Erzincan, 2015
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ABSTRACTS
INVITED LECTURERS
IL - 1. GENERATIONS @ WORK ______8 IL - 2. NANOMATERIALS IN COSMETICS ______9 IL - 3. FEATURE-BASED 3D PHARMACOPHORE MODELS: EFFICIENT MEDICINAL CHEMISTRY DECISION SUPPORT TOOLS ______10 IL - 4. COLLOIDAL CARRIERS AT BIOLOGICAL BARRIERS: CHALLENGES AND NEW CONCEPTS FOR DERMAL AND PULMONARY APPLICATION ______11 IL - 5. “HOW A MOLECULE CAN BE CALLED AS A MEDICINAL PRODUCT”: REGISTRATION PROCEDURES IN TURKEY ______12 IL - 6. RESEARCH AND DEVELOPMENT ACTIVITIES IN PHARMACEUTICAL SECTOR FROM AN ACADEMICIAN POINT OF VIEW ______13 IL - 7. TOXİCİTY OF MYCOTOXİNS ______14 IL - 8. NEW HORIZONS IN NANOTHERAPEUTICS: NANOTUBES, QUANTUM DOTS, LIPID BASED CARRIERS, NANOVAULTS, NANOBOATS ______15 IL - 9. APPLICATION OF NEW NANO-BASED ELECTROCHEMICAL AND SPECTROSCOPIC SENSORS IN PHARMACEUTICAL ANALYSIS ______17 IL - 10. ACTUAL ASPECTS OF THE GLOBAL MARKET OF MEDICAL COSMETICS ______19 IL - 11. TOXICITY OF DRUG ______HATA! YER İŞARETİ TANIMLANMAMIŞ.
ORAL PRESENTATIONS
OP - 1. QUALITY CONTROL OF HERBAL MEDICINES BY CAPILLARY ELECTROPHORESIS COUPLED WITH LASER INDUCED FLUORESCENCE DETECTOR ______21 OP - 2. TRANSFER OF ADVANCED KNOWLEDGE AND TECHNOLOGIES TO MODERN-DAY EDUCATION ___ 22 OP - 3. CHEMOMETRIC SIGNAL PROCESSING METHODS IN DRUG ANALYSIS ______23 OP - 4. LIPOSOME FORMULATIONS FOR COSMETIC TEXTILE APPLICATIONS ______24 OP - 5. PREPARATION AND EVALUATION OF NOVEL MICROEMULSION-BASED HYDROGELS FOR DERMAL DELIVERY OF BENZOCAINE ______25 OP - 6. IMPLEMENTATION OF CLINICAL PHARMACY PRACTICES IN HACETTEPE HOSPITALS? ______26 OP - 7. HOW MUCH PROGRESS HAS PSYCHIATRY MADE IN THE LAST CENTURY? DO WE KNOW ENOUGH ABOUT THE HUMAN PSYCHE TO PRESCRIBE THE MEDICATION?______27 OP - 8. HUMAN MEDICINES REGISTRATION PROCESS IN TURKEY ______28 OP - 9. THE PHARMACY MANAGEMENT DEPARTMENT’S STUDIES IN TURKEY ______29 OP - 10. ANTIMUTAGENIC POTENTIALS OF FLAVONOIDS FROM ACHILLEA MILLEFOLIUM L. AND ACHILLEA BIEBERSTEINII AFAN. ______30 OP - 11. STABILITY INDICATING HPLC-PDA ANALYSIS OF FEBUXOSTAT UTILIZING DESIGN OF EXPERIMENTS 31 OP - 12. KOZMETİK SEKTÖRÜNÜN ENDÜSTRİYEL AÇIDAN DEĞERLENDİRİLMESİ ______32 OP - 13. FORMULATION AND EVALUATIONS OF BETA CYCLODEXTRIN AND POLYETHYLENE GLYCOL MEDIATED BINARY AND TERNARY COMPLEXES OF SYLIMARINE ______33 OP - 14. FILM COATING OF TABLETS ______34
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OP - 15. PROTECTIVE ROLE OF OLEUROPEIN ON ZNOTIO2 NANOCOMPOSITE- INDUCED SOME DEVELOPMENTAL TOXICITY ON DROSOPHILA MELANOGASTER ______35 OP - 16. TAURINE IMPROVES CHEMOTHERAPY INDUCED GASTROINTESTINAL TOXICITY IN ACUTE LYMPHOBLASTIC LEUKEMIA. ______36 OP - 17. ANTIBREASTCANCER ACTIVITY OF NANOPROPOLIS INDONESIA ON INDUCED MAMMARY TUMOR GLAND BY DMBA IN VIRGIN SPRAGUE-DAWLEY RATS ______37 OP - 18. IN VITRO EVALUATION OF THE POTENTIAL OF PREACTIVATED POLY ( ACRYLIC ACID) THIOMERS TO INHIBIT MRP2 EFFLUX TRANSPORTER ______38 OP - 19. UV-SPECTROPHOTOMETRIC-ASSISTED CHEMOMETRIC METHOD FOR THE SIMULTANEOUS DETERMINATION OF QUINAPRIL HYDROCHLORIDE AND HYDROCHLOROTHIAZIDE IN PHARMACEUTICAL FORMULATIONS ______39 OP - 20. SECONDARY METABOLITES OF CULTIVATED ARTEMISIA DRACUNCULUS L. ______40 OP - 21. EFFECT OF AGING, EXERCISE AND CATALASE OVEREXPRESSION ON VARIOUS PROTEIN OXIDATION PRODUCTS IN MICE ______41 OP - 22. DETERMINATION OF IN-VITRO ANTIOXIDANT CAPACITY OF Β - AGONISTS ______42 OP - 23. DEVELOPMENT AND VALIDATION OF LC-MS METHOD FOR DETERMINATION OF HALOPERIDOL IN HUMAN PLASMA ______43 OP - 24. LABEL-FREE SENSING PLATFORM FOR DETECTION OF CHOLESTEROL ______44
POSTER PRESENTATIONS
PP - 1. CYTOTOXIC EFFECT OF HELIX ASPERSA EXTRACT ON HUMAN BREAST CANCER CELL LINE HS578T 46 PP - 2. DETERMINATION OF FRUCTOSE IN SWEETENED FOODS AND BEVERAGES ______47 PP - 3. DEVELOPMENT OF TECHNOLOGY AND DOSAGE FORM DESIGN FOR TARGETED DRUG DELIVERY 48 PP - 4. TAURINE IMPROVES CARBAMAZEPINE INDUCED DROWSINESS. ______49 PP - 5. "ANTI-ASTHMATIC ACTIVITY OF EUPHORBIA GRANDIALATA R. CULTIVATED IN EGYPT" ______50 PP - 6. DETERMINATION OF DABIGATRAN IN PHARMACEUTICAL PREPARATIONS BY DIFFERENTIAL PULSE VOLTAMMETRIC METHOD ______51 PP - 7. DETERMINATION OF SOME METAL LEVELS IN MULTIVITAMIN PREPARATIONS WITH ICP-OES AFTER DRY, WET AND MICROWAVE DIGESTION METHODS ______52 PP - 8. LIPOIDAL MATTERS, FLAVONOID CONTENT AND HYPOLIPIDEMIC ACTIVITY OF SPINACH ROOTS AND FLOWERS ______53 PP - 9. ANTIOXIDANT AND ANTIMICROBIAL ACTIVITIES OF LEPIDIUM SATIVUM EXTRACTS ______54 PP - 10. DESIGN, SYNTHESIS AND CYTOTOXIC ACTIVITY EVALUATIONS OF N-HETROARYL DICHLOROACETAMIDE DERIVATIVES AS ANTICANCER AGENTS ______55 PP - 11. SAFETY ASSESSMENT OF OSTHOLE ISOLATED FROM PRANGOS FERULACEA: ACUTE AND SUBCHRONIC TOXICITIES AND MODULATION OF CYTOCHROME P450 ______56 PP - 12. STABILIZATION OF AMORPHOUS CANDESARTAN CILEXETIL AS AN APPROACH TO INCREASE ITS AQUEOUS SOLUBILITY ______57 PP - 13. SYNTHESIS AND ANTIMICROBIAL EVALUATION OF NEW 3-ALKYL(ARYL)-4-(2-PHENYLACETOXY-3- ETHOXYBENZYLIDENAMINO)-4,5-DIHIDRO-1H-1,2,4-TRIAZOL-5-ONES* ______58
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PP - 14. EFFECT OF OZONE ON REMOTE ORGAN INJURY IN RATS WITH HEPATIC ISCHEMIA-REPERFUSION INJURY ______59 PP - 15. DEVELOPMENT OF A NANOEMULSION FORMULATION OF WILD OREGANO ESSENTIAL OIL _____ 60 PP - 16. ELECTRO-OXIDATION BEHAVIOR OF DEXAMETHASONE ON THE MODIFIED-MULTI WALLED CARBON NANOTUBE ELECTRODE AND ITS APPLICATION TO BIOLOGICAL SAMPLES ______61 PP - 17. HIGHLY EFFICIENT, ONE POT, SOLVENT FREE ACCESS TO SOME NOVEL QUINAZOLINONE DERIVATIVES USING PTSA (P-TOLUENESULFONIC_ACID) AS CATALYST: SYNTHESIS AND ANTIFUNGAL ACTIVITY EVALUATION ______62 PP - 18. SIMULTANEOUS DETERMINATION OF CLORSULON AND IVERMECTIN IN VETERINARY INJECTABLE PREPARATION BY A NEW UPLC METHOD ______63 PP - 19. CHEMICAL COMPOSITION OF LIMONIUM THOUINII (VIV.) KUNTZE (PLUMBAGINACEAE) AND THE DPPH FREE RADICAL SCAVENGING ACTIVITY ______64 PP - 20. FORMULATION AND EVALUATION OF KETOCONAZOLE LIPOSOMES USING INJECTION METHOD _ 65 PP - 21. DEVELOPMENT AND VALIDATION OF AN UV SPECTROPHOTOMETRIC METHOD FOR THE DETERMINATION OF CAPSAICIN IN THE RED HOT CHILLI PEPPER ______66 PP - 22. DEVELOPMENT AND VALIDATION OF A VIS SPECTROPHOTOMETRIC METHOD FOR THE DETERMINATION OF TOTAL PHENOLIC COMPOUNDS IN THE RED HOT CHILLI PEPPER ______67 PP - 23. AN INVESTIGATION ON PROTECTIVE EFFECT OF GILABURU (VIBURNUM OPULUS L.) FRUIT AGAINST ISCHEMIA/REPERFUSION-INDUCED OXIDATIVE STRESS AFTER LUNG TRANSPLANTATION IN RAT 68 PP - 24. APITERAPY ______69 PP - 25. ENTOMOTHERAPY AND TURKEY ______70 PP - 26. THE POTENTIAL OF ARTHROPODS CAUSES VENOM ALLERGY AT TURKEY ______71 PP - 27. DIABETES MELLITUS AND ASSOCIATED FACTORS IN HUMAN IMMUNODEFICIENCY VIRUS-INFECTED INDIVIDUALS AT JIMMA UNIVERSITY SPECIALIZED HOSPITAL, SOUTHWEST ETHIOPIA ______72 PP - 28. DETERMINATION TOXIC EFFECT OF NEW SYNTHESIZE CHEMICAL COMPOUNDS IN VITRO. _____ 73 PP - 29. GENOTOXIC AND ANTIGENOTOXIC EFFECT OF NEW SYNTHESIZE CHEMICAL COMPOUNDS ON HUMAN LYMPHOCYTE IN VITRO. ______74 PP - 30. ACTIVATORS OF CARBONIC ANHYDRASE I AND II: OSAJIN AND POMIFERIN ______75 PP - 31. GENOTOXIC AND ANTIGENOTOXIC EFFECT OF SOME LICHENS______76 PP - 32. DETERMINATION OF ANTIOXIDANT CAPACITY OF TWO LICHENS IN VITRO ______77 PP - 33. THE POTENTIAL OF PLANTS ARE IMPORTANT IN TERMS OF IMPLICATION THE HONEY, POLLEN, PROPOLIS USED IN APITHERAPY ______78 PP - 34. DETERMINATION OF GENOTOXIC AND ANTIGENOTOXIC EFFECT OF NEW SYNTHESIZE ORGANIC COMPOUNDS ______79 PP - 35. DETERMINATION OF CYTOTOXIC AND ANTICYTOTOXIC EFFECT OF NEW SYNTHESIZE CONPOUNDS ______80 PP - 36. GENOTOXIC AND ANTIGENOTOXIC EFFECT OF SOME LICHENS______81 PP - 37. DETERMINATION OF ANTIOXIDANT CAPACITY OF TWO LICHENS IN VITRO ______82
PP - 38. CHE INHIBITION AND AΒ42 AGGREGATION ACTIVITIES OF 1H-INDENE-2-CARBOXAMIDE DERIVATIVES AS ANTI-ALZHEIMER AGENTS ______83 PP - 39. PURIFICATION, CHARACTERIZATION AND BIOTECHNOLOGICAL APPLICABILITY OF ALKALINE PROTEASE BY AERIBACILLUS PALLIDUS C10 ______84 PP - 40. ANTIOXIDANT POTENCIES OF SEMPERVIVUM ARMENUM METHANOL EXTRACTS ON HUMAN LYMPHOCYTES IN VITRO ______85
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PP - 41. INVESTIGATION GENE EXPRESSION ANALYSIS OF SOME FOXO SIGNALING PATHWAY GENES IN DROSOPHILA MELANOGASTER ______86 PP - 42. RİSK ASSESSMENT TRİALS İN THE ASPECT OF QUALİTY BY DESİGN ______87 PP - 43. COPEPTİN: A CANDİDATE BİOMARKER OF PULMONARY THROMBOEMBOLİSM ______88 PP - 44. COPEPTIN: A PROMOSING PROGNOSTIC MARKER IN ACUTE APPENDICITIS ______89 PP - 45. PHARMACOGNOSTICAL INVESTIGATION OF ТRIGONELLA ORTOSERAS GROWING IN UZBEKISTAN 90 PP - 46. IN VITRO INHIBITION OF ALFA-CARBONIC ANHYDRASE ISOZYMES BY SOME ANIONS ______91 PP - 47. PURIFICATION OF CARBONIC ANHYDRASE FROM DIFFERENT ORGANISM AND ASSESSMENT OF ENZYME KINETICS AGAINST SULFOAMIDES ______92 PP - 48. INTERACTION OF SOME CARBONIC ANHYDRASE ISOZYMES WITH SOME NATURAL PHENOLIC COMPOUNDS ______93 PP - 49. DESIGN, MOLECULAR MODELING AND SYNTHESIS OF SOME NOVEL HETERO ALKYL OXIME DERIVATIVES AS ANTIFUNGAL AGENTS ______94 PP - 50. LYCIUM BARBARUM USE EFFECTS ON SOME BIOCHEMICAL PARAMETERS AND RANKL CYTOKINE LEVELS OF WISTAR ALBINO RATS WITH OSTEOPOROSIS MODEL INDUCED BY GLUCOCORTICOID AND OVARIECTOMY ______95 PP - 51. THE AWARENESS OF APITERAPY AT ERZINCAN UNIVERSITY ______96 PP - 52. DETERMINATION OF PANTOPRAZOLE IN PHARMACEUTICAL PREPARATIONS AND HUMAN SERUM BY SQUARE WAVE AND DIFFERENTIAL PULSE POLAROGRAPHY METHODS ______97 PP - 53. NEW VALIDATED METHODS FOR THE SIMULTANEOUS DETERMINATION OF TWO MULTICOMPONENT MIXTURES CONTAINING NIMESULIDE AND LIDOCAINE IN COMBINED PHARMACEUTICAL PREPARATION BY USING CHEMOMETRIC CALIBRATION METHODS (PCR AND PLS) ______98 PP - 54. LIDOCAINE HCL IN COMBINED PHARMACEUTICAL FORMULATIONS BY USING CHEMOMETRIC CALIBRATION METHODS (PCR AND PLS) ______99
PP - 55. VITAMIN B12 AND FOLATE LEVELS IN COLOSTRUM AND TRANSITIONAL MILK FROM MOTHERS OF TERM INFANTS ______100 PP - 56. ANTIOXIDANT ACTIVITIES OF THE ESSENTIAL OILS OBTAINED FROM BAYBURT AND DADAŞKÖY ECOTYPES OF ARTEMISIA DRACUNCULUS L. ______101 PP - 57. CLONING, EXPRESSION AND CHARACTERIZATION OF HUMAN BRAIN ACETYLCHOLINESTERASE 102 PP - 58. DETERMINATION OF EFFECTS OF PHARMECEUTICALS SUCH AS GEMFIBROZIL AND Β-ESTRADIOL ON CUCUMIS MELO L SEED GERMINATION ______103 PP - 59. THE EFFECTS OF PHARMECEUTICALS SUCH AS GEMFIBROZIL AND Β-ESTRADIOL ON CUCUMIS SATIVUS L. SEED GERMINATION ______104
PP - 60. VITAMIN B12 AND FOLATE LEVELS IN HUMAN MILK FROM MOTHERS OF PRE-TERM INFANTS AT DIFFERENT LACTATION STAGES ______105 PP - 61. OXIDATIVE STRESS IN TYPE 2 DIABETIC NEPHROPATHY: TUNISIAN EXPERIENCE ______106 PP - 62. PROTEIN OXIDATION LEVELS IN DIFFERENT ORGANS OF RATS EXPOSED TO AROCLOR 1254 AT DIFFERENT SELENIUM STATUS ______107 PP - 63. ADIPONECTIN IN METABOLIC SYNDROME ______108 PP - 64. SOME LICHEN ACIDS MAY BE USED AS A POTENTIAL DRUG FOR CANCER THERAPY; BY INHIBITING MITOCHONDRIAL THIOREDOXIN REDUCTASE ______109 PP - 65. NOVEL GENOMIC AND PROTEOMIC EFFECTS OF HYDROXYFASUDIL IN PS INDUCED RAT BLADDER; PRELIMINARY RESULTS ______110
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PP - 66. PHYSICOCHEMICAL CHARACTERIZATION AND PHARMACOLOGICAL EVALUATION OF EZETIMIBE-PVP K30 SOLID DISPERSIONS IN HYPERLIPIDEMIC RATS ______111 PP - 67. PHARMACOLOGICAL AND HISTOLOGICAL EXAMINATION OF ATORVASTATIN-PVP K30 SOLID DISPERSIONS ______112 PP - 68. MEDICINAL PLANTS FROM THE GENUS ALCHEMILLA (ROSACEAE): A REVIEW OF PHYTOCHEMISTRY, PHARMACOLOGY AND ETHNOBOTANY ______113 PP - 69. PHOTOPHYSICAL CHARACTERIZATION OF INTERACTION OF INDOLE COMPOUND WITH MODEL MEMBRANE SYSTEMS IN 5,14-DIMETHYL-5,6,7,8,9,14-HEXAHYDROINDOLO[2’,3’:3,4] CYCLOOCTA[1,2-B]. ______114 PP - 70. DYE-MEMBRANE INTERACTION: A SPECTROSCOPIC STUDY ______115 PP - 71. SERUM AMYLOIDE A AND HIGH SENSITIVITY C-REACTIVE PROTEIN IN ACUTE PHASE OF ACUTE CORONARY SYNDROME WITH ST-SEGMENT ELEVATION ______116 PP - 72. HOMOCYSTEIN AND HIGH SENSITIVITY C-REACTIVE PROTEIN IN ACUTE PHASE OF ACUTE CORONARY SYNDROM ______117 PP - 73. MICROWAVE ASSISTED SYNTHESIS AND BIOLOGYCAL ACTIVITY STUDIES OF SOME NEW DEIVED FROM ANTIPYRINE ______118 PP - 74. SOLID PHASE EXTRACTION - HIGH PERFORMANCE LIQUID CHROMATOGRAPHY-UV METHOD FOR DETERMINATION OF RIVAROXABAN IN HUMAN PLASMA ______119 PP - 75. CLONING AND EXPRESSION OF RAT (RATTUS NORVEGICUS) BRAIN ACETYLCHOLINESTERASE GENE ______120 PP - 76. THE DETERMINATION OF THE ANTIOXIDATIVE PROPERTIES OF WATER, ETHANOL-WATER, METHANOL AND CHLOROFORM EXTRACTS OBTAINED FROM CİNNAMON, CUMİN AND SUMAC, İN VİTRO ______121 PP - 77. CHITOSAN COATED POLYCAPROLACTONE INSERTS OF TERBAFINE HCL: PREPARATION AND EVALUATIONS ______122 PP - 78. STABILITY INDICATING HPLC METHOD FOR THE DETERMINATION FULVESTRANT IN PHARMACEUTICAL FORMULATION IN COMPARISON WITH LINEAR SWEEP VOLTAMMETRIC METHOD ______123 PP - 79. STUDY OF THE BORON LEVELS IN SERUM AFTER IMPLANTATION OF DIFFERENT RATIOS NANO- HEXAGONAL BORON NITRIDE-HYDROXY APATITE IN RAT FEMURS ______124 PP - 80. DESIGN, SYNTHESIS AND EVALUATION OF BENZOFURAN-ACETAMIDE SCAFFOLD AS POTENTIAL ANTICONVULSANT AGENT ______125
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Generations @ Work Buket AKSU
A generation has a shared memory of important events and similar assumptions about what matters based on their formative experiences. A generation is defined by common tastes, attitudes, and experiences; a generational cohort is a product of its times and tastes. Because generations share a place in history and have events, images, and experiences in common, they develop their own unique personalities. There are four generations in the workplace who due to the era in which they grew up have divergent values and preferences. The four generations are Veterans-also known as Traditionalists (born between 1920 and 1940); the Baby Boomers (born between 1947 and 1967); Generation X (born between 1970 and 1980); and Generation Y, also known as Millennials, (born between 1980 and 1999). The four generations that occupy today's workplace are clearly distinguishable their demographics, their early life experiences, the headlines that defined their times, their heroes and music and sociology, and their early days in the workplace. Yet few organizations look at generational preferences when developing diversity strategies. As a result, poor workplace performance can result. Their differences can be a source of creative strength and a source of opportunity, or a source of stifling stress and unrelenting conflict. It is critical to creating harmony, mutual respect and joint effort, where today there is suspicion, mistrust and isolation. The 2020 workplace which will be formed by mostly Millennials and Linksters : An organizational environment that provides an intensely personalized, social experience to attract, develop, and engage employees across all generations and geographies. Millennials're the first generation to grow up immersed in digital media. For them, technology is as natural as air. They expect to work more than 40 hours a week to achieve the lifestyle they want. Whereas Gen Xers have never seen the point of working beyond the standard nine to fıve day, Millennials expect to go above and beyond. Managing Millennials is all about engaging them. Engagement is far more than simply communicating effectively. Engaged employees are those who are fully involved in their work. They are committed to their own growth and growth in their jobs. Generation Linkster, born after 1995, so called because no other generation has ever been so linked to each other and to the world through technology. The essential ingredients used to create engaged employees are similar to those present in a satisfying personal relationship: mutual trust, authentic communication, respect, shared values, and a commitment to growing together. There are four main areas that can contribute to an engaged workforce: recruiting, connecting employees through advanced communication methods, learning, and leadership. The 2020 workplace will be fluid, diverse in age and ethnicity, flexible, collaborative, mobile, global, and, above all, hyperconnected. Get ready to live it!
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Nanomaterials in Cosmetics Assoc.Prof. Evren ALĞIN YAPAR
The Ministry of Health of Turkey, Turkish Medicines and Medical Devices Agency, Ankara, Turkey.
E-mail:[email protected]
Abstract
Nanotechnology based nanomaterials have been widely used in cosmetics for recent years. However debate on their definition and insufficient quantification methods are major problems still occur in the nanomaterial field (1,2). The use of nanomaterials in cosmetics has been offering some advantages such as efficiency, transparency, unique texture, protection of active ingredient, enhance solubility and facilitating its transport to the skin. In this context nanotechnology-based delivery systems in cosmetology give opportunity to control the release of actives and to deliver them to the desired site. In terms of delivery of nanoparticles via dermal route main factors can be counted as location and skin conditions at the application site, physicochemical properties of the penetrating molecule, and physicochemical properties of the vehicle dispersing the penetrating molecule. Nanocarriers have also presented some advantages such as facilitate direct interaction of sensitive agents with skin, delayed release of sensitizing agents, reduction in the amount of agents and additives, increased lifespan and hence greater product acceptability. Either soft or rigid nanoparticles have been used in a wide range of spectrum in cosmetic field such as sunscreens, hair products, skincare products, etc. (3). The effect of nanomaterial in terms of desired and undesired effects could be envisaged by nanoparticle’s characteristics (e.g., shape, size, surface charge, surface composition, coating, type of materials) and other components in the nanoparticle’s formulations (4). In this speech requirement and novel approaches in nanotechnology-based carrier systems designed for various applications for cosmetology have been summarized in particular for production, characterization, and usage of nanocarriers.
Keywords: Nanomaterials, cosmetics, characterization methods, preparation methods, safety issues.
References 1. Mihranyan, A., Ferraz, N., Stromme, M. Current status and future prospects of nanotechnology in cosmetics. Progress in Materials Science, 57: 875-910, 2012. 2. Alğın Yapar, E., İnal Ö. Nanomaterials and cosmetics. J. Fac. Pharm. Istanbul, 42(1):71-98, 2012. 3. Pal, T.K., Mondal, O. Prospect of nanotechnology in cosmetics: Benefit and risk assessment. World Journal of Pharmaceutical Research, 3(2), 1909-1919, 2014. 4. Mu, Li., Sprando, R.L. Application of nanotechnology in cosmetics. Pharm Res, 27: 1746–1749, 2010.
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Feature-based 3D Pharmacophore Models: Efficient Medicinal Chemistry Decision Support Tools T. Langer1, S. D. Bryant2, G. Ibis2, T. Seidel1, M. Wieder1
1 Department of Pharmaceutical Chemistry, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria 2 Inte:Ligand GmbH, Mariahilferstrasse 74b/11, 1070 Vienna, Austria
Abstract
Pharmacophore-based compound modeling, virtual screening, and bio-activity profiling has become a popular in silico technique for supporting medicinal chemists in their hit finding, hit expansion, hit to lead, and lead optimization programs. [1]
At Inte:Ligand GmbH, we have developed the LigandScout [2] platform as an integrated software solution containing rapid and efficient tools for automatic interpretation of ligand-protein interactions and subsequent transformation of this information into 3D chemical feature-based pharmacophore models. Additionally, pattern recognition-based algorithms were developed for ligand-based pharmacophore modeling in the absence of a target 3D structure, as well as for establishing novel accurate virtual screening procedures. Our recent interest is to incorporate the results of molecular dynamics simulation trajectories into the pharmacophore description, in order to develop pharmacophore ensembles representing the dynamic event of binding and to make this functionality available as LigandScout KNIME [3] extensions.
In the presentation, we will highlight successful applications of chemical feature-based 3D pharmacophore modeling within the early drug discovery process. Such examples range from drug repurposing, to in silico fragment-based hit discovery and discovery of novel protein-protein interface inhibitors.
References
[1] Langer, T., Pharmacophores in Drug Research, Mol. Inf. 2010, 29, 470-475.
[2] Wolber, G., Langer, T. ; LigandScout: 3D Pharmacophores Derived from Protein-Bound Ligands and their Use as Virtual Screening Filters, J. Chem. Inf. Model. 2005, 45, 160-169. Available from Inte:Ligand GmbH (http://www.inteligand.com/ligandscout)
[3] KoNstanz Information MinEr. Available from KNIME.COM AG, Zurich, Switzerland (http://knime.org)
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Colloidal carriers at biological barriers: challenges and new concepts for dermal and pulmonary application Marc Schneider
Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbrücken, Germany
Abstract
The 21st century is believed to be the advent of nanotechnology. Not only in electronics and material sciences but also in medicines and pharmaceutics large potential is seen. The nano-sized carrier systems offer sizes which allow to behave differently with biological system. Thus the transport and provision of drugs is facilitated and the efficiency is increased. The interaction of the carrier in terms of drug protection and release and also the interaction with the biological barriers such as epithelial barriers to overcome them or deliver drugs into the barriers need to be investigated. Different application routes pose different problem and barrier characteristics for delivery. In the present presentation the potential of nanoparticles for transdermal drug delivery across healthy human skin will be discussed. Besides the effect of drug loaded particles a more systematic approach to address skin penetration of nanoparticles will be presented.1
Besides this, pulmonary application will be in focus. Here the treatment of cystic fibrosis will be presented, the potential to apply nano-sized drug carriers and the potential application to the lung. In addition, the potential barriers such as mucus will be discussed.2 A new concept addressing the communication between Pseudomonas aeruginosa is in focus3 but also an intriguing way to delivery antibiotics such as Ciprofloxacin. In both approaches, suitable carrier for inhalation need to be prepared and characterized. In this context non-spherical particles, i.e. cylinders for drug delivery, will be introduced.4
References
(1) Labouta, H. I.; El-Khordagui, L. K.; Kraus, T.; Schneider, M. Nanoscale 2011, 3, 4989. (2) Kirch, J.; Schneider, A.; Abou, B.; Hopf, A.; Schaefer, U. F.; Schneider, M.; Schall, C.; Wagner, C.; Lehr, C. M. Proceedings of the National Academy of Sciences of the United States of America 2012, 109, 18355. (3) Nafee, N.; Husari, A.; Maurer, C. K.; Lu, C.; de Rossi, C.; Steinbach, A.; Hartmann, R. W.; Lehr, C.-M.; Schneider, M. Journal of Controlled Release 2014, 192, 131. (4) Kohler, D.; Schneider, M.; Krüger, M.; Lehr, C.-M.; Möhwald, H.; Wang, D. Advanced Materials 2011, 23, 1376.
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“How a molecule can be called as a medicinal product”: Registration Procedures in Turkey Dicle Balbay
Director of Governmental Affairs Department
Servier Ilac ve Arastırma A.S. Istanbul/Turkey
Abstract
Objective: Since the mid-1980’s there have been great changes in the way clinical research is performed due to the evidence based approaches and approvals. In order to enable research to be done cost effectively with less duplication of efforts and reduction in exposure of animals and humans all requirements for registration of Pharmaceuticals for Human use are in the process of harmonizing and local authorities set up their own system accordingly. We aimed to introduce Turkish registration system with the historical development.
Keywords: Registration, application, GMP, MOH,
Introduction
It is possible to market only a medicinal product for human use, approved by the Ministry of Health (MOH), presented into the market in ready form, in a special package, with a specific name. No medicinal product for human use can be marketed unless authorized by the MOH pursuant to the Regulation. Therefore the authorization holder is obligated to assign a responsible qualified person to get registration and complete the registration procedure when the product is launched into the market.
In this presentation, there is brief description of the registration process;
-regulatory authority’s structure and approach
-since 2009, a GMP certificate issued by Turkish Authority for imported products after physical audit is a prerequiste. Priority of audit is based on necessity of product in Turkey.
Why the Turkish Authority is asking for GMP inspection?
- how a molecule can be called as a medicinal product in Turkey.
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Research and development activities in pharmaceutical sector from an academician point of view Prof. Dr. M. Fethi Şahin
Eastern Mediterranean University, Faculty of Pharmacy, Pharmaceutical Chemistry Department, North Cyprus.
Abstract
One should classify pharmaceutical sector in two parts; originators and generic industry. This very rational way.
Therefore one can divide R and D activities in two classes. Original drug R and D has the innovative feature. And it depends on the discovery of new drugs. Generic drug R and D is development of a similar drug which is existing in the market. Therefore innovative aspect of generic drug R and D is lower in comparison. Existing R and D activities in Turkey totally generic R and D. Therefore one can say that the R and D in Turkish pharmaceutical sector is cheap and the surplus value is low.
In addition, One cannot incline to say that there is a good accumulation of capital in Turkish Pharmaceutical sector. In the other words, The capital in Turkish pharmaceutical sector is fragile and shallow. R and D understanding of the owners and decision makers of Turkish pharmaceutical sector is very poor. There will be a broad review of the Turkish Pharmaceutical Sector n the meeting
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Toxicity of Mycotoxins Prof. Dr. Gönül Şahin
Eastern Mediterranean University Faculty of Pharmacy
Abstract
Naturally occuring toxicants produced by microorganisms, such as bacteria and fungi (molds), contaminate foods and feeds; these foodborne hazards pose a serious health risk to mammals, fish and poultry. Mycotoxins are products of secondary metabolism of molds such as Aspergillus, Penicillium, Fusarium, Alternaria and Claviceps. Mycotoxin contamination of crops has been a world wilde problem for thousands of years. The level of mycotoxin contamination of crops varies from year to year, depending on climatic conditions, commodity and location in a country. It has been estimated that one quarter of the world’s food crops is at risk owing to mycotoxin contamination. Mycotoxic molds generally attack the kernels of grain robbing the nutrients and lower the fat, protein, and vitamin content of the grain. The mold also often changes the color of the kernels, the texture, and often imparts an odor that causes feed refusal in animals. These effects lead to economic losses due to impaired health in animals and humans, reduced productivity (reduced production of eggs, milk, and weight gain), and in severe cases death to animals and humans. When the grain is processed into final products like flour or feed, the visible mold may be removed, but the majority of toxins are not and can still cause poisoning. Only in the last thirty or forty years has technology allowed researchers to isolate the fungal mycotoxins and study the effects on feed crops, livestock and their affects on humans. Mycotoxins are nearly all cytotoxic, disrupting various cellular structures such as membranes, and interfering with vital cellular processes such as protein, RNA and DNA synthesis. They have very real toxic side effects to higher plants, animals and humans. The mycotoxins are mostly produced by the so-called storage fungi: however, some unique mycotoxicoses such as ergotism, lupinosis and facial eczema are caused by some parasitic and saprophytic fungi.
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New horizons in nanotherapeutics: nanotubes, quantum dots, lipid based carriers, nanovaults, nanoboats İsmail Tuncer Değim Gazi University, Faculty of Pharmacy, Department of Pharmaceutical Technology, 06330, Etiler, Ankara, Turkey e-mail: [email protected] Nanotechnology is growing and developing rapidly especially in engineering and medical sciences. In recent years it has been proposed that carbon materials can be used for drug delivery. Latest study results indicate that transdermal route is the safest way for nanosized materials. If carbon nanotubes (CNTs) are able to penetrate through skin layers or if they can be able to provide enough drug molecules on to the skin surface they can be used to deliver active drug substances for therapeutic purposes but exploration of these kind of pharmaceutical delivery systems and their applications are still at a very early stage of development1. It has been shown that single-walled carbon nanotubes (SWNTs) and multiwalled carbon nanotubes (MWNTs) can be internalized by living cells and they can pass across the biological membranes in cell culture studies2. The internalization of carbon nanotubes by corneocytes has been shown3 in the literature but their drug carrying properties through the skin have not been fully evaluated. In our previous study it has been first shown MWNTs can be used to deliver drug molecules through deeper skin layers. The application of iontophoresis using carbon nanotube electrode having adsorb drug molecules on their surface has been shown and molecules transferred successfully to deeper skin layers4. CNTs have been also used to increase dermal penetration of drugs5,6. The penetration enhancement was found to be higher with double walled carbon nanotubes (DWCNTs) and MWCNTs, however the mechanism was still unknown. Penetration of indomethacin was found to be much higher when indometahcin molecules were introduced to the skin surface with CNTs5. Other materials like quantum dots can also be used for diagnosis and monitoring of living cell trafficking7. Recently it has been proposed that quantum dots can be used for drug delivery8. Similarly, Zhang et al. have synthesized highly uniform quantum dot-doped chitosan nanobeads for traceable siRNA delivery9 and most recently Jia et al. have combined PEI-coated carbon nanotubes with quantum dots for antisense oligodinucletide delivery10. Lipid based drug delivery systems including liposomes, their derivatives, solid lipid nanoparticles and recently developed system called “Cochleates” have been shown to deliver actively drug susbstance to targeted tissues. Among them cochleates may be the most interesting ones being recently developed system and they have been recently tested for anticancer drug delivery and enhanced effectiveness on tumor tissues11,12. Naturally occurring nanosized "vaults," shaped like barrels, to deliver special "nanodisks" packed with therapeutic drugs. The nanovaults were engineered to slowly release a protein or other molecules into targeted organs or to the tumors. The nanovaults have been engineered to slowly release the protein into the tumor, acting like a time-release capsule. They are new and effective systems13. Nanobot have been preparing using DNA, a long single-stranded DNA scaffold is folded into the shape of a hexagonal barrel by short oligonucleotide 'staple' strands. The assembled nanobot consist of two aptamer-encoded locks, a barrel-shaped body and a bound molecular cargo. Cargo mcan be a drug molecule or a protein. The molecular payload is then released to bind to target cells and activate signaling pathways14. This new systems are also seems to be very promising for future applications to deliver drug molecules to the target sites. As a conclusion some literature based information and experimental results will be discussed with some case studies for carbon materials, quantum dots and lipid based carriers in the talk. Recent developments, important factors for formulations, ingredients will be given and the mechanisms will be
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References 1- Martin CR, Kohli P, The emerging field of nanotube biotechnology, Nat. Rev. Drug Discov. 2:29 (2003). 2- Lacerda L, Raffa V, Prato M, Bianco A, Kostarelos K, Cell penetrating carbon nanotubes in the delivery of therapeutics, Nano Today, 2: 38 (2007). 3- Monteiro-Riviere NA, Inman AO, Wang YY, Nemanich RJ, Surfactant effects on carbon nanotube interactions with human epidermal keratinocytes, Nanomedicine: Nanotechnology, Biology and Medicine, 1: 293 (2005). 4- Martínez-Pla JJ, Martín-Biosca Y, Sagrado S, Villanueva-Camañas RM, Medina-Hernández MJ, Evaluation of the pH effect of formulations on the skin permeability of drugs by biopartitioning micellar chromatography, J. Chromatogr. A.,1047: 255 (2004). 5-Degim IT, Burgess DJ, Papadimitrakopoulos F, Carbon nanotubes for transdermal drug delivery, J Microencapsul. 27: 669 (2010). 6- Ilbasmiş-Tamer S, Yilmaz S, Banoğlu E, Degim IT, Carbon nanotubes to deliver drug molecules, J Biomed Nanotechnol., 6:20 (2010). 7- Sonvico E, ,Dubernet C, Colombo P, Couvreur P,. Metallic Colloid Nanotechnology, Applications in Diagnosis and Therapeutics, Current Pharmaceutical Design, Volume 8,Number 16, June 2005, pp. 2091-2105(15) 8- Tan WB, Jiang S, Zhang Y, Quantum-dot based nanoparticles for targeted silencing of HER2/neu gene via RNA interference. Biomaterials, 28:1565 (2007). 9- Jia N , Lian Q, Shen H, et al. Intracellular delivery of quantum dots tagged antisense oligodeoxynucleotides by functionalized multiwalled carbon nanotubes. Nano Lett , 7:2976 (2007). 10- Degim IT and Kadioglu D, Cheap, Suitable, Predictable and Manageable Nanoparticles for Drug Delivery: Quantum Dots Current Drug Delivery, 10, 32-38 (2013). 11-Yucel C, Degim Z, Yilmaz S, Nanoparticle and liposome formulations of doxycycline: Transport properties through Caco-2 cell line and effects on matrix metalloproteinase secretion, Biomedicine & Pharmacotherapy, 67, 459 (2013). 12- Mutlu Agardan, B, Degim, Z, An investigation on tamoxifen or raloksifen (SERM - Selective estrogen receptor modulators) containing new drug delivery systems, PHD Thesis, Gazi University, Faculty of Pharmacy, Ankara Turkey (2013). 13- Kar UK, Srivastava MK, Andersson A, Baratelli F, Huang M, Kickhoefer VA, Dubinett SM, Rome LH, Sharma S, Novel CCL21-Vault Nanocapsule Intratumoral Delivery Inhibits Lung Cancer Growth, PLoS ONE, 6 (5), : e18758, (2011). 14- Fu J, Yan H, Controlled drug release by a nanorobot, Nature Biotechnology 30, 407–408, (2012).
