution profile.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S343
LATINFARMA 2013 Resúmenes/Abstracts
PFB 023: ORAL AND INTRAVENOUS BIOAVAILABILITY OF PFB 024: EFFECTS OF METFORMIN IN LOCAL AND SYSTEMIC QUERCETIN AND RELATIONSHIP WITH THE HYPO- ANTIHYPERALGESIC ACTION OF INDOMETHACIN, GLYCEMIC EFFECT DICLOFENAC AND PARECOXIB González A, Fuentes I, Coral T, Ramírez M, Ortiz R. Torres-López JE, Guzmán-Priego CG, Méndez-Mena R, Zapot-Martínez JC. Facultad de Química, Universidad Autónoma de Yucatán (UADY), México. E-mail: [email protected] Centro de Investigación, División Académica de Ciencias de la Salud-Universidad Juárez Autónoma de Tabasco, México. E-mail: [email protected]
Introduction: Quercetin is the flavonoid most widely and abundantly present in herbs and foods. It has been reported to exert numerous pharmacological activities, such as antidiabetic and hypoglycemic, and Introduction: In the present study, we evaluated the peripheral role of their potential usefulness in the treatment and complications of COX-1 and COX-2 in an animal model of established hyperalgesia. Also, Diabetes. However, data on the bioavailability of free form of quercetin this work was undertaken to determine whether metformin has any are scarce and contradictory. Therefore, in this study we attempted to effect on the antihyperalgesic activity of COX inhibitors. compare the bioactivities and pharmacokinetics of quercetin in rats. Methods: Hyperalgesia was induced by injection of carrageenan into Material and methods: Quercetin was administered intravenously rat footpads. Then we investigated the effects of therapeutic treatment (38 mg/kg) and intragastric (300 mg/kg). Blood samples were with a selective COX-2 inhibitor (parecoxib) and with non-selective withdrawn via cardiopuncture at different time points. An HPLC COX inhibitors (indomethacin and diclofenac) on carrageenan-induced validated method was used to determine the plasmatic concentrations thermal hyperalgesia (reduced hind paw-withdrawal latency).Test of quercetin. Subsequently, hypoglycemic effects were determined in compounds were administered 3 hr after carrageenan challenge, and normoglycemic rats, by measuring the variation of glucose during the then hyperalgesia was evaluated. For treatment with metformin (local times set. peripheral or systemic), the NSAIDs were administered after metformin injection, and then hyperalgesia was evaluated. Results: After oral administration, only 13.4% of unchanged quercetin was bioavailable. The oral absorption rate of quercetin was 68% Results: Local (50, 100, 200 y 400 µg/paw) or systemic (10 mg/kg, compared to intravenous administration after dose correction. Cmax of i.p.) administration of COX-2 inhibitor and non-selective COX inhibitors free form of quercetin were observed at 5 and 240 minutes after produced antihyperalgesic activity. a) Administration of either COX intravenous and oral administration, respectively. While Emax inhibitor after establishment of hyperalgesia (3 hr after carrageenan) (hypoglycemic effects) were in the range of 90 to 220 minutes. reversed thermal hyperalgesia in a dose-dependent manner. b) The anti-hyperalgesic potency evaluated as ED50 was diclofenac > Conclusions: In a normoglycaemic rats, appears not show evidence indomethacin > parecoxib. c) Local pre-treatment with metformin toexist relationship between the free form of quercetin and reversed the local antihyperalgesic action of indomethacin, but not the hypoglycemic effects, because the greater hypoglycemic effects are not antihyperalgesic action of diclofenac and parecoxib. However, systemic proportional to the increase in plasma concentrations of free form. This pre-treatment with metformin reversed systemic antihyperalgesic indicate that the effects on glucose homeostasis are linked to the activity of administration of diclofenac, but not of indomethacin. products of metabolism of quercetin (glucuronides and sulfates, mostly), having a similar behavior to a prodrug. Conclusions: Based in the pharmacological profile of the NSAIDs tested and our results, particularly these observed with parecoxib, we suggest that at least peripheral COX-1, if not both COX-1 and COX-2 are necessary for the maintenance of carrageenan-induced hyperalgesia. Treatment with metformin decrease antihyperalgesic effects of indomethacin and diclofenac.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S344
LATINFARMA 2013 Resúmenes/Abstracts
PFB 025: DETECTION OF INSULIN POLYMERS IN PLASMA PFB 026: IS 15-EPI-LIPOXIN A4 THE MEDIATOR OF THE FROM OBESE PATIENTS AND ITS RELATIONSHIP WITH EFFECT OF ASPIRIN ON EXPERIMENTAL INFECTION WITH INSULIN RESISTANCE Trypanosoma cruzi? García JR, Rincón MJ, Olivares IM. Campos-Estrada C, Molina-Berrios A, Faúndez M, Torres G, Escanilla S, Kemmerling U, Leiva M, Morello A, Maya JD, López-Muñoz R. Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional. México D.F., México. E-mail: Programa de Farmacología Clínica y Molecular, ICBM, Facultad de Medicina, [email protected] Universidad de Chile, Chile. E-mail: [email protected]
Introduction: It has been described that the reactive oxygen species Introduction: Currently there are 10 million people with Chagas (ROS) modified the chemical structure and the function of human disease in Latin America and in 2008, more than 10,000 people died recombinant insulin (HRI). Using in vitro models, HRI and blood from from this cause. This disease is caused by the flagellate protozoan patients with diabetes or obesity as a source of ERO, we demonstrated Trypanosoma cruzi. To control parasite replication during the initial that the blood of these patients have the capacity to induce chemical stage of infection, an inflammatory response is produced including modifications and a loss of the hormone function. Recent studies have increased production of prostanoids, which contribute to cardiac shown that these changes generated polymers of insulin with a remodeling and other functional disorders of the heart in the chronic molecular weight of 70 kDa. Therefore, the polymerization of the phase of Chagas disease. Therefore, prostanoid synthesis inhibition hormone in vivo might be a mechanism of insulin inactivation or emerges as a potential therapeutic target. Acetylsalicylic acid (ASA) insulin resistance. increases macrophage trypanocidal capacity, enhancing the antichagasic effect of nifurtimox and benznidazole. ASA acetylates Aim: To determine the presence of insulin polymers in plasma from COX-2, redirecting its catalytic activity to generate other eicosanoid, obese patients. 15-epi-lipoxin A4, a potent anti-inflammatory and pro-resolutory of Material and methods: Women of 20 to 40 years old were included in inflammation. Therefore, we studied the effect of aspirin in Balb/c the study. One group with Body Mass Index (BMI) of 30 to 34.9 (O1) mice and in macrophages infected with T. cruzi, to determine whether and another with BMI > 40 (O3). Healthy women with BMI of 20 to the effect of ASA is related to the generation of 15-epi-lipoxin A4. 24.9 (HW) were included as control group. A polyclonal antibody Material and methods: In macrophages infected with T. cruzi and against insulin polymers was generated, it was coupled to magnetic treated with ASA, we determined the expression of COX isoforms by particles and this complex was incubated in plasma of HW, O1 and O3. Western blotting and the levels of PGE2, LTB4, and 15-epi-LXA4 by Magnetic beads were recovered with a magnet, washed with buffer ELISA. Furthermore, Balb/c mice infected with T. cruzi were treated PBS plus SDS 0.5% and treated with loading SDS-buffer. SDS- with aspirin and 15-epi-LXA4 to analyze mortality, parasitemia, heart polyacrylamide gel (10%) was performed and western blot was used histology and parasite load in heart by q-PCR. to evidence the presence of insulin polymers. Finally, densitometry analysis of the insulin polymers was performed and correlated with Results and conclusion: During infection, there was increased HOMA values. expression of COX-2 and PGE2 levels. With ASA, decreased PGE2 production and increased production of 15-epi-LXA4 was observed. Results: The markers of oxidative stress in the plasma from obese Aspirin and 15-epi-LXA4 decreased mortality, parasitemia and heart patients were increased vs. healthy women. Western blot revealed an damage at low doses, but not at high doses. In conclusion, the effect of insulin polymer in plasma and we found a positive correlation between 15-epi-LXA4 may explain, in part, the effect of ASA on Chronic Chagas levels insulin polymers and HOMA values (Pearson r = 0.5274; p < Cardiomyopathy. 0.01).