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Application of New Nano-based Electrochemical and Spectroscopic Sensors in Pharmaceutical Analysis Ali A. Ensafi
Department of Analytical Chemistry, College of Chemistry, sfahan University of Technology, Isfahan, Iran; Tel.: +98-31- 33913269; E-mail: [email protected]
The development of commercial electrochemical and optical sensors is one of the most efficient methods to achieve a high specificity, short response time, and low analysis cost. The key factor involved in the fabrication of new platforms is the improvement of their chemical, physical and electrochemical properties, depending on the envisaged applications. For the past decade, the field of pharmaceutical diagnostics has been interested in using nanoparticles for analyzing different pharmaceuticals. Nanoparticles offer advantages as nanosensors in rapid and high-throughput detection methods. The strong physical confinement of electrons or holes at the nanoscale makes NPs attractive candidates for electrochemical sensing. Their small size gives them correspondingly large surface-to- volume ratios. In addition, they have chemically tailorable physical properties, which are directly related to their size, composition, and shape. Surface-modified nanocolloids, such as gold nanoparticles, quantum dots, magnetic nanoparticles and carbon nanotubes may have specific target-binding properties. Thus, the extremely small size, synergic effect, electrocatalytic behavior and exceptional nanoscale properties make nanoparticles useful for new-generation of electrochemical and spectroscopic sensors.
Electrochemical sensors have been widely developed as an inexpensive, simple method to sensitively detect a variety of biological analytes. Moreover, nanomaterial optical sensors are among the most important types of chemical sensors that have been produced in the recent past for the continuous, real time monitoring of diverse analytes. Depending on the origin of the optical signals, these sensors may be roughly classified into luminescence-based and absorbance-based sensors. Here, I will introduce the development of nanomaterial optical and electrochemical sensors and their applications to the field of pharmaceutical analysis including dopamine at a glassy carbon electrode modified with NiFe2O4 magnetic nanoparticles decorated multiwall carbon nanotubes [1], nanocomposite-based sensor for simultaneous determination of isoproterenol, acetaminophen and tryptophan [2], impedimetric DNA- biosensor for the study of anticancer action of mitomycin C [3], electrochemical DNA-biosensor for monitoring of chrysoidine foods and textile effluents [4], NiFe2O4 nanoparticles decorated MWCNTs as a selettive and sensitive electrochemical sensor for determination of epinephrine [5], caffeine electrochemical sensor using imprinted film as recognition element based on polypyrrole, sol-gel and gold nanoparticles hybrid nanocomposite modified pencil graphite electrode [6], atropine sulfate sensor based on DNA-biosensor [7], codeine and morphine based on porous silicon/palladium nanostructure [8], a fluorimetric biosensor for protamine and cyanide detection based on modified CdTe quantum dots [9,10], copper/porous silicon nanocomposite [11] and graphene nanosheets functionalized-nile blue as sensitive glucose sensors [12], and the real time assessment of drug-release profile from therapeutic nanoparticles [13].
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References:
Ali A. Ensafi et al., Material Sciences & Engineering C, 2014, 39, 78-85. H. Karimi-Maleh, et al., Measurement, 2014, 51, 91-99. Ali A. Ensafi et al., Biosensors & Bioelectronics, 2014, 59, 282-288. Ali A. Ensafi et al., Sensors & Actuators B, 2014, 202, 224-231. Ali A. Ensafi et al., Analytical Methods, 2014, 6, 6885-6892. B. Rezaei et al., Biosensors & Bioelectronics, 2014, 60, 77–83. Ali A. Ensafi et al., Talanta, 2015, 131, 149-155. Ali A. Ensafi et al., Talanta, 2015, 134, 745-753. Ali A. Ensafi et al., Biosensors & Bioelectronics, 2015, 71, 243-248. Ali A. Ensafi et al., RSC Advances, 2015, 5 (50), 40088-40093. Ali A. Ensafi et al., Electriochimica Acta, 2014, 123, 219–226. Ali A. Ensafi et al., Electrochimica Acta, 2015, 173, 619-629. Ali A. Ensafi et al., Electroanalysis, 2014, 26(4), 776–785.
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Actual Aspects of the Global Market of Medical Cosmetics Makhmudjanova K., Narkevich I.A., Nemyatyh O.D., Fitisova A.I. [email protected], [email protected] ,[email protected]
Abstract The modern market competitive of medical cosmetic is rapidly developing, due to the changing needs of consumers, scientific innovation, as well as a rational use of resources. In recent years, security problems related to dermatological cosmetics has been of particular importance. It is crucial to emphasise, that out of 15–25% of consumers «pharmaceutical cosmetics» there were «unexpected» reactions, which in turn, emphasises the need for governmental control over the handling of this category of pharmaceutical products. Despite the significant discrepancies in the sphere of regulation of cosmetic products the supplier countries today are doing emphasis on safety of finished products. In the EU Member States in the sphere of cosmetic industry, which cover the one third of the world market, become tougher requirements to the ingredients contained in the final product, the labeling of the primary and secondary packaging, expanded requirements for manufacturing companies, importers and distributors, formed a responsible approach to the marketing communications. In the US, therapeutic cosmetic must meet the requirements for drug and cosmetics. The aim was to analyse, in a comparative aspect, the central vectors in the plane of regulation of cosmetic treatment in international pharmaceutical practice. Analysis of the principles of classification and mechanisms of regulation treatment of perfumes and cosmetic products in the context of the European Union, Japan and USA showed that in world practice there is no uniform access to the formation of the concept of cosmetic products, as well as determining the place of cosmetic products among traditional cosmetics and pharmaceutical products. The term «therapeutic (active, dermatological) cosmetics», in the global market used principally as a formulation of marketing, covers a purpose of use, method and place of application of the drug. In the context of legal regulation in the EC Union, it plays a leading role in Regulation 1223/2009 of the European Parliament and of the Council, as well as registration in Cosmetic Products Notification Portal, in USA with regards to the treatment of cosmetics which is subject to requirements of the Federal Food, Drug and Cosmetic Act, as well as Fair Packaging and Labeling Act. In the Russian regulatory and legal framework it should be noted Tehnicheskiy reglament Tamozhennogo soyuza 009/2011. It should further be emphasised that the law regarding therapeutic cosmetics is separate in categories to pharmaceutical products and subjects to the exclusive pharmaceutical legislation in Japan. Attention is drawn to the fact, that in Europe a specialised authority is required to monitor the quality of pharmaceutical cosmetics, a ‘Standing Committee’ on cosmetic products, in USA function Cosmetic Ingredient Review, which investigates the ingredients of cosmetics. In the context of regulating the quality of pharmaceutical cosmetics it is important to emphasise procedures for the declaration of conformity and the state registration (Russian Federation), Cosmetic Product Safety Report, Declaration of Conformity (EC Declaration of Compliance) in Europe, as well as certificates of conformity in the Japanese practice. While in Japan there are standards of Good Post Marketing Surveillance Practice, which are applicable to manufacturers, importers and distributors. Thus, summing up all of the above, it is reasonable to conclude, that statutory regulations for cosmetic products (for the majority of States), don’t contain requirements for active pharmacological ingredients. Models of state regulation regardingthe treatment of cosmetics on the international market requires a balanced and scientifically substantiated approach that is dictated by the unpredictable consequences of uncontrolled use of dermatological products
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Quality Control of Herbal Medicines by Capillary Electrophoresis Coupled with Laser Induced Fluorescence Detector Zeynep Kalaycıoğlua, Parya Hashemia, Keriman Günaydınband F. Bedia Erima
aIstanbul Technical University, Department of Chemistry, Maslak, Istanbul, Turkey; bIstanbul University, Department of Molecular Biology and Genetics, Fatih, Istanbul, Turkey e-mail: [email protected]
Abstract
The strong controls applied to drug products are not applied to herbal medicines. Checks conducted on commercial herbal supplements show that some contain amounts of active ingredients differing from the indications on the label. Turmeric (Curcuma Longa) is one of the most extensively studied plant in the last few decades to establish its pharmacological actions. Recent investigations on pharmacological activities has revealed the anti-bacterial, anti-oxidant, anti-inflammatory, anti-cancer and anti-diabetic effects of turmeric [1, 2]. Curcuminoids namely curcumin, demethoxy curcumin (DMC), and bisdemethoxy curcumin (BDMC) are responsible for these effects of turmeric. However, the curcuminoid content in turmeric is not high. Recently, the popularity of commercial turmeric-curcumin supplements that contain significant amounts of curcuminoids have been growing. Commercial turmeric-curcumin products contain mixtures of curcumin, DMC, and BDMC. The labels state only total curcuminoid contents. However, the individual components of the curcuminoids show different bioactivities, thereby each curcuminoid content should be monitored in order to estimate their dietary intakes.
In this study, curcumin, DMC, and BDMC were isolated from turmeric and a sensitive capillary electrophoresis method coupled with laser induced fluorescence detector (CE-LIF) was developed for the simultaneous determination of curcuminoids [3]. The background electrolyte was selected as borate at pH 9.6 and (2-Hydroxypropyl)-β-cyclodextrin (2-HP-β-CD) was added to increase the fluorescence intensities of molecules. With the addition of 2-HP-β-CD to the separation electrolyte, the fluorescence signal intensities of curcuminoids were enhanced considerably by 30, 40, and 54 fold for curcumin, DMC, and BDMC, respectively. The LOD and LOQ values for the developed method were equal to or less than 0.081 and 0.270 µg.mL-1, respectively, for all curcuminoids. The developed method was applied for the determination of three curcuminoids in turmeric samples and commercial turmeric- curcumin supplements. This method yields very short analysis time (less than 4.5 min), good accuracy, reproducibility, and high sensitivity for the determination of individual curcuminoids in herbal medicines. References:
[1] J. Epstein, I. R. Sanderson, T. T. MacDonald, Brit. J. Nutr. 103 (2010) 1545. [2] A. Noorafshan, S. Ashkani-Esfahani, Curr. Pharm. Des. 19 (2013) 2032. [3] Z. Kalaycıoğlu, P. Hashemi, K. Günaydın, F. B. Erim, Electrophoresis (2015), in press.
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Transfer of advanced knowledge and technologies to modern-day education
Kirillova E.N a., Narkevich I.A. b
a Kirillova E.N., Saint-Petersburg State Chemical pharmaceutical Academy, 197376, St.-Petersburg, Street prof. Popova, 14; e-mail: [email protected]; b Narkevich I.A., Saint-Petersburg State Chemical pharmaceutical Academy, 197376, St.-Petersburg, Street prof. Popova, 14; e-mail: [email protected]
In October 2014, the Saint-Petersburg State Chemical pharmaceutical Academy, one of the oldest Russian institutions of higher education, celebrated its 95th anniversary. The major stages of the Academy’s development are inseparably linked with the history of Russian higher pharmaceutical education and the training of engineers for chemical pharmaceutical industry. The foundation of the Petrograd Chemical pharmaceutical Institute in 1919 gave a powerful boost for Russian pharmaceutical industry. The subsequent reorganization of the Institute and the most important events in its educational, scientific, and practical activities should be considered in the context of the general history of pharmaceutical science and practice in Russia. The Academy has made significant contributions to Russia pharmacy and higher pharmaceutical education. The continuity of classical pharmacy traditions should be borne in mind when elaborating the innovative educational strategies of the higher educational establishment and progressive areas of research and pharmaceutical practice. The activities of the Saint Petersburg State Chemical pharmaceutical Academy in training the staff in the specialties of Pharmacy, Chemical Engineering, and Biotechnology are described in detail. Programs for additional professional education within an internship for pharmacists and those for the advanced training and retraining of specialists in the main areas of educational activities of the Academy are successfully being implemented; goal-oriented training of specialists is under way at a fast pace. A present-day teaching process of main educational programs requires that high-quality methodical developments be made for active and interactive learning forms and educational and practical training. Saint-Petersburg State Chemical pharmaceutical Academy is developing new educational programs according to needs of the employer, creating a «road map» from the survey employer to the formation of competencies and then training programs. The developed educational programs are widely used modern educational technologies. By now, the Academy has renewed the effective system envisaging that the students should undergo practical training at the core enterprises visited by training supervisors. The academic mobility of the students and teaching staff is also an integral component of modern-day education. Implementation of educational projects of the Ministry of Education of the Russian Federation and the Saint Petersburg Committee for Economic Development, Industrial Policy, and Trade has demonstrated the high competitiveness of the Academy’s teaching staff that ensures the qualitative training of graduates.
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Chemometrıc Sıgnal Processıng Methods In Drug Analysıs Erdal DİNÇ
Ankara University Faculty of Pharmacy, Department of Analytical Chemistry, Tandoğan, Ankara, TURKEY
Abstract
The instrumental analysis methods are based on the estimation of analytical signals, chromatograms, spectra, kinetic curves and others provided from instruments or devices. The use of the mentioned raw signals may not always give the expected results for the chemical and pharmaceutical analysis. In this situation, the application of the chemometric signal processing methods for the analytical signals or data can be necessary for the quantitation of drugs in multicomponent pharmaceutical preparations. One of the newest chemometric signal processing methods has been wavelets. Wavelet transform (WT) can be classified into two categories; discrete wavelets transform (DWT) and continuous wavelets transform (CWT). The WT approach is a powerful signal processing tool for data reduction, de-noising, baseline correction and resolution of overlapping spectra, voltammograms and chromatograms. In our previous studies, the WT signal processing tools in combination with conventional spectral analysis techniques were applied for the determination and dissolution testing of drugs in multicomponent dosage forms [1-2]. Very recently, fractional wavelet transform was successfully applied to increase the lower signal content and to reduce the spectral data length for the drug analysis. Moreover, traditional instrumental methods coupled with wavelet signal processing methods enhance their ability of the quantitative resolution of drugs in samples. In my lecture, I will explain some typical examples of the wavelet applications to spectrophotometric, voltammetric and chromatographic signals for drug analysis.
References:
1. E. Dinç, N. Özdemir, Ö. Üstündağ, & M. G. Tilkan, Continuous Wavelet Transforms for the Simultaneous Quantitative Analysis and Dissolution Testing of Lamivudine–Zidovudine Tablets. Chemical and Pharmaceutical Bulletin, 61(12), (2013). 1220-1227.
2. E. Dinç, & D. Baleanu, A review on the wavelet transform applications in analytical chemistry. In Mathematical Methods in Engineering (2007). pp. 265-284. Springer Netherlands.
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Liposome Formulations for Cosmetic Textile Applications
Sakine Tuncay Tanrıverdi 1, Güneş Sayıt 2, , Esen Özdoğan 2, Özgen Özer 1
1Department of Pharmaceutical Technology, Ege University, Turkey 2Department of Textile Engineering, Ege University, Turkey
Today, consumers request the basic characteristics of textile products alongside having extra functions like health and beauty protection, improving quality of life, being nature, and not damaging human beings and the environment while performing all these functions (1). This fact causes focusing the studies on the production of bioactive or biofunctional textile. These types of textiles comprise therapeutic or cosmetic compound which is absorbed by the skin or effective on the skin surface (2). Thus, the production methods of these fabrics which are interacted with the skin should be improved by combining pharmaceuticals and textile knowledge together. The cosmetic textile is defined as the textile product which has the main purpose of showing cosmetic effects and includes cosmetic product having time-release property (3). The liposome vesicular systems can be used for production of cosmetic textile (4). The aim of this study is to produce cosmetic textile which has cosmetic property. First of all, allantoin loaded liposome was prepared. The characterization of liposome formulation was performed. After these steps, allantoin loaded liposome formulation was applied to textile fabric.
The thin film hydration method was used to produce the liposome formulation (5). Egg lecithin and cholesterol were used for preparation of the formulation. The z-average mean (Z-size), polydispersity index (PDI), pH, the entrapment efficiency (EE), electrical conductivity of the liposome formulation was determined. In vitro release of the liposome was also performed by dialysis bag method. After characterization of liposome formulation, application to the textile product was performed.
Liposome formulation has desired particle size to apply to the textile fabric. Zeta potential of the liposome formulation was -5 and pH was found 3.87. The electrical conductivity was 518 µs/cm. Because of the hydrophilic character of allantoin entrapment efficacy was 5.43. In vitro release of liposome was 83.19%. The liposomes were seen on the fabric surface according to SEM analysis. As a conclusion, allontoin loaded liposome was found suitable for textile application.
References
1. Ripoll L., Bordes C., Etheve S., Elaissari A., Fessi H., Cosmeto-textile from formulation to characterization: an overview, e-Polymers no.040 (2010). 2. Shi H., Xin J. H., Cosmetic Textiles: Concepts, Application and Prospects 3. Ksilak D., Lajnscek M., Golob D., Voncina B., Cosmetotextile as Innovation in the Production Of Protective Clothing, Sigurnost 53 (2), 103-108, (2011) 4. Botello F., Petit N., Gonzalez D., Uraquijo C., Liposomes for the Treatment Textile Materials, WO2011101153. 5. Tanrıverdi, T. S., and Özer, Ö. Novel topical formulations of TBF-HCL for treatment of onychomycosis, European Jornal of Pharmaceutical Sciences, 2013; 48, 628-636.
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Preparation And Evaluation of Novel Microemulsion-Based Hydrogels for Dermal Delivery of Benzocaine
Neslihan Üstündağ Okur a, Emre Şefik Çağlar a, Muhammed Davut Arpa a, H. Yeşim Karasulu b aIstanbul Medipol University, School of Pharmacy, Department of Pharmaceutical Technology, Beykoz, 34810 Istanbul, Turkey; e-mail: [email protected] bEge University, Faculty of Pharmacy, Department of Pharmaceutical Technology, 35100, Izmir, Turkey e-mail: [email protected]
Abstract Because of skin’s specific advantages dermal drug delivery has been promising pathway for a long time [1]. Local anesthetic drugs induce pain relief by binding to the sodium channel of excitable membranes, thus blocking the influx of sodium ions and the conduction of the nervous impulse [2]. The aim of the current research was to prepare and evaluate the potential use of microemulsion-based hydrogel formulation for dermal delivery of benzocaine (BZN). The microemulsions were prepared with titration method. The Pseudo-ternary phase diagrams were constructed for various microemulsions composed of isopropyl myristate (IPM) as oil phase, Span 20, Span 80, Cremophor EL and Cremophor EH40 as surfactants, ethanol as co-surfactant and water as aqueous phase. Finally, concentration of BZN in all microemulsions was 2% (w/w). The physicochemical properties such as conductivity, viscosity, pH droplet size, polydispersity index and zeta potential of microemulsions were measured. Solubility and lipid partition coefficient of BZN were also evaluated. Stability tests of the formulations were performed at 4 oC, 25 oC and 40 oC. The results showed that optimized microemulsion (M3) formulation was composed of IPM (20.64%), Span 20 (12.75%), Cremophor EL (24.65%), ethanol (18.70%) and distilled water (23.25%). Carbopol 940 was used to convert BZN-loaded microemulsions (M1-M4) into gel form. Besides this, the microemulsion-based hydrogel (MBH-1-4) formulations were evaluated for drug content, pH, rheological properties and in vitro drug release through synthetic membrane and excised rat abdominal skin in comparison with optimum microemulsion. This optimum microemulsion and MBH-3 showed good stability. MBH-3 showed highest flux values and high release rate values, and furthermore, they had low surfactant content. Finally, to learn the formulations localization within the dermal penetration, formulations were labeled with red oil O and subjected to fluorescence observation (Figure 1). In conclusion, BZN loaded MBHs could be offered as a promising strategy for dermal drug delivery.
Figure 1: Penetration of red oil O labeled MBH3.
References [1] B. K. A. Rasool, et al., Trop J Pharm Res; 9 (2010) 355-363. [2] P.Mura, et al., Eur J Pharm Biopharm 67 (2007) 86–95. Acknowledgments The authors would like to acknowledge İstanbul Medipol University, REMER for enabling us to use its laboratory instruments.
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Implementation of Clinical Pharmacy Practices in Hacettepe Hospitals? Assoc. Prof. Kutay Demirkan, Pharm.D. Hacettepe University Faculty of Pharmacy Department of Clinical Pharmacy
Clinical pharmacy services are well developed in some countries (such as USA, Canada and the UK) and clinical pharmacists are integral members of the health care team. However, clinical pharmacy is a new arising issue in many countries and therefore education and provision of clinical pharmacy are not available yet.
Implementation of clinical pharmacy requires an extensive knowledge of therapeutics and medical terminology, a good understanding of disease and drug monitoring processes, therapeutic planning skills, ability to assess and interpret physical and laboratory findings and provision of information about medicines.
Responsibilities and duties of a clinical pharmacist include selection of the correct drug, proper dosage form, appropriate route of administration; choice and timing of specimens for therapeutic drug monitoring; interpretation of pharmacokinetics data, detection and prevention of drug interactions, adverse drug effects and toxicity.
It is clear that clinical pharmacists have the potential to contribute in reduction of drug expenditures and improving medication and patient safety. To achieve these outcomes, clinical pharmacists should obtain medication histories, perform medication reviews, attend ward rounds, provide recommendations on drug selection and follow-up, and provide counseling to patients and healthcare providers.
Implementing a new clinical pharmacy service in a hospital is challenging. Before the implementation of any service, the barriers such as lack of time, lack of communication skills, allocation of new resources, lack of training and lack of clinical pharmacist, lack of reimbursement need to be identified and the plans to overcome for each barrier need to be considered.
Since only few clinical pharmacists are available and clinical pharmacy practices are not routinely performed in hospitals in Turkey, most of the physicians are not familiar with clinical pharmacy practices. Clinical pharmacy practices have been first implemented in nine-bed medical intensive care unit (ICU) at the Hacettepe University Hospital in Türkiye. The practicing clinical pharmacist was a part-time provider; therefore clinical pharmacy service was limited to morning visits of ICU throughout almost all week-days. Also, the clinical pharmacist was available on call when needed. Implementation of clinical pharmacy practice was also started in nutrition unit and neuro-ICU unit upon requests from physicians after the ICU activities at the Hacettepe University Hospital. Other requests for implementation of clinical pharmacy services from other units such as oncology, infectious diseases are not fulfilled yet due to a lack of clinical pharmacist at the moment. Moreover, bed-side teaching for pharmacy students at the hospital was approved by the hospital administration office and chief physicians, where a clinical pharmacist act as a mentor during medication review process for undergraduate education.
The implementation of clinical pharmacy practice from a pilot unit and thereafter an establishment of a clinical pharmacy service at the hospital might be easier to prove the efficacy and necessity of the service. It is better to choose a pilot unit that patients are more complex and need more attention, so pharmacists can have more active role and interventions in short time period.
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How much progress has psychiatry made in the last century? Do we know enough about the human psyche to prescribe the medication? Prof. Dr. Vahdet Gül
Erzincan University, Medical Faculty, Psychiatrist
Psychiatry is the medical specialty devoted to the study, diagnosis, treatment, and prevention of mental disorders. These include various affective, behavioural, cognitive and perceptual abnormalities. The 20th century introduced a new psychiatry into the world, with different perspectives of looking at mental disorders. A remarkable progress has been made in psychiatry, including the understanding pathophysiology of mental illness, classification, diagnosis and the medical treatment of mental diseases. While the focus of psychiatry has changed little over time, the diagnostic and treatment processes have evolved dramatically and continue to do so. Since the late 20th century the field of psychiatry has continued to become more biological and less conceptually isolated from other medical fields.
At the turn of the century, the initial ideas behind biological psychiatry, stating that the different mental disorders are all biological in nature evolving into a new concept of "nerves" were put forward by Emil Kraepelin, founder of modern scientific psychiatry. Following Sigmund Freud’s pioneering work, ideas stemming from psychoanalytical theory also began to take root in psychiatry.
By the 1970s, however, the psychoanalytic school of thought became marginalized within the field. Biological psychiatry re-emerged during this time so that psychiatry became a rough approximation of neurology and neuropsychiatry. After the discovery of the first set of prototype psychotropic drugs and acetylcholine as the first known neurotransmitters, efforts have been focused on the treatment of the pathophysiology of mental symptoms with the employment of centrally acting drugs.
Modern psychiatric medication has advanced greatly in the second half of the century. The Reuptake hypothesis by Julius Axelrod formed the cornerstone of the development of modern psychotropic drugs.
Psychiatric treatments have changed over the past several decades. Treatment may be delivered on an inpatient or outpatient basis, depending on the severity of functional impairment or on other aspects of the disorder in question. In the past, psychiatric patients were often hospitalized for months or more, with some cases involving hospitalization for many years.
Today, people receiving psychiatric treatment are more likely to be seen as outpatients. If hospitalization is required, the average hospital stay is around one to two weeks, with only a small number receiving long-term hospitalization, thanks to the discovery of modern drugs used in psychiatry.
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Human Medicines Registration Process in Turkey
Oguzhan Koyuncua, Murat Çaglayanb, Özkan Unalc
aTurkish Medicines and Medical Devices Agency; e-mail: [email protected]; bTurkish Medicines and Medical Devices Agency; e-mail: [email protected]; cTurkish Medicines and Medical Devices Agency e-mail: [email protected]
Abstract
In a few words, human medicinal product registration process is defined as, the process which starts with the application of the company about human medicinal product registration and is over by issuing of license. In Turkey, the human medicinal product registration authority is Turkish Medicines and Medical Devices Agency. In terms of a country, having a good human medicinal registration process is very important for its’ patients to reach safe, efficient and qualified human medicines. In Turkey, there is a human medicinal product registration process based on international standards and scientific events, which is prepared by reviewing of World human medicinal products authorities, especially European Medicines Agency. This process consist of three parts. 1. Pre-assessment 2. Scientific assessment 3. Administrative assessment. Pre-assessment contains, assessment of documents which are prepared accordingly Common Technical Documents (CTD) format which is determined by International Conference of Harmonization (ICH) and is an international standard. Scientific assessment contains the assessment of application by commissions which consist of academicians and agency personnel according to application type (original, generic etc. ), depending on the application type, commissions asses the application clinically, pharmacologically, technologically, etc. Administrative assessment contains assessment of final format of SPC/PIL and primer/seconder package and last checking of documents and commission decisions.
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The Pharmacy Management Department’s Studies in Turkey
Elif Ulutaşa, Bilge Sözen Şahneb, Selen Yeğenoğluc
aHacettepe University Faculty of Pharmacy Department of Pharmacy Management Sıhhiye-Ankara/TURKEY; [email protected]; bHacettepe University Faculty of Pharmacy Department of Pharmacy Management Sıhhiye-Ankara/TURKEY; [email protected]; cHacettepe University Faculty of Pharmacy Department of Pharmacy Management Sıhhiye-Ankara/TURKEY; [email protected]
Abstract
In our country, it is known that the most preferred professions are the professions related health fields. Profession of Pharmacy takes part among them. By the 2014-2015 academic year, undergraduate education and training are continued at twenty four pharmacy faculties. It is known that there are three divisions and several departments in the pharmacy faculties. Differently from other areas, the Department of Pharmacy Management, which is located in the Department of Pharmaceutical Professional Sciences, operates as a platform, which provides education and makes researches about the social side of the pharmacy profession.
Currently, there are eleven Pharmacy Management Departments in our country. However, instructors who are expert in the field work in only four of them. At present, the studies continue with three professors, one associate professor, one assistant professor and eight research assistants who work in Ankara University, Hacettepe University, Istanbul University and Ege University.
In this presentation, the studies, which are made until today by Pharmacy Management academicians, will be examined. Moreover, it is aimed to give information about these studies and emphasize the importance of the department for the pharmacy profession.
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Antimutagenic potentials of flavonoids from Achillea millefolium L. and Achillea biebersteinii Afan.
Handan G. Sevindik a, Zühal Güvenalp a, Mehmet Karadayı b, Medine Güllüce b, L. Ömür Demirezer c
a Department of Pharmacognosy, Faculty of Pharmacy, Atatürk University, 25240 Erzurum, Turkey; [email protected] ; b Department of Biology, Faculty of Science, Atatürk University, 25240 Erzurum, Turkey; c Department of Pharmacognosy, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey
In the present study we investigated the mutagenic and antimutagenic potentials of flavonoids isolated from Achillea millefolium L. and Achillea biebersteinii Afan. by using Ames/Salmonella and E. coli WP2 bacterial test systems [1]. The genus Achillea L. (Asteraceae) comprises 85 species worldwide and 50 species in the flora of Turkey with more than 50 % endemism [2]. Luteolin, apigenin-7-O-β-D- glucoside, luteolin-7-O-β-D-glucoside, 6-OH-luteolin-7-O-β-D-glucoside were isolated from A. millefolium; quercetin-7-O-β-D-glucoside, patuletin-7-O-β-D-glucoside from A. biebersteinii. At the end of the activity tests the results showed that none of the compounds have mutagenic effects at all tested concentrations (1-5 µM/petri). Furthermore, all of the compounds showed antimutagenic activity against MNNG mutagenicity on E. coli WP2. The antimutagenic activities ranged from 39.31 % (luteolin) to 29.94 % (quercetin-7-O-β-D-glucoside) at the concentration of 5 µM/petri. Luteolin, apigenin-7-O-β-D- glucoside, luteolin-7-O-β-D-glucoside, 6-OH-luteolin-7-O-β-D-glucoside were showed antimutagenic activity on 9-AA mutagenicity on S. typhimurium TA1537. The activities ranged from 34.22 % (apigenin-7-O-β-D-glucoside) to 30.33 % (luteolin) at the concentration of 5 μM/petri. No antimutagenic activity was observed on NaN3 mutagenicity on S. typhimurium TA1535. 25-40 % inhibition was defined as moderate antimutagenicity; 40 % or more inhibition as strong antimutagenicity; and 25 % or less inhibition as no antimutagenicity [3].
References:
[1] K. Mortelmans, E. Zeiger, Mutat. Res. 55 (2000) 29. [2] A. Huber-Morath, In: Davis, P.H. (Ed.), Flora of Turkey and East Aegean Islands, 6 (1978), University Press, Edinburgh. [3] M. Güllüce, G. Agar, O. Baris, M. Karadayi, F. Orhan, F. Şahin, Phytother. Res. 24 (2010) 1014.
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Stability indicating HPLC-PDA analysis of febuxostat utilizing design of experiments Majed Y. Baradan1 and Ashok K. Shakya1
1Faculty of Pharmacy and Medical Sciences, Al-Ahliyya Amman University, Amman, Jordan [email protected]; [email protected]
Abstract
A simple, rapid, precise, sensitive, economical, robust and stability indicating high performance liquid chromatographic method has been developed for determination of febuxostat in formulation and bulk drugs. Design of experiments [1-3] using Box-Behnken design (BBD) was used to facilitate method development and optimization. Mobile phase was optimised using Design Expert® (Stat-Ease) software. Chromatographic ® separation was achieved on Hypersil -Gold C18 (100 x 4.6 mm, 3 µm, Thermo Fisher Scientific, USA), column at 25 ± 2 °C. The optimized mobile phase (using, Fig.1 Desirability plot) was 34% water (containing 0.25 ml/l triethylamine), 33% acetonitrile and 33% methanol (final pH adjusted 3.0 ± 0.1 using orthophosphoric acid) The analysis was performed at 315 nm using photodiode array detector. The mobile phase flow rate was 1.0 ml/min and injection volume 10µL. The method was validated for linearity, limits of quantitation and detection, accuracy, precision, ruggedness and robustness as per the ICH guidelines. The limit of detection and limit of quantitation were 0.190 and 0.575 μg/ml respectively. Calibrations curves were linear in the concentration range of 1-50 μg/ml. The correlation coefficients were higher than 0.9999. Stability studies indicate that the drug was stable when exposed to direct sunlight or UV light. The drug gives 4 different degraded products on exposure to 1M NaOH (alkaline stress). Slight degradation was observed in acidic and oxidative stressed condition. Degradation was higher in the alkaline condition compared to other stress conditions.
a. b.
Fig 1. (a) 2-D contour plot for resolution factor versus independent factor (A-buffer, B- acetonitrile and C-methanol); and (b) Point prediction utilizing desirability plot (Rs=11) References: [1]. http://www.americanpharmaceuticalreview.com/Featured-Articles/144191-Analytical-Quality-by-Design- AQbD-in-Pharmaceutical-Development/#disqus_thread [2]. Monks, K.E.; Rieger, H.-J.; Molnar, I. J. Pharm. Biomed. Anal. 2011, 56, 874. [3]. Dawud, E.R.; Shakya, A.K. HPLC- Arabian J. Chem. 2014, doi:10.1016/j.arabjc.2014.10.052
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Kozmetik Sektörünün Endüstriyel Açıdan Değerlendirilmesi Uluslararası Avrasya Eczacılık Kongresi, Erzincan, 3-7 Eylül 2015
Ecz. Ebru DEDEOĞLU Assos İlaç ve Kozmetik
Kozmetik ürün; insan vücudunun dış kısımlarına; epiderma, tırnaklar, kıllar, saçlar, dudaklar ve dış genital organlarına veya dişler ile ağız mukozasına uygulanmak üzere hazırlanmış, tek veya temel amacı bu kısımları temizlemek, koku vermek, görünümünü değiştirmek, bunları korumak, iyi bir durumda tutmak veya vücut kokularını düzeltmek olan bütün madde veya karışımlardır.
Kozmetik ürün üreticisi; ürün Türkiye sınırları içinde üretiliyor ise ürünü üreten, ıslah eden veya ürüne adını, ticari markasını veren gerçek/tüzel kişi, ürün Türkiye sınırları dışında üretiliyor ise üretici tarafından yetkilendirilen temsilci ve/veya ithalatçıyı tanımlamaktadır.
Kozmetik sektörüyle ilgili bilinmesi gereken bazı diğer kavramlar ise “nihai kullanıcı”, “profesyonel kullanıcı” ve “sağlık mesleği mensubu”dur. Nihai kullanıcı; kozmetik ürünü kullanan tüketici veya profesyonel olarak uygulayan kişiyi tanımlar. Profesyonel kullanıcı; kozmetik uygulama işlemini yapan, ürünü birey için hazırlayan, uygulayan; eğitimli, deneyimli, sağlık üzerindeki riskleri bilen kişidir. Sağlık mesleği mensupları ise hekim, eczacı, diş hekimi, hemşire, ebe gibi sağlık eğitimi almış kişilerdir.
Kozmetik ürün üreticilerinin yasal otoriteye ve kullanıcılara karşı bazı sorumlulukları vardır. Bu sorumluluklar; 1. Kozmetik Ürün ve UZEM Bildirimlerinde bulunulması, 2. Kozmetik Ürün Bilgi Dosyalarının hazırlanması, 3. Kozmetik ürün iddialarının belirlenmesi, 4. Kozmetovijilans faaliyetlerinin yürütülmesi şeklinde sıralanabilir. Kozmetik Ürün Bildirimi ve UZEM Bildirimi, Kozmetik Ürün Üreticisi tarafından T.C. Sağlık Bakanlığı Türkiye İlaç ve Tıbbi Cihaz Kurumu’na (TİTCK) yazılı ve sistem üzerinden elektronik başvurular ile gerçekleştirilir.
Kozmetik ürün üreticisi, üreticisi ve/veya ithalatçısı olduğu kozmetik ürün için “Ürün Bilgi Dosyası” adı verilen; ürünle ilgili analizler, test sonuçları, güvenlilik değerlendirmesi gibi ayrıntılı bilgiler içeren dokümanlardan oluşan bir dosyayı hazırlamakla ve bu dosyayı kozmetik ürünün etiketinde belirtilen, Türkiye’de yerleşik bir adreste bulundurmakla yükümlüdür. Üreticinin sorumluluğunda olan bir diğer konu ise kozmetik ürününe ait iddiaların belirlenmesidir. Bu iddialar; yanıltıcı olmamalı, kanıtlanabilir olmalı, gerçeği yansıtmalı, yasal gerekliliğe uyduğuna yönelik olmamalı, diğer ürünleri kötüleyici olmamalı, fiilen gerçekleştirdiği etkiyi yansıtmalı, abartılı olmamalı ve içeriğe değil, bitmiş ürüne yönelik olmalıdır. Son olarak, Kozmetovijilans faaliyetleri olarak tanımlayabileceğimiz kozmetik ürünlere ait güvenlilik verilerinin izlenmesi konusu da kozmetik ürün üreticilerinin sorumluluğu altındadır. Kozmetovijilans, yönetmeliklerde belirtilen anlamıyla kozmetik ürünlerin normal ya da öngörülebilir koşullar altında kullanımında gözlenen istenmeyen etkilerin spontan bildirimlerinin toplanması, değerlendirilmesi ve izlenmesidir. Bu anlamda üretici, kendisine sağlık mesleği mensuplarından ve nihai kullanıcılardan ulaşan istenmeyen etki bildirimlerini bünyesinde bulundurduğu Kozmetovijilans Yetkilisi aracılığıyla TİTCK’ya aktarmaktan sorumludur. Üreticinin yanı sıra, sağlık mesleği mensupları ve nihai kullanıcılar da doğrudan TİTCK’ya, resmi web sitelerinde yer alan Kozmetovijilans Bildirim Formlarını kullanarak istenmeyen etki bildiriminde bulunabilirler. Bir istenmeyen etki eğer geçici veya kalıcı fonksiyonel yetersizliklerle, sakatlıkla, ani yaşamsal risk ve ölümle sonuçlanıyorsa bu istenmeyen etki Ciddi İstenmeyen Etki (CİE) olarak nitelendirilir. CİE’ler 15 gün içinde TİTCK’ya bildirilmeli, mutlaka kayıt altına alınmalı ve ürün ile istenmeyen etki arasındaki ilişkinin doğru belirlenebilmesi için nedensellik değerlendirmesi yapılmalıdır. Tüm bu kozmetovijilans faaliyetleri sırasında ‘gizlilik’ büyük önem teşkil etmektedir.
Sağlıklı günler dileriz.
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Formulation and Evaluations of Beta Cyclodextrin and Polyethylene Glycol Mediated Binary and Ternary Complexes of Sylimarine
Mohammad Javed Ansari
College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi Arabia Email: [email protected]
Abstract
Silymarine (SLM), a flavonoid extracted from the seeds of Silybum marianum is found to possess several potential pharmacological activities [1-3]. It exhibits low and variable bioavailability due to its poor aqueous solubility and hence it require enhancement in the aqueous solubility and dissolution rate to improve its bioavailability and to derive its maximum therapeutic efficacy [4]. Cyclodextrins (CDs) are cyclic oligosaccharides, which are known to form molecular inclusion complexes with the interacting molecule thus affecting physical and chemical properties, like solubility and stability of several guest molecules [5]. It is reported in a few studies that addition of small amounts of water soluble polymers to cyclodextrin systems have improved both the complexing and solubilizing efficiencies of cyclodextrins[6,7]. Though cyclodextrins complexation [8] and use of PVP [9,10] for enhancing the solubility and dissolution rate of SLM have been investigated individually, no report is available on their combined use in enhancing the solubility and dissolution rate. In the present investigation the individual main effects and combined (or interaction) effect of BCD PVP on the solubility of SLM were investigated. The aqueous solubility of SLM was linearly increased as a function of the concentration of β- cyclodextrin alone and in the presence of polyethylene glycol. Solid inclusion complexes of Silymarine –β-cyclodextrinin1:1 ratios were prepared with and without polyethylene glycol by kneading method then evaluated for solubility dissolution and physical nature by FT-IR and X-ray diffractrometer. The solid inclusion complexes of βCD with PEG 6000 gave higher rates of dissolution than those of SLM and its complexes with βCD alone. SLM- βCD (1:1) kneaded complex gave a approximately two fold increase in the dissolution rate of SLM, whereas in the presence of PEG 6000, it gave a two and half fold increase. It has been concluded that addition of PEG 6000 has markedly enhanced the complexation and solubilizing efficiencies of βCD.
Acknowledgments: Author is grateful to the Dean, College of Pharmacy, for providing, instrumentation and facility to carry out and complete this research project.
References: 1. F. Kvasnicka, B. Biba, and R. Sevcik, J Chromatogr A, vol. 990 (2003), 239. 2. S. H. Yang, J.K. Lin, W.S. Chen, J.H. Chiu, J Surg Res, vol. 113 (2003), 133. 3. R. Saller, R. Meier, and R. Brignoli, Drugs, vol. 61 (2001), 2035. 4. W. Wu, Y. Wang, and L. Que, Eur J Pharm Biopharm, vol. 63 (2006), 288. 5. Do. Thomson, Crit Rev Ther Drug Carries Syst, vol. 14(1997), 1. 6. P. Mura, M. T. Faucci, and G.P. Bettinetti, Eur J. Pharm. Sci., vol.13 (2001), 187. 7. L.S. Koester, P. Mayorga and V.L. Bassani, Drug Dev. Ind. Pharm., vol. 29 (2003), 139. 8. A. Ghosh, S. Biswas, and T. Ghosh, J. Young Pharm.,vol. 3(2011), 205. 9. M.F.Qiu, W.Jia, S.S.Li, Z.H. Xu, X. Sun, X.R. Wang, Y.Y. Zhang, G.X. Xie. Adv Ther. 22(2005), 595. 10. F.Q. Li, J.H. Hu, H. Wang, Q.G. Zhu, H.J. Sun, Z. Cai. Yao Xue Xue Bao. 37 (2002), 294.
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Film coating of tablets
Flisjuk E.V. a , Kirillova E.N. b, Cherkasova A.V. c , Narkevich I.A. d
a Flisjuk E.V., Saint-Petersburg State Chemical pharmaceutical Academy, 197376, St.-Petersburg, Street prof. Popova, 14; e-mail: [email protected] ; b Kirillova E.N., Saint-Petersburg State Chemical pharmaceutical Academy, 197376, St.-Petersburg, Street prof. Popova, 14; e-mail: [email protected]; сCherkasova A.V. Saint-Petersburg State Chemical pharmaceutical Academy, 197376, St.-Petersburg, Street prof. Popova, 14; e-mail: [email protected]; d Narkevich I.A. Saint-Petersburg State Chemical pharmaceutical Academy, 197376, St.-Petersburg, Street prof. Popova, 14; e-mail: [email protected]
In manufacture of tablets drawing of coverings is final technological operation, therefore quality of let out {of released} tablets in many respects depends on the organization of this process.
During drawing a covering on a surface of the firm medicinal form the environment is formed of a material of a covering of the set thickness which provides the protective or prolonged functions. Considering, that thickness of an environment influences on disintegration and time of liberation of operating substance maintenance of uniformity of a covering - that is uniformity of distribution of a material of a covering on a surface of all firm medicinal forms within the limits of one technological party{set} is very important. At the modern pharmaceutical enterprise for drawing a covering on tablets devices fluid bed and enveloping installations of drum-type type, so-called "соаters" are used. In the given work process of drawing of coverings on tablets is considered{examined} as the complex, complex process, accompanied by various by-effects. Complexity of process of drawing of coverings consists that at course of this process there are also such collateral processes as abrasion of tablets at drying up of fluid bed, formation{education} of defects on a surface as a result of impact and ablation of a material of a covering during process. Besides drawing of coverings on tablets is combined with process of drying and, hence, is accompanied external heat-mass transport. Thus, for reception of high quality of a covering of tablets and definitions of optimum technological parameters this process is necessary for investigating in a complex, as uniform system, in view of all accompanying phenomena and design features of the used equipment.
In the present work results theoretical and an experimental research of drawing of film coverings on tablets, both in devices with fluid bed and in devices of drum-type type are resulted.
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Protective Role of Oleuropein on ZnOTiO2 Nanocomposite- Induced Some Developmental Toxicity on Drosophila melanogaster
Tuğba ATICI a, Deniz ALTUN ÇOLAK b
a Institute of Science, Erzincan University, Erzincan, TURKEY; e-mail: [email protected]; b Department of Biology, Faculty of Art and Science, Erzincan University, Erzincan, TURKEY; e- mail: [email protected]
Nanotechnology is widely used in the fields of medicine, public health, pharmacy, food technology, biotechnology, cosmetics and textile. The increasing use of nanoparticles has raised concern about their potential toxicity for humans and the environment [1]. Zinc oxide (ZnO) and Titanium dioxide (TiO2), nanoparticles represent a significant class of metal-based nanoparticles [2]. The aim of this study was to assess the possible toxic effect of ZnOTiO2 nanocomposite, especially used in cosmetics, on some developmental parameters on Drosophila melanogaster, and protective role of Oleuropein (OLE), a strong antioxidant, on these effects.
Drosophila melanogaster’s wild type has been used in experiments. Chemicals prepared in different concentrations (0.05, 0.1, 0.5 and 1mg/mL for ZnOTiO2; 100µM for OLE) have been applied to the larvae with nutrients to determine survival rate. It has been observed that ZnOTiO2 all concentrations applied to larvae have decreased the life span according to control group and OLE has increased survival rate. To identify ZnOTiO2 and OLE effects on first generation male and female individuals, in every application group only females have been exposed to chemicals on the other hand in other numbers in F1 progeny obtained from mated flies have been determined. In F1 progeny resulted from chemical application to male and female individuals, ZnOTiO2, caused a decrease in the number of younger individual, on the other hand OLE increased the number of younger individual. It has been observed that, in result of ZnOTiO2 have been applied to male individuals, ZnOTiO2 effect on younger individual number in F1 progeny is more sensitive than female individuals which have been exposed to chemicals.
Overall, herein this study we showed the mechanism of action that underlies the beneficial effect of . OLE, suggested as a protective role in the prevention of developmental toxicity against ZnOTiO2
Keywords: ZnOTiO2, OLE, Drosophila melanogaster, Toxicity, Percentage of survival, Number of offspring individuals
Acknowledgments: This study was supported by Erzincan University Research Foundation.The authors would like to thank Erzincan University for financial support for the project [ Project Number = 2013 / 090614-0088].
References:
1) S. J. Choi, J. H. Choy, Int J Nanomedicine. 2: 261-9, 2014. 2) E. Demir, F. Turna, G. Vales, B. Kaya, A. Creus, R. Marcos, Chemosphere. 93: 2304-10, 2013.
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Taurine improves chemotherapy induced gastrointestinal toxicity in acute lymphoblastic leukemia. Mina Islambulchilar1, Mohammadreza Sattari2 , Iraj Asvadi3.
1. Department of Pharmacology & Toxicology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran & Student Research Committee and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. email: [email protected] 2. Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran & Department of Pharmacology & Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. email: [email protected] 3. Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. email: [email protected]
Backgrounds: Taurine has multiple physiological activities and plasma taurine concentrations decrease significantly after chemotherapy and radiation. The purpose of our study was to evaluate the effect of oral taurine supplementation on the incidence of chemotherapy-induced gastrointestinal toxicity in patients with acute lymphoblastic leukemia (ALL).
Methods: Forty young patients aged over 16 (ranges: 16-23 years) suffering from ALL were recruited for the study at the beginning of maintenance course of their chemotherapy. The study population was randomized in a double blind manner to receive either taurine or placebo (2 gram per day orally, divided in two doses, taken 6 hours after chemotherapeutic agents) for 6 months. Life quality and adverse effects including nausea and vomiting, taste and smell alterations, and appetite were assessed using a questionnaire. Data were analyzed using Pearson’s Chi square test.
Results: Of forty participants, 32 finished the study (14 female and 18 male; mean age 19.2±1.9 years). Four treatment and four placebo arm patients discontinued: one immigrated from the province, one died during the study, and six refused to continue. The results indicated that taurine-supplemented patients reported a significant (P<0.05) improvement in chemotherapy-induced nausea and/or vomiting after taking taurine during study. Taurine co-administration significantly improved chemotherapy-induced taste and smell alterations (P<0.05). Moreover, taurine supplementation significantly increased appetite compared to placebo group (P<0.05). Other chemotherapy associated adverse effects including constipation, diarrhea and oral cavity problems were also evaluated but the data were not significantly different between the taurine and placebo patients.
Discussion & conclusion: In this study we tried to estimate the effectiveness of taurine as a chemo- protective agent in ALL patients. The possible mechanisms for the inhibitory effect of taurine on GI toxicity may have resulted from its neuroprotective or inhibitory neurotransmitter actions. This study showed that taurine co-administration decreased chemotherapy-induced gastrointestinal toxicity during the maintenance therapy in ALL.
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Antibreastcancer Activity of Nanopropolis Indonesia on Induced Mammary Tumor Gland by Dmba in Virgin Sprague-Dawley Rats Akhmad Endang Zainal Hasan1,2,3*, Djumali Mangunwidjaja2, Titi Candra Sunarti2, Ono Suparno2, and Agus Setiyono4 1Department of Biochemistry, Faculty of Mathematics and Sciences, Bogor Agricultural University, Indonesia. 2Department of Agroindustrial Technology, Faculty of Agricultural Engineering and Technology, Bogor Agricultural University, Indonesia. Darmaga Campus, PO Box 220, Bogor 16002, Indonesia. 3SEAMEO-BIOTROP Bogor, Indonesia *Email: [email protected], [email protected]. 4Department of Clinic, Reproduction and Pathology, Faculty of Veterinary, Bogor Agricultural University, Indonesia. Darmaga Campus, Bogor 16002, Indonesia.
Abstract
The objective of this study was to determine the effect of nanopropolis on 7,12- dimethylbenz(a)anthracene (DMBA) induced rat mammary tumor. After the first tumors appearance, the twenty rats were divided into seven groups. Group 1, 2 and 3 served as nanopropolis treatment of 8, 32 and 56 µg ml-1 groups; Group 4 as propolis treatment of 233 µg ml-1 group; Group 5 as treatment of doxorubicin group; Group 6 as DMBA group; and Group 7 as a normal group. The effect of nanopropolis of 32 ug ml-1 and propolis of 233 ug ml-1 were similar in reducing of tumor size, healing the wounds caused by the tumor and could be eliminate cancer cells. It turns out that there is a relationship between particle size absorbent materials. The study suggests that nanopropolis with small concentration was very effective for the treatment of rat mammary gland tumors and breast cancers. Keywords : nanopropolis, propolis, Sprague-Dawley rat, breast cancer.
Acknowledgement The authors wish to thank to BPPS Fellowship of Indonesian Ministry of Education and Culture, and SEAMEO BIOTROP for their financial supports and Bogor Agricultural University for its facilities for conducting this study.
References
Abbasalipourkabir R, Salehzadeh A, Abdullah R. 2010. Antitumor activity of tamoxifen loaded solid lipid nanoparticles on induced mammary tumor gland in Sprague-Dawley rats. Afr J Biotech. 9(43): 7337-7345. Aimi M, Nemori R, Ogiwara K; Inventor. 12 Nov 2009. Casien Nanoparticle. US 2009-0280148 A1. Bermúdez IC, García GS, Piloto AA, Pérez YF, Valdivieso AG. 2006. Effect of the Cuban propolis collected in Manzanillo area on the wounds healing in rats. Pharmacol. 3:416-421.
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In vitro evaluation of the potential of preactivated poly ( acrylic acid) thiomers to inhibit MRP2 efflux transporter
Ziba Islambulchilara,b, Javed Iqbalb, Sabine Hauptsteinb, Flavia Laffleurb, katharina leithnerb , Andreas Bernkop-Schnürchb
aDepartment of Pharmaceutics, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran; email: [email protected]; b University of Innsbruck, Institute of Pharmacy/Pharmaceutical Technology, CCB-Centrum of Chemistry and Biomedicine, Innrain 80-82, 6020 Innsbruck, Austria.
Abstract
The aim of the present study was to prepare a series of poly(acrylic acid)-cysteine-2- mercaptonicotinic acid (PAA-cys-2MNA) conjugates (preactivated thiomers) with a molecular mass of 100, 250 and 450 kDa and to evaluate their efficiency to act as an efflux pump inhibitor and compare them with those of unmodified poly acrylic acid (PAA) as well as poly(acrylic acid)-cysteine (PAA-cys) conjugates. In vitro permeation studies were performed on Caco-2 cell monolayers and rat small intestinal mucosa mounted in Ussing-type chambers, respectively. Sulforhodamine 101 was used as a representative MRP2 substrate. The involvement of efflux pump mediated transport was confirmed in all of the experiments by comparing the apiocal to basolateral transport of Sulforhodamine at 37 and 4°C. Permeation experiments with Caco-2 cells proved that permeability of Sulforhodamine 101 in the presence of PAA-cys-2MNA (100, 250 and 450 kDa) was respectively 1.79, 1.95 and 2.29-fold higher than control, and on rat intestinal mucosa it was 1.92, 2.79 and 3.05-fold improved in comparison to control, respectively. Thus according to the achieved results it seems that poly(acrylic acid)-cysteine- 2-mercaptonicotinic acid (PAA-cys-2MNA) conjugates could be a promising tool for the oral delivery of efflux pump substrates specially the substrates of MRP-2.
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UV-Spectrophotometric-Assisted Chemometric Method for the Simultaneous Determination of Quinapril Hydrochloride and Hydrochlorothiazide in Pharmaceutical Formulations
Betul Godekli, Elmas Polatdemir, Tuba Saruhan, Fatma Demirkaya Miloglu* Department of Analytical Chemistry, Faculty of Pharmacy, Ataturk University, 25240, Erzurum, Turkey; [email protected] Abstract Quinapril Hydrochloride is orally active non-sulfhydryl non-peptidic an giotensin converting enzyme (ACE) inhibitor. It is used for the treatment of hypertension and conges- tive heart failure [1].Quinapril Hydrochloride is combined with hydrochlorothiazide which is a thiazide diuretic. Thiazide diuretics believed to have a primary action to inhibit NaCl reabsorption in the distal convoluted tubule and have been used in the management of hypertension for over 50 years [2].Chemometric calibration techniques in spectral analysis are getting an increasing attention to the quality control on pharmaceutical preparations [3,4]. Partial Least Squares (PLS) is an algorithm applied successfully for building regression models. The combination of PLS and UV-Visible spectrophotometry has been reported for simultaneous determination of several common active principles in pharmaceutical preparations mainly in presence of two or more analytes with overlapping spectral [5,6].It is aimed to develop and validate a UV-Vis spectrophotometric method for simultaneous determination of quinapril hydrochloride and hydrochlorothiazide in combined pharmaceutical preparation by PLS calibration method. Calibration (25 samples) and validation (5 sample) sets including synhtetic mixture of quinapril HCl 4- 20 μg/mL and hydrochlorothiazid 2.5-12.5 μg/mL were prepared in methanol by factorial design method. Spectrum of calibration and validation sets were obtained in 200-360 nm wavelength with Δλ=1 nm bandwidth. After that PLS calibration was plotted by concentration and absorbance data matrix and validation of the developed method was performed. Percentage recovery values of PLS method for quinapril HCl and hydrochlorothiazide mixtures were found to be 100.3% and 101.5%, respectively. RSD % of this analysis was also calculated to be 3.77 and 2.76, respectively. In addition to this, it is determined that RMSECV, RMSEC and RMSEP values of the cross validation measurements for calibration and validation data sets were very low and corellation coefficient of the proposed method is close to 1.000. Pharmaceutical preprations named Accuzide Fort was analyzed by the developed spectrophotometric method and the obtained results were in good agreement with the values supplied by the manufacturers. It is claimed that developed and validated UV-spectrophotometric-assisted chemometric method can be applied onto routine quality control studies for simultaneous determination of combined pharmaceutical formulations for quinapril HCl and hydrochlorothiazide.
References [1] S.C. Olson, A. Horvath, B.M. Michniewicz, A.J. Sedman, W.A. Colburn, P.G. Welling, Angiology 40 (1989) 351. [2] M.D. Kyu Sig Hwang, M.D. Gheun-Ho Kim, Electrolyte Blood Press. 8(1) (2010) 51. [3] A.B. Moreira, L.L.T. Dias, G.O. Neto, E.A.G. Zagatto, M.M.C. Ferreira, L.T. Kubota, Talanta 67 (2005) 65. [4] A. El-Gindy, S. Emara, A. Mostafa, A., J. Pharm. Biomed. Anal 41(2006) 421. [5] M.C.F. Ferraro, P.M. Castellano, T.S. Kaufman J. Pharm.Biomed. Anal 26(2001) 443. [6] M.M. Sena, Z.F. Chaudhry, C.H.Collins, R.J. Poppi. J. Pharm. Biomed. Anal 36(2004)743.
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Secondary Metabolites of Cultivated Artemisia dracunculus L.
Hilal Özbeka, Benan Dursunoğlua, Yeşim Mualla Çilb, Cavit Kazazc, Kemalettin Karad, Zühal Güvenalpa
aDepartment of Pharmacognosy, Faculty of Pharmacy, Atatürk University, 25240, Erzurum, Türkiye; [email protected]; bDepartment of Forestry and Forestry Products, Oltu Vocational School, Atatürk University, 25400, Erzurum, Türkiye; cDepartment of Chemistry, Faculty of Science, Atatürk University, 25240, Erzurum, Türkiye; dDepartment of Agronomy, Faculty of Agriculture, Atatürk University, 25240, Erzurum, Türkiye Abstract In different cultures, Artemisa dracunculus (Asteraceae) have been used in traditional medicine as a digestive stimulant, anesthetic for toothache, antiepileptic, antispasmodic, carminative, diuretic, vermifuge, to increase appetite, to treat insomnia, skin wounds, irritations, allergic rashes, dermatitis, and to dull the taste of medicines. It is also used as a spice to flavor and aromatise foods [1,2]. A wide range of pharmacological properties are reported including antibacterial, antifungal, antiplatelet, anti- inflammatory, antidiabetic, antioxidant, hepatoprotective, gastroprotective, analgesic and anticonvulsant activities. The secondary metabolites that are previously isolated from A. dracunculus are coumarins, alkamides, flavonoids, chalcones, and phenylpropanoids [1].
In this study, methanol extract of cultivated A. dracunculus was dissolved in water and partitioned with chloroform, ethyl acetate and n-butanol, respectively. Chloroform extract was subjected to silica gel column consecutively to give a coumarin: herniarin; a new and a known phenylpropanoid: 4-(1,1,2,2- tetramethylpropyl)-1,2-benzenediol and 3-(p-methoxyphenyl)-1,2-propanediol, respectively. In addition, a flavonol glycoside named as rutin was obtained from n-butanol extract. Structures of the isolated compounds were identified by means of spectroscopic methods.
References:
[1] D. Obolskiy, I. Pischel, B. Feistel, N. Glotov, M. Heinrich, J. Agr. Food Chem. 59 (2011) 11367. [2] T. Baytop, Türkiye’de Bitkiler ile Tedavi (1999) 314.
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Effect of Aging, Exercise and Catalase Overexpression on Various protein oxidation products in Mice
Hatice Tohma1,2,3 Associate Professor Peter Arthur2 Professor Miranda Grounds3
1Erzincan University, Faculty of art and sciences, Department of chemistry, Yalnızbağ Yerleşkesi, Erzincan 2School of Biochemical, Biomolecular and Chemical Sciences, 3School of Anatomy and Human Biology; University of Western Australia, WA 6009
[email protected] [email protected] [email protected]
Increasing evidence suggest that aging is a major risk factor for cardio vascular diseases. Oxidative modification of cellular components by free radicals has been proposed to explain age related cardiac dysfunction at molecular level. This study has been designed to examine the role of oxidative stress on cardiac aging. If oxidative stress contributes cardiac aging, then increased antioxidant capacity would be expected to decrease pathology. Mitochondrial targeted overexpression of catalase, which is an antioxidant enzyme, has been shown to extend the lifespan up to 21% and reduced oxidative DNA damage in skeletal muscle and heart of mice. Exercise is an also important for prevention and treatment of cardiovascular diseases, with the beneficial effect of exercise possibly due to attenuation of oxidative protein damage. Therefore in this study we used three mice model and three biomarkers of oxidative stress. Mice models are normal aging mice, catalase overexpressing mice and exercised mice. Biomarkers of oxidative stress are lipofuscin, protein carbonylation and protein thiol oxidation. The major finding of this study was that the level of reversible protein thiol oxidation did not consistently increase in aged heart tissue. Furthermore, neither overexpression of the antioxidant enzyme catalase in mitochondria, nor life-long exercise consistently affected levels of protein thiol oxidation. For measures of oxidative damage the increased accumulation of lipofuscin in aged hearts was consistent with that oxidative stress is causing irreversible oxidative damage. In contrast, there was a lack of an increase in protein carbonyls in aged hearts, which were not changed in response to catalase over expression or exercise. These findings have implications for understanding the role of oxidative stress in aged heart muscle.
[1] Li, Shi‐Yan, et al. "Aging induces cardiac diastolic dysfunction, oxidative stress, accumulation of advanced glycation endproducts and protein modification." Aging cell 4.2 (2005): 57-64.
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Determination of in-Vitro Antioxidant Capacity of Β - Agonists Onur ŞENOL1, Yücel KADIOGLU2; 1Atatürk Universit, Faculty of Pharmacy, Department of Analytical Chemistry, Erzrurum, Turkey 2Erzincan University Faculty of Pharmacy, Erzincan, Turkey [email protected] Abstract Antioxidant are the molecules or enzymes that prevent the hazardous effect of free radicals onto the cells or tissues of whole body[1]. Many antioxidant molecules are recorded in literature and their power were measured by either in-vivo or in-vitro techniques[2]. In our study, it is aimed to determine antioxidant capacity of β – Agonists which are Terbutalin Salbutamol, Ritodrin, Fomoterol, Salmaterol In order to determine their antioxidant capacity of each drugs, different in-vitro antioxidant capacity methods were applied onto these drugs which are CUPRAC, FRAP and ABTS. In addition to these methods[1] Lipid peroxidation level of each drugs were also evaluated with thiobarbutaric acid method. In addition to these, Anti-cholinesterase activity of each drugs were evaluated According to the results, the decreasing order of CUPRAC assay was calculated to be Fomoterol > Terbutalin > Salmaterol > Ritodrin > Salbutamol while antioxidant activity of FRAP assay is measured as; Fomoterol > Ritodrin > Terbutalin > Salmaterol > Salbutamol and ABTS assasy is Terbutalin > Salbutamol > Ritodrin > Fomoterol > Salmaterol The results were evaluated and chemometrically interpreted. Partial least square discriminant analysis and hierarchial cluster analysis of these drugs were achieved and β – Agonists were successfully separated from theirselves in terms of their antioxidant, anticholinesterase and lipid peroxidation properties. According to the results, all drugs exhibited moderate and low antioxidant capacity which means that these drugs not only effect on pulmonary system but also can be used for oxidative stress.
References: [1] Huang DJ, Ou BX, Prior RL. The chemistry behind antioxidant capacity assays. Journal of Agricultural and Food Chemistry. 2005;53:1841-56. [2] Apak R, Guclu K, Ozyurek M, Karademir SE. Novel total antioxidant capacity index for dietary polyphenols and vitamins C and E, using their cupric ion reducing capability in the presence of neocuproine: CUPRAC method. Journal of Agricultural and Food Chemistry. 2004;52:7970-81.
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Development and Validation of LC-MS method for Determination of Haloperidol in Human Plasma Mehmet Emrah YAMAN1, Onur SENOL1, Yucel KADIOGLU2
1Atatürk Universit, Faculty of Pharmacy, Department of Analytical Chemistry, Erzrurum, Turkey
2Erzincan University Faculty of Pharmacy, Erzincan, Turkey [email protected]
Abstract Haloperidol (4-[4-(4-Chlorophenyl)-4-hydroxy-1-piperidyl]-1-(4-fluorophenyl)-butan-1-one ), is an atypical antipsychotic used in the treatment of schizophrenia, tics in Tourette syndrome, nausea and vomiting, delirium, agitation, acute psychosis, and hallucinations in alcohol withdrawal [1]. For normal doses (up to 15 mg per day), the serum concentration is usually below 0.05 mg/L. (50 ng-mL). There are several analytical methods for determination of Haloperidol in human plasma [2]. In the the present study, it was aimed to develop a simple and rapid plasma extraction presedure as a priority for analyzing of a series of samples and a sensitive liquid chromatography mass spectrometry (LC/MS) method allowing the determination of Haloperidrol in real plasma samples at therapeutical dosages. Risperidone was used as internal standard in the method. Isolation of Haloperidol from plasma was accomplished by a simple and rapid liquid-liquid exraction method and the separation of analytes was carried out on a reserved phase C18 column using in a isocratic mobile phase component and analyzed by MS using positive ion atmospheric pressure chemical ionization and multitape reaction monitoring. Developed method was validated in accordance with ICH Q2(R1) guideline. The linear concentration range was found as 5-50 ng/ml. The limit of detection was found as 1 ng/ml and the lowest quantification limit was 5 ng/ml with an acceptible precision. Inter-day accuracy (relative eror) and precision (relative Standard daviation) for Haloperidol was as 4.18 to 5.51 %, respectively. The avarage rand multitape recovery of exraction from spiked plasma samples was 91.2 ± 4.2 %. Total analysis time was 7 minutes and extraction procedure was taken 10 minutes for a sample. The validated method has been succesfully used to analyse of human plasma samples. References 1. Kirchherr H, Kühn-Velten W. Quantitative determination of forty-eight antidepressants and antipsychotics in human serum by HPLC tandem mass spectrometry: a multi-level, single-sample approach. Journal of Chromatography B, 2006, 843: 100-113.
2. Kishikawa N, Hamachi C, Imamura Y, Ohba Y, Nakashima K, Tagawa Y, Kuroda N. Determination of haloperidol and reduced haloperidol in human serum by liquid chromatography after fluorescence labeling based on the Suzuki coupling reaction. Analytical and bioanalytical chemistry, 2006, 386: 719-724
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Label-free sensing platform for detection of cholesterol
Sunita Kumbhat
Biosensor Laboratory, Department of Chemistry, J.N.V. University, Jodhpur, 342 003, India
[email protected], [email protected]
Abstract
Changing lifestyle in the present era has caused the elevated levels of blood cholesterol contributing to the cardiovascular diseases, cerebral thrombosis and arteriosclerosis. Sensitive and specific detection of cholesterol is therefore significant. The enzymatic analysis as well as the majority of biosensors reported till now exploits the catalytic activity of cholesterol oxidase wherein, the electrons released in oxidase catalyzed biochemical oxidation of cholesterol are taken up by the molecular oxygen to produce stoichiometrically equivalent amount of hydrogen peroxide which in turn is used up to oxidize a chromophore with the help of an additional bio-reagent, horse radish peroxidase (HRP); the colour intensity of oxidized chromophore is proportional (indirectly) to the concentration of substrate. Alternatively, electrons released in oxidase catalyzed biochemical oxidation of are taken up by the oxygen molecules to produce stoichiometrically equivalent amount of hydrogen peroxide which is subjected to take part in an electrochemical reaction in presence or absence of a charge transfer mediator at chemically and/or biochemically modified sensor/electrode surface; the resulting current is proportional to the amount of cholesterol. Surface plasmon resonance (SPR) based optical transducers to detects the changes in the refractive index with the change in the mass concentration close to a metal surface in real time without labeling and these transducers are now well established for monitoring enzyme catalyzed transformation [1], immunoreactions[2] and affinity reaction [3] of clinical importance. The binding between immobilized biological recognition element and the analyte, brings changes in the refractive index at the sensor surface, leading to the change in SPR angle, which can be monitored in real time. The magnitude of the change in SPR signal is directly proportional to the mass bound to the surface even at nanogram levels in complex biological samples. Herein, we present SPR based label-free immunoassay for highly sensitive and selective detection of cholesterol. Assay is based on immobilization of anti-cholesterol onto a nanogold surface employing self assembly and covalent amide linkage. The biosensor is highly specific for cholesterol and showed no significant interference from potent interferences such as ascorbic acid, uric acid and glucose.
References: 1. R. Gehlot, K. Sharma, M. Mathew, S. Kumbhat, Indian J. Chem. 47A (2008) 1804.
2. S. Kumbhat, K. Sharma, R. Gehlot, A. Solanki, V. Joshi, J. Pharm. Biomed. Anal. 52 (2010) 255. 3. S. Kumbhat, D. R. Shankaran, S. J. Kim, K. V. Gobi, V. Joshi, N. Miura Biosensors and Bioelectronics, 23 (2007) 421.
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Cytotoxic Effect of Helix aspersa Extract on Human Breast Cancer Cell Line Hs578T
Ibtissem EL OUAR1*, Cornelia BRAICU3,4, Dalila NAIMI1,2, Alexendru IRIMIE4,5,6 & Ioana BERINDAN-NEAGOE3,4,7
(1) Laboratory of microbiological engineering and application, University Mentouri Constantine- Algeria (2)National high school of Biotechnology, Ali Mendjli –Constantine. (3)Department of Functional Genomics and Experimental Pathology, Cancer Institute “Ion Chiricuta”, Cluj-Napoca, Romania. (4) Research Center for Functional Genomics. Biomedicine and Translational Medicine. Iuliu Hatieganu. University of Medicine and Pharmacy, Cluj-Napoca, Romania (5) Department of Surgery, Iuliu Hatieganu. University of Medicine and Pharmacy, Cluj-Napoca, Romania,(6) Department of Surgical Oncology, Iuliu Hatieganu. University of Medicine and Pharmacy, Cluj-Napoca, Romania. (7) Department of Immunology, Iuliu Hatieganu. University of Medicine and Pharmacy, Cluj-Napoca, Romania. E-mail: [email protected]. Abstract Helix aspersa, is a big land snail widely found in the Mediterranean countries, it is one of the most consumed species and commonly used in zootherapy. The aim of this study is to investigate, the antitumor activity of an aqueous extract from Helix aspersa on Hs578T; a triple negative breast cancer cell line. Firstly, the free radical scavenging activity of H. aspersa extract was assessed by measuring its capability for scavenging the radical 2,2-diphenyl-1-picrylhydrazyl (DPPH), and H2O2 as well as its ability to reduce ferric ion by the FRAP assay (ferric reducing ability). Total polyphenols content of the extract have been also evaluated. The cytotoxic effect of H. aspersa extract against Hs578T cells was studied by the MTT test (3-(4,5- dimethylthiazl-2-yl)-2,5- diphenyltetrazolium bromide)), while the mode of cell death induced by the extract has been determined by fluorescence microscopy using acredine orange/ethidium bromide (AO/EB) probe. Our results suggest that H. aspersa extract has an antioxidant activity, especially at high concentrations, it can scavenge H2O2 and reduce DPPH radical and ferric ion. The extract contains small quantities of polyphenols. It seems that the antioxydant activity resulted from the presences of the polyphenols. The MTT test shows that H. aspersa extract has a great cytotoxic effect against breast cancer cells, the IC50 value correspond of the dilution 1% of the crude extract. Moreover, the AO/EB staining shows that necrosis is the main form of cell death induced by the extract.