Conclusion: These data show for the first time, the existence of insulin polymers in plasma from obese patients and its relationship with the insulin resistance.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S345
LATINFARMA 2013 Resúmenes/Abstracts
PFB 027: SEARCH OF NEW THERAPEUTIC AGENTS: PFB 028: IN VIVO ANTITUMORAL EFFECT OF TRIPHENIL- PYRIDO[2,3-D]PYRIMIDINES PHOSPHONIUM-GALLIC ACID DERIVATIVES Acuña J, Ocampo Y, Castro J, Pájaro I, Trilleras, Franco L. Peredo L, Jara J, Castro V, Saavedra J, Madrid M, Kemmerling U, Ferreira J. Biological Evaluation of Promissory Substances Group. Faculty of Pharmaceutical Sciences. University of Cartagena, Colombia. E-mail: Department of Clinical and Molecular Pharmacology, Faculty of Medicine, [email protected] University of Chile, Santiago, Chile. E-mail: [email protected]
Introduction: Ring systems pyrido[2,3-d]pyrimidines are present in Introduction: Cancer is a genetic disease involving dynamic changes several biologically active compounds with known properties as in the genome that results in a complex series of events that result in cytotoxic, analgesic, antihistamine, diuretic, anti-inflammatory, an unlimited replication capacity, sustained angiogenesis, evasion of antioxidant and antibacterial. Therefore, researches on the synthesis of apoptosis, self-sustained growth, insensitivity to signals that stop new derivatives and the evaluation of their biological activities are growth, ability to invade tissues and metastasize, immune evasion and currently increasing. The present study was conducted to evaluate the reprogramming of energy metabolism. The generation of energy (ATP) in vitro antibacterial, antioxidant and anti-inflammatory activities of a by oxidative phosphorylation is essential for all nucleated cell, process series of ten pyrido[2,3-d]pyrimidines derivatives. that is altered in tumor cells, making mitochondria an interesting therapeutic target. Gallic acid is a natural compound used as Material and methods: Compounds were synthesized and antioxidant in foods and has antitumor activity. Thus, gallic acid- spectroscopically characterized. Antibacterial activity was evaluated cationic derivatives were synthesized (conjugated to delocalized using the microdilution method described by CLSI, against Gram- lipophilic triphenylphosphonium cation) which selectively target negative and Gram-positive strains from ATCC. The effect on NO• tumor cell mitochondria, guided by its high mitochondrial membrane production was assessed by determining nitrite concentration in potential. supernatants of LPS-stimulated RAW 264.7 macrophages, using Griess reagent. Cell viability was determined by MTT assay. Additionally, we Material and methods: To determine the degree of toxicity of these established the scavenging effect on NO•, DPPH, and ABTS free derivatives, in CAF1 Jax mice were estimated the maximum dose used radicals. Results were analyzed using ANOVA, P<0.05 was considered through Kaplan Meier survival curve. Furthermore, systemic effect of significant. these compounds after intraperitoneal administration was determined by histological analysis of heart, liver and kidney. To evaluate the Results: Bioassays demonstrated that the series of pyrido[2,3- antitumor activity of these derivatives, we used a syngeneic murine d]pyrimidine derivatives have not a significant effect on NO• model to evaluate the inhibition of tumor growth. production, as well as they do not exert an scavenging effect on NO•, DPPH, and ABTS radicals. With the exception of compound PVR-04, Results: The optimum dose of survival rate after 30 days of treatment + + antibacterial activity assays revealed that most of tested compounds for TPP C10 and TPP C12 was 10 mg/kg body weight, resulting similar did not affect bacterialgrowth.PVR-04 (128 µg/mL) inhibited more than that control group. Histological analyzes showed that the dose of than 70% of Klebsiella pneumonia growth, showing an IC50 value of 50 mg/kg body weight generates mild signs of toxicity in the liver but 102.8 (98.30-107.09) µg/mL. not on the kidney and heart, for both compounds, and the dose of 10 mg/kg body weight showed no considerable signs of toxicity in the Conclusion: Despite the known therapeutic potential of pyrido[2,3- + organs tested. Moreover, TPP C10 was significantly able to inhibit d]pyrimidines derivatives, tested compounds did not showed + tumor growth. On the other hand, TPP C12 only slightly inhibited the promissory activity. Our results, demonstrated that substituents play a tumor growth; this decrease was not significant respect control group. key role in bioactivity of derivatives from this ring system. Further analog synthesis is ongoing in order to improve their properties as Conclusion: Gallic acid-cationic derivatives inhibit tumor growth in therapeutic agents. vivo, without producing significant toxic effects.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S346
LATINFARMA 2013 Resúmenes/Abstracts
PFB 029: ALTERATIONS IN THE SYMPATHETIC PFB 030: DEVELOPMENT AND VALIDATION OF ANALYTICAL NEUROTRANSMISSION OF VAS DEFERENS FROM PRE- PROCEDURES TO DETERMINE LOSARTAN POTASSIUM IN HYPERTENSIVE AND HYPERTENSIVE RATS TABLETS AND PLASMA FOR THERAPEUTIC EQUIVALENCE STUDIES Peña M, Miranda-Ferreira R, Caricati-Neto A, Jurkiewicz NH, Jurkiewicz A. Baudrit O, Berrocal AL, Fonseca L.