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Determination of Fructose in Sweetened Foods and Beverages
Şana SUNGUR, Yusuf KILBOZ Mustafa Kemal University, Science and Letters Faculty, Department of Chemistry, Hatay, Turkey; [email protected]
Abstract
Dietary fructose is a naturally occurring sugar in fruits and vegetables. However, fructose is commonly added to soft drinks and juice beverages, and is incorporated into many convenient pre-packaged foods, such as breakfast cereals and baked goods. The general increases in consumption of calories, and specifically of refined carbohydrates and fructose, is clear and correlates positively with an alarming increases in metabolic syndrome [1]. In equal amounts, it is sweeter than glucose or sucrose and is therefore commonly used as a bulk sweetener. It is cheaper than other sweeteners. It does not make up satiety and fullness. From 1970 to 1990, consumption of fructose increased more than 1000 % and currently accounts for 40 % of all added caloric sweeteners [2].
Studies performed recently unveil a connection between amount of fructose consumed and metabolic disorders such as cardiovascular diseases, type 2 diabetes, hypertension, dyslipidemia, gout and obesity [3]. The incidence of metabolic diseases which are already affecting more than half of the adults has been increasing among children. Moreover, these types of foods are generally consumed by children. Therefore, in order to reduce the frequency of metabolic disorders in all ages, the amount of fructose in processed foods and beverages should also be taken into consideration.
There are currently no disclosures of fructose content in foods and beverages, and many nutrition databases only rely on product label information, it is challenging to accurately determine actual fructose consumption levels in nutrition research.
The objective of this study was to determine fructose content in commonly consumed sweetened foods and beverages (cake, chocolate, cookie, wafer, pudding, fruit yogurt, soda, cola, lemonade, mineral water, fruit juice, milk). These analyses were carried out using high-performance liquid chromatography (HPLC). Results showed that the total sugar content all of the samples ranged from 94 to 107 % of what was listed on the food label. Our results provide evidence of higher than expected amounts of fructose in most of the foods and beverages. They have a fructose-to-glucose ratio of approximately 60:40, and thus contain 50 % more fructose than glucose. The galactose and lactose were detected in small amounts in these products.
References:
[1] A. Korkmaz, TAF Preventive Medicine Bulletin. 7(4) (2008) 343. [2] M. E. Bocarsly, E.S. Powell, N.M. Avena, B.G. Hoebel, Pharmacology, Biochemistry and Behavior. 97 (2010) 101. [3] S.W. Rizkalla, Nutrition & Metabolism. 7 (2010) 82.
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Development of Technology and Dosage Form Design for Targeted Drug Delivery
A.Bakuridze1, A. Bozhadze1,M. Jokhadze1, L.Bakuridze1, D.Berashvili1, V.Vachnadze2, V.Mshvildadze2,3 Tbilisi State Medical University: 1Faculty of Pharmacy; 2I.Kutateladze Institute of Pharmacochemistry,Tbilisi, Georgia; 3University of Québec at Chicoutimi,Canada Corresponding authore-mail: [email protected]
Abstract
Malignant tumors are one of the leading causes of mortality. The number and incidence of new cancer cases are increasing annually. Chemotherapy is widely used along with other treatment methods. However, the shortcoming and the major problem is that chemotherapeutic drugs are not distinguished with selective cytotoxic activity and affect both tumor and normal cells.
Targeted delivery of medicinal substances to cancerous organs, tissues and cells significantly increases the effectiveness of the treatment and at the same time reduces drug side effects and toxicity [2]. Targeted delivery systems according to modern nomenclature include: liposomes, microcapsule, nanocapsuls, microspheres, nanospheres, nanosomes etc. Targeted drug delivery system consists of active substance interconnected with container with purpose to control targeted delivery and release kinetics [1, 3-5].
The goal of research was the development of technology and formulations of liposomal drug dosage forms. Object of research was total alkaloids obtained from the fruits Physalis alkekengi L., bark of Magnolia glauca L., leaves of Magnolia officinalis L. and Lipoid S75 (manufacturer - Lipoid AG, Steinhausen, Switzerland). Based on biopharmaceutical researches the technology and formulations of liposomal drug dosage forms by modified shaking method and injection method were developed. Main characteristics: the dimensions of nanoparticles and zeta-potential have been determined using modern instrumental methods of analysis. Comparative analysis of the results showed that the liposomal nanoparticles prepared with the shaking modified method reveal the optimal characteristics. Cytotoxic activity of total alkaloids obtained from fruits Physalis alkekengi L., bark of Magnolia glauca L., leaves of Magnolia officinalis L.and their liposomal nanoparticles solutions was studied at the UQAC (Université du Québec à Chicoutimi, Quebec, Canada). Resazurin and Hoechst methods were used to determine cytotoxic activity against three cell cultures: A-549 (lung carcinoma), DLD-1 (colon adenocarcinoma) and normal skin fibroblasts (WS-1). The solution of liposomal nanoparticles expressed cytotoxic effect on the lung and colon adenocarcinoma cell lines. Total alkaloids of M. glauca and the solution of liposomal nanoparticles expressed predominant activity. Moreover, the liposomal nanoparticles are characterized with selective cytotoxic activity, and they do not affect skin fibroblasts.
References [1] Sapra P, Tyagi P, Allen TM. 2005, Ligand-targetedliposomes for cancer treatment. Curr Drug Deliv, v. 2, pp.369– 381. [2] Ferrari M. 2005, Cancer nanotechnology: opportunitiesand challenges. Nat Rev Cancer;v.5, pp. 161–171. [3] Montet X, Montet-Abou K, Reynolds F, et al.2006, Nanoparticle imaging of integrinin tumor cells.Neoplasia, v. 8, pp. 214–222. [4] Pal A, Khan S, Wang YF, et al. 2005 Preclinical safety,pharmacokinetics and antitumor efficacy profileof liposome- entrapped SN-38 formulation.Anticancer Res, v. 25 pp. 331–341. [5] Vicent MJ, Duncan R. 2006,Polymer conjugates:nanosized medicines for treating cancer. TrendsBiotechnol,v. 24 pp. 39–47.
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Taurine improves carbamazepine induced drowsiness.
Mina Islambulchilar1, Mohammadreza Sattari2 , Hormoz Ayromlou3. 4. Department of Pharmacology & Toxicology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran & Student Research Committee and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. email: [email protected] 5. Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran & Department of Pharmacology & Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. email: [email protected] 6. Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. email: [email protected] Abstract
Backgrounds: Sleep and epilepsy are related, epilepsy could change sleep-awake cycles and sleep architecture. Taurine has multiple physiological activities. The purpose of our study was to evaluate the effect of oral taurine supplementation on the incidence of day-time drowsiness in epileptic patients receiving carbamazepine. Methods: Thirty eight young patients aged over 16 (ranges: 16-23 years) suffering from seizure were recruited for the study at the beginning of anticonvulsant therapy (all receiving carbamazepine). The study population was randomized in a double blind manner to receive either taurine or placebo (2 gram per day orally, divided in two doses, taken 6 hours after carbamazepine) for 6 months. Life quality and adverse effects were assessed using a questionnaire. Data were analyzed using Pearson’s Chi square test. Results: Of 38 participants, 32 finished the study (19 female and 13 male; mean age 17.84±1.53 years). Three taurine and three placebo arm patients discontinued. At the beginning of the study 25% of study population experienced degrees of day-time drowsiness and there were no significant differences observed at experiencing somnolence in both study groups (P>0.05). The results indicated that in placebo-supplemented patients day-time sleepiness significantly got worse (P<0.05). Moreover, taurine supplementation significantly improved feeling sleepy compared to placebo group (P<0.05). Discussion & conclusion: In this study we tried to estimate the effectiveness of taurine as a protective agent in anticonvulsant therapy. This study showed that taurine co-treatment decreased carbamazepine- induced sleepiness. The possible mechanisms for the inhibitory effect of taurine on drowsiness may have resulted from its neuroprotective or inhibitory neurotransmitter actions.
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"Anti-asthmatic activity of Euphorbia grandialata R. Cultivated in Egypt"
a b a a b Mona Ismail , Abeer A.A. Salama , Asmaa I. Owis , RababMohammed , Neamat Yassin , Mona Hettaa aPharmacognosy Department, Faulty of Pharmacy, Beni-Suef University, 62514, Egypt bDepartment of Pharmacology, National Research Centre, Cairo, Egypt. e-mail : [email protected]
Abstract
Asthma is a chronic disease characterized by inflammation of the airways associated with a hyper- responsiveness of the immune system. According to WHO about 300 million people worldwide suffered from asthma. Euphorbiaceae, the spurge family, is one of the largest families of flowering plants with 300 genera and around 7,500 species. The plants produce large number of diverse secondary metabolites such as terpenoids, tannins, polyphenols and flavonoids. Various species of the genus Euphorbia are used for the treatment of cancer, diarrhea and bronchial asthma.
The aim of this work is testing the activity of some Euphorbia grandialata R. as anti-asthmatic natural agents. The total alcohol extract of the collected Euphorbia grandialata R. was tested in vivo after induction of asthma in rats. Lung content of TNF-α, Ig-E, MDA and GSH was determined in blood samples of all rats after 24 hrs. Assessment of early airway reaction was performed 12 min. after the last challenge as Tidal volume (TV) and Peak expiratory flow (PEF).
Results showed that this collected Euphorbia grandialata R. significantly decreased TNF-α, Ig-E & MDA and significantly increased GSH, TV & PEF as compared with OVA (Challenge) group. It could be concluded that Euphorbia grandialata R. could be of great merit as natural anti-asthmatic agent.
References
1- Ohmori, K., K. Hayashi, T. Kaise, E. Ohshima, S. Kobayashi, T. Yamazaki, A. Mukouyama, 2002. Pharmacological, pharmacokinetic and clinical properties of olopatadine hydrochloride, a new antiallergicdrug.Jpn J Pharmacol., 88: 379 – 397. 2- Wang, W., R. Zhu, Q. Xie, A. Li, Y. Xiao, K. Li, H. Liu, D. Cui, Y. Chen, S. Wang, 2012. Enhanced bioavailability and efficiency of curcumin for the treatment of asthma by its formulation in solid lipid nanoparticles.Int J Nanomedicine., 7: 3667-3677. 3- Chopra, R.N., Nayar, S.L. and Chopra, I.C. (1956): In Glossary of Indian medicinal plants, Council of Scientific and Industrial Research, New Delhi.1;197. 4- Agarwal, A., (2005):Pharma Times 37(6): 9-11. 5- Macro JA, Sanz CJF (1997). Ingenanelathyranediterpenes from the latex Euphorbia canariensis.Phytochemistry, 45: 563-570. 6- Rahman, AHM MahbuburAkter, Momota (2013). "Taxonomy and Medicinal Uses of Euphorbiaceae (Spurge) Family of Rajshahi, Bangladesh." Research in Plant Sciences 1(3): 74-80.
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Determination of Dabigatran in Pharmaceutical Preparations by Differential Pulse Voltammetric Method
Bilal Yılmaz, Haluk Yaşar
Department of Analytical Chemistry, Faculty of Pharmacy, Ataturk University, 25240, Erzurum, Turkey E-mail: [email protected]
Abstract
Dabigatran is a novel oral direct thrombin inhibitor. In recent studies, dabigatran demonstrated its efficacy for prophylaxis and treatment of thromboembolic event during orthopedic surgery and curative treatment of hypercoagulability in atrial fibrillation [1].
The goal of this work was the development of new differential pulse voltammetry method for the direct determination of dabigatran in pharmaceutical preparations. Besides, the method was successfully applied for the quality control of two commercial dabigatran tablets form to quantify the drug and to check the formulation content uniformity.
The linear range was found to be 5-50 µg/mL. The regression equation obtained by least square regression was y=1.4996x+30.304 (y and x are mean peak current and concentration, respectively, r =0.991). The limits of quantitation (LOQ) and detection (LOD) were 1.80 µg/mL and 0.60 µg/mL, respectively. Intra- and inter-day precision as the relative standard deviation (RSD) was less than 3.14 %, and accuracy (relative error) was better than 2.73 %. The percent analytical recovery values were found to be 99.7 % (Pradaxa tablet; 75 mg/tablet) and 100.2 % (Pradaxa tablet; 110 mg/tablet), respectively.
The method has been effectively and efficiently used to analyze dabigatran pharmaceutical tablets without any interference from the pharmaceutical excipients. The voltammetric run time of 2 min allows the analysis of a large number of samples in a short period of time. Therefore, the method can be used effectively without separation for routine analysis of dabigatran in pure form and its formulations.
References:
[1] S.J. Connolly, M.D. Ezekowitz, S. Yusuf, P.A. Reilly, L.I. Wallentin, The New England J. Med. 363 (2010) 1875.
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Determination of Some Metal Levels in Multivitamin Preparations with ICP-OES after Dry, Wet and Microwave Digestion Methods
Merve TİMİRLİ ZURNACI a, Aysel KÜÇÜK TUNCA a, Ayşe ULUKOYLUa a Department of Chemistry, Arts and Sciences Faculty, Sakarya University, 54187, Sakarya, Turkey e-mail: [email protected]
Abstract
In this study, some metal levels in Supradyn and Pharmaton, very commonly used multivitamin tablets in Turkish market today, were determined using ICP-OES (Inductively Coupled Plasma-Optical Emission Spectrometry). Fe, Cu, Mn and Zn elements, which exists in both tablets, were chosen and dry, wet and microwave digestion methods were applied for solubilization. After digestion processes, the metal levels existed in Supradyn and Pharmaton preparations were determined with ICP-OES and the results obtained from three different digestion processes were compared with each other. Quite good recovery data was obtained from the analysis.
The study showed that there is almost no difference between the analysis results and the quantities given in the prospectuses of both drugs. Besides, the results obtained were assessed statistically in order to compare the findings and show the measurement validity.
Acknowledgments: This study is supported by a grant (Project Number: FBYLTEZ 2014 50-01-029) from Scientific Research Projects Committee of Sakarya University.
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Lipoidal Matters, flavonoid Content and Hypolipidemic Activity of Spinach Roots and Flowers
Abeer S. Moawad*Mona H. Hetta1,2, 1, Manal A. Hamed3, Ahmed S. Ismail1 1Pharmacognosy Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt e-mail: [email protected] 2Faculty of Postgraduate Studies of Advanced Sciences, Beni-Suef University, Beni-Suef, 62514.Egypt 3 Therapeutic Chemistry Department, National Research Center, Dokki, Cairo, Egypt. Abstract This study was designed in order to correlate the flavonoid and lipoidal matters content of Spinach roots and flowers to their hypolipidemic potential. The total flavonoid content was measured via complexation with aluminum chloride while determination of fatty acids methyl esters [1] and unsaponifiable matters in both organs was performed using GC/MS. In an in vitro study, the crude ethanol extracts of both organs and their different fractions were separately examined for inhibition of β-hydroxy-β-methyl glutaryl coenzyme A reductase (HMGCoA reductase); the rate limiting enzyme of cholesterol biosynthesis. The root crude alcohol extract exhibited 78.19% inhibition as compared to control, while the flower crude extract showed 27.68% inhibition. The crude alcohol extracts of both organs were further examined in vivo. Results showed that treatment with both extracts improved the investigated parameters by variable degrees as compared with Lipanthyl reference drug. The root extract showed significant improvement of TC, HDL-C, LDL-C, TG and total lipids (52.75, 209.85, 21.84, 49.26 and 29.62% respectively) when compared to cholesterolemic rats. The histopathological picture of liver showed a noticeable amelioration after treatment with root extract. The flavonoid content was higher in flower than root (983.4 and 300.2 mg/kg respectively) while the percentage of sterols and triterpenes in roots was greater than flowers (27.87% and 20.45 % respectively). In conclusion, the root ethanolic extract recorded more potent effect than flower as hypolipidemic agent either in vitro or in vivo examination which was more correlated to the sterol content than to the flavonoid content.
References
[1] M. F. Abu Bakar, M. Mohamed, A. Rahmat, and J. Fry . Food Chem., vol. 113, no. 2, pp. 479– 483, 2009.
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Antioxidant and antimicrobial activities of Lepidium sativum extracts
Bouamra Dalila1, Baki Chekib-Arslane1, Touabet Lilia1, Meliani Souheyla1, Bouchebour Abdelhamid1, Dahamna Saliha1 and Harzallah Daoud2
1 Laboratory of Phytotherapy Applied to Chronic Diseases, Department of Animal Biology and Physiology, Faculty of Natural and Life Sciences, University Ferhat Abbas, Setif, 19000, Algeria. E-mail address: [email protected] 2 Laboratory of Applied Microbiology, Department of Microbiology, Faculty of Natural and Life Sciences, University Ferhat Abbas, Sétif, 19000, Algeria.
Abstract Lepidium sativum, commonly known as Habarachad, is an edible grass with fast growth potential belonging to the Brassicaceae family. The seeds of this medicinal plant are diuretic and tonic; they are used to treat bacterial and fungal infections. The main aim of this study is to evaluate the phenolic composition, the antioxidant and antimicrobial activities of extracts prepared from L. sativum seeds. The yield of the extraction was 12.09% and 0.87% for Methanol (MeOH) and Aqueous (Aq.) Extracts respectively. The Aq. extract presented the highest content of total polyphenols (39.38 ± 0.001 mg. Gallic Acid equivalent /g. of extract), followed by the MeOH extract (31.38 ± 0.024 mg G.A.E. /g. of extract), whereas the contents of flavonoids were 14.12 ± 3.69 and 7.10 ± 7.86 mg. Rutin equivalent /g. dry extract for MeOH and Aq. extracts respectively. Moreover, the antioxidant activity was evaluated by using DPPH test whereas the antimicrobial activity was assessed via disc-diffusion method. The results revealed that the two extracts showed significant effects on the radical DPPH; with an IC50 for the Aq. Extract (0.104 ± 0.006 mg/ml) then the MeOH extract (0.166 ± 0.007 mg/ml). Furthermore, the study of the antimicrobial activity of the two extracts showed some effects against Aspergillus flavus (28.33 mm. in diameter for the Aq. extract) and Aspergillus niger (21 mm. in diameter for the same extract). However, no effect on the bacterial strains was recorded for both extracts.
Keywords: Lepidium sativum, methanol extract, aqueous extract, polyphenols, antioxidant activity, antimicrobial activity.
Acknowledgments: The authors would like to thank the DGRSDT, Ministry of Higher Education and Scientific Research of Algeria for financial assistance.
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Design, Synthesis and Cytotoxic Activity Evaluations of N-hetroaryl dichloroacetamide Derivatives as Anticancer Agents
Masood Fereidoonnezhada, Zeinab Faghiha, Ayyub Mojaddamia, Zahra Rezaeia aDepartment of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran; e-mail: [email protected] Abstract Extensive research have been focused into the progression of strategies designed in order to selectively induce apoptosis in cancer cells [1]. The Pyruvate dehydrogenase kinases (PDKs) that regulate the mammalian Pyruvate dehydrogenase complex (PDC) are a novel therapeutic target in oncology. Current studies shows that sodium dichloroacetate (DCA) as a pyruvate mimetic compound through inhibition of the PDKs, can selectively promotes mitochondria-regulated apoptosis, depolarizing the hyperpolarized inner mitochondrial membrane potential to normal levels, inhibit tumor growth and reduce proliferation by shifting the glucose metabolism in cancer cells from anaerobic to aerobic glycolysis [2, 3]. Here, in this study more than 200 DCA analogues (Scheme 1) have been designed and drug-likeness, molecular docking and descriptor analysis of them were performed to find out a drug candidate for synthesis with less toxicity and better binding affinity than DCA. The compounds that have better modeling results, were synthesized as a series of novel N-hetroaryl dichloroacetamide derivatives and their cytotoxic activities against different cancer cell lines such as A549 (human lung cancer), KB (human oral epidermoid carcinoma) and MCF-7 (human breast cancer) were evaluated. Molecular docking of them were performed by means of an in house batch script (DOCKFACE) for automatic running of AutoDock 4.2. The initial conformations of the PDK, were taken from PDB ID: 2BU8.
Scheme 1. The designated DCA analogues
The result of this study, showed that these compounds had an acceptable anti-cancer activity. Among them, the best compound, 2,2-dichloro-N-(9,10-dioxo-9,10-dihydroanthracen-1-yl)acetamide, had an IC50 of 2.5 μM against A549 cells, 6.5 μM against KB cells and 8.5 μM against MCF-7 cancer cell lines. Acknowledgments: The authors would like to thank department of medicinal chemistry at school of pharmacy, Shiraz University of Medical Sciences for its kind contribution in providing the needed facilities for this work. References: [1] L. Galluzzi, et al., Mol. Aspects. Med. 31 (2010). 1. [2] L. H. Stockwin, et al., Int. J. Cancer. 127(2010) 2510. [3] S. Kankotia, S, P.W. Stacpoole, Biochim. Biophys. Acta. 1846(2014) 617.
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Safety assessment of osthole isolated from Prangos ferulacea: Acute and subchronic toxicities and modulation of cytochrome P450
Leila Hosseinzadeha*Yalda Shokoohiniab, Sahar Bazarganc, Shahram Miraghaecd, Etrat Javadirade aPharmaceutical Sciences Research Center, Faculty of pharmacy, Kermanshah University ofMedical Sciences, Kermanshah, Iran;. [email protected];bPharmaceutical Sciences Research Center, Faculty of pharmacy, Kermanshah University ofMedical Sciences, Kermanshah, Iran; [email protected]; cPharmaceutical Sciences Research Center, Faculty of pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran;[email protected];d Pharmaceutical Sciences Research Center, Faculty of pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran; [email protected];eDepartment of pathology, Faculty of medicine, Kermanshah University of Medical Sciences,Kermanshah, [email protected]
Abstract Osthole, a natural coumarin derivative, has exhibited various pharmacological properties and the possibility of its development as a promising lead compound for drug discovery has been proposed [1,2]. However, there is little toxicological information regarding the safety of repeated exposure to this coumarin. The present study evaluated the potential toxicity of osthole after acute and subchronic administration in rodents. Also, we investigated the effect of osthole on different hepatic CYP gene expression in the male rats receiving the highest dose of osthole. In the acute toxicity study, single doses of osthole (100, 500 and 1000 mg/kg) were administered to mice and the mice were then monitored for 14 days. In the subchronic toxicity study, osthole was administered orally to rats at doses of 5, 25 and 50 mg/kg/day for 45 days. The results of acute study indicated that the LD50 of osthole is about 710 mg/kg. There was no significant difference in body weight, relative organ weight or hematological parameters in the subchronic toxicity study. Biochemical analysis showed some significant changes including creatinine, potassium, glucose, albumin and urea levels. Some serious abnormality of internal organs were observed between treated and control groups. Furthermore, osthole treatment caused an induction in CYP1A2, CYP2E1, and CYP2C11. Finally, the obtained data supported the evidence of renal function impairment by osthole. The no- observed adverse-effect level (NOAEL) of osthole for both male and female rats is considered to be less than 5 mg/kg. Acknowledgment: This study was financially supported by the research council of Kermanshah University of Medical Sciences. References:
[1] Venugopala KN, Rashmi V, Odhav B. Biomed. Res. Inter. 2013 (2013)426. [2] Kleiner H. E., Xia X., Sonoda J. , Zhang J. , Pontius EToxicol. App. Pharmacol. 23 (2008) 2337.
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Stabilization of amorphous Candesartan Cilexetil as an approach to increase its aqueous solubility
Mai S. Khanfar a, Bashar M. Altaani b, Eman A Mohammad aAddress Author 1; e-mail: [email protected]; bAddress Author 2; e-mail: [email protected]
Abstract
One attractive approach to increase aqueous solubility of poorly aqueous soluble drugs is to formulate them in the amorphous form since amorphous state exhibit higher apparent solubility than the crystalline counterparts. The objective of the present study was to prepare stable amorphous solid dispersions of the model drug Candesartan Cilexetil with different types of silica, non-porous (Aerosil 200) or porous silica (Sylysia 350) by using spray-drying method.
Powder X-ray diffraction results showed that Candesartan Cilexetil in the prepared solid dispersion was in amorphous form irrespective of the used silica. In DSC analysis, the melting peak of Candesartan Cilexetil in prepared solid dispersion disappeared.
Dissolution property of Candesartan Cilexetil was remarkably improved by formulating with silica particles. In comparing the effect of the type of the silica particles, the dissolution rate of Candesartan Cilexetil from the solid dispersion prepared with Sylysia 350 was faster than that of Aerosil 200 irrespective of the drug content. It was also shown that the formulation did not recrystallize when storing at severe storage conditions (40°C, 75% RH) for three months, while amorphous Candesartan Cilexetil without silica easily crystallized under same conditions.
Acknowledgments: Authors acknoweledge Deanship of Research in Jordan University for financial support.
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Synthesis and Antimicrobial Evaluation of New 3-Alkyl(Aryl)-4-(2-phenylacetoxy-3- ethoxybenzylidenamino)-4,5-dihidro-1H-1,2,4-triazol-5-ones* Faruk KARDAŞa, Haydar YÜKSEKb, Özlem GÜRSOY-KOLb, Murat BEYTURb, Önder ALBAYRAKc, Muzaffer ALKANc
aErzincan University, Education Faculty, 36100 Erzincan – Turkey bKafkas University, Department of Chemistry, 36100 Kars – Turkey cKafkas University, Education Faculty, 36100 Kars – Turkey Abstract 1,2,4-triazole and 4,5-dihydro-1H-1,2,4-triazol-5-one derivatives are reported to possess a broad spectrum of biological activities such as antimicrobial, antitumor and anti-HIV properties [1-3]. In this study, 9 different compounds were synthesized from the reactions of 2-phenylacetoxy-3- ethoxybenzaldehyde (2) with 3-alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-one (1) compounds and characterized by IR, 1H NMR, 13C NMR and UV spectral data. Then, antibacterial properties of 3- Alkyl(Aryl)-4-(2-phenylacetoxy-3-ethoxybenzylidenamino)-4,5-dihidro-1H-1,2,4-triazol-5-ones (3) by using Agar hole methods of against B. subtilis, Y.enterocolitca, B. cereus, S. aureus, E. coli, P. multocida and K. Pneumoniae strains and data were recorded.
OC2H5 O
OH + Cl C CH2
CHO
Et3N -2HCl OC2H5 O
OC2H5 O C CH2 N NH O AcOH + O C CH2 CH R N O -2H2O N NH2 CHO R N O
N NH 1 2 3
Figure 1. Synthesis route of compounds 2 and 3
* This study is supported by a grant (Project Number: 2011-FEF-31) from Scientific Research Projects Coordination Unit of Kafkas University. References N. Demirbas, R. Ugurluoglu, A. Demirbas, Bioorgan. Med. Chem. 2002, 10, 3717-3723. Z. Y. Li, Y. Cao, P. Zhan, C. Pannecouque, J. Balzarini, E. De Clercq, X.Y. Liu, Lett. Drug Des. Discov. 2013, 10, 27-34. Ö. Aktaş-Yokuş, H. Yüksek, Ö. Gürsoy-Kol, Ş. Alpay-Karaoğlu, Med. Chem. Res. 2015, DOI: 10.1007/s00044-015-1334- 8.
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Effect of Ozone on Remote Organ Injury in Rats with Hepatic Ischemia- Reperfusion Injury
Levent Demirtaş1, Cebrail Gürsul2, İlyas Sayar3, Mehmet Gürbüzel4, Şenol Biçer5, Emin Murat Akbaş6
1 Department of Internal Medicine, Faculty of Medicine, Erzincan University, Erzincan 2 Department of Physiology, Faculty of Medicine, Erzincan University, Erzincan 3 Department of Pathology, Faculty of Medicine, Erzincan University, Erzincan 4 Department of Medical Biology, Faculty of Medicine, Erzincan University, Erzincan 5 Department of Child Surgery, Faculty of Medicine, Erzincan University, Erzincan 6 Department of Endocrinology, Faculty of Medicine, Erzincan University, Erzincan
In this study, the effect of ozone therapy on tissue damage in the lungs and kidneys of rats consisting of hepatic ischemia-reperfusion was investigated. Reactive oxygen species (ROS) significantly increased in the tissue suffering from ischemia and following reperfusion, especially in the first stage. It is known this increase causes tissue damage in organs, including livers, lungs, and kidneys. Hepatic ischemia-reperfusion (I/R) injury is a clinical syndrome that may occur after liver transplantation and resection, as well as cardiogenic and hemorrhagic shock [1, 2]. Hepatic I/R cause liver function disorders and liver failure [1], as well as damage in other organs, such as lungs and kidneys [3, 4]. In recent years, ozone (O) use as a therapeutic agent in orthopedics, neurology, and endocrinology. O is known as an activator of antioxidative system [2]. This study was approved by the Ethics Committee of Atatürk University (Issue: 36643897-112, Resolution No. 92) for the use of experimental animals. Twenty-one Sprague-Dawley male rats weighing 250– 300 g were used. This study consisted of three groups. The control (C) group opened the abdomens of the rats with abdominal incision. After the abdomens were opened, the livers were closed with a thin suture. In the I/R group, the abdomens were opened with abdominal incision. The hepatic artery, portal vein, and bile duct were clamped using vascular clamps. The clamps were removed after 70 min and reperfusion was supplied up to 2 h. The I/R+O group was given 0.5 mg/kg O intraperitoneally before ischemia (70 min) and reperfusion (2 h). Before starting the animal applications, the rats were anesthetized. Tissue from the animals was maintained at -80 ° C. Similar results were obtained in both lung and kidney. Compared with the C group, the malondialdehyde (MDA) level and glutathione reductase (GR) activities increased in the I/R group. In addition, compared with the I/R group, these parameters increased in the I/R+O group. Compared with the C group, catalase (CAT) and superoxide dismutase (SOD) activities were decreased in the I/R group; compared with the I/R group, these enzyme parameters were increased in the I/R+O group (p< 0.05). According to the first observations, O is effective in eliminating tissue damage in the lungs and kidneys. References [1] Duenschede F, Erbes K, Kicher A, Westermann S, Schad A, Riegler N, Ewald P, Dutkowski P, Kiemer AK, Kempski O, Junginger T. Protection from hepatic ischemia/reperfusion injury and improvement of liver regeneration by α-lipoic acid. Shock, 2007, 27.6: 644–651. [2] Re L, Mawsouf MN, Menéndez S, León OS, Sánchez GM, Hernández F. Ozone therapy: clinical and basic evidence of its therapeutic potential. Arch Med Res 2008; 39: 17–26. [3] Chan KC., Lin CJ, Lee PH, Chen CF, Lai YL, Sun WZ, Cheng YJ. Propofol attenuates the decrease of dynamic compliance and water content in the lung by decreasing oxidative radicals released from the reperfused liver. Anesth Analg 2008:107(4), 1284–1289. [4] Lee HT, Park SW, Kim M, D'Agati, VD. Acute kidney injury after hepatic ischemia and reperfusion injury in mice. Lab Invest 2009; 89:196–208.
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Development of a nanoemulsion formulation of wild oregano essential oil
Elena Trajkoska-Bojadziskaa, Jana Simonovskaa, Olga Popovskaa, Zoran Kavrakovskib, Vesna Rafajlovskaa aSs. Cyril and Methodius University in Skopje, Faculty of Technology and Metallurgy Rudjer Boskovic 16, 1000 Skopje, Republic of Macedonia; [email protected]; [email protected]; [email protected]; [email protected]; Ss. Cyril and Methodius University in Skopje, Faculty of Pharmacy Majka Tereza 47, 1000 Skopje, Republic of Macedonia; [email protected] Abstract Essential oils have been widely utilized in several different fields such as pharmacy, sanitary, cosmetic, agriculture as well as in the food industry [1]. As a complex mixture, essential oils are made up of a large number of volatile substances such as terpenoids, phenol-derivatized aromatic compounds and aliphatic hydrocarbons. These kinds of compound can easily undergo oxidation, obtaining allergenic products and/or products with reduced biological activity [1,2]. In order to overcome these obstacles, the nanoemulsions have been proposed due to their capability of improving the solubility, stability and efficacy of essential oil-based formulations [2].
The aim of this study was to identify and to select the appropriate surfactants or surfactant mixtures (Smix) as well as the amount of the wild oregano essential oil in preparing the nanoemulsions. In addition, the phase behavior of oil and different surfactant/surfactant mixture combinations was studied. It is prudent to note that several different factors such as the type of the non-ionic surfactant (Tween 80, Tween 20 and Span 80) and the presence of soluble enhancer (propylene glycol, PG) affect the appearance of the phase behavior in the process of nanoencapsulation. Pseudo ternary phase diagrams consisting of oregano essential oil, surfactant/Smix and double distilled water were developed utilizing the aqueous titration method [3]. Following the period of one solar day (24 hours) with the addition of water every hour, the samples were visually observed for transparency and flowability. The phases were identified as transparent/translucent emulsion, transparent gel, turbid gel or turbid/milky emulsion.
Tween 80 and Smix (Tween 80 and Span 80) in different volume ratios (2:1 v/v and 1:1 v/v) led to obtain limited nanoemulsion area (maximum water 23%). Following the substitution of Tween 80 with Tween 20 and changing the aqueous phase from double distilled to double distilled water/PG, (1:1 v/v), the obtained nanoemulsions area was enhanced. The nanoemulsion could be fully diluted with aqueous phase without converting into turbid dispersion utilizing oil and surfactant in the weight ratio of 1:9 w/w. The absence of the transparent emulsion was recorded utilizing a mixture of Tween 80 and Span 80 (1:2 v/v).
References:
[1] C. Turek, F. C. Stintzing, Compr. Rev. Food Sci. Food Saf. 12 (2013) 40. [2] A. R. Bilia, C. Guccione, B. Isacchi, C. Righeschi, F. Firenzuoli, M. C. Bergonzi, Evid. Based Complement. Alternat. Med. 2014 (2014) 1. [3] H. K. Syed, K. K. Peh, Acta Pol. Pharm. 71 (2014) 301.
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Electro-Oxidation Behavior of Dexamethasone on the Modified-Multi Walled Carbon Nanotube Electrode and Its Application to Biological Samples
Ersin DEMİR a,b, Onur İNAMc, Recai İNAMb
a,bOkan University, Vocationcal School of Health Services, Perfusion Techniques, 34959, Istanbul Turkey, [email protected]; cHacettepe University, Faculty of Medicine, Department of Ophthalmology, Ankara, Turkey, [email protected]; cGazi University, Faculty of Art & Science, Department of Chemistry, 06500, Ankara, Turkey; [email protected]
Abstract Chemically modified electrodes have numerous advantages such as reducing over potentials, increasing the sensitivity and the reaction rate or improvement of the selectivity of the selectivity. Multi-walled carbon nanotubes have been attracting a great interest in recent years, due to the structural, mechanical, geometrical and chemical properties. It is also known that metal or metal oxide (MO) combining with MWCNT composite to be helpful the transmission of the electron during electrochemical reaction [1]. However, Modified-MWCNTP electrodes are widely used in routine drug analysis biological samples due to have significant advantages such as low cost, simple measurement system, fast analysis, low sample volumes and high selectivity [2]. In this study, voltammetric methods were applied for the determination of dexamethasone drug which is a type of steroid medication in biological samples. The oxidation behavior of dexamethasone (8.0 x10-6 M, Briton-Robison supporting electrolyte at pH 2.3) was investigated by using cyclic voltammetry (CV), Linear sweep (LSV), differential Pulse (DP), Square wave stripping (SWSV) and differential Pulse Stripping (DPSV) methods (Figure 1).
Figure 1. Chemical structure of dexamethasone and its voltammograms.
References:
[1] E. Demir, R. İnam, S. A. Özkan, B. Uslu, J. Solid State Electrochem., 18 (2014) 2709. [2] A. M. Ashrafi, S. Kurbanoglu, K. Vytras, B. Uslu, S. A. Ozkan, J Electroanal. Chem.712(2013) 178.
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Highly Efficient, One Pot, Solvent Free Access to Some Novel Quinazolinone Derivatives Using PTSA (p-Toluenesulfonic_acid) As Catalyst: Synthesis and Antifungal Activity Evaluation
Masoumeh Divar a, Soghra Khabnadidehb Research Institue of Pharmacutical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran. e-mail: [email protected] , [email protected]
Abstract The recent literature contains much information concerning the synthesis and pharmacological activity of the quinazolines. The quinazolinone skeleton is a building block for the preparation of natural purine bases, alkaloids, many biologically active compounds and intermediates in organic synthesis. Several derivatives of quinazoline have been cited as useful hypnotics, antimalarial, anti-HIV, anti- inflammatory, antifungal, analgesic, anticonvulsant, antihypertensive, antiviral effect, anticancer activity and antitubercular properties [1,2]. In addition to their diverse biological activity, the quinazolinone nucleus is also a key component in a relatively varied range of colored products. Compounds containing a fused quinazoline ring belong to a broad class of compounds which have received a considerable attention over the past years due to their wide range of biological activities. Some of amino quinazoline derivatives were found to be cardiac stimulants, they were also found as inhibitors of the tyrosine kinase or dihydrofolate reductase enzymes. Besides biological activity, quinazolines have O and N donor atoms, so they can act as good chelating agents [3]. Considering the biological acitivity of quinazolinone scafold, we designed an efficient and practical procedure for the synthesis of 3-substituted 2-methyl quinazoline-4(3H)-ones with anthranilic acid, acetic anhydride and primery amines in the presence of PTSA (p-Toluenesulfonic_acid) (Scheme 1).
Scheme 1. Synthetic route for the preparation of some novel quinazolinone derivatives
The antifungal activity of the synthesized compounds is under evaluation and will be reported in the future
Acknowledgments: We acknowledge the financial support from the research Institute of Pharmaceutical Sciences, also we are thankful Dr. S. Khabnadideh for helpful discussions.
References:
[1] J. Y. Melvin, et al., J. Med. Chem. 34 (1991) 1505. [2] N. P. Peet, et al., J. Med. Chem. 29 (1986) 2403. [3] J. Y. Melvin, et al., J. Med. Chem. 34 (1991) 1505.
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Simultaneous Determination of Clorsulon and Ivermectin in Veterinary Injectable Preparation by a New UPLC Method
Erdal DİNÇ, Z. Ceren ERTEKİN, Yunus Emre ÖREN
Ankara University Faculty of Pharmacy, Department of Analytical Chemistry, Tandoğan, Ankara, TURKEY [email protected], [email protected], [email protected] Abstract Combination of clorsulon (CLO) and ivermectin (IVE) is used in cattle in order to control internal and external parasites. In a previous study, CLO and IVE were simultaneously determined by artificial neural network [1]. This study aimed to develop an accurate, fast and simple ultra-performance liquid chromatography (UPLC) method to simultaneously quantify CLO and IVE in their pharmaceutical preparation for routine analysis and quality control procedures. The chromatographic elution and quantitation of CLO and IVE was performed with a Waters Acquity UPLC BEH C18 column (50 mm x 2.1 mm i.d., 1.7 μm) at 60 °C, using a mobile phase of water and acetonitrile (16:84, v/v) at a constant 0.40 mL/min flow rate. Stock solutions and all samples were prepared in acetonitrile. Optimum wavelengths for quantification of CLO and IVE to get their calibration curves were determined to be 246.4 nm and 226.3 nm, respectively. Retention times for CLO and IVE were 0.30 and 1.27 min, respectively. Representative chromatograms are presented in Figure 1. The calibration curves were obtained by plotting the peak area versus concentration. Linear regression lines were between 2.5-35.0 µg/mL for CLO and 3.0-48.0 µg/mL for IVE.
Figure 1. UPLC chromatograms of 20.0 µg/mL CLO and 24.0 µg/mL IVE at the optimum detection wavelength of each compound.
After method validation studies, the analysis of related veterinary drugs in commercial injection solutions was performed. The analysis results were found as 98.20 mg and 9.92 mg per millilitre for CLO and IVE, respectively (Label claim: 100 mg CLO and 10 mg IVE per one mL solution).
References: [1] G. Pektaş, E. Dinç, D. Baleanu, Revista de Chimie, 59:10, (2008), 1156
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Chemical composition of Limonium thouinii (Viv.) Kuntze (Plumbaginaceae) and the DPPH free radical scavenging activity
Lefahal M1, Djarri L*1, Benahmad M2, Zaabat N1, Hay AE3, Medjroubi K1, Dijoux-Franca M-G3, Laouer H4 and Akkal S1.
1 Université de Constantine1, Unité de Recherche Valorisation des ressources naturelles Molécules bioactives et Analyses Physico-Chimiques et Biologiques, Département de Chimie, Facultés des Sciences exactes, Algérie. 2 Université Larbi Tébessi Tébessa Laboratoire des molécules et applications, Algérie. 3 Université de Lyon, F-69622, Lyon, France; Université Lyon 1, Villeurbanne; CNRS, UMR 5557, Ecologie Microbienne, ISPB, 69373 Lyon, France. 4 Université Ferhat Abbas Sétif 1, Laboratoire de valorisation naturelles biologiques, Département de Biologie et écologie des ressources végétales, Algérie. * corresponding author: [email protected]
Abstract
The present work is interesting to the phytochemical investigation and DPPH free radical-scavenging activity of the aerial parts of Limonium thouinii (Viv.) Kuntze (Plumbaginaceae). The aerial parts of Limonium thouinii (Viv.) Kuntze allowed the isolation of four flavonoids: Quercetin 1, Vitexin 2, Isoorientin 3 and Cannabiscitrin 4. Their structures were elucidated on the basis of spectroscopic analysis including UV, MS and NMR techniques. The DPPH free radical-scavenging activity was evaluated on crude extracts (MeOH, EtOAc and n-BuOH extracts).
Keywords: Plumbaginaceae, Limonium thouinii, Flavonoids, free DPPH radical scavenging activity.
R3 OH R2 HO O R4
R1 R5 OH O
R1 R2 R3 R4 R5 1 H H OH H OH 2 H Glu H H H 3 Glu H OH H H 4 H H OH O-glu OH
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Formulation and evaluation of ketoconazole liposomes using injection method
Olga Popovskaa, Elena Trajkoska-Bojadziskaa, Jana Simonovskaa, Zoran Kavrakovskib, Vesna Rafajlovskaa aSs. Cyril and Methodius University in Skopje, Faculty of Technology and Metallurgy Rudjer Boskovic 16, 1000 Skopje, Republic of Macedonia; [email protected]; [email protected]; [email protected]; [email protected]; Ss. Cyril and Methodius University in Skopje, Faculty of Pharmacy Majka Tereza 47, 1000 Skopje, Republic of Macedonia; [email protected] Abstract Liposomes as models of cell membranes have become an ideal system for delivering drugs such as antifungal agents [1,2] at a specified rate in the body over a certain period of time [3]. The utilization of liposomes was increased due to their unique characteristics such as flexibility, non–toxicity and biodegradation [2]. Phospholipids and cholesterol are considered as the main components in the liposomal bilayers [1,4]. Ketoconazole is an antimycotic drug, utilized in the treatment of supercritical and systemic fungal infections in pharmaceutical dosage formulations such as tablets, cream and shampoo [4]. It is highlighted to connect the utilization of the drug to its safety formulations such as liposomes [4,5].
The large unilamellar vesicles (LUV) as liposomal formulations of ketoconazole were prepared by using an injection method. Ketoconazole, cholesterol and L-α-phosphatidylcholine (egg yolk) in the weight ratio of 3.3:1:3.3 w/w/w were dissolved in 5 mL olive oil. Following the homogenization on a magnetic stir (1000 min-1), the mixture was slowly injected in preheated distilled water (80ºC) and it was left during 1 hour at 65ºC. Drug loading and entrapment efficiency were determined by UV spectrophotometer at 296 nm, optical microscope and zeta potentiometer [Figure 1].
А
296 nm
Wavelength (nm) Figure 1. An UV spectrum of the loaded ketoconazole in liposomes obtained via the injection method
The proposed method was successfully applied for the preparation of ketoconazole liposomal formulations. The drug encapsulation efficiency was up to 40%, while the ζ–potential value was -30.21 mV. In addition, the utilization of olive oil enables to obtain safety formulations.
References: [1] H. Chanda, P. Das, R. Chakraborty, A. Ghosh, J. Pharm. Biomed. Sci. 5 (2011) 1. [2] M. Devi, M. S. Kumar, N. Mahadevan, IJRAPR 4 (2011) 37. [3] R. Kumar, A. C. Rana, R. Bala, N. Seth, Int. J. Drug Dev. & Res. 4 (2012) 348. [4] R. P. Patel, H. Patel, A. H. Baria, IJDDT 1 (2009) 16. [5] S. H. Sahasrabuddhe, N. Bajpai, S. Bais, S. Ganesan, IJAPS 3 (2012) 109.
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Development and validation of an UV spectrophotometric method for the determination of capsaicin in the red hot chilli pepper
Jana Simonovskaa, Olga Popovskaa, Elena Trajkoska-Bojadziskaa, Zoran Kavrakovskib, Vesna Rafajlovskaa aSs. Cyril and Methodius University in Skopje, Faculty of Technology and Metallurgy Rudjer Boskovic 16, 1000 Skopje, Republic of Macedonia; [email protected]; [email protected]; [email protected]; [email protected]; Ss. Cyril and Methodius University in Skopje, Faculty of Pharmacy Majka Tereza 47, 1000 Skopje, Republic of Macedonia; [email protected] Abstract Capsaicin (8-methyl-N-vanillyl-trans-6-nonenamide) is a crystalline, colorless, odorless and lipophilic alkaloid [1]. It is the major active compound of the capsaicinoids which causes the pungency in the red hot chilli pepper [2,3]. It is prudent to note that several different analytical methods have been described for the determination of capsaicin in the red hot chilli peppers such as thin–layer chromatographic (TLC) method [1,4], ultraviolet–visible (UV–Vis) spectrophotometric method [1] and high–pressure liquid chromatographic (HPLC) method [5].
A simple, precise and rapid UV spectrophotometric method was developed for the determination of capsaicin in the extracts of the red hot chilli pepper Capsicum annuum L. (pericarp, placenta, seed and stalk). The absorption maximum of capsaicin solutions in ethanol was recorded at 281 nm. The linearity for capsaicin in ethanol was found in the range of 3–100 μg/mL. The coefficient of determination (R2) was higher than 0.999. The intra– and inter– day assay was within 2% relative standard deviation. The limit of detection (LOD) and the limit of quantification (LOQ) were 4.184 μg/mL and 12.682 μg/mL, respectively.
The UV spectra of capsaicin solution in ethanol (A) and placenta extract in ethanol (B) are shown in Figure 1.
А А А B
Wavelength (nm) Wavelength (nm) Figure 1. The UV spectra of capsaicin solution in ethanol (40 μg/mL) (A) and placenta capsaicin extract in ethanol (49.5 μg/mL) (B) within the linearity range at 281 nm.
The proposed method was successfully applied for the determination of capsaicin in the extracts of red hot chilli pepper (pericarp, placenta, seed and stalk). The most abundant part with capsaicin content was found in the placental tissue of the red hot chilli pepper Capsicum annuum L.
References: [1] N. J. Amruthraj, R. J. P. Preetam, L. L. Antoine, IJPCR 6 (2014) 159. [2] S. K. Cheema, M. R. Pant, Res. J. Pharm. Biol. Chem. Sci. 2 (2011) 701. [3] K. Sanatombi, G. J. Sharma, Not. Bot. Hort. Agrobot. Cluj 36 (2008) 89. [4] S. Bhuvaneshwari, S. K. Prasanna, K. Alice, Int. J. Pharm. Biol. Sci. Arch. 4 (2013) 1186. [5] Z. A. A. Othman, Y. B. H. Ahmed, M. A. Habila, A. A. Ghafar, Molecules 16 (2011) 8919.
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Development and validation of a Vis spectrophotometric method for the determination of total phenolic compounds in the red hot chilli pepper
Jana Simonovskaa, Olga Popovskaa, Elena Trajkoska-Bojadziskaa, Zoran Kavrakovskib, Vesna Rafajlovskaa aSs. Cyril and Methodius University in Skopje, Faculty of Technology and Metallurgy Rudjer Boskovic 16, 1000 Skopje, Republic of Macedonia; [email protected]; [email protected]; [email protected]; [email protected]; Ss. Cyril and Methodius University in Skopje, Faculty of Pharmacy Majka Tereza 47, 1000 Skopje, Republic of Macedonia; [email protected] Abstract Capsaicinoids are a group of phenolic compounds commonly present in the genus Capsicum, of which capsaicin is the most abundant [1,2]. In the literature, several different analytical methods have been described for the determination of the total phenolic compounds in the red hot chilli peppers, including thin–layer chromatographic (TLC) method [2] and ultraviolet–visible (UV–Vis) spectrophotometric method [3].
A simple, accurate, rapid and sensitive Vis spectrophotometric method was developed for the determination of the total phenolic compounds in the extracts of the red hot chilli pepper Capsicum annuum L. (pericarp, placenta, seed and stalk). The method was based on the reaction between Gibbs’ reagent (0.05% in ethanol) and phenolic compounds in the extracts of the red hot chilli pepper at pH adjusted to 9. The optimal reaction time was carried out in the dark, for 30 min. The absorption maximum was recorded at 600 nm within the linearity in the concentration range of 10–300 μg/mL. The limit of detection (LOD) and the limit of quantification (LOQ) were 13.41 μg/mL and 40.66 μg/mL, respectively.
The Vis spectra of the derivatized standard capsaicin solution with Gibb’s reagent in ethanol (A) and derivatized stalk extract with Gibb’s reagent in ethanol (B) are shown in Figure 1.
А А А B
600 nm 600 nm
Wavelength (nm) Wavelength (nm) Figure 1. The Vis spectra of derivatized standard capsaicin solution with Gibb’s reagent in ethanol (80 μg/mL) (A) and derivatized stalk extract with Gibb’s reagent in ethanol (96.5 μg/mL) (B) within the linearity range at 600 nm. The optimized Vis spectrophotometric method was successfully applied for the determination of the total phenolic compounds in the extracts of the red hot chilli pepper Capsicum annuum L. (pericarp, placenta, seed and stalk).
References: [1] S. Bhuvaneshwari, S. K. Prasanna, K. Alice, Int. J. Pharm. Biol. Sci. Arch. 4 (2013) 1186. [2] S. K. Cheema, M. R. Pant, Res. J. Pharm. Biol. Chem. Sci. 2 (2011) 701. [3] N. J. Amruthraj, R. J. P. Preetam, L. L. Antoine, IJPCR 6 (2014) 159.
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An Investigation on Protective Effect of Gilaburu (Viburnum opulus L.) Fruit against Ischemia/Reperfusion-Induced Oxidative Stress after Lung Transplantation in Rat
Ayşe Ekena, Orhan Yücelb, İ. İpek Boşgelmeza, Ayşe Baldemirc, A. Hakan Çermikd, Sezai Çubukb, Akın Yıldızhanb, Adem Gülere, Müberra Koşarf aDepartment of Pharmaceutical Toxicology, Erciyes University, Kayseri, Turkey; e-mail:[email protected]; bDepartment of Thoracic Surgery, Gulhane Military Medical Academy, Ankara, Turkey cDepartment of Pharmaceutical Botany, Erciyes University, Kayseri, Turkey dDepartment of Pathology, Gulhane Military Medical Academy, Ankara, Turkey eDepartment of Cardiac and Vascular Surgery, Gulhane Military Medical Academy, Ankara, Turkey fDepartment of Pharmacognosy, Erciyes University, Kayseri, Turkey Abstract The objective of this study was to investigate the possible protective effect of Gilaburu (Viburnum opulus L.) fruit extract against ischemia/reperfusion (I/R)-induced oxidative stress during the lung transplantation.
In the method of this study, female Wistar albino rats were randomly divided into 3 groups; the control, I/R and Gilaburu+I/R. Gilaburu fruit extract (200 mg/kg) was administered intraperitoneally to the Gilaburu+I/R group before and immediately after lung transplantation. Lung injuries were assessed by multiple parameters, including malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), total oxidant status (TOS), total antioxidant capacity (TAC), total glutathione, protein carbonyl, oxygenation index (PaO2/FiO2), and histologic examination.
Our results show that the concentration of MDA as a result of lipid peroxidation was increased in I/R group. Administration of Gilaburu fruit extract resulted in significant reduction of tissue MDA levels in Gilaburu+I/R group. Moreover, this level remained unchanged in this group compared to the control group. Similarly, the extract-treatment ameliorated/ alleviated the increase/ rise in protein carbonyl level as compared with I/R group. Ischemia/reperfusion resulted in decrease of SOD, GPx and CAT enzyme activities as well as glutathione level as compared with control group, while this effect was compensated by Gilaburu treatment. Moreover, we observed that serum TOS levels were significantly higher and TAC levels were significantly lower with I/R group as compared to Gilaburu+I/R group and controls. In comparison to I/R group, the PaO2/FiO2 level was significantly decreased at 2 hours after reperfusion among the other groups. Histological examination of the lung tissue subjected to I/R process showed the distinctive pattern of ischemic injury. In the control group, lung tissue sections had a normal morphology. Treatment with Gilaburu fruit extract significantly decreased the histological injury score in Gilaburu+I/R group compared with I/R group.
In conclusion, findings show that Gilaburu extract exerts protective effect on I/R during lung transplantation probably by the radical scavenging and antioxidant activities. Therefore, Gilaburu fruit extract could be alternative therapeutic strategy for the prevention of lung toxicity-induced oxidative stress.
Acknowledgments: This research was financially supported by Turkish National Scientific Council-TÜBİTAK (Project number: 213S045).
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Apiterapy
1Engin KILIÇ, 1Yücel KADIOGLU, 1Ismail Çağrı AYDIN, 1Sefa, GÖZCÜ 1Büsra ODABASI 1 K. Gizem YILDIZTEKİN, 2Adem DÖLEK 1Erzincan University, Faculty of Pharmacy 2Erzincan University, Faculty of Theology
Abstract Especially in the last decade WHO member states, led by the EU countries, have shown growing interest in evidence-based, Traditional, Complementary and Alternative Medicine (TCAM). It can be seen that TCAM has started to be integrated into the health systems of many countries around the world. Likewise, TCAM practices fill an important gap in human health, especially in those cases when modern medicine neglects or is different to human beings. One of the TCAM practices is apitherapy. Apitherapy is the use of honeybee products such as honey, bee pollen, bee venom, propolis, bee waxy and royal jelly for medical purposes. Today, in many countries have got apitherapy center, for example, USA, Germany, Austria, Hungary, Russia, China, Eastern Europe, and the Balkans, especially in Romania. In this country, apiterapy is used for treating multiple sclerosis (MS), osteoarthritis, rheumatoid arthritis, pain after a shingles infection, and bee sting allergies. It is also used for cough, herpes simplex virus, premenstrual syndrome (PMS), hay fever, high cholesterol, and the common cold. Other uses include improving athletic performance and wound healing after mouth surgery. In this article we review what are bee products, the history of apiterapy, some theological massage about apiterapy, why do we choose the apiterapy for medicine, what is apiterapy situation at Turkey, what is current research situation of apiteray research is discussed, as well as its future at Turkey. Key Words: medicine, honey, pollen, propolis, bee venom, royal jell, bee waxy, Turkey
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Entomotherapy and Turkey Engine KILIÇ Erzincan University, Faculty of Pharmacy, Department of Microbiology and Parasitology, Erzincan, TURKEY. [email protected]
Abstract Traditional medicine considers drug and food to be homologous in function for human health. As an important component of traditional medicine, insects have long been used in the world. It has been verified that many insects’ species can directly or indirectly be used to cure common human diseases since antiquity. Entomotherapy is the use of insect for medicinal and nutritional purpose. Turkish fauna biodiversity is quite high compared with the biodiversity of other countries in the temperate zone. There are many more medicinal insects species in Turkey are such as; Apis mellifera, Bombyx mori L., Lepisma saccarina, Mantis spp., Vespa spp., Polistes spp.. Gryllotalpa spp., Laccifer spp., Nezara spp., Tabanus spp., Blatta spp., Periplanata spp., Cynips galletincoria, Dactylopius coccus, Aphis spp, Psylla spp., and some Coccoida species. We focus on in this review the potential and use of medicinal insect in Turkey. We briefly are writing generally the history of medicinal insects, current situation medicinal insects, which form (eggs, larvae, adult) is using for medicine and their future. Key words: Insects, Entomology, Pharmacy, Medicine, Turkey
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The Potential of Arthropods Causes Venom Allergy at Turkey Engin KILIÇ Erzincan University, Faculty of Pharmacy, Department of Microbiology and Parasitology, Erzincan, TURKEY Abstract As is known, allergy is an abnormal reaction to substances. Allergy is a number of conditions caused by hypersensitivity of the immune system. They include hay fever, food allergies, atopic dermatitis, allergic asthma, and anaphylaxis. Symptom may include red eyes, itchiness, and runny nose, eczema, hives. Food allergies and reactions to the venom of stinging insects more often results in severe reactions. There are two classes of arthropods that causes venom allergy are the class Insecta, which includes bees, wasps, yellow jackets, fleas, ants, caterpillars, bedbugs, and lice; and the class Arachinida, which includes spiders, ticks and scorpions at the world. There are many more insects and arachnida species at Turkey. These are Apis mellifera and its subtypes, Bombus spp., Vespula spp., Polistes spp., some formicidae species (Insecta: Hymenoptera); Anopheles spp., Aedes spp., Clulex spp., Musca domestica, Tabanus spp., (Insecta: Diptera); Cimex lectularius (Insecta: Hemiptrea), Pediculus spp., (Insecta: Phthiraptera) Tunga penetrans (Insecta: Siphonaptera); Ixodes spp, Amlyomma spp., Rhipicephalus spp., Dermacentor spp., Hyalomma spp., (Arachnida: Ixodidae); Argas spp., Ornithodorus spp., Otobius spp., (Arachnida: Argasidae); Loxosceles spp., Androctonus spp., Leiurus spp., Mesabothus spp., (Arachnida: Scorpiones) In this article we review the species of Insect and Arachnida causes venom allergy at Turkey and we separated two groups that causes venom allergy these are the biters (ant, mosquito, horsefly, bedbug, wheel bug, blister beetle, flea, spider, tick and mite) and the stingers (honey bee, bumblebee, hornet, yellow jacket, scorpion) Key word: Venom allergy, Insecta, Arachnida, Arthropods, Pharmacy, Medicine, Turkey
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Diabetes mellitus and associated factors in human immunodeficiency virus-infected individuals at Jimma University Specialized Hospital, Southwest Ethiopia
Abdurehman Eshete Mohammed1, Tilahun Yemane Shenkute1, Waqtola Cheneke Gebisa1 1Department of Medical Laboratory Sciences and Pathology, College of Health Sciences, Jimma University, Jimma, Ethiopia Address Abdurehman Eshete Mohammed ([email protected] , Jimma University, Ethiopia) Tilahun Yemane Shenkute ([email protected] , Jimma University, Ethiopia) Waqtola Cheneke Gebisa([email protected] , Jimma university, Ethiopia) Abstract Background: Globally, diabetes is rising dramatically causing high health burden in low- and middle- income countries [1]. It is estimated that about 382 million people had diabetes in 2013. In 2013, diabetes caused 5.1 million deaths globally. Almost 80% of diabetes deaths occur in low- and middle-income countries [2]. Purpose: To assess the magnitude of diabetes mellitus (DM) and associated risk factors in human immunodeficiency virus (HIV)-infected individuals. Methods: An institution-based cross-sectional study was conducted from April to May 2014 at Jimma University Specialized Hospital. Convenient sampling technique was implemented. Socio-demographic and anthropometric data were collected by senior clinical nurses. Venous blood was collected from each study participant. Serum glucose and lipid profile of the study participants was measured using HumaStar 80 spectrophotometer. Data were analyzed using SPSS version 20. Bivariate and multivariate logistic regressions were utilized. Results: A total of 393 HIV-infected individuals of age ranging from 21 years to 75 years had enrolled in this study. The overall prevalence of DM in this study was 6.4% (n=25). Two hundred and ninety-one (74%) and 77 (19.6%) of the study participants had normal (70–110 mg/dL) and impaired (111–125 mg/dL) fasting blood glucose values, respectively. After adjusting for the other variables, age (adjusted odds ratio [AOR] =4.812, 95% confidence interval [CI]: 1.668–13.881, P=0.004), duration of highly active antiretroviral therapy (HAART) (AOR =26.928, 95% CI: 3.722–194.822, P=0.001), hypertension (AOR =4.779, 95% CI: 1.646–13.874, P=0.004), and low-density lipoprotein cholesterol (AOR =5.669, 95% CI: 1.849–17.382, P=0.004) were significantly associated with DM. Conclusion: HAART may have an impact on the cause of diabetes. Hence, HIV-infected individuals should be screened for diabetes, both before and after initiation of HAART. Acknowledgment: We acknowledge Jimma University, Bedele woreda prison administrators and Bedele woreda prisoners who were involved in this study. References [1] M.A. Hanson, P.D. Gluckman, R.C. Ma, P Matzen, R.G. Biesma. Early life opportunities for prevention of diabetes in low and middle income countries. BMC Public Health. 2012; 12:1025. [2] International Diabetes Federation Diabetes Atlas. 6th ed; 2013. Available from: http://www.idf.org/diabetesatlas/update-2014.Accessed June 17, 2014.
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Determination Toxic Effect of New Synthesize Chemical Compounds in Vitro. Mustafa Anar1, Hatice Gebiç Gökdag2, Ayşen Alaman Agar3, Guleray Agar3, Serap Sunar4
1Ataturk University, Faculty of Science, Department of Molecular Biology and Genetics, Erzurum 2Ondokuzmayıs University, Faculty of Science and Art, Department of Chemistry, Samsun 3Atatürk University, Faculty of Science, Department of Biology, Erzurum 4Erzincan University, Faculty of Pharmacy, Department of Pharmaceutical Botany,Erzincan E-mail: [email protected]
Abstract
Lots of chemical compounds have toxicological weak or strong effects. For this reason, Researchers demonstrate efforts to determine the effects of chemicals on living organisms. Especially, new chemical materials are synthesized and investigated their biological activities on human cells. In this study, we aimed to determine cytotoxic effects of (Z)-6-(2-(((2-methoxyphenyl) imino) methyl) phenoxy) tetrahydro-2H-pyran-2,3,4,5-tetraol and (Z)-6-(2-(((4-methoxyphenyl) imino) methyl) phenoxy) tetrahydro-2H-pyran-2,3,4,5-tetraol.
Chemical materials-1 Chemical materials-2
The cytotoxic effects of new synthesized chemical compounds were investigated with Lactate Dehydrogenase (LHD) assay kit. According to the results, this chemical compounds have no cytotoxic effect, while have anticytotoxic effects. For this reason, this material might be used as anticancer agent after further research. References: [1] Anar, M., Kizil, HE., Agar, G. 2014. The determination of antioxidative effect and anticancer potential of vulpinic acid. Journal of Biotechnology 185S, S37–S125. [2] Kizil, HE., Agar, G., Anar, M. 2014. Cytotoxic and antiproliferative effects of evernic acid on HeLa cell lines A candidate anticancer drug. Journal of Biotechnology 185S, S18–S36.
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Genotoxic And Antigenotoxic Effect of New Synthesize Chemical Compounds on Human Lymphocyte in Vitro. Mustafa Anar1, Serap Sunar2, Hatice Gebiç Gökdag3, Ayşen Alaman Agar3, Guleray Agar4
1Ataturk University, Faculty of Science, Department of Molecular Biology and Genetics, Erzurum 2Erzincan University, Faculty of Pharmacy, Department of Pharmaceutical Botany, Erzincan 3Ondokuzmayıs University, Faculty of Science and Art, Department of Chemistry, Samsun 4Atatürk University, Faculty of Science, Department of Biology, Erzurum E-mail: [email protected] Abstract Today, many chemicals are synthesized and their biological effects are being investigated. This synthesized chemicals are being used different areas from medicine to drug industy. So, scientists investigated toxicological effects of chemical compounds on human DNA. In this preliminary study, we aimed to determine genotoxic and antigenotixic effects of (E)-N-(2,4-dichlorophenyl)-1-(5- nitrothiophen-2-yl)methanimine and (E)-(2-hydroxy-5-nitrobenzylidene)carbamic acid on human lymphocyte with the sister chomatid exchange (SCEs) [1,2] .
Compounds-1 Compounds-2
Healthy and non-smokers 4 volunteer people (2 men and 2 women) blood collected and incubated with AFB1. This study results showed that two compounds have no genotoxic effects on human lymphocyte. In addition, this two compounds protected human lymphocyte against mutajenic effects of AFB1. In conclusion, the biological effects cytotoxic, proliferative and anticancer activities of this chemical compounds must be investigated with different biological test systems. These compounds may be alternative approach cancer treatment.
References: [1] Latt, S.A., and Schreck, R.R., 1980. Sister chromatid exchange analysis. American Journal of Human Genetics, 32(3), 297-313. [2] Perry, P. and Evans, H.J., 1975. Cytological Detection Of Mutagen-Carcinogen Exposure By Sister Chromatid Exchange, Nature, 258, 121-125).
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Activators of carbonic anhydrase I and II: osajin and pomiferin
Esra Dileka, Claudiu T. Supuranb
a Erzincan University, Pharmacy Faculty, Division of Pharmaceutical Basic Sciences, Department of Biochemistry, 24030, Turkey-Erzincan; e-mail: [email protected]; b Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino (Florence), Italy; e-mail: [email protected]
Abstract The fruit of M. pomifera is also well-known for its rich isoflavonoid content as well as a content of xanthones [1]. Several biological activities of the plant were reported up to date including antimicrobial, estrogenic, anti-inflammatory, antidepressants, antitumor and antinociceptive activities [2].
In this study, our aim was to investigate in vitro carbonic anhydrase I and II (CAI and II) potential of M. Pomifera major isoflavonoids osajin (1) and pomiferin (2). 10-15 pieces of fruit were harvested from M. pomifera tree that it grows at a park in Kilis/Turkey in October. Osajin and pomiferin substance was purified by TLC method and its structure was elucidated by NMR methods. Then, we have purified CA I and II from human erythrocytes and examined the in vitro effects of these substances on these important enzymes, by using the esterase activity of CA I and II, with 4-nitrophenyl acetate as substrate.
We found that osajin (1) and pomiferin (2) are a potent activator of CA I and II.
Table 1. KA-s for the activation of osajin (1) and pomiferin (2) against hCA I and II
KA (µM) Compound hCA I hCA II Pomiferin 1.8 3.7 Osajin 0.013 0.045
Acknowledgments: Esra Dilek acknowledges FONDECYT for financial support, Claudiu T. Supuran acknowledges for helpful calculations activation constants.
References:
[1] G. Toker, I. Erdogan, J. Fac. Pharm. Gazi Univ. 15 (1998), 29. [2] D.M. Teixeira, C. Costa, Journal of Chromatography A. 1062 (2005) 175
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Genotoxic And Antigenotoxic Effect of Some Lichens
Mustafa Anar1,Ali Aslan2, Guleray Agar3, Hamit Emre Kizil3,4 1Ataturk University, Faculty of Science, Department of Molecular Biology and Genetics, Erzurum 2Ataturk University, Kazim Karabekir Education Faculty, Department of Biology Education, Erzurum 3Atatürk University, Faculty of Science, Department of Biology, Erzurum Bayburt university, 4Bayburt University, Vocational School of Health Services, Bayburt, Turkey *Corresponding author. E-mail: [email protected].
Abstract Lichens are symbiotic organisms. Lichens have been used very different treatment from ages. People used to lichens for treatment according to the morphology. In addition, lichens have been used for treatment some diseases like tuberculosis for several years [1]. Studies showed that some seconder metabolites stimulate apoptosis in colon [2] and prostate [3] cancers. The protective role of lichens are getting more important. In this study the genotoxic and antigenotixic activity of the methanol extracts of two lichen species (Anaptychia ciliaris, Bryoria fuscescens) were investigated. Sister Chromatid Exchange (SCE) test were used for determining the genotoxic contamination and the results showed that two lichen extracts inhibited the mutagenic effects of AFB1. We also determined that our lichen samples have no genotoxic effect. In addition, Anaptychia ciliaris, Bryoria fuscescens lichen species have strong antigenotoxic effects on human lymphocytes againt AFB1 mutagenic effect.
Key words: Antigenotoxicity, SCE, AFB1 References: [1] Vartia, KO., 1973. Antibiotics in lichens. In: Ahmadjian, V., Hale, M.E. (Eds.), The lichens.Academic Press, New York, p. 547. [2] Perry, P. and Evans, H.J., 1975. Cytological Detection Of Mutagen-Carcinogen Exposure By Sister Chromatid Exchange, Nature, 258, 121-125). [3]Russo, A., Piovano, M., Lombardo, L., Garbarino, J. & Cardile, V., 2008. Lichen metabolites prevent UV light and nitric oxide-mediated plasmid DNA damage and induce apoptosis in human melanoma cells. Life Sciences, 83(13-14): 468-474.
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Determination of Antioxidant Capacity of Two Lichens in vitro
Mustafa Anar1, Hamit Emre Kizil2,3, Ali Aslan4, Guleray Agar2, 1Ataturk University, Faculty of Science, Department of Molecular Biology and Genetics, Erzurum 2Atatürk University, Faculty of Science, Department of Biology, Erzurum 3Bayburt University, Vocational School of Health Services, Bayburt, Turkey 4Ataturk University, Kazim Karabekir Education Faculty, Department of Biology Education, Erzurum
*Corresponding author. E-mail: [email protected].
Abstract Lichens are symbiotic organisms. Lichens have been used very different treatment from ages. People used to lichens for treatment according to the morphology. In addition, lichens have been used for treatment some diseases like tuberculosis for several years [1]. Studies showed that some seconder metabolites stimulate apoptosis in colon [2] and prostate [3] cancers. In this study, we investigated antioxidant capacity of Parmotrema chinensa and Xanthoria candelaria lichen species in vitro. Antioxidant properties of P. chinensa and X. candelaria were determined by measuring the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione (GSH) and level of malondialdehyde (MDA) against the oxidative stress of AFB1 in human lymphocytes in vitro. It was observed that the levels of antioxidant enzymes were decreased dramatically and level of malondialdehyde (MDA) increased after treatment with AFB1 but the antioxidant enzymes were increased and MDA levels decreased in case of applying the lichen methanol extracts. We also determined that our lichen samples have strong antioxidant activities againt AFB1.
Key words: Lichen, Oxidative stress References: [1] Vartia, KO., 1973. Antibiotics in lichens. In: Ahmadjian, V., Hale, M.E. (Eds.), The lichens.Academic Press, New York, p. 547. [2] Perry, P. and Evans, H.J., 1975. Cytological Detection Of Mutagen-Carcinogen Exposure By Sister Chromatid Exchange, Nature, 258, 121-125). [3]Russo, A., Piovano, M., Lombardo, L., Garbarino, J. & Cardile, V., 2008. Lichen metabolites prevent UV light and nitric oxide-mediated plasmid DNA damage and induce apoptosis in human melanoma cells. Life Sciences, 83(13-14): 468-474.
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The potential of plants are important in terms of implication the honey, pollen, propolis used in apitherapy
1Engin KILIÇ, 2Şebnem YÜREKLİ, 3Mustafa KORKMAZ
1Erzincan University, Faculty of Pharmacy, Department of Microbiology and Parasitology, Erzincan, TURKEY 2Erzincan University, Faculty of Pharmacy, Department of Pharmasotic Botanic, Erzincan, TURKEY 3Erzincan University, Faculty of Art and Science, Department of Biology, Erzincan, TURKEY Abstract Apitherapy is the use of honeybee products such as honey, bee pollen, bee venom, propolis, bee waxy and royal jelly for medical purposes. The quality of these products is so important for apiterapy. Because they have to be pure, rich chemical component and they must find plentifully. Likewise, people who interesting in apiterapy must know the source of their products they can take an affective result for treatment. In this purpose we separate some groups for honey plants, pollen plants and propolis plants. As a measure of honey -making capacity of the plant species, the concept of honey potential has been developed. Plants are divided into six classes according to their potential of honey. The highest potential group is the sixth group, honey potential of 501 kg / ha, while with the lowest group is the fırst group whose honey potential is 0-25 kg/ha. In these six groups a total of 200 different plant species are located. Pollinated plants are divided into four groups in terms of the pollen yield (dominant, secondary, minor and trace). Most of pollen-producing plants are considered in the dominant group of plants and the number of plant species which have importance in terms of apitherapy is 51different species. The most of propolis plants are generally woody plants and the numbers of plant species which are having importance in terms of apitherapy is 15 different species. In this review we evaluated that the potential of plants which are important in terms of implication of the honey, pollen and propolis and gave their list used in apitherapy.
Key words: Medicine, pharmacy, honey plants, pollen plants, propolis plants, apiterapy.
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Determination of Genotoxic And Antigenotoxic Effect of New Synthesize Organic Compounds
Mustafa Anar1, Seher Meral2, Ayşen Alaman Agar2, Guleray Agar3
1Ataturk University, Faculty of Science, Department of Molecular Biology and Genetics, Erzurum 2Ondokuzmayıs University, Faculty of Science and Art, Department of Chemistry, Samsun 3Atatürk University, Faculty of Science, Department of Biology, Erzurum *Corresponding author. E-mail: [email protected]
Abstract In recent years, researchers have produced new chemicals to fight with different diseases. The importance of the investigation of the biological effects of these chemical substances has been increasing day by day. For this reason, we aimed to investigate genotoxic, antigenotoxic properties of new synthesized organic compounds. (Z)-6-(2-((p-tolylimino)methyl)phenoxy)tetrahydro-2H-pyran- 2,3,4,5-tetraol and (Z)-6-(2-((o-tolylimino)methyl)phenoxy)tetrahydro-2H-pyran-2,3,4,5-tetraol chemical compounds genotoxic, antigenotoxic effects were analyzed with the SCEs (sister chomatid exchange) [1,2].