Escola Paulista de Medicina - Federal University of São Paulo, Brazil. Instituto de Investigaciones Farmacéuticas, Facultad de Farmacia, Universidad de Costa Rica, Costa Rica. E-mail: [email protected]
Introduction: Alterations in sympathetic neurotransmission have been linked to the catecholaminergic dysfunctions observed in the Introduction: Two rapid, safe and reliable HPLC procedures were pathophysiology of arterial hypertension (AH). Studies have shown developed for use in losartan bioanalysis in human plasma and quality that impaired neurotransmission in AH are due to increased calcium studies of losartan potassium tablets. levels that stimulate the neurotransmitter hypersecretion. This calcium is finely controlled by a functional triad formed by voltage- Material and methods: In the procedure in plasma, losartan was dependent calcium channels (VDCC), mitochondria (MIT) and extracted from 1 mL of this biological matrix through solid phase endoplasmic reticulum (ER). However, we do not know if alterations of extraction and an elution with methanol, HCl pH2 (90:10, v/v). HPLC the triad initiates before or after the establishment of AH. Our aim is to analysis was performed on C18 reversed-phase column using investigate the sympathetic neurotransmission of vas deferens (VD) phosphate buffer (pH 3.0), acetonitrile (50:50, v/v) as mobile phase from normotensive (NWR) and spontaneously hypertensive rats with a flow rate of 1 mL/min. A wavelength of 225 nm was selected in (SHR), young and adults. a UV detector. The same conditions were applied in vitro assay of losartan solutions dissolved in methanol. Validation protocols of Methodology: Using NWR and SHR aging from 4-8-12-16-20 weeks, analytical procedures were based on the guidelines of the International we studied: 1) the secretion of catecholamines from sympathetic Conferences of Harmonization (ICH, 1995), the World Health nerves of VD using Nicotine (10-6M) and measured by means of Organization, the Food and Drug Administration (FDA, 2001) and electrochemical detector; 2) Neurogenic contraction through electrical European Medicines Agency (EMEA, 2011). stimulation (0.2 Hz, 60V) of sympathetic nerves: 2a) increase of neurogenic contraction with Nicotine (10-6 - 10-4M); 2b) blockade of Results: The validation procedure for tablets showed a precision neurogenic contraction with VDCC blocker Nifedipine (10-7M); 2c) lower to 2% of RSD in repeatability, 5% in intermediate precision and increase of neurogenic contraction using CCCP (10-6M) to break the linearity between 50 and 300 ng/mL. Bioassay's procedure also calcium storage from MIT. demonstrated compliance with the recommendations of international guidelines in terms of percent recovery, the stability of spiked plasma Results: Compared with the NWR, the SHR presented an increase of with losartan potassium (to 3 freeze/thaw cycles), specificity, linearity the following responses: (1) secretion of catecholamines - 4-8 week: (over the range of 50-200 ng/mL) and accuracy. The detection limit 18%, 12 week: 65%, 16 week: 43%, 20 week: 104%. (2) Effects of was 10 ng losartan potassium per mL of plasma and the incertitude nicotine on electrical stimulation - 2a) Emax: 8-12 weeks: 12%, 16 result of LOQ's concentration was 3.5 ng/mL with 95% of confidence. weeks: 21%, 20 weeks: 46%; 2b) pD2: 4-8 weeks: 14%. (3) Effect of CCCP on electrical stimulus – 8 week: 19%, 12 week: 28%, 16 week: Conclusion: Both procedures are suitable for use in studies of 50%, 20 week: 90%. However, the blockade of neurogenic contraction therapeutic equivalence of multisource products of losartan potassium with Nifedipine was lower in SHR (4) 16 and 26 week - 20% and 30%, tablets. respectively. p < 0.05 - t student and ANOVA with Bonferroni post-test. Conclusion: The sympathetic neurotransmission in SHR is increased because the higher involvement of VDCCs and MIT, promoting greater catecholamine secretion observed in the pathophysiology of hypertension. All observed changes began before settling of AH.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S347
LATINFARMA 2013 Resúmenes/Abstracts
PFB 031: Nocardia brasiliensis AS BIOFILM GROWING ON PFB 032: STUDY ON POSSIBLE MECHANISM OF ACTION OF VARIOUS INERT SURFACES OZONE INDUCES SEIZURES PENTYLENETETRAZOL Monroy G, Castrillón RL, Palma R. Donoso Cedeño R, León OS, Dranguet J, Mallok A.
Laboratorio de Inmunología. Departamento de Sistemas Biológicos. Universidad Centro de Investigación y Evaluaciones Biológicas, La Habana, Cuba. E-mail: Autónoma Metropolitana. Unidad Xochimilco México D.F., México. E-mail: [email protected] [email protected]
Introduction: Epilepsy is a severe neurodegenerative disease with a Introduction: Biofilms are microbial communities that are the most high incidence worldwide. Current Antiepileptic drugs have limited successful colonization of microorganisms, are ubiquitous in nature effectiveness given by the high number of adverse reactions and drug and responsible for many pathologies. These communities embedded problems they present. The mechanisms of action of conventional in an extracellular matrix growing inside autoproduced drugs are intended only to slow down the propagation of downloads exopolysaccharide and attached irreversibly to an inert surface or a and not towards epileptogenesis. Ozone therapy by oxidative living tissue. Biofilm formation occurs as a continuous process with preconditioning mechanism could provide an alternative therapy for various stages of development. In Nocardia brasiliensis this disease. actinomycetoma grains are formed in vivo consisting of a polysaccharide bonding cement which amalgamates these bacteria. Material and methods: For the study we used 77 males OF1 mice The aim of this study was to obtain Nocardia brasiliensis biofilms with an average weight of 25 ± 2 g, which were divided into 11 groups growing in different inert surfaces such as acetates and catheters. of 7 animals each: control group, PTZ, PTZ + O2 (5, 10, 15 and 20 treatments) and PTZ + O2/O3 (5, 10, 15 and 20 treatments), DPCPX Material and methods: We performed a N. brasiliensis CECT3032 (adenosine antagonist) + O2/O3 + PTZ. After administering the growth curve in Sabouraud broth obtaining a logarithmic phase proconvulsant (PTZ 90 mg/kg ip) were assessed the time of onset of between 24 and 72 hours. For attachment of the organism in the the first seizure and the percentage of mortality. Subsequently was surfaces to be tested, we used 24 well plate with 2 mL of a culture extracted the brain from the animals for spectrophotometric medium (Sabouraud broth) and 1x1 cm acetates: APOLLO, PCM, determinations of biochemical parameters (SOD, Catalase and MDA). Kronaline or Catheters of 0.2, 0.5 and 1 cm diameter were used as inert materials. These plates were inoculated with 200 x 10 ⁶ CFU per well Results: The result showed that 15 ozone treatments succeeded in and incubated during 50 days. Readings were made every third day for increasing the latency time of the first crisis and the percentage of a week and then every week until 50 days. Were quantified colony mortality and the result related biochemical parameters, which forming units (CFU) microscopically and biofilm formation by crystal showed a significant increase in activity of SOD and Catalase compared violet staining and reading of acetic acid extract. to controls and a reduction in the MDA. Results: From the third day were found attached to the material N. Conclusion: In conclusion ozone was able to increase the time of onset brasiliensis CFU and increasing with time to form a uniform layer only of the first seizure and the percentage of mortality, also managed to in the acetates (biofilms). However in catheters only increase in CFU activate the enzymes SOD and Catalase decreasing oxidative stress found in materials set and was not observed the formation of biofilms. generated during epileptogenesis and damage to membrane lipids through a mechanism oxidative preconditioning that involves Conclusion: N. brasiliensis adhesion was observed in all materials Adenosine A1 receptors. tested as CFU growth, however, the biofilm is found only in the acetates tested so the catheter material does not promote this type of microbial association.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S348
LATINFARMA 2013 Resúmenes/Abstracts