Organic compounds-1 Organic compounds-2 (Z)-6-(2-((p-tolylimino)methyl)phenoxy)tetrahydro-2H-pyran-2,3,4,5-tetraol and (Z)-6-(2-((o- tolylimino)methyl)phenoxy)tetrahydro-2H-pyran-2,3,4,5-tetraol showed no genotoxic effects. Three different doses were used. High dose showed strong antigenotoxic effects. Pharmaceutical chemistry is important for new treatment. The synthesis of new substances in the treatment of diseases has led to the emergence of new approaches. Therefore, these compounds might be new approach for antigenotoxic studies.
Key words: Antigenotoxicity, SCE, Organic compound References: [1] Latt, S.A., and Schreck, R.R., 1980. Sister chromatid exchange analysis. American Journal of Human Genetics, 32(3), 297-313. [2] Perry, P. and Evans, H.J., 1975. Cytological Detection Of Mutagen-Carcinogen Exposure By Sister Chromatid Exchange, Nature, 258, 121-125).
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Determination of Cytotoxic And Anticytotoxic Effect of New Synthesize Conpounds
Mustafa Anar1, Seher Meral2, Ayşen Alaman Agar2, Guleray Agar3
1Ataturk University, Faculty of Science, Department of Molecular Biology and Genetics, Erzurum 2Ondokuzmayıs University, Faculty of Science and Art, Department of Chemistry, Samsun 3Atatürk University, Faculty of Science, Department of Biology, Erzurum *Corresponding author. E-mail: [email protected]
Abstract Pharmaceutical chemistry have important role to produce new drugs or chemicals. Nowadays, scientists are producing new chemical compounds, having biological activity, looking for drug potential. In this study, we aimed to investigate cytotoxic or anticytotoxic effects of new synthesized organic compounds. We studied two organic compounds. This new synthesized organic compounds have no cytotoxic effects. Anticytoxic effects of (E)-N-(4-methoxyphenyl)-1-(5-nitrothiophen-2-yl) methanimine and (E)- N-(4-bromophenyl)-1-(5-nitrothiophen-2-yl) methanimine was investigated Lactate Dehydrogenase assay kits (LDH) [1,2].
Organic compounds-1 Organic compounds-2
The results showed that this new synthesized organic compounds have anticytoxic activity in human blood cell culture in vitro. In conclusion, this new synthesized organic compounds can be studied different biological activity for drug potential.
Key words: Antigenotoxicity, LDH, Organic compound References: [1] Anar, M., Kizil, HE., Agar, G. 2014. The determination of antioxidative effect and anticancer potential of vulpinic acid. Journal of Biotechnology 185S, S37–S125. [2] Kizil, HE., Agar, G., Anar, M. 2014. Cytotoxic and antiproliferative effects of evernic acid on HeLa cell lines A candidate anticancer drug. Journal of Biotechnology 185S, S18–S36.
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Genotoxic And Antigenotoxic Effect of Some Lichens
Mustafa Anar1,Ali Aslan2, Guleray Agar3, Hamit Emre Kizil3,4
1Ataturk University, Faculty of Science, Department of Molecular Biology and Genetics, Erzurum 2Ataturk University, Kazim Karabekir Education Faculty, Department of Biology Education, Erzurum 3Atatürk University, Faculty of Science, Department of Biology, Erzurum Bayburt university, 4Bayburt University, Vocational School of Health Services, Bayburt, Turkey
*Corresponding author. E-mail: [email protected]
Abstract Lichens are symbiotic organisms. Lichens have been used very different treatment from ages. People used to lichens for treatment according to the morphology. In addition, lichens have been used for treatment some diseases like tuberculosis for several years [1]. Studies showed that some seconder metabolites stimulate apoptosis in colon [2] and prostate [3] cancers. The protective role of lichens are getting more important. In this study the genotoxic and antigenotixic activity of the methanol extracts of two lichen species (Anaptychia ciliaris, Bryoria fuscescens) were investigated. Sister Chromatid Exchange (SCE) test were used for determining the genotoxic contamination and the results showed that two lichen extracts inhibited the mutagenic effects of AFB1. We also determined that our lichen samples have no genotoxic effect. In addition, Anaptychia ciliaris, Bryoria fuscescens lichen species have strong antigenotoxic effects on human lymphocytes againt AFB1 mutagenic effect.
Key words: Antigenotoxicity, SCE, AFB1 References: [1] Vartia, KO., 1973. Antibiotics in lichens. In: Ahmadjian, V., Hale, M.E. (Eds.), The lichens.Academic Press, New York, p. 547. [2] Perry, P. and Evans, H.J., 1975. Cytological Detection Of Mutagen-Carcinogen Exposure By Sister Chromatid Exchange, Nature, 258, 121-125). [3]Russo, A., Piovano, M., Lombardo, L., Garbarino, J. & Cardile, V., 2008. Lichen metabolites prevent UV light and nitric oxide-mediated plasmid DNA damage and induce apoptosis in human melanoma cells. Life Sciences, 83(13-14): 468-474.
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Determination of Antioxidant Capacity of Two Lichens in vitro
Mustafa Anar1, Hamit Emre Kizil2,3, Ali Aslan4, Guleray Agar2, 1Ataturk University, Faculty of Science, Department of Molecular Biology and Genetics, Erzurum 2Atatürk University, Faculty of Science, Department of Biology, Erzurum 3Bayburt University, Vocational School of Health Services, Bayburt, Turkey 4Ataturk University, Kazim Karabekir Education Faculty, Department of Biology Education, Erzurum
*Corresponding author. E-mail: [email protected]
Abstract Lichens are symbiotic organisms. Lichens have been used very different treatment from ages. People used to lichens for treatment according to the morphology. In addition, lichens have been used for treatment some diseases like tuberculosis for several years [1]. Studies showed that some seconder metabolites stimulate apoptosis in colon [2] and prostate [3] cancers. In this study, we investigated antioxidant capacity of Parmotrema chinensa and Xanthoria candelaria lichen species in vitro. Antioxidant properties of P. chinensa and X. candelaria were determined by measuring the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione (GSH) and level of malondialdehyde (MDA) against the oxidative stress of AFB1 in human lymphocytes in vitro. It was observed that the levels of antioxidant enzymes were decreased dramatically and level of malondialdehyde (MDA) increased after treatment with AFB1 but the antioxidant enzymes were increased and MDA levels decreased in case of applying the lichen methanol extracts. We also determined that our lichen samples have strong antioxidant activities againt AFB1.
Key words: Lichen, Oxidative stress References: [1] Vartia, KO., 1973. Antibiotics in lichens. In: Ahmadjian, V., Hale, M.E. (Eds.), The lichens.Academic Press, New York, p. 547. [2] Perry, P. and Evans, H.J., 1975. Cytological Detection Of Mutagen-Carcinogen Exposure By Sister Chromatid Exchange, Nature, 258, 121-125). [3]Russo, A., Piovano, M., Lombardo, L., Garbarino, J. & Cardile, V., 2008. Lichen metabolites prevent UV light and nitric oxide-mediated plasmid DNA damage and induce apoptosis in human melanoma cells. Life Sciences, 83(13-14): 468-474.
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ChE inhibition and Aβ42 aggregation activities of 1H-Indene-2-carboxamide derivatives as anti-Alzheimer agents
Mehmet Koca1, Baris Anil2, Ibrahim Ozyürek2, Zeynep Kasap1, Ekrem Karabiber1, Kadir Ozden Yerdelen1
1Ataturk University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry 2Ataturk University, Faculty of Pharmacy, Department of Organic Chemistry
Abstract AD (Alzheimer’s disease) is the neurodegenerative disorder characterized with memory [1] dysfunction and difficulty in cognotive skills. Decreasing cholinergic activity and [2] increasing β amyloid plaques are pathologic findings of patiens with AD. Aβ42 (amyloid) aggregation, (acetylcholinesterase) and BuChE (butyrylcholinesterase) inhibition activities are important properties for a molecule in the treatment of AD.[3] Donepezil have been used from1996 for the treatment of mild to moderate AD. 5,6-dimethoxyindanone ring system of donepezil, is the responsible structural part on binding to the PAS (peripheral anionic site) of AChE. In this study, the indanone ring system of donepezil was converted to -1H-indene ring for measuring the effect of the replacement of ring systems on ChE inhibition and Aβ42 (amyloid) aggregation. The synthesized compounds were evaluated against [4] ChE enzymes using the colorimetric method described by Ellman et al. Inhibition of self-induced Aβ42 aggregation was measured using a Thioflavin T (ThT)-based fluorometric assay.[5] The results revealed that the compounds showed higher inhibitory activity against BuChE than AChE. Compound 1 was found the most potent BuChE inhibitor with the respective IC50 value, 1.23 µM. Especially the compounds 1, 2 and 3 displayed notable inhibition of amyloid (Aβ42) aggregation. These results suggest that especially compound 1 may be a promising multifunctional drug for the treatment and prevention of AD.
References: [1] M. Pievani, W. de Haan, T. Wu, W.W. Seeley, G.B. Frisoni, Lancet Neurol. 10 (2011) 829. [2] P.M. Arce, R.I.M. Franco, G.C.G. Munoz, C. Perez, B. Lopez, M. Villaroya,G.M. Lopez, G.A. Garcia, J. Med. Chem. 22 (2009) 7249 [3] M. Singh, M. Kaur, H. Kukreja, R. Chugh, O. Silakari, D. Singh, Eur. J. Med. Chem. 70 (2013) 165. [4] G. L. Ellman, K. D. Courtney, V., Jr. Andres, R. M. Feather-Stone, Biochem. Pharmacol. 7 (1961) 88. [5] M. Rosini, E. Simoni, M. Bartolini, A. Cavalli, L. Ceccarini, N. Pascu, D.W. McClymont, A. Tarozzi, M.L. Bolognesi, A. Minarini, V. Tumiatti, V.Andrisano, I.R. Mellor, C. Melchiorre, J. Med. Chem. 51(2008) 4381.
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Purification, Characterization And Biotechnological Applicability of Alkaline Protease by Aeribacillus pallidus C10
Vildan Yildirim a, Berna Genc a,b, Mustafa Ozkan Baltaci a, Melda Sisecioglu a and Ahmet Adiguzel a
aAtaturk University, Science Faculty, Department of Molecular Biology and Genetics, 25240 Erzurum, Turkey; [email protected]; [email protected]; [email protected];[email protected]; bGumushane University, Faculty of Engineering and Natural Science, Department of Genetic and Bioengineering, 29100, Gumushane Turkey; [email protected] Abstract Microbial proteases which constitute nearly 40% of the enzyme market volume in the world, have wide applications in various industries such as detergents, cosmetics, food, medicine, leather and recovery of silver [1,2]. Proteases have characteristic features based on temperature, pH, specificity, activity and stability and these parameters determine the potential use of enzyme in industry [3].
In this study, an extracellular alkaline protease from thermophilic Aeribacillus pallidus C10 was purified 4.85 fold with 26.9% yield by ammonium sulfate precipitation, dialysis and DE52 anion-exchange chromatography, orderly. The molecular weight of the purified enzyme was determined as approximately 38.35 kDa by SDS- PAGE (Sodium dodecyl sulphate-polyacrylamide gel electrophoresis). The optimum pH and temperature for the enzyme was 9 and 60°C respectively. The enzyme was found to retain more than 80% of its activity at 20-80°C especially at 60, 70 ve 80°C after 1 h incubation. When effect of metal ions on the activity of protease purified from A. pallidus C10 examined, it was observed that the enzyme exhibited high stability in the presence of Fe2+, Mn2+ and Co2+ ions while Mg2+, K+, Ca2+, Zn2+ and Ag+ ions were increased the activity. The enzyme lost its activity with oxidants and surfactants; however a 16% increase in activity was determined in the presence of 5% SDS. The enzyme activity was found to retain more than %70 of its activity in the presence of organic solvents. The protease enzyme showed highest activity against casein. The protease was completely inhibited by serine protease inhibitor, PMSF (Phenylmethanesulfonylfluoride). KM and Vmax values of the purified protease were calculated as 0.197 mg/ml and 7.29 µmol.ml-1.dk-1, respectively. Retention of enzymatic activity in the presence of EDTA (Ethylenediaminetetraacetic acid), SDS (Sodium dodecyl sulfate) and detergents that sold commercially shows good detergent additive as it would be potentially useful in the industrial field.
Acknowledgments: This work was financially supported by Atatürk University Scientific Research Projects Coordination Commission (ATAUNI-BAP) with project number 2013/297.
References:
[1] CG Kumar, H. Takagi, Biotechnol Adv. Microbial alkaline proteases from a bioindustrial viewpoint. 17 (1999) 561–94. [2] R. Gupta, Q. Beg, P. Lorenz, Appl Microbiol Biotechnol. Bacterial alkaline proteases: molecular approaches and industrial applications. 59 (2002) 15–32. [3] R. Mahajan, S. Badgujar, Journal of Pharmacy Research. Biological aspects of proteolytic enzymes: A Review. 3 (2010) 2048-2068.
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Antioxidant potencies of Sempervivum armenum methanol extracts on human lymphocytes in vitro
Serap Sunar1, Mustafa Anar2, Guleray Agar3, Meryem Sengul4
1Department of Pharmaceutical Botany, Faculty of Pharmacy, Erzincan University, Erzincan Turkey. 2Department of Molecular Biology and Genetics, Faculty of Science, Ataturk University, Erzurum 25240 Turkey. 3Department of Biology, Faculty of Science, Ataturk University, Erzurum 25240 Turkey. 4Department of Biology, Faculty of Science, Ataturk University, Erzurum 25240 Turkey. Corresponding Autors: Department of Pharmaceutical Botany, Faculty of Pharmacy, Erzincan
E-mail: [email protected] Abstract
Therapy with preparations of Sempervivum species can be traced back to the origins of antiquity herbal medicine, Howewer, extracts of S. armenum leaves have not been introduced into medical practice yet. S.armenum Boiss. et Huet subsp. armenum well known medicinal plant is distributed in the Eastern Anatolia (Erzurum – Kars) region of Turkey [1].
In this study, we examined the antioxidant potential of methanol extracts, obtained from S. Armenum (MSA), against AFB1 by using superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities and the malondialdehyde (MDA) levels, in cultured human blood cells. Cotreatments of 5, 10, 20 mg/mL concentrations of MSA decreased the frequencies of the malondialdehyde (MDA) level and increased amount of superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities and glutathione (GSH) level. The results of this experiment have clearly shown that MSA has strong antioxidative effects.
Acknowledgments: This research was financed by a grant from Research Fund of the Erzincan University. The authors are grateful to the Erzincan University for financial support (Project no: BAP SAG-A- 140613-0029). References: [1] Meryem SK (2014). Investigation of heavy metals content in medicinal plant sempervivum armenum Boiss. & Huet Huet subsp. armenum (Crassulaceae) from Erzurum, Turkey. Research journal of chemistry and environment18(8).
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Investigation gene expression analysis of some FOXO signaling pathway genes in Drosophila melanogaster
Hakan AŞKIN a, Ömer Faruk BAY b, Hilal KIZILTUNÇ ÖZMEN c aAtaturk University, Science Faculty, Department of Molecular Biology and Genetics, Erzurum, TURKEY [email protected] bAtaturk University, Institute of Science, Department of Molecular Biology and Genetics, Erzurum, TURKEY [email protected] cAtaturk University, Medicine Faculty,Department of Radiation Oncology, Erzurum, TURKEY [email protected]
Abstract Understanding the mechanisms that control lifespan in living is among the most challenging biological problems [1]. Many complex human diseases are associated with aging. It is clear that the aging process and the maximum lifespan of species can be various mechanisms regulated [2]. Today, delaying aging, studies are underway to capture high quality and long life. Scientists for it is follow various paths by using some models that allow operational advantage organisms such as especially Drosophila melanogaster (fruit fly) and Caenorhabditis elegans (nematode) [3]. One of them elements that lead to aging is to take preventive measures. They do this by applying the dietary restriction. In recent years, molecular and genetic studies in Drosophila, has focused on the relationship between aging and diet [4]. Our aim is to present a realistic anti-aging plan. Hence our research examined changes in the transcriptomic and proteomic level of expression profiles in many genes related to fruit flies containing the homologous FOXO signaling pathway genes (FOXO and SIR2) to the human aging mechanism of nutritional strategy performed manipulations [5]. For these reasons, in our research using Real-Time PCR and Western Blot methods performed to determine the effects on gene expression and longevity of dietary restrictions and application of antioxidant in the fruit fly, study of genetic indispensable organisms. As a result, It is our hope that a better understanding of molecular mechanisms that control of human lifespan will lead to new therapeutic approaches to aging and related diseases.
Acknowledgments: This study was supported Scientific Research Projects of Ataturk University (project number: BAP 2013/292)
References: [1] Eleftherianos, I. and Castillo, J.C. Molecular mechanisms of aging and immune system regulation in Drosophila. Int J Mol Sci, 2012. 13(8), 9826-9844. [2] Alper, S. Model systems to the rescue: The relationship between aging and innate immunity. Commun. Integr. Biol. 2010. 3, 409-414. [3] Aşkın, H., Uysal, H., Altun, D. and Ayar. A. The determination of the genotoxic effects of genistein that an environmental pollutant on Drosophila melanogaster. Ekoloji, 2010. 19,(75), 82-87. [4] Clancy, D.J., Gems, D., Hafen, E., Leevers, S.J. and Partridge, L. Dietary restriction in long-lived dwarf flies. Science, 2002. 296(5566), 319. [5] Frye, R.A. 2000. Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins. Biochem Biophys Res Commun, 273(2), 793-798.
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Risk Assessment Trials in The Aspect of Quality by Design Gizem Yeğena, Buket Aksub, Yıldız Özsoya and Erdal Cevhera aIstanbul University, Faculty of Pharmacy, Department of Pharmaceutical Technology, Istanbul, Turkey; bIstambul Kemerburgaz University, Faculty of Pharmacy, Department of Pharmaceutical Technology, Istanbul, Turkey; e-mail: [email protected] Abstract Orodispersible tablets (ODT) are solid dosage forms that rapidly disintegrate to release the drug when it is taken in the mouth, and eliminate the need to use water and chewing during administration. Because of special attention is required during the development stage of ODT forms, to increase the product quality advanced control and formulation design techniques must be adopted 1. Quality by Design (QbD) is defined in ICH Q8 3 as systematic drug development approach that emphasizes expediency of understanding the process and product based on science and quality risk management starting with pre-defined objectives. Design of Experiment (DoE), a methodology that includes how to plan and perform the tests to obtain maximum amount of information out of minimum number of analyzes, is the first thing to perform to create a Design Space the most important step to implement QbD. Using DOE is not feasible for all variables. Therefore, variables rated low to high during risk assessments remain constant considering feasibility studies or previous knowledge and understanding of process are provided by evaluation of high-risk variables within the DOE. Defining Quality Target Product Profile (QTPP), Critical Quality Attributes (CQAs), Critical Proses Parameters (CPPs) and Critical Material Attributes (CMAs) that effect the CQAs are stages that forms DOE. In this study, CQAs, CMAs and CPPs (Table 1) determined by Design FMEA and Risk Ranking Methods while developing an ODT form contains Metoprolol tartrate. 24 tablet formulation was prepared by direct compression according to designated CMAs and CPPs then various physical and chemical tests were applied to the tablets in order to evaluate the quality properties. According to the test results it was concluded that the formulation which shows appropriate values for CQAs have also adequate results on non-critical properties. In conclusion, determining the properties that affect the quality of the product during drug development stage and to concentrate on the risky parameters was seen to gain in terms of manpower, time and cost in this study. Table 1. CQAs, CMAs and CPPs designated in the study for ODT formulations CQAs • Hardness • Water Absorption Ratio • Friability • Disintegration Time • Wetting Time • Dissolution Profile CMAs Disintegrating Excipient Type Parteck ® ODT Sodium Starch Glycolate + Mannitol Disintegrating Excipient Amount 30/55/80 % (of 250mg Total Tablet Weight) (Determined by pre-formulation studies) Lubricant Type Magnesium Stearate Sodium Stearyl Fumarate Lubricant Amount % 0.5 % 1.2 CPPs Compression Pressure 400 / 800 psi (Determined by pre-formulation studies)
References: 1 S Velmurugan, S Vinushitha, Oral disintegrating tablets: An overview IJCPS 1 (2010) 1. 2 International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, Pharmaceutical Development Guideline, Q8 (R2), 2009.
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Copeptin: A candidate biomarker of pulmonary thromboembolism
Nurinnisa Ozturka, Nurcan Kilic Baygutalpb, Atıf Bayramogluc, Harun Polata, Mehmet Ali Gula, Ebubekir Bakana, Sahin Aslanc, Ozge Nur Gunesa
aAtaturk University, Faculty of Medicine, Department of Medical Biochemistry, Erzurum, Turkey Nurinnisa Ozturk;e-mail: [email protected] ;Harun Polat; e-mail:[email protected] ; Mehmet Ali Gul; e-mail: [email protected] ; Ebubekir Bakan; e-mail: [email protected] ; Ozge Nur Gunes; e-mail:[email protected] bAtaturk University, Faculty of Pharmacy, Department of Pharmacy Management, Erzurum, Turkey Nurcan Kilic Baygutalp; e-mail: [email protected] cAtaturk University, Faculty of Medicine, Department of Emergency, Erzurum, Turkey Atıf Bayramoglu; e-mail:[email protected] ;Sahin Aslan;e-mail:[email protected] Abstract Background-Aim: Factor V Leiden (FV Leiden) and prothrombin Factor II are two of the most common mutations related with thromboembolic disease. As hyperhomocysteinaemia is suggested to be an independent risk factor for arterial, venous and pulmonary thromboembolism; both C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene has been investigated in patients with thromboembolic disease up to date [1]. The role of copeptin, a sensitive marker for arginine vasopressin release, is examined as a prognostic biomarker in a variety of indications including traumatic brain injury, acute coronary syndrome and stroke [2]. We aimed to determine serum copeptin levels of patients and compared to the results of healthy controls. Additionally we aimed to define and genotype single point mutations at human FV, FII and MTHFR genes and determine the incidence in patients with acute pulmonary embolism. Methods: 32 patients (18 male, 14 female) with pulmonary embolism and 24 healthy controls (13 male, 11 female) were included to the study. The prevalence of factor V Leiden (FV Leiden), prothrombin factor II G20210A (FII G20210A), C677T and A1298C of methylenetetrahydrofolate reductase (MTHFR) mutations were studied in patients with acute pulmonary embolism. Verigene hypercoagulation panel nucleic acid test was performed on Verigene (Nanosphere Inc, Northbrook, IL) system which is based on a nanotechnological molecular diagnosis method. Serum copeptin levels of patients and healthy controls were determined by ELISA with commercial available kit. Results:There was no significant difference between age and gender distribution of patients and healthy controls (p>0.05). The mean age of patients and controls were 68,44±15,49 and 64,33± 14,81 ages respectively. 31 patients (96,9%) were wild type for FII, whereas 1 subject (3,1%) had heterozygous mutant genotype. 29 patients (90,6%) were h wild type for FV Leiden, whereas 3 subject (9,4%) had heterozygous mutant genotype.16 patients (50 %) were wild type for MTHFR, 14 patients (43 %) had heterozygous, 2 patients (6 %) had homozygous mutant genotype. Serum copeptin levels were significantly higher in patient group (36,74±18,92 pg/mL) compared to control group (17,45 ±4,37 pg/mL)(p=0,00). Conclusions We can conclude that; FV, FII and MTHFR mutation frequencies for acute pulmonary embolism are not different from the previously reported literature data in our region. Copeptin can be considered as a candidate biomarker of acute pulmonary embolism . Key words acute pulmonary embolism, Factor II, Factor V, MTHFR, copeptin
References [1] Nizankowska-Mogilnicka E, Adamek L, Grzanka P, Domagala TB, Sanak M, Krzanowski M, Szczeklik A.Genetic polymorphisms associated with acute pulmonary embolism and deep venous thrombosis. Eur Respir J 2003; 21: 25-30. [2] Schurtz G, Lamblin N, Bauters C, Goldstein P, Lemesle G.Copeptin in acute coronary syndromes and heart failure management: State of the art and future directions. Arch Cardiovasc Dis 2015;108(6-7):398-407.
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Copeptin: A promosing prognostic marker in acute appendicitis
Nurinnisa Ozturka, Nurcan Kilic Baygutalp b , Salih Kara c , Harun Polata, Mehmet Ali Gula, Kadriye Akpinara, Gürkan Ozturk c, Nuri Bakana aAtaturk University, Faculty of Medicine, Department of Medical Biochemistry, Erzurum, Turkey Nurinnisa Ozturk;e-mail: [email protected] ; Harun Polat; e-mail:[email protected] ; Mehmet Ali Gul; e-mail: [email protected]; Kadriye Akpinar; e-mail: [email protected] ; Nuri Bakan; e-mail:[email protected] bAtaturk University, Faculty of Pharmacy, Department of Pharmacy Management, Erzurum, Turkey Nurcan Kilic Baygutalp; e-mail: [email protected] cAtaturk University, Faculty of Medicine, Department of General Surgery, Erzurum, Turkey Salih Kara; e-mail:[email protected];Gurkan Ozturk; e-mail:[email protected] Abstract Background-Aim Acute appendicitis is the most common surgical emergency case and diagnosed mainly with physical examination, non-specific laboratory findings and radiological imaging techniques [1]. Some undiagnosed cases may cause to negative explorations. We aimed to evaluate the levels of serum copeptin, a biomarker of acute stress related diseases, in patients with acute appendicitis [2]. Methods Forty (21 male, 19 female) patients hospitalized in the general surgery clinic of our hospital with a preliminary diagnosis of acute appendicitis and whose diagnosis was pathologically confirmed after surgery were taken as patient group. Forty-eight age and gender related healthy individuals were taken as control group. Venous blood samples were taken from patients before surgery and from controls and sera were obtained. The serum copeptin concentrations was determined by ELISA method using commercial available kit. Results The mean age of patients and controls were 37,21±15,31 and 39,12 ±17,16 ages respectively. Serum copeptin levels was significantly higher in patient group (20,19±5,42 pg/mL) compared to control group (16,65±2,13 pg/mL) (p=0,00; 95%CI [-1,76-0,60]). Conclusions This is the first study reporting elevated serum copeptin levels in patients with acute appendicitis. Further studies with large patient series determining predictive cut-off values for copeptin may lead to define a new biomarker for acute appendicitis.
References [1] E.G. Dumlu, M. Tokac, B. Bozkurt, M.B. Yildirim, M. Ergin, A. Yalcin, Mc Kilic.Clinics (Sao Paulo). 69:10 (2014) 677. [2] J. Siegenthaler, C. Walti, S.A. Urwyler, P. Schuetz, M. Christ-Crain. Eur J Endocrinol. 171:6 ( 2014) 737.
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Pharmacognostical investigation of Тrigonella Ortoseras growing in Uzbekistan
Alikhodjaeva M.I.1a, Rixsibaeva M.O. 2b, Muhitdinov C.3c aTashkent pharmaceutical institute, Uzbekistan, Aybek str.,45, Tashkent;e-mail:[email protected]; bHead department of drug and medical eqippment quality control,Public healthMinistry of the Republic of Uzbekistan, Ozod str., K.Umarov passge,16, Tashkent, Uzbekistan, e-mail:[email protected];.cTashkent pharmaceutical institute, Uzbekistan, Aybek str.,45, Tashkent;e-mail:[email protected]; Abstract Out of 520 plants described in the second book of "Canon" Avicenna approximately 50% of them have subtropical and tropical origin, thus it is really hard to find them in Uzbekistan. From the rest of the number of plants there are 178 plants including both wild (108) and cultured (68) which can be found in our country [1]. Fenugreek Trigonella foenum graecum L. – is an old folk remedy. Abu Ali Ibn Sina used it as an emollient for coughs and asthma, enveloping for gastric diseases, as well as abrasions, tumors and to ease childbirth. Decoction of seeds is recommended to use as an antitussive, enveloping and anthelmintic in scientific medicine [2]. Official fenugreek senny included in the drugs such as Phytolysinum and pasenin has its own related type called Trigonella ortoseras which is growing in Uzbekistan and it has been newly studied. The main purposes of the research were solving the issues related to the expansion of domestic official nomenclature plant materials by basing on deep and comprehensive study of Ibn Sina’s heritage and Pharmacognostical investigation of with the aim to implement it in medical practice. The analysis of wild medicinal plants in Uzbekistan, described by Ibn Sina was conducted and systematized for use in medicine. Also, we studied species Fenugreek (Hulba, Shambhala) - Trigonella foenum graecum, applied Ibn Sina and identified biological activity of the substance (Тrigonella ortoseras). The experiments carried out on plants. Qualitative analysis showed the presence of alkaloids, coumarins, flavonoids and saponins in plant material. While via phytochemical analysis the biological active component of above-ground parts of Trigonella orthoceras was isolated and determined. The results were as follows: sum of alkaloids comprised 1.12%, the percentages of saponins and flavonoids were - 6.68% and 1.32% respectively. High Performance Liquid Chromatography (HPLC) analysis identified individual flavonoids ethyl acetate fraction obtained from alcoholic extract of the plant. The conditions of chromatography are as follows: Column - Eclipce, Zorbax C8 150x3,0 mm; Grained sorbent - 3.5 microns; Column temperature – room temperature; Flow rate - 1 ml / min; Detector Wavelength - 263 nm; Mobile phase A / B: Methanol / 0.020 mMol KH2PO4 buffer solution; pH 3.0; A gradient mobile phase at the beginning of chromatography: A component-methanol (30%) and B buffer (70%), and at the end Chromatography - A methanol (70%) and B buffer (30%). Calculation of the content of flavonoids in the ethyl acetate fraction was carried out based on correlation of the peak areas of the sample and the standard. As a result the following flavonoids were identified with retention time: Ruthin (8.327 min.), Orobol (10,320 min.), Biochanin A (15.609 min.) and quercetin (11.412 min.).
References: 1. Holmatov H.H, Dostchanov B.O, Sobirov R.S. “The medical plants used by Abu Ali Ibn Sino” 2003, 174 p. 2. Irgashev Sh.B. and other co-authors, “Herbal remedies of Abu Ali Ibn Sina (Avicenna)” 2003, 457 p.
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In Vitro Inhibition of Alfa-Carbonic Anhydrase Isozymes by Some Anions İmdat Aygüla, Hakan Söyütb, Deniz Ekincic, Murat Şentürkd
aGümüşhane University, School of Health Services, 29100 Gümüşhane, Turkey; [email protected]; bBayburt University, Education Faculty, 69000 Bayburt, Turkey; [email protected]; cOndokuz Mayıs University, Agricultural Faculty, 55139 Samsun, Turkey; [email protected]; dAgri Ibrahim Cecen University, Art and Science Faculty, 04100 Agri, Turkey; [email protected] Abstract
Carbonic anhydrase (EC 4.2.1.1, CA) is a family of metalloenzymes that catalyze the conversion of CO2 - + to HCO3 and H , being involved in many physiologic processes [1]. CA isoforms are found in a variety of tissues where they participate in several important biological processes such as acid-base balance homeostasy, respiration, carbon dioxide and ion transport, bone resorption, gluconeogenesis, lipogenesis, electrolyte secretion, and tumorigenesis among others [1]. CA isozymes involved in these processes are important therapeutic targets with the potential to be inhibited/activated for the treatment of a range of disorders such as oedema, glaucoma, obesity, cancer, epilepsy and osteoporosis [1-2]. In this study, CA isoenzymes were purified from rainbow trout (Oncorhynchus mykiss) muscle, kidney, bovine liver, and human erythrocyte. The purification procedure consisted of a single step affinity chromatography. The kinetic parameters of this enzyme were determined for its esterase activity, with 4------2- nitrophenyl acetate (NPA) as substrate. The following anions, Br , Cl , I , SCN , NO2 , NO3 , N3 , CO3 , 2- 2- SO3 , and SO4 showed inhibitory effects on the enzyme. Sulfate, iodide, thiocyanate, and sulfide - - exhibited the strongest inhibitory action, in the micromolar range (KI-s of 0.97-1.143 µM). NO2 , NO3 , - and N3 were moderate inhibitors, whereas other anions showed only weak actions. All tested anions inhibited the enzyme in a competitive manner. Our findings indicate that these anions inhibit the vertebrate CA isoenzymes in a similar manner to other α-CAs from mammals investigated earlier, but the susceptibility to various anions differs significantly between the fish and mammalian CAs.
Acknowledgments: This study was financed by TUBITAK (Project no: 114Z731) for (M.Ş.).
References:
[1] C.T. Supuran, Nature Rev. Drug Discov. 7 (2008) 168. [2] D. Ekinci, S.B. Ceyhun, M. Senturk, D. Erdem, O.I. Kufrevioglu, C.T. Supuran, Bioorg. Med. Chem. 19(2011) 744.
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Purification of Carbonic Anhydrase from Different Organism and Assessment of Enzyme Kinetics Against Sulfoamides İmdat Aygüla, Murat Şentürkb, Deniz Ekincic a; Gümüşhane University, School of Health Services, 29100 Gümüşhane, Turkey; [email protected]; bAgri Ibrahim Cecen University, Art and Science Faculty, 04100 Agri, Turkey; [email protected]; cOndokuz Mayıs University, Agricultural Faculty, 55139 Samsun, Turkey; [email protected] Abstract Carbonic anhydrase (CA; Carbonate hydrolyase, EC 4.2.1.1) is a metalloenzyme family that catalyzes the rapid conversion of carbon dioxide to bicarbonate and protons, and involved in the biomineralization process [1]. Sulfonamides have found extensive use as both carbonic anhydrase and matrix metalloproteinase inhibitors, which are a family of zinc containing enzymes implicated in a number of diseases such as arthritis and cancer [1]. Studies performed on sulfonamides revealed that inhibition of these enzymes is brought about by their ability to mimic the tetrahedral transition state when binding to catalytic zinc ions located at the active site of the enzymes [2,3]. Sulfonamides have also shown antibacterial diuretic, hypoglycemic, and most recently, antitumor activity. Sulfonamide/sulfamate CAIs targeting various mammalian α-CAs have been in clinical use for more than 60 years [1-3]. CA isoenzmes were purified from human erythrocyte, sheep heart, and rainbow trout gill. The purification procedure consisted of a single step new affinity gel (cellulose-phenyl-sulphonamide) affinity chromatography. The kinetic parameters of this enzyme were determined for its esterase activity, with 4-nitrophenyl acetate (NPA) as substrate. Sulfanilamide, mafenide, acetazolamide, sulfaguanidine, sulfadiazine, sulfapyridine, and sulfamethazine showed inhibitory effects on these isoenzymes. Acetazolamide exhibited the strongest inhibitory action, sulfanilamide and mafenide were moderate inhibitors, whereas other sulfonamides showed only weak inhibitory actions. All tested sulfonamides compounds inhibited the enzyme in a competitive manner. Our findings indicate that these compounds inhibit these CA isoenzyme in a similar manner to other α- CAs from mammals investigated earlier, especially human CA I, II and IX, but the susceptibility to various sulfonamides differs significantly between other organism and mammalian CAs. Acknowledgments: This study was financed by TUBITAK (Project no: 114Z731) for (M.Ş.).
References:
[1] C.T. Supuran, Nature Rev. Drug Discov. 7 (2008) 168. [2] D. Ekinci, M. al-Rashida, G. Abbas, M. Senturk, C.T. Supuran, J. Enzyme Inhib. Med. Chem. 27 (2012) 744. [3] C.T. Supuran, A. Scozzafava, A. Casini, Med. Res. Rev. 23 (2003) 146.
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Interaction of Some Carbonic Anhydrase Isozymes with Some Natural Phenolic Compounds Murat Şentürka, Deniz Ekincib, İmdat Aygülc
aAgri Ibrahim Cecen University, Art and Science Faculty, 04100 Agri, Turkey; [email protected]; bOndokuz Mayıs University, Agricultural Faculty, 55139 Samsun, Turkey; [email protected] a; Gümüşhane University, School of Health Services, 29100 Gümüşhane, Turkey; [email protected]; Abstract Carbonic anhydrase (CA; EC 4.2.1.1) is a metalloenzyme family that catalyzes the rapid conversion of carbon dioxide to bicarbonate and protons. CA isoforms are found in a variety of tissues where they participate in several important biological processes such as acid-base balance homeostasy, respiration, carbon dioxide and ion transport, bone resorption, ureagenesis, gluconeogenesis, lipogenesis, electrolyte secretion, and tumorigenesis among others [1]. CA isoenzmes were purified from human erythrocyte, bovine heart, and bovine kidney. The purification procedure consisted of a single step new affinity gel (cellulose-phenyl-sulphonamide) affinity chromatography. The kinetic parameters of this enzyme were determined for its esterase activity, with 4- nitrophenyl acetate (NPA) as substrate. Salicylic acid, catechol, resorcinol, quercetin, morin, and rutine showed inhibitory effects on these isoenzymes. Catechol and resorcinol were exhibited the strongest inhibitory action, salicylic acid and morin were moderate inhibitors, whereas other natural phenols showed only weak inhibitory actions. All tested natural compounds inhibited the enzyme in a competitive manner. Our findings indicate that these compounds inhibit these CA isoenzyme in a similar manner to other α-CAs from mammals investigated earlier, especially human CA I-XIV, but the susceptibility to various phenolic compounds differs significantly between mammalian CAs. Acknowledgments: This study was financed by TUBITAK (Project no: 114Z731) for (M.Ş.).