PFB 033: TRISULFATED HEPARIN DISACCHARIDE CONFERS PFB 034: POPULATION PHARMACOKINETIC ANALYSIS OF CARDIOPROTETION AGAINST CARDIAC ISCHEMIA AND NIMOTUZUMAB IN COMBINATION WITH CHEMOTHERAPY REPERFUSION INJURY IN RATS IN PATIENTS WITH BREAST CANCER Caricati-Neto A, Tavares JGP, Vasques ER, Menezes-Rodrigues FS, Rodríguez L, Fernández E, Ramos M, Soriano JL, Peraire C, Colom H. Jurkiewicz A, Godoy CMG, Tersariol IL. Department of Pharmacology & Toxicology, Institute of Pharmacy and Foods, Department of Pharmacology and Biochemical - Escola Paulista de Medicina, University of Havana, Cuba. E-mail: [email protected], [email protected] Federal University of São Paulo, Brazil. E-mail: [email protected]
Introduction: Epidermal growth factor receptor (EGFR) Introduction: In this work, we investigate if blockade of the Na+/Ca2+ overexpression has been detected in many epithelial origin tumors, exchanger (NCX) by trisulfated heparin disaccharide (THD) reduce specifically in breast cancer, and it’s often associated with tumor incidence of ventricular arrhythmias (VA), atrioventricular block growth advantages and poor prognosis. The nimotuzumab is a (AVB) and lethality (LET) caused by cardiac ischemia and reperfusion genetically engineered humanized antibody (MAb) that recognizes an (I/R) injury in rats. epitope located in the extracellular domain of human EGFR. The aims of this study were to develop a population pharmacokinetic (PPK) Methods: Male Wistar rats (300 ± 30 g) anesthetized (urethane, 1.25 model for nimotuzumab in combination with doxorubicin- mg/kg, i.p.) and kept under mechanical ventilation were submitted to cyclophosphamide in patients with breast cancer and to identify surgical I/R procedure by means occlusion of left anterior descendent demographic determinants, predictive factors of the pharmacokinetic coronary artery by 10 min and reperfusion for 120 min. To evaluate variability. the effects of THD on the cardiac activity in I/R injury, the rats were coupled to electrocardiogram system to evaluate incidence of VA, AVB Material and methods: A phase I, single center, non-controlled and and LET. THD (0.025, 0.05 and 0.2 mg/kg, i.v.) were administrated open clinical study with histopathological diagnosis of locally advanced before (pre-I) or after (post-I) ischemia. stage III breast cancer was carried out. Nimotuzumab was administered weekly by intravenous continuous infusions over 10 Results: In rats submitted I/R and treated with saline solution 0.9% weeks. Three patients were enrolled at each of the following fixed dose (n=33), a high incidence of VA (85%), AVB (79%) and LET (70%) was levels: 50, 100, 200 and 400 mg. Blood samples were drawn for observed. Pre-I (n=30) treatment with THD reduced incidence of VA pharmacokinetic assessments on weeks 1st (0-168 h) and 10th (until (30 - 50%), AVB (0 - 30%) and LET (0 - 30%) caused by I/R. Post-I 624 h). A simultaneous analysis of 323 concentration-time data was (n=30) treatment with THD reduced incidence of VA (30 - 50%), AVB performed by the nonlinear mixed-effect modeling (NONMEM) (10 - 20%) and LET (0 - 30%) caused by I/R. program ver. 7.2. The first-order conditional estimation method with Conclusion: These results indicate that agents that attenuate cytosolic interaction was used throughout the modeling process. 2+ Ca overload during ischemia or reperfusion by means blockade of Results: The model that best described the nimotuzumab NCX reduce incidence of cardiac arrhythmia and lethality, conferring pharmacokinetics was an open model of two compartments with protection against I/R injury. Michaelis-Menten elimination from the central compartment, parameterized in terms of maximal elimination rate (VM), concentrations of the drug at which the elimination rate is half maximal (KM), central and peripheral distribution volumes (Vc and VP, respectively), and distributional clearance (CLD) . Interpatient variability modeled assuming a log normal distribution could be associated to VM (38.3%) and Vc (37.8%). The proportional error model described adequately the residual error associated to the concentrations. Neither anthropometric variable nor the age was found to be predictive factors of the variability of either CL or V. The final model parameter estimates (RSE%, relative standard error) were VM: 3.8 (48.9%) mg/h, KM: 551 (60.4%) mg/L, Vc: 0.965 (11.9%) L, CLD: 0.022 (2.2%) L/h, VP: 2870 (355%) L. Goodness of fit plots and the prediction corrected visual predictive check suggested that the model adequately described the data. Conclusion: This study demonstrated not interaction between the clearance of nimotuzumab and chemotherapy.
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LATINFARMA 2013 Resúmenes/Abstracts
PFB 035: HSG CELLS CULTURED IN 3D EXPRESSING PFB 036: ROLE OF HISTAMINE H3 RECEPTORS IN THE SYNAPTOTAGMIN I AND SECRETE AMYLASE: MODEL TO INHIBITION OF THE CARDIO-ACCELERATOR SYMPA- STUDY THE OVEREXPRESSION OF SYNAPTOTAGMIN I IN THETIC OUTFLOW IN PITHED RATS SJÖGREN'S SYNDROME Pinacho-García LM, Villalón CM. Cortés J, Aguilera S, Hidalgo J, Bahamondes V, Urra H, Barrera MJ, Departamento de Farmacobiología, Cinvestav-IPN (Sede Sur), Czda. de los Castro I, González S, Molina C, Leyton C, Urzúa U, González MJ. Tenorios 235, Col. Granjas-Coapa, Deleg. Tlalpan, 14330, México D.F., Mexico. E- ICBM-Facultad de Medicina, Universidad de Chile, Santiago, Chile. E-mail: mail: [email protected], [email protected] [email protected]
Introduction: It has been shown in pithed rats that activation of Introduction: Exocytosis and Ca2+ signaling are polarized processes in histamine H3 receptors inhibits the vasopressor sympathetic outflow. acinar-cells. Ca2+ signals are sensed by the Synaptotagmin-I (Syt-I) The present study has investigated the pharmacological profile of the protein, which additionally may act as a linker between Ca2+ stimulus histamine receptors (H1, H2, H3 and H4) that inhibit the cardio- and the exocytic machinery. Acinar-cells of labial salivary glands (LSG) accelerator sympathetic outflow in pithed rats by using selective from SS-patients show a significant upregulation of Syt-I mRNA, a Ca2+ agonists and antagonists of these receptors. response less sensitive to acetylcholine stimulation and an impaired Material and methods: Male Wistar rats (250–300 g; n=106) were cell-polarity. Here, we measured Syt-I mRNA and protein levels and pithed and prepared for selective preganglionic (C7-T1) spinal localization in LSG. Further, we characterized 3D-HSG cell acini in stimulation (0.03-3 Hz; 50 V; 2 ms pulses) of the cardioaccelerator culture as a model to study the overexpression of synaptotagmin I in sympathetic outflow, as previously reported (Villalón et al., Life Sci., 64, exocytosis. 1839-1847, 1999). Methodology: The relative levels of Syt-I mRNA and protein were Results: Electrical sympathetic stimulation or i.v. bolus injections of determined by qPCR and Western blot, respectively. Syt-I subcellular exogenous noradrenaline resulted in frequency-dependent and dose- localization was addressed by immunofluorescence and confocal dependent tachycardic responses, respectively. Moreover, i.v. 2+ microscopy. Ca signaling was measured in normal and polarity- continuous infusions of the H3/H4 receptor agonist immepip (3 and 10 altered 3D-HSG cell acini cultures using fluorescent dyes upon µg/kg.min), but not of physiological saline, dose-dependently inhibited carbachol and isoproterenol stimulation. The exocytic events were the tachycardic responses to sympathetic stimulation, but not those to assessed by amperometry and FM 1-43. noradrenaline, implying a sympatho-inhibitory effect. The cardiac Results: In LSG of SS-patients, Syt-I showed a significant increase of sympatho-inhibition by immepip (10 µg/kg.min) was: (i) unaffected mRNA and protein levels without changes of subcellular localization. after i.v administration of the vehicles (1 mL/kg of saline or DMSO 5%) Increased Syt-I immunofluorescence intensity was observed. Ca2+ or the antagonist ketotifen (H1; 100 µg/kg), ranitidine (H2; 3000 signaling was dependent on extracellular Ca2+ and acinar cell-polarity µg/kg) or JNJ7777120 (H4; 300 µg/kg); and (ii) abolished by the in cultured 3D-HSG. Furthermore, 3D-HSG responded to cholinergic antagonist thioperamide (H3; 100 µg/kg). The above doses of and adrenergic stimulation secreting amylase into the medium. antagonists: (i) were considered high enough (on the basis of their binding affinities) to completely block their respective receptors; and Conclusions: Increased Syt-I levels in SS-patients suggest Ca2+ (ii) did not modify per se the tachycardic responses to sympathetic signaling alterations. Therefore, 3D acini could be useful to assess the stimulation. Syt-I overexpression and its effect on exocytosis. Conclusion: the above results, taken together, suggest that the cardiac Fondecyt 1120062, Beca Doctorado Conicyt (JC, HU and MJB), Beca Apoyo de sympatho-inhibition induced by 10 µg/kg.min immepip is mainly tesis. mediated by stimulation of the histamine H3 receptor, with no pharmacological evidence for the role of the H1, H2 and H4 receptors.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S350
LATINFARMA 2013 Resúmenes/Abstracts
PFB 037: EFFICIENCY OF THE ARJ-DH12 AS ANALGESIC IN PFB 038: BIODISTRIBUTION AND PHARMACOKINETIC OF PATIENTS WIHT ACUTE ARTICULAR PAIN 1E10 MONOCLONAL ANTIBODY AFTER SUBCUTANEOUS ADMINISTRATION IN HEALTHY MICE Bermúdez MI, Sánchez C, Linares F. León M, Casacó A, Aldana L, García L, Castro Y, Ayra F, Hernández I, Group of Biopharmaceutical and Chemical Productions. LABIOFAM, Havana, Cuba. E-mail: [email protected] Leyva R. Isotope Centre, Havana, Cuba. E-mail: [email protected] Introduction: The joint pains are one of the most frequent causes of medical consultation, becoming a global health problem. Introduction: 1E10 monoclonal antibody was developed at Centre of Objective: To evaluate the analgesic effect of the ARJ-DH12 in patients Molecular Immunology (CIM) as antitumoral drug with proved efficacy with acute articular pain. in experimental models. In the present investigation, biodistribution and pharmacokinetic studies were conducted with the help of radio Material and methods: It was designed an experimental longitudinal isotopic labeling. prospective study in patients with acute articular pain attended in consultation during the period of January-April 2012, was carried out. Aim: To evaluate biodistribution and pharmacokinetic of the 1E10, the 125 It was studied a sample of 66 patients, according to the inclusion and molecule was radio labelled with I and incorporated into a cold exclusion criteria. The patients were selected at random in the two antibody formulation. treatment groups from which, 35 were treated with ARJ-DH12 (a Material and methods: Isotopic labeling was carried out by means of product obtained from the Rhopalurus junceus scorpion venom) and 31 standardized methods.1E10 was supplied by CIM and labeled with 125I with conventional treatment. It was described the evolution of the by the yodogen method. To male Balb/c mice from CENPALAB a single patients 3 times during a week. The main variables of the study were: subcutaneous administration of 1 mg/kg was performed in the supra age, sex, pain´s evolution and adverse reactions. scapular region and accommodated in metabolic cages during Results: The feminine sex and the group between 39 and 59 of age experiments. Blood samples were taken alternating five groups of were the most affected. The 62,9% of the patients with homeopathic three animals according with a sparse data design. Biodistribution was treatment achieved the disappearance of the pain and only in the 6,5% carried out by direct organ sampling and radioactive counting. of the patients with the conventional treatment. Pharmacokinetic was performed by compartmental analysis. Urine and faces were collected at regular time intervals. Conclusions: The homeophatic product ARJ-DH12 is effective in the treatment of acute articular pain. Results and conclusion: Observed pharmacokinetic behavior is typical of an immunoglobulin in the assay system used, showing a slow clearance and a small volume of distribution. Biodistribution shows no preference for any sampled organs or tissues. Only a high relative uptake was observed in axillar and brachial lymph nodes close to administration site.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S351
LATINFARMA 2013 Resúmenes/Abstracts
PFB 039: EFFECTS OF 17β-IMINOESTROGENS ON THE PFB 040: LONG-TERM INHIBITION OF CRAC CHANNELS SEXUAL BEHAVIOR OF FEMALE RATS ACTIVITY AND ALLERGIC ASTHMA IN EXPERIMENTAL CONDITIONS Jiménez L, Figueroa A, Jiménez L, Lemini C. Sutovska M1, Kocmalova M1, Adamkov M2, Franova S.1 Departamento de Farmacología, Facultad de Medicina. Universidad Nacional Autónoma de México. Apdo postal 70-297, CP 04510, México D. F. E-mail: 1Department of Pharmacology Jessenius Faculty of Medicine, Comenius [email protected] University, Martin, Slovakia. 2Institute of Histology and Embryology Jessenius Faculty of Medicine, Comenius University, Martin, Slovakia. Introduction: The estrogenic activity of the 17β-aminoestrogens compounds related to 17β-estradiol (E2) in sexual behavior has been investigated in animal models. These studies could contribute to a Introduction: Well-studied store-operated Ca2+ channels, Ca2+ release better understanding the structure-activity relationships of these activated Ca2+ (CRAC) channels identified in immune and airway compounds to the developing of safer alternatives of agents in the smooth muscle cells, are stimulated by depleted endoplasmic hormone replacement therapy. The aim of this work was the reticulum Ca2+ pool and mediate Ca2+ influx essentially important for evaluation of the 17β-iminoestrogens related to dedamine, butolame Ca2+ restoration and cellular functions. Emerging evidence points to and prolame compared to E2 and estradiol benzoate (EB) as facilitators their involvement in allergic airways diseases. This study evaluated on the rat lordotic behavior. therapeutic potency of CRAC blocker using experimental animal model of allergic asthma. Material and methods: Female Wistar rats (N=25), 8-9 weeks old (200 to 250 g bw) were bilaterally ovariectomized (Ovx) and kept at Methodology: Allergic inflammation of the airways was induced by constant temperature (20-22°C) and reversed 12 h light/dark cycle repetitive exposure of guinea pigs to ovalbumine and followed by 14 with ad libitum access to food and water through the experiments. days therapy by CRAC channels blocker (3-fluoropyridine-4-carboxylic Steroids were dissolved in corn oil as vehicle (V) and subcutaneously acid, FPCA). In vivo changes of specific airways resistance (sRaw) (s.c.) injected. A single or three subcutaneous (s.c.) consecutive evaluated bronchodilatory effect of FPCA and salbutamol. The method administration of E2 (≈30 μg/kg), EB (≈40 μg/kg), 17β-iminoestrogens of citric acid-induced cough reflex assessed antitussive activity of FPCA (≈440 μg/kg), or 300 μL/rat of V as control (≈1.2 mL/kg/day) were and codeine. The measurement of exhaled NO (ENO), expression of administered. All administrations were performed at 9.00 am. On the inducible NO-synthase (iNOS) by RT-PCR, immunohistochemical fourth day progesterone (P) was injected (I mg/rat in 100 μL of V). staining of airways tissue and levels of cytokines in plasma as well as Behavior testing began 4 hr after P injection. A lordosis quotient (LQ) bronchoalveolar lavage (BALF) by ELISA verified anti-inflammatory (number of lordosis/number of mounts x 100) was calculated as a effect of FPCA and budesonid. measure of sexual receptivity. Results: Long-term administration of FPCA resulted in significant Results: 17β-iminoestrogens treatment followed by a single injection cough suppression and bronchodilation, both comparable to the effect of P induces lordosis in Ovx female rats in a similar manner than E2, of control drugs, antitussive codeine and bronchodilator salbutamol. with less potency and greater efficacy. FPCA significantly decreased ENO, iNOS expression, levels of IL 4, IL 5 and IL 13 in plasma and BALF, which together with immuno- The authors thank Mr Rogelio Hernández de la Vega for technical assistance; the histochemical analysis validated its anti-inflammatory effect support by the Faculty of Medicine, and the grant PAPIIT IN218813, UNAM. comparable to corticosteroid budesonid. Conclusions: Presented data confirmed CRAC channels as a promising target for treatment of respiratory diseases causally associated with allergic inflammation.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S352
LATINFARMA 2013 Resúmenes/Abstracts
PFB 041: ROLE FOR THE TRPV1 CHANNEL IN GLUCOSE PFG 001: CYP1A1, GSTM1 AND GSTT1 METABOLIZING GENE HOMEOSTASIS POLYMORPHISMS AND SUSCEPTIBILITY TO CORONARY ARTERY DISEASE AMONG CIGARETTES SMOKERS Díaz-García CM, Morales-Lázaro SL, Sánchez-Soto C, Velasco M, Rosenbaum T, Hiriart M. Belkhiria MN, Maatouk F, Ben Hamda K.