References:
[1] C.T. Supuran, Nature Rev. Drug Discov. 7 (2008) 168. [2] A. Innocenti, D. Vullo, A. Scozzafava, C.T. Supuran, Bioorg. Med. Chem.16 (2008) 7424.
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Design, Molecular modeling and Synthesis of Some Novel Hetero Alkyl Oxime Derivatives as Antifungal Agents
Zeinab Faghiha , Masood Fereidoonnezhada, Ali Khalafi-Nezhadb, Zahra Rezaeia aDepartment of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran. bDepartment of Organic Chemistry, Faculty of Science, Shiraz University of Sciences, Shiraz, Iran; e-mail: [email protected] Abstract Azole antifungal agents are the largest class of synthetic antimycotics. About 20 agents on the market today, in the other hand, many famous drugs with various chemotherapeutic activities contain an oxime or oxime ether moiety in their structure. So with the aim of synthesis of some novel biological active compounds inspired by Oxiconazole and hydroxizine, we explained for the first time the synthesis and characterizations of some novel oxime ether derivatives of imidizole and benzimidazole [1,2].
Here, In the present study, more than 100 novel oxime ether derivatives of different azoles (Scheme 1) have been designed and drug-likeness, molecular docking and descriptor analysis of them were performed to find out a drug candidate for synthesis, and the development of new method for synthesis of this copmpounds also been studied (MCRs). The Docking analysis of synthesized compounds was carried out using Lanosterol 14 α-demethylase receptor by AutoDock 4.2 and the antifungal activity of compound are under evaluation.
R1 O B R N 2
R1,R2 = alkyle,aryl,benzyle,...
O N N O N 2 N N N N , , N , , B = N N N H N N N H H H H O imidazole benzimidazole benztriazole theophylline 5(4) Nitro-imidazole
Scheme 1. The designated Oxime ether Derivatives.
Since of the wide application of oxime ether derivatives of nitrogen compounds in medicinal studies, we report clean, simple and efficient method for preparation oxime ether by using multi component reactions (MCRs) method and The Docking analysis of synthesized compounds was satisfying. Evaluating antifungal activities of these compounds until now shows they are active compounds against some fungi species even more than Fluconazole as a positive control. Acknowledgments: The authors would like to thank department of medicinal chemistry at school of pharmacy, Shiraz University of Medical Sciences and Department of Organic Chemistry, shiraz university for its kind contribution in providing the needed facilities for this work.
References:
[1] A. Khalafi-Nezhad, et al., Tetrahedron. 58 (2002). 10341. [2] S. Khabnadideh, et al., Bioorg.Med.Chem.Lett..13 (2003) 2863
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Lycium barbarum Use Effects on Some Biochemical Parameters and Rankl Cytokine Levels of Wistar Albino Rats with Osteoporosis Model Induced by Glucocorticoid and Ovariectomy Ebru BEYTUT1, Canan KART2 1University of Erzincan, Faculty of Medicine, Department of Physiology 2 State Hospital of Burdur, Physiotherapist In this study, it was aimed to investigate the effect of Goji (Lycium barbarum) extract on some serum parameters and RANKL ( Reseptor Activator Nuclear Factor Ligand) levels in the experimental model of osteoporosis induced by ovariectomy with or without glucocorticoid treatment in the rats. In the study, 8-9 month-old 42 Wistar-Albino rats were divided into 6 groups including 7 rats each. While group 1 (control) received no treatment, rats in group 2, 3, 4 and 5 underwent overiectomy. Osteoporosis was induced by intramuscular 7 mg/kg dexamethasone (glucocorticoid, Dekorta © ampule, cortisone) injection in group 4 and 5. Rats in group 6 were given only goji extract. Osteoporosis-induced rats in group 3 and 4 were also given Goji extract at a dose of 100 mg/kg for 10 weeks. All groups were fed ad-libitum throughout the study. At the end of study, samples obtained from the treatment groups via cardiac puncture were used to determine total cholesterol, alkaline phosphatase (ALP), estradiol (E2), calcium (Ca) and phosphorus (P) levels using autoanalyser, while RANKL levels were determined spectrophotometrically. Serum ALP levels in all treatment groups were significantly elevated (p<0.05), while the highest increase was observed in group 2 with 202.6 IU/L. On the other hand, it was found to be a significant decrease in group treated with goji only as compared to overectomized group (group 2) at 0.05 level. While there was a significant decrease in serum P level of all groups (p<0.05), the most remarkable decrease was determined in group 6. Serum Ca levels were not significantly changed in the treatment groups compared to that of control. Furthermore, serum E2 levels in the groups showed non-significant decrease compared to those of controls. Serum cholesterol levels were found to be significantly elevated in all treatment groups except for group 4 and 6 (p<0.05). In terms of RANKL levels, it was determined that RANKL levels were significantly increased in group 3, 4 and 5 compared to control (p<0.05). In conclusion, since there is no available study associated with the effect of Goji on glucocorticoid- induced osteoporosis model in rats, our data need to be supported by subsequent studies. In addition, the effectiveness of goji on glucocorticoid-induced osteoporosis should be tested by a long term studies and histomorphometric studies. In studies consisting of histomorphometric models, investigating the effectiveness of Goji on glucocorticoid-induced osteoporosis could contribute in the revelation of different possible mechanisms in other models.
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The awareness of apiterapy at Erzincan University
1Engın KILIÇ, 2Furkan YILMAZ, 2Hatice CANPOLAT, 2Sultan Mehtap AKIN, 2Ayşe CİVAŞ, 2Hümeyra YAŞAR, 2Mehmet SÖZGEN, 2Seda Nur AYDOĞDU, 2Mine BUĞA, 2Erol YÜZGÜLLÜ,2Sefa ESEN, 2Emine SÖNMEZ, 2Süleyman GÜZELGÖZ, 2Merve B. ÖZÇELIK, 2Ayşe M. YÖNET
1Erzincan University, Faculty of Pharmacy, Department of Microbiology and Pharasitology, Erzincan, TURKEY 2Erzincan University, Faculty of Pharmacy, Erzincan, TURKEY Abstract In this study, it is aimed to determine the academicians’, university students’ and administrative staffs’ awareness of apitherapy. The data were obtained with face-to-face survey method applied to 310 participants at Erzincan University during the academic year 2014-2015. As a data collection instrument a survey including demographic questions about the participants and 31 three items having two or three options. Demographic data analysis showed those participants are originally from 80 cities of Turkey, half of them (50.3%) are female, 59.0% of them are between 18-25 years old, high majority of them (56.8%) are students and 79% of them are graduated from a university. Survey data analysis indicated that the participants prefer mostly both modern medicine and traditional methods having complementary and alternative medicine (74.8%) and accept the alternative natural medicine in therapy (57.7 %). Participants say that they do not know apitherapy (42.3%) and 49.4% of them have some information about it. To the question about the recognition of apitherapy products, the participants say that they know the products: honey (84.9%), pollen (65.5%), bee bread (9.0%), propolis (35.5%), royal jelly (50%), bee poison (45.4%) and wax(70%). To the question about apitherapy related to the treatment, they say that they use wax as body care products (20.6%), honey for energizing and therapeutic treatment (37.8%), bee bread for energizing and treatment (5.5%), propolis for body care products and treatment (25.8%), royal jelly for treatment (57.7%), bee venom for only treatment purposes (40%). The 26.4% of the participants known that apiteraphy is a department of a section in the Turkish Ministry of Health and 16.1 % of them think that treatment costs of apiteraphy are different in state and university hospitals.
Key words: medicine, pharmacy, apiterapy, awareness, Erzincan, Turkey
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Determination of Pantoprazole in Pharmaceutical Preparations and Human Serum by Square Wave and Differential Pulse Polarography Methods Tuba Saruhan, Fatma Demirkaya Miloglu*
Department of Analytical Chemistry, Faculty of Pharmacy, Ataturk University, 25240, Erzurum, Turkey; [email protected] Abstract Pantoprazole is a selective and irreversible third proton pump inhibitor widely used in the treatment of duodenal and gastric ulcers by decreasing the amount of acid produced in the stomach [1,2]. It is highly useful for the relief of symptoms and healing of gastro esophageal reflux disease, peptic ulcer, helicobacter pylori infection, and other gastric-related disorders [3]. The goal of this work was the development of new polarographic methods for the direct determination of pantoprazole in pharmaceutical preparations and spiked human serum samples without any time-consuming extraction or evaporation steps prior to drug assay.
In this study, the polarographic behaviour of pantoprazole was determined by using square wave (SWP) and differential pulse (DPP) polarographic methods. The influence of several variables (nature of the buffer, pH, concentration, scan rate, drop size, etc.) was examined in both methods for pantoprazole. The best square wave and differential pulse polarography responses were obtained in buffer (pH 5.0). The peak currents were measured with a static mercury drop electrode versus Ag/AgCl. The linearity was established over the concentration range of 5-60 g/mL for both methods in supporting electrolyte and human serum. These studies were fully validated with validation parameters. The recovery results of pantoprazole in serum samples and pharmaceutical preparations were found as 98.7 and 97.3 for SWP; 97.3 and 96.0 for DPP, respectively.
The optimized and validated methods were successfully applied for the determination of pantoprazole in protein-free spiked human serum samples and pharmaceutical preparations (Protonex, Pandev and Panref). The results of the drug analysis obtained from the proposed methods were in close agreement with the claimed value and the results of the proposed SWP and DPP methods were evaluated statistically as compared with a spectrophotometric method. According to the results of t - and F-tests, the variances between the methods were found to be insignificant at 95% probability level, indicating that no significant differences exist between the performances of the methods regarding their accuracy and precision.
The proposed polarographic methods were simple, rapid, selective and sensitive; therefore, these methods could possibly be applied for the determination of pantoprazole in pharmaceutical samples as well as for quality control laboratories.
References:
[1]. S.M. Cheer, A. Prakash, D. Faulds, H.M.Lamb, Drugs 63(2003) 33. [2]. G. Bianchi Porro, M. Lazzaroni, V.Imbesi, F.Montrone , T.Santagada Dig Liver Dis 32(2000) 201. [3]. M. Noubarani, F. Keyhanfar, M. Motevalian , M. Mahmoudian J Pharm Pharm Sci 13(2010)1.
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New Validated Methods for the Simultaneous Determination of Two Multicomponent Mixtures Containing Nimesulide and Lidocaine in Combined Pharmaceutical Preparation by Using Chemometric Calibration Methods (PCR and PLS)
Fadime Uzun, Elif Tas, Elmas Polatdemir, Tuba Saruhan, Fatma Demirkaya Miloglu* Department of Analytical Chemistry, Faculty of Pharmacy, Ataturk University, 25240, Erzurum, Turkey; [email protected] Abstract Nimesulide, a selective inhibitor of the inducible isoform of the enzyme cyclooxygenase (COX-2), belongs to the sulfonanilide family of the non-steroidal anti-inflammatory drugs (NSAIDs) [1]. Various NSAIDs have been demonstrated to enhance analgesia such as lidocaine which is a local anesthetic. The efficacy profile of lidocaine as a local anesthetic is characterized by a rapid onset of action and intermediate duration of efficacy [2]. Recently, several multivariate methods such as PLS (partial least squares) and PCR (principal component regression) have been applied to mixtures of drugs in pharmaceutical formulations in the presence of a variety of excipients [3,4]. It is aimed to develop and validate simultaneous quantitative analysis of nimesulide and lidocaine in combined pharmaceutical preparation by the UV-Visible spectrophotometric method without any separation process by using the data obtained from chemometric calibration methods.
The concentration data matrix was prepared by using the mixtures containing nimesulide (2-10 μg/mL) and lidocaine (2.5-15 μg/mL) by using a factorial design method. The absorbance data matrix corresponding to the concentration data matrix was obtained by the measurements of absorbance in the range of 200-500 nm in the intervals with Δλ=1 nm. The validations of the developed multivariate methods were performed. Recoveries (%) obtained for nimesulid and lidocaine were 100.5% and 99.7% using PLS method and 100.5% and 100.8% using PCR method, respectively. These proposed multivariate methods were successfully applied to the simultaneous assay of the two mentioned drugs in combined pharmaceutical preparations and obtained results found to be in good agreement with the label claim.
The UV-spectrophotometric-assisted chemometric methods were found suitable for simple precise in routine quality control analysis of nimesulide and lidocaine in the combined pharmaceutical preparations.
References:
[1] A. Ward, R.N. Brodgen, Drugs 36 (1998) 732. [2] I.H. Wagman, R.H.de Jong, D.A.Prince, Anesthesiology 8 (1967)72. [3] H.C. Goicoechea, A.C. Olivieri, Talanta 49 (1999) 793. [4] M.S. Collado, V.E. Mantovani, H.C. Goicoechea, A.C. Olivieri, Talanta 52 (2000) 909.
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Lidocaine HCl in Combined Pharmaceutical Formulations by Using Chemometric Calibration Methods (PCR and PLS)
Sururi Esenbuga, Elmas Polatdemir, Tuba Saruhan, Fatma Demirkaya Miloglu * Department of Analytical Chemistry, Faculty of Pharmacy, Ataturk University, 25240, Erzurum, Turkey; [email protected] Abstract Ceftriaxone is an antibiotic belonging to the third-generation of cephalosporins [1,2]. Cephalosporins are antibiotics, which widely used for the treatment of bacterial infections. Various antibiotics have been demonstrated to enhance analgesia such as lidocaine which is a local anesthetic. Chemometric methods in spectral analysis offer versatile applications for determination of multicomponent mixtures that exhibit severe spectral overlapping [3]. It is aimed to develop and validate simultaneous quantitative analysis of ceftriaxone and lidocaine HCI in combined pharmaceutical preparation by the UV-Visible spectrophotometric method without any separation process by using the data obtained from chemometric calibration methods (PCR-principal component regression and PLS-partial least squares).
Synthetic mixtures solutions including ceftriaxone (2.03-16.3 μg/mL) and lidocaine, (2.5-20 μg/mL) were prepared by using a factorial design method. The absorbance data in UV spectra were measured in the 200-400 nm spectral regions (Δλ = 1 nm intervals). PCR and PLS calibrations were constructed by using the absorption data matrix corresponding to the concentration data matrix and validation was performed. Recovery values of PCR and PLS methods were calculated to be 103.6% and 103.3% for ceftriaxone; while these values were calculated to be 100.8% and 101.5% for lidocaine HCI. The optimized models were successfully applied to the simultaneous determination of ceftriaxone and lidocaine HCI in synthetic mixture and pharmaceutical formulations and obtained results found to be in good agreement with the label claim.
The proposed UV-spectrophotometric-assisted chemometric methods are simple, rapid and can be easily used in the quality control of drugs as alternative analysis tools.
References:
[1] S.L. Barriere, J.F. Flaherty, Clin. Pharm. 3 (1984) 351. [2] M.C. Nahata, W.J. Barson, Drug Intell. Clin. Pharm. 19 (1985) 900. [3] H. Martens, T. Naes, Multivariate Calibration, Wiley, Chichester, UK, 1989.
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Vitamin B12 and folate levels in colostrum and transitional milk from mothers of term infants Betül Alkan Polata, MeryemAydemir Atasevera, Nurcan Kilic Baygutalpc, Harun Polatb, Mustafa Atasevera, Nurinnisa Ozturkb, Ebubekir Bakanb aAtaturk University, Faculty of Veterinary Medicine, Department of Food Hygiene and Technology, Erzurum, Turkey MeryemAydemir Atasever; e-mail: [email protected]; Mustafa Atasever;e-mail: [email protected] bAtaturk University, Faculty of Medicine, Department of Medical Biochemistry, Erzurum, Turkey Nurinnisa Ozturk;e-mail: [email protected] ;Harun Polat; e-mail: [email protected] ; Ebubekir Bakan; e-mail: [email protected] ; cAtaturk University, Faculty of Pharmacy, Department of Pharmacy Management, Erzurum, Turkey Nurcan Kilic Baygutalp; e-mail [email protected] Abstract Background-Aim: Human milk is considered as the optimal food for infants’s growth and immunological protection. The only source of B-vitamins and folate is human milk in infants who are only fed with human milk. The vitamin and other nutrient contents of human milk differ according to the lactation stage. Studies conducted up to date on human milk present a great variation of folate and vitamin B12 levels[1]. These variations may be due to nutritional status of mothers before birth, the stage of lactation and different folate measurement methods[2]. Colostrum contains lower amounts of carbohydrates, lipids, and potassium than mature milk and is a very rich source of proteins and vitamins[3]. The aim of the study was to determine vit B12 and folate levels of human milks sampled from mothers with preterm infants in two different lactation stages and compare results. Methods: Fifty mothers who gave birth to infants on term were included to the study. Milk samples were obtained from twice: First in the 3rd day of lactation (colostrum milk), second in the 10th day of lactation (transitional milk). Folate and vitamin B12 levels were studied in Beckman Coulter DXI 800 (Beckman Coulter Tokyo, Japan) hormon analyzer by ECLIA method with respective kits. Results: The mean age of mothers was years (27.96±4.80)( p: 0.076). In milk samples from premature infants' mothers, the vit B12 levels were significantly higher in colostrum (126,23±107,92 pg/ml), compared to transitional milk (64,26±40,76 pg/ml) (p=0,00), and the folate levels were not significantly higher in colostrum (10,12±4,79 ng/ml), compared to transitional milk (8,90±3,91 ng/ml) (p=0,310). Conclusions Lower vitamin B12 levels in transitional milk compared to colostrum underlines the crucial importance of colostrum for infants. The significantly higher vitamin B12 levels in colostrum may be due to nutritional status of mothers. Our results have provided additional data to the inconsistent reports previously published about folate status in human milk.
Key words Vitamin B12 levels, folate levels, colostrum milk, transitional milk, term infants References [1] Molloy AM1, Kirke PN, Brody LC, Scott JM, Mills JL. Effects of folate and vitamin B12 deficiencies during pregnancy on fetal, infant, and child development. Food Nutr Bull. 2008 Jun;29(2 Suppl):S101-11; discussion S:112-5. [2]Taşkın L. Doğum ve Kadın Sağlığı Hemşireliği, 1. Baskı, Ankara, Sistem Ofset Matbaacılık, 2005: 381-394. [3] Neyzi O, Ertuğrul T. Sağlıklı Çocuğun Beslenmesi, Pediatri, 1. Baskı, İstanbul, Nobel Tıp Kitabevi, 2002:183-198
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Antioxidant Activities of the Essential Oils Obtained from Bayburt and Dadaşköy Ecotypes of Artemisia dracunculus L. Handan Gökben Sevindika, Yeşim Mualla Çilb, Sefa Gözcüc, Hafize Yucaa, Benan Dursunoğlua, Kemalettin Karad, Zühal Güvenalpa
aDepartment of Pharmacognosy, Faculty of Pharmacy, Atatürk University, 25240, Erzurum, Türkiye; bDepartment of Forestry and Forestry Products, Oltu Vocational School, Atatürk University, 25400, Erzurum, Türkiye; cDepartment of Pharmacognosy, Faculty of Pharmacy, Erzincan University, 24100, Erzincan, Türkiye; [email protected]; dDepartment of Agronomy, Faculty of Agriculture, Atatürk University, 25240, Erzurum, Türkiye Abstract The genus Artemisia that belongs to the Asteraceae family has approximately 22 species in Turkey [1]. The origin of Artemisia dracunculus L. is Central Asia or Siberia and it spreads throughout Eurasia from this region [2]. Antibacterial, antifungal, and anticonvulsant activities of the essential oil of Artemisia dracunculus were reported in previous studies [3].
In this study, the Dadaşköy and Bayburt ecotypes of Artemisia dracunculus have been harvested in July (D1, B1) and September (D2, B2). Essential oils were obtained by hydro distillation from the aerial parts of plants and evaluated in terms of their antioxidant activity. Determination of antioxidant capacity was performed by in vitro ABTS•+ (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) scavenging [4], DPPH• (1,1-diphenyl-2-picrylhydrazyl) scavenging [5], superoxide anion radical scavenging [6] and ferric thiocyanate [7] methods.
D1 exhibited the highest ABTS•+ scavenging activity about 40 μg/mL concentration, D2 exhibited the highest DPPH• activity about 10 μg/mL concentration, B1 exhibited the highest superoxide anion radical scavenging activity about 25 μg/mL concentration and B1 exhibited the highest lipid peroxidation inhibition activity about 200 μg/mL concentration in ferric thiocyanate method.
References:
[1] S. Kordali, R. Kotan, A. Mavi, A. Cakir, A. Ala, A. Yildirim, J. Agric. Food Chem. 53 (2005) 9452. [2] A.M. Aglarova, I.N. Zilfikarov, O.V. Severtseva, Pharm. Chem. J. 42 (2008) 81. [3] D. Obolskiy, I. Pischel, B. Feistel, N. Glotov, M. Heinrich, J. Agr. Food Chem. 59 (2011) 11367. [4] R. Re, N. Pellegrini, A. Proteggente, A. Pannala, M. Yang, C. Rice-Evans, Free Radic. Biol. Med. 26 (1999) 1231. [5] M.S. Blois, Nature 181 (1958) 1199. [6] J. Zhishen, T. Mengcheng, W. Jianming, Food Chem. 64 (1999) 555. [7] I. Gulcin, Amino Acids 32 (2007) 431.
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Cloning, Expression and Characterization of Human Brain Acetylcholinesterase Hamid CEYLANa, Orhan ERDOĞANa, aAtatürk University, Faculty of Science, Molecular Biology and Genethics Department, 25240, Erzurum, Turkey [email protected] Abstract The molecular structure of acetylcholinesterase (AChE) attracts respectable interest, because of its significant role in cholinergic system [1]. The objective of the present study was to clone full-length cDNA sequence of human brain acetylcholinesterase (hAChE) into pET SUMO vector and successfully express. This recombinant clone was over expressed in Escherichia coli BL-21 (DE-3). After transformation, we produced 6x His tagged fusion protein by IPTG induction. The fusion protein was purified by affinity chromatography. The fusion protein was confirmed by SDS-PAGE gel stained with Coomassie blue and It has an apparent molecular mass of almost 80 kDa. The enzyme activity of the purified recombinant hAChE measured by the spectrophotometric method of Ellman. Specific enzyme activity of the purified recombinant hAChE was determined by using spectrophotometric Ellman method. Optimum pH and temperature was found to recombinant human acetylcholinesterase (rhAChE) for maximum AChE enzyme activity
We aim that the results to be obtain from this study is considered to be contribute for further researchs that may result in the annotation of new therapeutic drugs improvement or treatment strategy for AChE related diseases.
Keywords: Acetylcholinesterase, cloning, recombinant protein, enzyme
References: [1] S. Fitzpatrick-McElligott, G. S. Stent. J Neurosci 1 (8): (1981) 901-907.
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Determination of Effects of Pharmeceuticals such as Gemfibrozil and β-estradiol on Cucumis melo L Seed Germination
1 1 1 1 Etem Osma , Handan İnce , Yavuz Çığır , Eda Türkoğlu
1Erzincan University, Faculty of Science and Arts, Department of Biology, Erzincan, Turkey e-mail: [email protected]
Abstract
In recent years,due to the excessive increase in the usage of medicines and personal care products, the percentege of PPCPs (Personal Care Products) in aquatic ecosystem is increasing.Active pharmaceutical ingredients and personal care products especially reach the ecosystems through the hospital’s waste water, human feces and from the leakage of waste water treatment facility. Most of these substances get rid of from the waste water treatment facility without any treatment fort the usage of different purposes and they finally reach the ground water. Studies in recent years show that active pharmaceutical ingredients that reachs the water supply and food chain are treating the human health. Herein this study, melon was used as a sample. We investigated the effect of active pharmeceutical ingredients such as Gemfibrozil ve β-estradiol on melon seeds germination. Melon seeds were treated with differenet concentrations of PPCPs (control, 5 mg/mL, 25 mg/mL, ve 125 mg/mL). The seeds were planted in petri dishes and each of the petri dishes had 16 seeds in it. After 3 days, we caunted the number and the percentage of the germinated seeds. Following the our investigations, the increase in the concentration of PPCPs like Gemfibrozil ve β-estradiol cause a decrease in the seed germination rate. We found also that, through a rise of the micro pollutant in the water that are used for irrigation cause too much batch loss. Overall,we look forward to search for rules that will decrease the level of pollutant using in the environment. And also in order to protect the environment the usage abd discharge of medicines is needed to be shortened.
Keywords: PPCPs, β-estradiol, Gemfibrozil, Cucumis melo L.
Acknowledgments: This study was supported by the Erzincan University BAP FEN-A-080715-0159.
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The Effects of Pharmeceuticals such as Gemfibrozil and β-estradiol on Cucumis Sativus L. Seed Germination Etem Osma1, Eda Türkoğlu1, Yavuz Çığır1, Handan İnce1
1Erzincan University, Faculty of Science and Arts, Department of Biology, Erzincan, Turkey e-mail: [email protected]
Abstract
In recent years, in consequnce of extremely launching to the market Pharma and Personal care products, the concentration of PPCPs (Pharmaceutical and Personal Care Products) increased significiantly in aquatic ecosystem. Active pharmaceutical ingredients and Personal care products merge the ecosystem from human feces, hospital waste water and water leakage from waste water systems. The most of these materiels flow into the underground water through the waste water could not dispose by refining plants and merget into used various purposes waters. Studies in recent years indicated that the active pharmaceutical ingredients merged the water springs and food chain became a substantial healh risk for ecosystem and living organism health. Cucumber is used sample organsm in this study. We investigated the effect of active pharmeceutical ingredient Gemfibrozil and β-estradiol to cucumber germination. PPCPs experimented in cucumber seeds with different concentration (control, 5 mg/mL, 25 mg/mL and 125 mg/mL). Equal size of 20 cucumber seeds were planted into the petri plates. After 3 days, through counting the we calculated the percentage of seed germination. According to our, depending on the increase in Gemfibrozil and β- estradiol concentrations, we observed a decrease the percentege of seed germination. Overall we look forward to search for rules that will decrease the level of pollutant using in the environment. And also in order to protect the environment the usage abd discharge of medicines is needed to be shortened.
Keywords: PPCPs, β-estradiol, Gemfibrozil, Cucumis sativus L.
Acknowledgments: This study was supported by the Erzincan University BAP FEN-A-080715-0159.
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Vitamin B12 and folate levels in human milk from mothers of pre-term infants at different lactation stages
Betül Alkan Polata, MeryemAydemir Atasevera, Harun Polatb ,Nurcan Kilic Baygutalpc , Mustafa Atasevera, Nurinnisa Ozturkb, Ebubekir Bakanb aAtaturk University, Faculty of Veterinary Medicine, Department of Food Hygiene and Technology, Erzurum, Turkey MeryemAydemir Atasever; e-mail: [email protected]; Mustafa Atasever;e-mail: [email protected] bAtaturk University, Faculty of Medicine, Department of Medical Biochemistry, Erzurum, Turkey Nurinnisa Ozturk;e-mail: [email protected] ;Harun Polat; e-mail:[email protected] ; Ebubekir Bakan; e-mail: [email protected] ; cAtaturk University, Faculty of Pharmacy, Department of Pharmacy Management, Erzurum, Turkey Nurcan Kilic Baygutalp; e-mail: [email protected] Abstract Background-Aim As human milk is a rich source for nutrition and immunological defense, WHO recommends all infants especially prematures to be fed with human milk for the first 6 months of life. The vitamin and other nutrient contents of human milk differ according to the lactation stage [1]. Colostrum is a very rich source of vitamins. Previous studies on vitamin B12 and folate levels in human milk have been reported a wide spectrum of results depending on nutritional status and the stage of lactation [2]. Vitamin B12 levels may be inadequate in human milk because of either prenatal low stores or postnatal low intake of mother [3]. In this study we aimed to evaluate the vitamin B12 and folate levels of human milk sampled from mothers with preterm infants in two different lactation stages and compare results. Infants fed with human milk poor in vitamin B12 has represented slower motor development and weight gaining compared to those fed with human milk a source of adequate vitamin B12.
Methods Fourty-six mothers who gave birth to premature infants were included to the study. Milk samples were obtained from twice: First in the 3rd day of lactation (colostrum milk), second in the 10th day of lactation (transitional milk). Folate and vitamin B12 levels were studied in Beckman Coulter DXI 800 (Beckman Coulter Tokyo, Japan) hormon analyzer by ECLIA method with respective kits. Results The mean age of mothers was 32,02±6,82 years. In milk samples from premature infants' mothers, the vitamin B12 levels were significantly higher in colostrum (87,74±32,97 pg/ml) compared to transitional milk (53,38±39,83 pg/ml) (p=0,00); and the folate levels were not significantly different in colostrum (5,75±2,65 ng/ml) compared to transitional milk (6,46±3,42 ng/ml) (p=0,323). Conclusions The low levels of vitamin B12 in transitional milk compared to colostrum may be attributed to the low dietery intake of mothers in postpartum period. The non-significance of folate levels in different lactation stages points out the contradictious reports of literature. Key words Vitamin B12 , folate , human milk, preterm infants
References [1] X. Ren, Z. Yang, B. Shao, S. Yin, X. Yang. PLoS One 10(7) (2015) e0133285. [2] J.M. Cooperman, H.S. Dweck, L.J. Newman, C. Garbarino, R. Lopez. The American Journal of Clinical Nutrition 36 (1982) 576.. [3] L.H. Allen . Adv Nutr 3(3): (2012) 362.
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Oxidative stress in type 2 diabetic nephropathy: Tunisian experience BEN DBIBIS M a, ESSADI Ra , BEN HADJ MOHAMED Ma, KHELIL Sa, Jabbalah Aa , ZINE EL ABEDINE Ab, TLILI Hc, CHAHED Ha, FERCHICHI Sa, MILED Aa
a :Biochemistry Laboratory, Hospital F. Hached Sousse Tunisia ; [email protected] b:Laboratory in center intermediate group of basic health Sousse-Tunisia c : endocrinology department in center intermediate group of basic health Sousse-Tunisia Abstract Background: Type 2 diabetes is a worldwide metabolic disorder that affects millions of people. Most diabetic type 2 patients develop serious macrovascular complications, such ascoronary artery disease, stroke, and peripheral vascular disease, as well as serious microvascular complications, such as nephropathy. Our aim was to evaluate the oxidative stress markers: thiobarbituric acid-reactive substances (TBARS), total antioxidant status (TAS), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR). Methods: This study included 150 type 2 diabetic patients (mean age 58.9±11.3 years) and 150 healthy subjects (mean age 51.1±3years) were recruited from endocrinology department in center intermediate group of basic health (Sousse-Tunisia). Patients were divided into two groups according to their level of microalbuminuria: Group 1 included 100 diabetic patients with normoalmicroalbuminuria (microalbuminuria 30-100 mg/24 h), group 2 included 50 diabetic patients with nephropathy (microalbuminuria 100-300 mg/24 h), and group 3 included 150 healthy controls (microalbuminuria<30 mg/24 h).The TBARS assay was performed by fluorimetric assay (Yagi method). TAS and erythrocyte SOD, GPx and GR activities were determined by spectrophotometric methods (Randox kits). Results: Group 2 had significant higher concentration of serum TBARS compared to the -3 group3(TBARS(gp2/gp3):1.71±0.5µmol/lvs0.65±0.35µmol/l;P<10 )and to the group1 -3). (TBARS(gp2/gp1)1.71±0.50µmol/lvs1.47±0.56µmol/l;P<10 TAS and the activity of SOD, GPx and GR -3 was lower in groupe 2 compared group 3 (TAS(gp2/gp3): 1.14±0.13 mmol/l vs 1.75±0.22 mmol/l; P<10 , -3 SOD (gp2/gp3):1004.06±287.39 U/gHb vs1718±604.37 U/ gHb; P <10 ,GPx(gp2/gp3):83.81±14.94U/gHb vs -3 -3 142.85±38.27U/gHb;P<10 ,GR(gp2/gp3):6.34±14.94 U/gHbvs7.80±2.71U/gHb;P<10 )but was no difference compared to group1 (TAS(gp2/gp1):1.14±0.13mmol/lvs1.13±0.14mmol/l,SOD(gp2/gp1):1004.06±287.39U/gHbvs956.4±218.76U/ gHb,GPx(gp2/gp1):83.81±14.94U/gHbvs83.9±16U/gHb,GR(gp2/gp1):6.34±14.94U/gHbvs6.13±3U/gHb). Discussion and Conclusion :The variation levels of these different parameters in our population reflect that oxidative stress represents a key factor in the development of type 2 diabetes complications such as nephropathy. Other hand the source of this variation may be related to auto-oxidation of glucose and non-enzymatic glycation [2]
References : [1] : Tatjana C., Branka M., Gordana L., et al: Oxidative stress parameters as possible urine markers in patients with diabetic nephropathy. Journal of Diabetes and Its Complications 2009; 23 :337–342. [2] : Beisswenger, P. J., Drummond, K. S., Nelson, R. G., How, S. K et al: Susceptibility to diabetic nephropathy is related to dicarbonyl and oxidative stress. Diabetes 2005; 54: 3274−3281.
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Protein Oxidation Levels in Different Organs of Rats Exposed to Aroclor 1254 at Different Selenium Status
Aylin Balcia, Unzile Yamanb, Pinar Erkekogluc, Ali Ascıd, Gizem Yıldıztekine, Didem Oralf, Belma Kocer Gumuselg
aHacettepe University, Faculty of Pharmacy, Department of Toxicology, 06100 Ankara, Turkey; email:[email protected]; bHacettepe University, Faculty of Pharmacy, Department of Toxicology, 06100 Ankara, Turkey; email:[email protected]; cHacettepe University, Faculty of Pharmacy, Department of Toxicology, 06100 Ankara, Turkey; email:[email protected]; dAtaturk University, Faculty of Pharmacy, Department of Toxicology, Erzurum, Turkey; email:[email protected]; eErzincan University, Faculty of Pharmacy, Department of Toxicology, Erzincan, Turkey; email:[email protected]; fHacettepe University, Faculty of Pharmacy, Department of Toxicology, 06100 Ankara, Turkey; email:[email protected]; gHacettepe University, Faculty of Pharmacy, Department of Toxicology, 06100 Ankara, Turkey; email: [email protected] ;
Abstract Aroclor 1254 is a widely used derivative of Aroclors, which are highly abundunt polychlorinated biphenyls. Studies on laboratory animals have reported that Aroclor 1254 has caused oxidative stress 1. Although the evidences are limited, it seems reasonable that Aroclor 1254 may have a potential for similar adverse effects in humans 1. Selenium is a trace element which is known to play a critical role in testis and in the modulation of intracellular redox equilibrium, Selenium is also crucial for male reproduction 2. By taking into account the high prevalence of inadequate selenium intake, essentiality of selenium in testicular structure and functions, this study was designed to investigate the effect of Aroclor 1254 on protein oxidation levels in different organs of selenium-deficient male rats and selenium- supplemented rats. Selenium deficiency was generated by feeding 3-week old Sprague Dawley rats with 0.05 Se mg/kg diet for 5 weeks. Supplementation group were on 1 mg Se/kg diet. Aroclor 1254-treated groups received 10 mg/kg dose by gavage during the last 15 days of feeding period. Aroclor 1254 did not induce protein oxidation in liver, testis and kidney. However, there was a significant increase in protein oxidation in the heart of Aroclor 1254-exposed rats (42% increase). Selenium supplementation decreased the protein oxidation in heart while selenium deficiency caused more increases in protein oxidation compared to Aroclor 1254 receiving group. Further studies are needed to show the mechanism of protein oxidation in the heart caused by Aroclor 1254.
Acknowledgements: This study is supported by Hacettepe University Research Fund.
References: 1 U.S. Dept Health & Human Services/Agency for Toxic Substances & Disease Registry; Toxicological Profile for Polychlorinated biphenyls (PCBs) (2000) 301 TP17. 2 P. Erkekoglu, N.D. Zeybek, B. Giray, E. Asan, J. Arnaud, F. Hincal. Drug Chem Toxicol. 34 (2011) 379.