Department of Neural Development and Physiology, Division of Neurosciences. Faculté de Médecine, Université de Monastir, Tunisia. Instituto de Fisiología Celular. Universidad Nacional Autónoma de México, Mexico City, Mexico. Introduction: Epidemiological evidence has demonstrated a strong relationship between cigarette smoking and coronary artery disease Introduction: Transient receptor potential channels have been put (CAD). CYP1A1, GSTM1 and GSTT1 contribute to the detoxification forward as regulators of insulin secretion. The role for TRPV1 has not process of organic compounds produced by cigarette smoking. The aim been evidenced in beta cells from primary cultures. of this study was to evaluate the interaction of the genetic Methodology: Here, we explored whether TRPV1 is functionally polymorphisms of CYP1A1 Msp1, GSTM1 and GSTT1 with cigarette expressed in cultures of beta cells from neonate and adult rats. Using a smoking and the risk of CAD in a Tunisian population. combination of fluorescent and electrophysiological techniques we Methods: Genomic ADN was obtained from 68 patients with CAD and 2+ examined if capsaicin could increase the intracellular Ca or to activate 73 healthy controls. All samples were analyzed by multiplex PCR and cationic non-selective currents. PCR-RFLP to determine GSTM1, GSTT1 and CYP1A1 Msp1 genotypes. Results: Our results show that TRPV1 channels are not functional in Results: We found that the GSTT1 null allele is associated with risk for insulin-secreting cells. We then wondered if nerve growth factor could CAD (odds ratios OR, 2.43, confidence interval CI, 1.09-5.41). induce expression of TRPV1 in beta cells from newborn rats and Considering the effect of GSTM1 gene polymorphisms on the smoking RINm5F cells but we failed to observe changes in TRPV1 function in related CAD, smokers with GSTM1 null genotype had more increased -/- either case. Nonetheless, by examining Trpv1 mice we observed that risk for CAD than non-smokers with GSTM1 present genotype (OR, these animals presented lower fasting insulin levels than their wild- 2.65, 1.05-6.72). Also the effect of GSTT1 gene polymorphism on type C57BL/6J littermates, although the glucose tolerance test smoking-related CAD showed the same tendency as GSTM1 gene: indicated no differences between both experimental groups. Moreover, smokers with GSTT1 null genotype had higher risk of CAD than non -/- no differences were observed in insulin secretion from Trpv1 mice smokers with GSTT1 present genotype (OR, 4.62, CI, 1.51-14.13). beta cells in response to basal (5.6 mM) or high glucose (15.6 mM) and However, the results did not show any significant association between KCl (40 mM) as compared to the wild-type animal cells. Thus, we CYP1A1 Msp1 polymorphism and CAD risk. decided to explore how the beta-adrenergic tone in the Trpv1-/-mice was affected the systemic response to propranolol. Propranolol Conclusion: Our results suggest that GSTM1 and GSTT1 increased insulin sensitivity in wild-type animals, but did not cause a polymorphisms may be a susceptibility factor to smoking-related CAD further reduction in the insulin tolerance curve of Trpv1-/-. in the Tunisian population. Conclusions: Our data show that TRPV1 does not contribute to glucose-induced insulin secretion in beta cells, but rather contributes to the adrenergic control of insulin sensitivity.
M.H. laboratory was supported by grants from CONACYT CB2009-131647, and DGAPA-PAPIIT IN215611, UNAM. C.M.D.G was supported by a doctoral fellowship from CONACyT. T.R. laboratory was supported by grants from the Marcos Moshinsky Foundation, CONACyT 129474 and PAPIIT IN204111. S.L.M.L. is supported by the postdoctoral scholarship program of UNAM (DGAPA).
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S353
LATINFARMA 2013 Resúmenes/Abstracts
POt 001: PTAQUILOSIDE RESIDUALITY CANCER COMPOUND POt 002: DESIGN AND EVALUATION OF L-ARGININE PELLETS IN MILK FROM CATTLE FARMS INVADED BY Pteridium TO IMPROVE DEVELOPMENT AND REPRODUCTION IN arachnoideum (KAULF.) MAXON IN THE PROVINCE OF RUMINANTS BOLÍVAR, ECUADOR Sánchez Z, Ruíz de Chávez JA, Mendoza G, Sandoval H, Melgoza LM. Calderón A, Sánchez LM, Mancebo B, Marrero E, Chiriboga X, Lucero D, Maestría en Ciencias Farmacéuticas. Universidad Autónoma Metropolitana –
Silva J. Xochimilco. Calzada del Hueso 1100, Col. Villa Quietud, Delegación Coyoacán, Universidad Estatal de Bolívar, Av. Che Guevara s-n y Gabriel Secaira Guaranda- 04960 México D.F., México. E-mail: [email protected] Ecuador. E-mail: [email protected]
Introduction: Arginine plays an important role in growth, Introduction: In different agricultural regions of the world, development and reproduction in ruminants. This semi-essential particularly in Latin America, has been reported toxic invasion for the amino acid is used to synthesize protein, nitric oxide (NO), urea, Gender ferns Pteridium, referring to the norsesquiterpene ptaquiloside, polyamines etc. NO stimulates the soluble intracytoplasmatic enzyme adversely affecting animal husbandry vaccine and presents a potential guanylate cyclase, responsible for the synthesis of cyclic guanosine risk to humans from the waste of the toxic component of the plant, in monophospate (cGMP) that participates in ovarian function and meat and milk. ovulation. The aim of the present investigation was to elaborated Methodology: The aim of this study was to determine the residual pellets which release L-arginine in the rumen and small intestine of toxic ptaquiloside in bovine milk from three Municipalities of the ruminants to be used in the synthesis of proteins and NO, respectively. Bolivar Province, Ecuador, by High Resolution Liquid Chromato- Material and methods: Pellets elaborated consisted of two different graphy. Milk samples were collected from farms invaded by bracken coating layers. In the first layer were incorporated L-arginine•HCl and Pteridium arachnoideum (Kaulf.) Maxon located at different altitudes. barium sulfate. Thereafter, pellets were protected with a pH dependent Results: The results showed the presence of residual levels polymer to release L-arginine•HCl in the small intestine. In vitro L- ptaquiloside in 89.29% of the samples analyzed, with maximum arginine•HCl release experiments from protected pellets were carried concentrations obtained in Chimbo of 2641.13 mg/mL, in San Miguel out by basket method on Hanson dissolutor. The experiment was de Bolívar of 2219.67 g/mL and Echeandía of 2130.12 g/mL. adapted based on the different pH of the rumen gastrointestinal tract Considering that this is the cause of producing toxic gastric cancer in and the residence time of the pellets in each compartment: rumen, humans, it is estimated that consumers of fresh milk in the Canton abomasum and small intestine. Samples were quantified using the Chimbo would be eating a ptaquiloside average concentration of technique of Moore and Stein. 894.13 mg/0.5 L/day of fresh milk. Results: The amount of L-arginine•HCl incorporated per gram of Conclusions: From the results it can be inferred the high risk to public pellets was 294mg. Barium sulfate was incorporated to provide density health from gastric cancer, due to repeated consumption of milk with to the pellet (1.3g/ml) and thus prevent them from being damaged toxic waste (ptaquiloside), emphasizing the rural sectors exposed. with rumination. In vitro release, a 48% of L-arginine•HCl was quantified during the first ten hours at pH 6 (rumen); no release of amino acid was observed in pH 3 (abomasum). Finally, the release of L- arginine was markedly increased in pH 7.5 in small intestine. Conclusions: L-arginine•HCl released in rumen can be used by ruminal microorganism for protein synthesis and later, the animal can use this microbial protein, but only in nutritional aspect. Amino acid released in small intestine is used to synthesize nitric oxide and improve reproduction in ruminants.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S354
LATINFARMA 2013 Resúmenes/Abstracts
POt 003: PATENTABILITY TEST IN COSTA RICA: CRITERIA POt 004: RETROSPECTIVE STUDY ON DRUG’S PATENTA- USED IN PHARMACY AND COMPARISON WITH FOREIGN BILITY IN COSTA RICA GUIDELINES Madrigal G. Vargas R. Faculty of Pharmacy, University of Costa Rica, Costa Rica. E-mail: Instituto de Investigaciones Farmacéuticas (INIFAR), Universidad de Costa Rica, [email protected] Costa Rica. E-mail: [email protected]
Introduction: Since admission of Costa Rica to the World Trade This study determined the reasoning of pharmaceutical experts during Organization (WTO) has been forced to sign a series of international the evaluation of the patentability in Markush formulas, polymorphs, treaties such as the Patents on Cooperation Treaty (PCT) and the Paris pharmaceutical compositions, enantiomers, methods of treatment, Convention, also by the signing Free Trade Agreement with the United Swiss-type claims, among other common forms of protection in Costa States of America has had to change the patent laws starting in the year Rica. 2008, these changes substantially impacted the patenting of various products, especially drugs. The target was to determine the criteria of experts in regular pharmacy claims, to establish what can be unified, to determine the Methodology: The present study is a retrospective diagnosis on the criteria outlined in the guidelines of other countries, and to draw a subject of drug patentability in Costa Rica between the years 2008- proposal of unified standards-based guideline to facilitate the 2012, the main variables used in the study are the number of patent submission and evaluation of patent applications. applications, patent applications granted, and the criteria patentability in the area of medicines. The study of the first two variables was made This exploration was performed in the context of qualitative research, using the database of the National Property Registry to quantify and following the particularistic ethnographic methodological design. The classify the number of applications in the pharmaceutical field. For the information was obtained through semi-structured interviews with study of the last variable was used unrestricted random sampling of specialists and analyzing documents published by patent offices in five the total population of patent applications evaluated to obtain a countries and a regional office. With the results, in first place, the representative sample with 95% confidence, and from there to classify criteria used by people taking the test for patentability of the major criteria for granting or rejecting of applications. Finally pharmaceutical patent applications were determined. Then the criteria compared the number of applications granted, with the registration of of patentability assessment manuals in Argentina, Spain, India, Canada, drug patents protected registered with the Ministry of Health. United Kingdom and the European Patent offices were identified. Finally, a comparison was made between the two sets of criteria, Results: Among the results of the study found a clear upward trend in determining the preponderance of congruence between the two the number of patent applications for drugs at the time of study, a clear groups, rather than differences. increase in the number of patents granted of drugs at the time of study, the main conclusions of the study, I was able to determine the main With this information, a proposal was drafted that will serve to guide criteria for the Costa Rican Office for the granting or rejecting of patents the experts responsible for carrying out the substantive examination of in the pharmaceutical field, and determined the non-correlation patentability within the pharmaceutical field. A useful summary of the between the number of patents granted and the number of patents guide, in tabular form was made, for quick reference of the proposed reclaimed by pharmaceutical companies when requesting a Sanitary guideline for each mode of protection in pharmaceutical patent Register. applications.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S355
LATINFARMA 2013 Resúmenes/Abstracts
POt 005: PHARMACOKINETICS AND TISSUE PENETRATION POt 006: PHARMACOKINETICS AND TISSUE DAMAGE OF CEFTAZIDIME ADMINISTERED DURING ABDOMINAL EVALUATION OF TWO PREPARATIONS OF CEFTAZIDIME HYSTERECTOMY AND OOPHORECTOMYIN BITCHES ADMINISTERED VIA INTRAMUSCULAR ROUTE IN GOATS De Gatica L, Villagra S, Prozzi G, Torres S, Farina H, Rule R. Lacunza J, Prozzi G, Villagra S, Muro A, Cordiviola C, Rule R.
Applied Pharmacology, Faculty of Medicine, Buenos Aires, Argentina. E-mail: Applied Pharmacology, Faculty of Medicine, Buenos Aires, Argentina. E-mail: [email protected] [email protected]
Introduction: The ceftazidime is an antibiotic which belongs to the Introduction: Ceftazidime is a third-generation cephalosporin. The group of cephalosporins. The aims of the present study were to antibiotics prepared using slow release vehicles and administered via determine the serum pharmacokinetics and the tissue penetration of intramuscular route may damage muscular tissue. The aims of this the ceftazidime during the abdominal hysterectomy and oophorectomy project were to determine the pharmacokinetic behaviour and in bitches. evaluate the tissue damage of two preparations of ceftazidime administered in goats. Material and methods: The study was divided in Trial 1 (T1) and Trial 2 (T2). In T1 there were used female canines (n=30), healthy. All Material and methods: These were used in two Trial: (T1 and T2) the animals were anaesthetised and, prior to the abdominal Creole goats (n=12), healthy, and without milk production. Throughout hysterectomy and oophorectomy, they received a single dose of T1, goats were administered a single dose of ceftazidime pentahydrate ceftazidime (20 mg/kg) by intravenous route; later, simultaneously, (20 mg/kg) via intramuscular route, prepared with conventional there were taken blood and tissue samples from: right ovary (RO), left formulation (CF). Throughout T2, the animals received a single dose of ovary (LO), body of uterus (BU), peritoneum (P), subcutaneous tissue ceftazidime pentahydrate (20 mg/kg), prepared with 50% propylene (ST) and skin (S). These samples were taken from the animals (n=6 in glycol (PG). Throughout the course of T1 and T2, blood samples were each period) during the following intervals: 0.5-1, 1-1.5, 1.5-2, 2-3 and taken in controlled periods of time with the aim of quantifying the 3-4 hours. During T2, 10 animals which had participated in T1 were antibiotic using a biological method, and carrying out the appropriate selected with the purpose of doing pharmacokinetic studies. biochemical determinations.
Results: The Cmax (0.5-1 h) and Cmin (2-3 h)(Means) of ceftazidime in Results: The pharmacokinetic parameters of ceftazidime in PG and CF tissues were: RO= 52.8 and 0.3; LO= 54.6 and 0.4; BU= 38.2 and 1.1; formulations were: λz= (PG) 0.5 ± 0.3 and (CF) 0.3 ± 0.1h-1; Kab= (PG) PP= 34.5 and 4.6; ST= 32.3 and 8.0 and P= 54.6 and 1.0 µg/mL, 0.9 ± 1.7 and (CF) 3.5 ± 2.5 (h); t½= (PG) 1.6 ± 0.9 and (CF) 2.0 ± 0.4 (h); respectively. The indices of penetrations in tissue obtained in interval t½ab= (PG) 0.6 ± 0.5 and (CF) 0.2 ± 0.1 (h); Cmax= (PG) 46.5 ± 9.6 and 0.5-1.0 h were: RO= 1.0; LO= 1.2; BU= 0.75; PP= 1.1, ST= 0.53 and P= (CF) 55.5 ± 3.8 (µg/mL); tmax= (PG) 1.3 ± 0.7 and (CF) 0.7 ± 1.1 (h); 1.0. The pharmacokinetics (Mean ± SD) parameters were: t½= 1.03 ± AUC= (PG) 201.8 ± 24.5 and (CF) 219.0 ± 21.6 (µg.h/mL); F(relative)= 0.33 h; AUC= 100.6 ± 46.9 μg/mL.h; AUMC= 174.1 ± 88.6 μg/mL.h; (PG) 92.1 ± 19.9 (%). Varea= 297.2 ± 137.5 mL/kg; Vss= 343.1 ± 166.8 mL/kg; CL= 174.5 ± 50.2 mL/kg and TMR= 1.78 ± 0.61 h. Conclusions: The mean absorption time of the PG formulation was 2.4 times superior to the one observed in the CF, although the mean lives Conclusion: The serum pharmacokinetics and the penetration of and the relative bioavailability were similar for both formulations. The ceftazidime in tissues suggest that it is possible to use them clinically in CK serum levels were superior to the values obtained with formulation the prophylaxes of postoperative infections during the abdominal CF within 24 hours post-administration of ceftazidime. hysterectomy and oophorectomy in bitches.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S356
LATINFARMA 2013 Resúmenes/Abstracts
POt 007: STRATEGIC PROJECT MANAGEMENT IN THE POt 008: INTERACTIONS BETWEEN CUBA AND BRAZIL: PHARMACEUTICAL INDUSTRY: THE ROLE OF THE PRODUCTION SCIENCE, HUMAN RESOURCES TRAINING IN CONTRACT RESEARCH ORGANIZATIONS NEUROSCIENCE Slaninka Miceska M, Kikerkov I, Kikerkova I, Shuturkova LJ. Calabró L, Baggio S, Souza D.
Department of Preclinical and Clinical Pharmacology and Toxicology, Medical Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 – Anexo Faculty, Ss.Cyril and Methodius University of Skopje, Republic of Macedonia. E- Porto Alegre, RS, Brazil. E-mail: [email protected] mail: [email protected]
In countries where Science is sponsored mostly by public investments, The pharmaceutical industry is facing rapid changes of its business the evaluation of scientific activity is crucial. As the investments are strategy necessary for survival in terms of severe competition on the limited, competition among different segments of the society receiving global market. In the field of pharmacy and biotechnology the government funding is constant. To ensure the contribution of Science outsourcing or the cooperation with contract research organizations in economic, social and political achievements, and the financial has been evidenced as the most attractive method in favor of cost investments needs, the evaluation of scientific activity is vital. rationalization and optimal usage of recourses available. The practice of engaging contract research organizations (CROs) has not been a Recently, there was an increase in Brazilian scientific production, novelty for pharmaceutical industries; however it has been 8%/year, which now account for 45% of all production in Latin tremendously intensified during the last two decades. Outsourcing has America. This justifies the efforts provided to indicators prospection especially great importance for the pharmaceutical companies in the for assisting the Science and Technology strategies. These data are field of generic drug development. Including Central and Eastern even more impressive, as the scientific productivity and the number of European countries as full members of the EU, a part of the Balkan indexed Brazilian scientific journals by ISI are in constant growth. states, among which belongs our country as well, became attractive for The diffusion of science in books, articles, thesis and scientific events conducting projects sponsored by pharmaceutical companies that are key elements of scientific communication used for scientific activity originate from the EU. Up-to-date experience confirmed that also evaluation. institutions of higher education are able to comply with the role of single-window providers for the needs of the pharmaceutical industry. In Brazil, the major scientific production comes from the universities. Also, the Faculty of Medicine at the “Ss. Cyril and Methodius University” Such institutions stimulate members of their community to step up in Skopje has established a six-decade tradition of well developed their scientific production and human resources training, grounded in system of cooperation with the domestic pharmaceutical industry. the requirements of Brazilian agencies that evaluate and sponsor the Lately it started to develop cooperation with foreign pharmaceutical scientific and technological research, as CAPES, CNPq, FINEP and FAPs. companies, as well. For the successful accomplishment of this kind of research it is necessary to fulfill the following preconditions: presence Part of this significant increase in Brazil participation in the of highly qualified personnel; knowledge of the national and international science is attributed to interactions among Brazilian international legislation and regulation on generic drugs; established research groups with groups from other countries. standard operation procedures required; following deadlines up to the Thus, this work aims to evaluate the scientific and production (No. of contract; well-established infrastructure, capacity and technology publications, h-index, citations), the training of human resources and under controlled working conditions; experience in laboratory the scientific collaboration network in the agreement Brazil – Cuba, practices; quality data-management; etc. The preparation and the using the databases from Scopus - Elsevier and Web of Science – ISI. conduct of the research is a multitasking process where activities should be performed by a precisely defined schedule and established With this work, we shall identify, with the researchers participants of criteria. this agreement, whether there was an intensification of the scientific exchange and observing the experience of undergraduate and post- graduate students from both human health research institutions, Brazilian and Cuban.
http://jppres.com/jppres J Pharm Pharmacogn Res (2014) 2(Suppl. 1):S357