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Adiponectin in metabolic syndrome SAHLI Sa,Khlifi L b a Laboratory of biochemistry CHU Farhat Hached Sousse (TUNISIA); [email protected]; b Laboratory of biochemistry CHU Farhat Hached Sousse (TUNISIA); [email protected] Abstract Metabolic syndrome (MetS) is known as the cluster of criteria (hypertension, hyperglycemia, obesity, abnormal lipid metabolism). Adiponectin is an adipocyte secreted protein that circulates in high concentrations in the serum, and can regulate glucose levels, insulin action and lipid metabolism. The aim of this study was to investigate the association of adiponectin and various risk-factors with Met S. We determined serum adiponectin level and MetS components in 200 participants. Serum total cholesterol and triglyceride were determined by enzymatic methods. Insulin resistance was calculated using the homeostasis model assessment (HOMA-IR): fasting insulin (uIU/ml) *fasting plasma glucose (mmol/L)/22,5 and serum adiponectin levels were measured using a Human Adiponectin ELISA (Abcys). The study population comprised 100 patients, 86 of whom were females and 14 were males. The MetS, as defined by the National Cholesterol Education Program Adult Treatement Panel III criteria, was diagnosed in 72% of subjects with hypertension, 84% of whose with abdominal obesity and 83 % of participants with elevated fasting glucose. Mean age was 54±11years in patients and 51±10 years in controls and the mean levels of HOMA-IR were 5,23±3,52 and1,83±0,93 for patients and controls, respectively. Compared with subjects controls, patients had significantly higher levels of triglycerides (1,64±0,88 mmol /L vs 1,07±0,43 mmol/L ; p=0,03) and lower levels of high-density lipoprotein (HDL) cholesterol (1,26±0,41 mmol/L vs 1,58±0,30 mmol/L ; p=0,04). In addition, there was a significant difference in serum adiponectin levels between the patients and controls (13,96±5,23 µg/ml vs 22,24±9,07 ; p=0,006) and there was no significant correlation between this hypoadiponectinemia and the others parameters.
Our study in the Tunisian population suggested possible association between adiponectin, insulin resistance and MetS.
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Some Lichen Acids May Be Used As A Potential Drug For Cancer Therapy; By Inhibiting Mitochondrial Thioredoxin Reductase
Ilknur Ozgencli1, Harun Budak2, Mehmet Ciftci3, Mustafa Anar2 1Atatürk University, Faculty of Science, Department of Chemistry, Erzurum 2Ataturk University, Faculty of Science, Department of Molecular Biology and Genetics, Erzurum 3Bingol University, Faculty of Science and Art, Department of Chemistry, Bingol *Corresponding author. E-mail: [email protected] Abstract
Thioredoxin reductase (E.C 1.6.4.5.; TrxR), is a widely distributed flavoprotein, catalyzes the NADPH- dependent reduction of thioredoxin (Trx) in many cellular events including DNA synthesis, redox signaling, antioxidative defence, selenium metabolism, and the regulating of apoptosis. Although TrxR protects healthy cells from oxidative stress, the overexpression of TrxR also promotes to tumor growth and progression in the cell. Thus, the inhibition of TrxR has been targeted for chemotherapy approaches [1,2]. In this study, it was the first time the enzyme was purified from rat lung in two steps as the preparation of homogenate and 2',5'-ADP Sepharose 4B affinity chromatography. After the purification procedure, in vitro inhibition effect of some lichen acids [3] including diffractaic acid, evernic acid, lobaric acid, lecanoric acid, and vulpinic acid on mitochondrial TrxR was investigated. All of the lichen acids exhibited strong inhibitory effect on the enzyme same as the anticancer agents.
Key words: Thioredoxin Reductase, Cancer, Lichen Acids References: [1] Wang Y, Zhang H, Holmgren A, Tian W, Zhong L. 2008. Oncol. Rep. 20:1479–1487. [2] Fan, C., Zheng, W., Fu, X., Li, X., Wong, Y-S., Chen, T. 2014. Cell Death Dis. April; 5(4): e1191. [3] Rankovic, B., Kosanic, M., Manojlovic, N., Rancic, A., Stanojkovic, T. 2014. Chemical composition of Hypogymnia physodes lichen and biological activities of some its major metabolites Med Chem Res, 23:408–416.
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Novel Genomic and Proteomic Effects of Hydroxyfasudil in PS Induced Rat Bladder; Preliminary Results Aliseydi BOZKURT1, Harun BUDAK2, Hüseyin Serkan EROL3, Serpil CAN4, Tolga MERCANTEPE5, Yiğit AKIN6,Isa ÖZBEY7,Murat ÇANKAYA8, T. Abdulkadir ÇOBAN9, Mesut Bünyamin HALICI3 1Erzincan University, Medicine Faculty,Department of Urology; [email protected]; 2. Atatürk University, Science Faculty, Department of Molecular Biology and Genetics; [email protected]; 3. Atatürk University, Faculty of Veterinary Medicine, Department of Biochemistry; [email protected]; 4.Kafkas University, Faculty of Medicine, Department of Physiology; [email protected]; 5.Recep Tayyip Erdoğan University, Faculty of Medicine, Department of Histology- Embryology; [email protected]; 6. Harran University, Medicine Faculty,Department of Urology; [email protected]; 7. Atatürk University, Medicine Faculty,Department of Urology; [email protected]; 8. Erzincan University, Science and Art Faculty, Department of Biology; [email protected]; 9 Erzincan University, Medicine Faculty, Department of Biochemistry; [email protected].
Abstract
The aim of this study was to examine anti-inflammatory effects of hydroxyfasudil (HF) at the enzymatic and molecular level on visceral tissues in a protamine sulfate (PS) induced cystitis rat model. We set up four animal groups. Healthy group, only saline was administration. Control group, 0.2mL saline was administered intraperitoneal route after 3 days intravesical PS administration. Treatment group, Rho-kinase inhibitor hydroxyfasudil was administered intraperitoneal route after 3 days intravesical PS administration. HF group, each time 0.2mL saline was administered for 3 days intravesical, and then HF was administered intraperitoneal route. Molecular and biochemical analyses were performed for antioxidant enzyme, and pathological evaluations were investigated. While the expression of catalase was decreased in HF group compared with other groups, superoxide dismutase expression was not affected in kidney. All groups were compared with each other, the expression of catalase and superoxide dismutase was changed in heart and liver. Lipid peroxidation levels, reduced glutathione levels and enzymatic activities of superoxide dismutase and catalase in these three tissues were significantly changed. Present study showed that hydroxyfasudil has effects on peripheral antioxidant system with either molecular and protein level. Thus, hydroxyfasudil might be used for therapies in appropriate doses to eliminate interstitial cystitis.
Acknowledgments: This study was performed in Experimental Laboratories of Ataturk University, Erzurum, Turkey and Erzincan University Scientific Research and Project Units (11.02.09). Conceived and designed the experiments: TAC (group leader) and ASB, HB, MBH. Performed the experiments: ASB, HB, MBH, HSE, MC, TAC. Analyzed the data: ASB, HB, MBH, SC, TM, YA, IO, TAC. Contributed reagents/materials/analysis tools: ASB, HB, MBH, YA, IO. Wrote the paper: ASB, HB, MBH, IO, YA, TAC.
References: [1] Akin Y, Bozkurt A, Erol HS, Halici M, Celebi F, Kapakin KAT, Gulmez H, Ates M, Coban A, Nuhoglu B (2014). LUTS. doi: 10.1111/luts.12058.
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Physicochemical characterization and pharmacological evaluation of ezetimibe-PVP K30 solid dispersions in hyperlipidemic rats
Azin Jahangiri a, Khosro Adibkia b
a Students Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; [email protected]. b Drug Applied Research Center, and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran; [email protected]
Abstract
The aim of this study was to improve the physicochemical properties as well as the therapeutic efficacy of ezetimibe (EZT), through preparation of the solid dispersion (SD) [1]. SDs were formulated using Polyvinylpyrrolidone-K30 (PVP K30) via solvent method. The physicochemical properties and in vitro drug release patterns of the prepared SDs were examined. To estimate the therapeutic efficiency of prepared SDs, in vivo studies including measurement of serum lipid levels, liver index and histological analysis of the liver tissue in hyperlipidemic rats were performed. Differential scanning calorimetry (DSC) and powder X-ray diffractometery (PXRD) showed that the drug crystallinity was remarkably decreased during the preparation process. Faster drug release pattern of SDs was proved by in vitro dissolution test. Administration of EZT in SD form led to a significant decrease in serum total cholesterol (TC) and LDL-C level, as well as liver index in hyperlipidemic rats (P<0.05) compared to the PM. Furthermore, histological analysis of the liver tissue confirmed the improved efficacy of the SDs on the liver steatosis. In the present study, it was shown that the SDs of EZT with improved physicochemical characteristics had favorable effects on liver steatosis, liver index and serum lipid levels in the high fat diet-induced hyperlipidemic rats. According to the obtained results, In vivo efficiency of EZT SDs were significantly correlated with in vitro release profiles, suggesting that the release property of EZT SDs could estimate the performance of the formulation.
Acknowledgments: The authors would like to thank the Drug Applied Research Center, Tabriz University of Medical Sciences, for financial support of this study.
[1] C.L. Vo, C. Park, B.J. Lee, Current trends and future perspectives of solid dispersions containing poorly water-soluble drugs, Eur. J. Pharm. Biopharm., 85 (2013) 799.
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Pharmacological and histological examination of atorvastatin-PVP K30 solid dispersions
Azin Jahangiri a, Khosro Adibkia b
a Students Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; [email protected]. b Drug Applied Research Center, and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran; [email protected]
Abstract The objective of the present study was to investigate the pharmacological efficiency of orally administered atorvastatin calcium (ATV) solid dispersions (SDs). SDs of ATV were prepared using polyvinylpyrrolidone K30 (PVP) through solvent evaporation method [1]. Physicochemical characteristics of the prepared formulations were assessed benefitting scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and powder X-ray diffractometry (PXRD). The drug dissolution rates (under sink and non-sink conditions) as well as solubility studies were also examined. Serum lipid levels, liver index and histological analysis of the liver tissue in hyperlipidemic rats were considered to evaluate the pharmacological efficiency of prepared SDs. According to our findings, the drug crystallinity was reduced and the drug dissolution characteristics were improved in the prepared SDs. In vivo studies revealed that oral administration of ATV (3 mg/kg/day) in the SD form (ASDT) for 14 days along with high fat diet (HFD) to the hypercholesterolemic rats led to a significant decline (P< 0.05) in serum level of total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C). Moreover, ASDT exhibited more beneficial effects on the liver steatosis compared to ATV physical mixture (APMT) and hyperlipidemic control (HC) groups. In the present study, it was concluded that the SDs of ATV with improved physicochemical characteristics provided an increased therapeutic potential for management of hyperlipidemia compared to the corresponding physical mixtures (PMs). Acknowledgments: The authors would like to thank the Drug Applied Research Center, Tabriz University of Medical Sciences, for financial support of this study.
[1] F. Frizon, J. de Oliveira Eloy, C.M. Donaduzzi, M.L. Mitsui, J.M. Marchetti, Dissolution rate enhancement of loratadine in polyvinylpyrrolidone K-30 solid dispersions by solvent methods, Powder Technol., 235 (2013) 532.
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Medicinal plants from the genus Alchemilla (Rosaceae): A Review of Phytochemistry, Pharmacology and Ethnobotany
Sezen Karaoglan E.
Ataturk University, Faculty of Pharmacy, Department of Pharmaceutical Botany; [email protected]
Abstract
Alchemilla sp. (Rosaceae) known publicly to be Lady’s mantle are plants used for the treatment of several gynaecological disorders. Turkey inhabits 113 taxa named in Turkish to be aslanpençesi, kurtayağı, dokuztepe, paraotu, fındıkotu and sarı çiçek [1]. In the present study, a review was completed using the scanning software of SciFinder and Google Scholar. It was stated in phytochemical studies in literature that Alchemilla sp. include mainly the substances in flavonoid structure. In addition, the species involving the substances in triterpene, phenolic acid, volatile oil, sterol, tanen and carbonhydrate structures are also registered. In also the pevious pharmaceutical studies, it was reported that Alchemilla species can be utilised in the treatment of endometriosis and can show antibacterial, antioxidant, anti influenza, acetylcholinesterase, inhibitor, vasorelaxant and wound healing activities. Ethnobotanical studies revealed that in addition to gynaecological diseases, Alchemilla species can be used publicly to cure inflammation, disorders in respiratory system, renal failures and diseases in stomach and intestinal system [2]. It was determined as the result of the present study that Alchemilla species are valuable medicinal plants rich in flavonoids and Turkey shelters these species in its several parts diversely.
References:
[1] M. Stanilova, R. Gorgorov, A. Trandafilova, M. Nikolova, A. Vitkova, ınfluence of nutrient medium composition on in vitro growth, polyphenolic content and antioxidant activity of Alchemilla molis, Nat. Pro. Com. 2012,7(6), 761-766. [2] S. Akbulut. Z.C. Ozkan , Traditional Usage of Some Wild Plants in Trabzon Region (Turkey), Kastamonu University Lournal of Forestry Faculty, 2014, 14 (1), 134-145.
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Photophysical characterization of interaction of indole compound with Model Membrane Systems in 5,14-Dimethyl-5,6,7,8,9,14-hexahydroindolo[2’,3’:3,4] cycloocta[1,2-b].
Burcu Meryem AYDINa, Sıdkı AYGÜNa, Oktay TALAZb, Mahmut TOPRAKc
aErzincan University Department Of Chemistry; Erzincan, Turkey. e-mail: [email protected], [email protected] b Karamanoğlu Mehmetbey University Department Of Chemistry; Karaman, Turkey. e-mail: [email protected] cBingöl University Department Of Chemistry; Bingöl, Turkey. e-mail: [email protected] Abstract Surfactant molecules equilibrate on a specific surfactant concentration known as critical micellar concentration (CMC) thermodynamically and have a different structure. This structure is the simple model of biological membranes. Therefore, these systems have been used as a model while examining the biological membranes [1]. Dyes having a fluorescence features have been used as a probe in examining the physicochemical, biochemical and biological systems. These probes can be used in biological membranes; for fluidity, lipid-protein interactions, membrane potentials, bondings, surface antigens, and cell-virus interactions, membranes fragmentations, in proteins; for denaturation, conformational transitions and any other researches [2]. Photophysical features of these types of molecules change according to its environment. For that reason, it is highly important to determine the behaviors of the fluorescence substances in different environments and to develop effective systems. Bisindole structure within so many alkaloids that have biological activity stands as a main frame. Caulerpin is one of the bisindole alkaloids that contain two indole rings in anti position in eight membered ring [3]. In this paper, the interaction between the model membrane system and 5,14- Dimethyl-5,6,7,8,9,14-hexahydroindolo[2’,3’:3,4] cycloocta[1,2-b] indole compound that shows rigid antioxidant features and having a biological activity and that is one of the constitutional isomers of Caulerpin molecules have been investigated in terms of photophysical features[4]. In this paper, photophysical features of compound in micella environment that is the model system have been explained by using steady-state fluorescence spectroscopy techniques and UV- Visible absorption in Sodium Dodecyl Sulfate (SDS) micellar environment. Quantum yield, transfer rate constant radiative and nonradiative and Stoke's shift has been specified to examine the dye-membrane interaction of this molecule that has fluorescence features. Shifts have been observed in the absorption and emission band maximums of molecule [5]. Having a high quantum yield and its fluorescence lifetime show compound to be used as a fluorescence probe[6].
References:
[1] Ganguly P., Journal of Molecular Liquids, 151 (2010) 67. [2] B.Valeur, Molecular Fluorescence:Principles and Applications. Wiley-VCH Verlag GmbH, Weinheim, 2001. [3] O. Talaz, N. Saracoğlu, Tetrahedron, 66 (2010) 1902. [4] O. Talaz, İ. Gülçin, S. Göksu, N. Saraçoğlu, Bioorganic & Medicinal Chem.,17 (2009) 6583. [5] Y.Onganer, E.L.Quitevis, J. Phys. Chem. B.,96 (1992) 7996. [6] E. Fındık, M. Arık, M. Ceylan, Turk J Chem., 33 (2009) 677.
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Dye-Membrane Interaction: A Spectroscopic Study Sıdkı AYGÜN a, Burcu Meryem AYDINa, Murat ACARb, Kadem MERALb
aErzincan University Department Of Chemistry; Erzincan, Turkey.e-mail: [email protected], [email protected] bAtatürk University, Department of Chemistry, Erzurum, Turkey. e-mail: [email protected] , [email protected]
Abstract Pyronine Y (PyY) is a xanthene derivative dye compound used in this study. Therefore, PyY is used in model biologic systems and laser spectroscopy widely [1]. Xanthene derivatives are very efficient laser dyes and fluorescent probes that offer outstanding photophysical properties. Photophysical properties of this kind of dyes depend on media [2]. Thus, it is important to determine behavior of PyY in different media. Dyes having a fluorescence features have been used as a probe in examining the physicochemical, biochemical and biological systems. These probes can be used in biological membranes; for fluidity, lipid-protein interactions, membrane potentials, bondings, surface antigens, and cell-virus interactions, membranes fragmentations, in proteins; for denaturation, conformational transitions and any other researches.
Surfactant molecules equilibrate on a specific surfactant concentration known as critical micellar concentration (CMC) thermodynamically and have a different structure. This structure is the simple model of biological membranes. These systems have been used as a model while examining the biological membranes [3].
In this study, the photophysical properties of PyY have been investigated by using UV- Visible absorption and steady-state fluorescence spectroscopy techniques in Sodium Dodecyl Sulfate (SDS) micellar environment. Significant photophysical parameters as band shifts, fluorescence quantum yields and fluorescence lifetimes were determined to understand how photophysical and spectroscopic features of the dye compounds were affected by dye-membrane interaction.
As a result, the fluorescence lifetimes of the dyes in the micelles were determined by the time- resolved fluorescence decay studies. Evaluation of the fluorescence lifetimes calculated for pyronin dye in the micelles showed that by adding electrolyte affected the fluorescence lifetimes of pyronin dye. The fluorescence quantum yields increased.
Acknowledgement: We are greatly indebted to Erzincan University Scientific Research Fund (EU-BAP) for financial supports of this work ( the project number 12.02.11) References: [1] Dare-Doyen S., Doizi D., Guilbaud Ph., Djedaini-Pilard F., Perly B., Millie Ph., J.Phys. Chem. B, 107 (2003) 13803. [2] Valeur B., Molecular Fluorescence:Principles and Applications. Wiley-VCH Verlag GmbH, Weinheim, (2001). [3] Ganguly P., Journal of Molecular Liquids, 151 (2010) 67.
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Serum Amyloide A and high Sensitivity C-reactive protein in acute phase of Acute coronary syndrome with ST-segment elevation
Bouzidi Nadiaa,b, Khlifi Latifaa,b, Dandana Azzaa,b, Chahed Hinda,b, Guider Jeridic, Miled Abdelhedia,b, Ferchichi Salimaa,b. aResearch Unit UR 06/07,Faculty of Pharmacy, Monastir, Tunisia; e-mail: [email protected]; bDepartment of Biochemistry, Farhat hached Hospital of Sousse, Tunisia; cDepartment of Cardiology, Farhat hached Hospital of Sousse, Tunisia.
Abstract Background: Atherosclerosis is widely accepted as a chronic inflammatory disease initiated by different vascular and extravascular sources. An unstable, and subsequently ruptured, atherosclerotic coronary plaque with superimposed thrombosis constitutes the most common, general, and pathological background of the acute coronary syndrome (ACS). SAA and CRPus, markers of acute phase reactants appear as early markers of atherogenesis. Our stydy aim to determine the interest of these markers in ACS with ST-segment elevation ACS(ST+). Methods: The present study consisted of 31 patients (19 women and 12 men, mean age 63±12 years) ,who were admitted to cardiology departement CHU Farhat Hached Sousse for ACS with ST-segment elevation. The control group consisted of 55 healthy subjects (mean age 40 ± 10 years). HsCRP concentrations were measured by Immunoturbidimetry using a COBAS INTEGRA 400 analyser (Roche). Serum amyloid A(SAA) level was determined by nephelometric method using a BN ProsPec (Dade Behring Diagnostic, Marburg, Germany). Database management and statistical analyses were carried out using SPSS (Statistical Package for the Sociological Sciences), version 17.0. Results: In the SCA, our results showed: a statistically significant increase hsCRP and SAA in patients with ACS(ST+) compared with the control group (hsCRP: 9,79±6,85 vs 1,3±0,8mg/L (p=0,001); (SAA: 6,94±2,87 vs 3,06±2,16mg/L (p=0,001). Both inflammatory markers exhibit a statistically significant correlation (p=0.01) after thrombolysis. Conclusion: In post infarction, CRPus and SAA increase, reflecting and participating perhaps in the inflammation that accompanies tissue necrosis. SAA together with hs-CRP have been associated with a major number of complicated lesions in patients with ACS [1]. References: [1] R. Di Stefano, V. Di Bello and al. Inflammatory markers and cardiac function in acute coronary syndrome: Difference in ST-segment elevation myocardial infarction (STEMI) and in non-STEMI models, Biomedicine & Pharmacotherapy 63 (2009) 773 e780.
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Homocystein and high Sensitivity C-reactive protein in acute phase of Acute coronary syndrom
Bouzidi Nadiaa,b, Khlifi Latifaa,b, Dandana Azzaa,b, Chahed Hinda,b, Guider Jeridic, Miled Abdelhedia,b, Ferchichi Salimaa,b. aResearch Unit UR 06/07,Faculty of Pharmacy, Monastir, Tunisia; e-mail: [email protected]; bDepartment of Biochemistry, Farhat hached Hospital of Sousse, Tunisia; cDepartment of Cardiology, Farhat hached Hospital of Sousse, Tunisia.
Abstract Background: Laboratory studies have demonstrated that inflammation plays a pathophysiological role in atherogenesis and may promote the development of atherosclerotic plaques in coronary arteries. Hyperhomocysteinemia may lead to an enhancement of the adverse effects of risk factors like hypertension, smoking, lipid and lipoprotein metabolism, as well as promotion of the development of inflammation. Our study was undertaken to determine a possible relationship between inflammation markers and elevated levels of homocystein, which are important risk factors for Coronary artery diseases. Methods: The present study consisted of 65 patients (26 women and 39 men, mean age 63 ± 12 years) ,who were admitted to the emergency CHU Farhat Hached Sousse for ACS. The control group consisted of 55 healthy subjects (mean age 40 ± 10 years). HsCRP concentrations were measured by Immunoturbidimetry using a COBAS INTEGRA 400 analyser (Roche). Serum total homocysteine (tHcy) level was determined by a fluorescence polarization immunoassay (FPIA). Database management and statistical analyses were carried out using SPSS (Statistical Package for the Sociological Sciences), version 17.0. Results: In the SCA, our results showed: a statistically significant increase hsCRP and cTnI in patients with acute coronary syndrome compared with the control group (hsCRP: 7.07 ± 5.91 mg / l vs 1 44 ± 1.27 mg / l, p = 0.001) (Hcy:13,56± 2,13 µmol/l vs 8,25±1,5 µmol/l, p=0,05). Conclusion: Homocysteine is known to mediate cardiovascular problems by its adverse effects on cardiovascular endothelium and smooth muscle cells with resultant alterations in subclinical arterial structure and function [1]. These results are consistent with the hypothesis that systemic inflammation, manifested by hs-CRP levels, may possibly be associated with increased cardiovascular risk by promoting atherosclerotic plaque destabilization, in addition to exerting a possible direct effect on atherogenesis [2]. References: [1] A. Baszczuk, Z. Kopczynski, Hyperhomocysteinemia in patients with cardiovascular disease. Postepy Hig Med Dosw. 68(2014)579. [2] B. D. Johnson, E. Kevin, Serum Amyloid A as a Predictor of Coronary Artery Disease and Cardiovascular Outcome in Women. Circulation 109(2004)726.
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Microwave Assisted Synthesis and Biologycal Activity Studies of Some New Deived from Antipyrine
a b Serpil Demirci , Sengül Alpay Karaoglu a) Giresun University, School of Applied Science, Department of Crop Production and Technology, Giresun, Turkey b) Recep Tayyip Erdogan University, Department of Biology, Rize, Turkey [email protected] Abstract Antimicrobial resistance, infectious diseases became responsible for a significant proportion of deaths worldwide. Although World Health Organization defines the antimicrobial agents as miracle drugs leading weapons for the treatment of infectious diseases, a number of the current clinically efficacious antimicrobial agents are becoming less effective as a result of the development of antimicrobial resistance [1, 2].
Despite the continued threat of resistance, β-lactams remained the most important antibacterial in current clinical use. Another privileged scaffold thiazolidinone constitute a very attractive target for combinatorial synthesis due to its structure activity relationship, and it belongs an important class of N and S containing heterocycles, which are widely used as key building blocks in the field of drugs and pharmaceutical agents [3].
In this study, some new penicillin derivatives containing 1,3-thiazole moiety have been synthesized and screened for their antimicrobial activities
References:
[1] Raparti, V. Chitre, K., Bothara, V. Kumar, S. Dangre, C. Khachane, S. Gore, B. Deshmane, Eur. J. Med. Chem., 2009, 44, 3954–3960. [2] Demirci S., Basoglu S., Arif B., Demirbas N., Med Chem Res, 2013, vol. 22, pp. 4930–4945. [3] Demirci S., Demirbas A., Ulker S., Bozdeveci A., Karaoglu S.A., Demirbas N., Arch. Pharm. Chem. Life Sci., 2014, vol. 347, pp. 200–220.
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Solid Phase Extraction - High Performance Liquid Chromatography-UV Method for Determination of Rivaroxaban in Human Plasma
Mustafa Çelebier, Tuba Reçber, Engin Koçak, Sacide Altınöz, Sedef Kır
Hacettepe University, Faculty of Pharmacy, Department of Analytical Chemistry, 06100, Ankara, Türkiye-mail: [email protected]
Abstract
Rivaroxaban (RIV) is an oral oxazolidinone-based anticoagulant and it is a potent and selective direct inhibitor of factor Xa for the prevention of venous thromboembolism in adult patients after total hip replacement or total knee replacement surgery [1].
A solid phase extraction (SPE)–HPLC-UV method was developed in this study for determination of RIV in human plasma samples. The SPE procedure was applied by using Phenomenex Strata-X 33µm polymeric reversed phase 30 mg/3 mL SPE tubes, thus, the concentration of RIV in plasma samples was increased 7.5 times and the interference coming from matrix components was avoided.
The extracted samples of RIV were analyzed by using an HPLC-UV method. A Phenomenex Luna 5 µm C18 100 Å LC Column (250 x 4.6 mm) was used for separation of RIV and prednisolone (internal standard). The total analysis time was shorter than 6 minutes where RIV and internal standard eluted at 4.3 and 5.1 minutes, respectively.
RIV in spiked human plasma samples provided linear data over a range of 0.01 – 4.00 µg mL-1.
The validated SPE-HPLC-UV method according to the Food and Drug Administration (FDA) guideline [2] could be proposed for further analysis and pharmacokinetic studies of RIV.
References:
1. S.T. Duggan, Am. J. Cardiovasc. Drug. 12 (2012) 57. 2. FDA, Guidance for Industry, Bioanalytical Method Validation http://www.fda.gov/downloads/Drugs/Guidance Compliance Regulatory Information/ Guidances/UCM368107 (Accessed August 10, 2015).
,
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Cloning and Expression of Rat (Rattus norvegicus) Brain Acetylcholinesterase Gene
Ahmet KARAKUŞa, Hamid CEYLANa, Orhan ERDOĞANa
aAtatürk University, Science Faculty, Department of Molecular Biology and Genetic, 25240, Erzurum, Türkiye [email protected]
Abstract
The gene region of rat (Rattus norvegicus) brain acetylcholinesterase enzyme was amplified in PCR with designed forward and reverse primers and it was ligated into a pET SUMO vector under suitable conditions. This recombinant vector was transformed to competent E.coli cells and it was grown in liquid LB medium including kanamycin. Colony PCR was performed from growing colony and PCR products were checked with agarose gel electrophoresis. The correct colonies were grown in a liquid medium for plasmid isolation. After plasmid isolation, these recombinant constructs were used for whether the gene inserts properly with cross-PCR. After determining the accuracy of the plasmid, recombinant vectors were transferred into the E.coli BL21(DE3) cells to perform protein production. Cells were grown in IPTG induced larger 7 hours and samples were taken each two hours. Enzyme activity and SDS-PAGE analysis were performed from homogenate for each treatment samples.
In this way, comprehensive information about the molecular structure and function of AChE that enzyme shown as the chemotherapeutic target for drug design enzyme will be obtained. We believe that this information will allow to design of the selective inhibitors. These inhibitors can be used as drug treatment in Alzheimer's disease.
Keywords: Rattus norvegicus, molecular cloning, expression, recombinant protein
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The Determination of the Antioxidative Properties of Water, Ethanol-Water, Methanol and Chloroform Extracts Obtained from Cinnamon, Cumin and Sumac, in vitro Ozlem Aydin BERKTASa, Fehmi Odabasoglua, Fadime ATALAYb, Zerrin KUTLUa
aAtatürk Üniv. Eczacılık Fak. Biyokimya Anabilim Dalı, 25240, Erzurum bKafkas Üniv. Tıp Fak. Biyokimya Anabilim Dalı, 25240, Kars
Abstarct In this research; as experiment material, also spices such as cinnamon, cumin and sumac widespread using in our country were investigated. The water, ethanol-water, methanol and chloroform extracts of each type of spices samples were produced using appropriate methods according to literature. We determined the antioxidant activities, phenolic compound amounts and reducing powers of these extracts. Results were presented to compared with control groups, were discussed as comperative with literatures. The antioxidant activity assay showed that it is the highest levels in water extracts of cinnamon and cumin, lowest levels in chloroform extracts, and moderate levels in other extracts.In ethanol-water and methanol extracts of sumac, amounts of total phenolic compounds were the highest levels. Entire of chloroform extracts had the lowest in its amounts. On the other hand, their amounts were in varying levels in all of other extracts. Our results; of reducing power assays showed the highest levels in methanol extract of sumac, the lowest levels in all of chloroform extracts. Notwithstanding it was in different levels in the other extracts. As a result; in this study, the all of species spices which we used as experimental material, demonstrated potentially antioxidative properties. Further, these results will be primarily developed leading to biological activity studies.
Key words: cinnamon, cumin, sumac, antioxidant activity, phenolic compounds
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Chitosan Coated Polycaprolactone Inserts of Terbafine HCl: Preparation and Evaluations
Neslihan Üstündağ Okura, Panoraia Siafakab, Dimitrios Bikiarisb aIstanbul Medipol University, School of Pharmacy, Department of Pharmaceutical Technology, Beykoz, 34810 Istanbul, Turkey; e-mail: [email protected] b Aristotle University of Thessaloniki, Laboratory of Organic Chemical Technology, Department of Chemistry, GR-541 24 Thessaloniki, Greece
Abstract
The eye is one of the most complex organs of the body. The unique anatomy and physiology of the eye renders it is highly protected organ, and the unique structure restricts drug entry at the target site of action [1]. Typically topical ocular drug administration is accomplished by eye drops, but they have only a short contact time on the eye surface [2]. To overcome these problems, designing a drug delivery system with ability to retain in the eye for long period of time will improve ocular drug bioavailability. Ocular inserts are one of the new classes of drug delivery systems, which are gaining worldwide praise for their ability to release drugs at a pre-programmed rate for a longer period by increasing the pre- ocular residence time [3]. The aim of the current investigation was to prepare and evaluate the potential use of insert formulation for ocular delivery of Terbinafine HCL. The inserts were prepared with solvent casting method. 30% solutions of polycaprolactone were used in DCM/ DMF mixtures (70/30). Terbinafine (1%) was dissolved in this solvent mixture. The mixture was poured on a glass petri dish and allowed to evaporate at 30 °C for 12 h in an oven. The modification of the chitosan coating was conducted via direct immersion method. Three different chitosan solutions 0.2/0.4/0.8 % w/v were used. The obtained films were cut by a circular molder into circular pieces of definite size. The ocular inserts were then stored in an airtight container (desiccator) under ambient condition. Inserts were evaluated for diameter, thickness uniformity, weight uniformity, drug content, moisture absorption and moisture loss. The inserts were prepared successfully with solvent casting method. After inserts were prepared and dried, they had uniform image and it had simply removable property from the petri dishes. The inserts had a thickness varying from 0.33 ± 0.01 to 0.45 ± 0.01 mm. The surface pH, % moisture absorption or moisture loss and weight variation values were obtained in satisfactory range. From the investigation, it can be concluded that developed chitosan coated polycaprolactone ocular inserts of Terbinafine were prepared successfully by using solvent casting method for ocular drug delivery. The developed inserts may be useful in clinical practice to maintain fungal keratitis.
References [1] R.C. Nagarwal, S. Kant, P.N. Singh, P. Maiti, J.K. Pandit, J. Control. Release 136 (2009) 2. [2] R. Dhanapal, J.V. Ratna, I.J.I.D.D. 2 (2012) 4. [3] M.P.C. Rao, M. Nappinnai, S. Raju, V.U. Maheshwara Rao, B. Venkateshwara Reddy, J. Pharm. Sci. Res. 11 (2010) 693. Acknowledgments The authors would like to acknowledge İstanbul Medipol University, REMER for enabling us to use its laboratory instruments.
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Stability indicating HPLC method for the determination fulvestrant in pharmaceutical formulation in comparison with linear sweep voltammetric method
Alptug ATILA, Bilal YILMAZ, Yucel KADIOGLU
Department of Analytical Chemistry, Faculty of Pharmacy, Ataturk University, 25240, Erzurum, Turkey
Abstract
Fulvestrant (Fig. 1), 7-alpha-[9-(4,4,5,5,5-penta fluoropentylsulphinyl) nonyl]estra-1,3,5- (10)-triene-3,17-beta-diol, is estrogen receptor antagonist drug that used for treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women (1). Temoxifen has been a great precious in the treatment of breast cancer. Also, some of its features make it less than ideal (2,3).
This study describes two rapid, sensitive and specific methods for the determination of fulvestrant in pharmaceutical preparations by high performance liquid chromatography (HPLC) and linear sweep voltammetry (LSV). HPLC method was used to study the degradation behavior. Fulvestrant was subjected to degradation under the conditions of hydrolysis (acid and alkali), oxidation (30% H2O2). The linearity was established over the concentration range of 5-50 g mL-1 for LSV and 0.5-20 g mL-1 for HPLC method. The intra- and inter-day relative standard deviation (RSD) was less than 3.96 and 3.07% for LSV and HPLC, respectively. Limits of quantification were determined as 4.8 and 0.15 g mL-1 for LSV and HPLC, respectively. No interference was found from tablet excipients at the selected assay conditions.
The methods were applied for the quality control of commercial fulvestrant dosage form to quantify the drug and to check the formulation content uniformity.
References: [1] A. Howell, J.F. Robertson, A.J. Quaresma, A. Aschermannova, L. Mauriac, U.R. Kleeberg, I.Vergote, B. Erikstein, A. Webster, C. Morris, J Clin Oncol 20 (2002) 3396.
[2] A. E. Lykkesfeldt, Acta Oncol 35 (1996) 9.
[3] J. R. Robertson, A. Howell, D. DeFeriend, Brit J Cancer 74 (1996) 300.
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Study of the boron levels in serum after implantation of different ratios nano- hexagonal boron nitride-hydroxy apatite in rat femurs Alptug Atila1, Zekai Halici2, Elif Cadirci2, Emre Karakus3, Saziye Sezin Palabiyik4, Nuran Ay5, Feray Bakan6, Sahin Yilmaz7
1Department of Analytical Chemistry, Ataturk University Faculty of Pharmacy, Erzurum, Turkey, 25240 2Department of Pharmacology, Ataturk University Faculty of Medicine, Erzurum, 25240, Turkey 3Department of Pharmacology and Toxicology, Ataturk University School of Veterinary Medicine, Erzurum, 25240, Turkey 4Department of Pharmaceutical Toxicology, Ataturk University Faculty of Pharmacy, Erzurum, 25240, Turkey 5Department of Material Science and Engineering, Anadolu University Faculty of Engineering, Eskisehir, 26555, Turkey 6Sabancı University Nanotechnology Research and Application Center (SUNUM), Istanbul, 34956, Turkey 7Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, Istanbul, 34755, Turkey e-mail: [email protected]
Abstract Boron isotopes, 10B and 11B, are found in nature with approximate abundances of 19% and 81%, respectively. Boron occupies a biologically essential place for the growth of higher plants; it is also present in organisms such as animals and humans, but has not been determined to be essential [1, 2]. Boron and its derivatives are effective on bone recovery and osteointegration. However, increasing the boron levels in body liquids may cause toxicity. The aim of our study is to investigate serum boron levels using ICP-MS after implantation of different ratios of nano-hBN– HA composites in rat femurs. All rats (n=126) divided into five experimental groups (n=24) and one healthy group (6 rats); healthy (Group1), femoral defect + %100HA (Group2), femoral defect + %2.5hBN+%97.5HA (Group3), femoral defect + %5hBN+%95HA (Group4), femoral defect + %10hBN+%90 HA (Group5), femoral defect + %100hBN (Group6). The femoral defect was created in the distal femur (3 mm drill-bit). Each implant group was divided into four different groups (n=24) also 6 rats sacrificed for each groups in one week intervals during four weeks. In our results; at 1, 2, 3, and 4 weeks after implantation near bone tissue, serum levels of boron were evaluated using ICP-MS. We demonstrated that neither short-term nor long-term implantation of hBN–HA composite resulted in statistically increased serum boron levels in experimental groups compared to healthy group. In conclusion, this study investigated the implant material produced form hBN–HA for the first time. Our data suggest that hBN is a new promising target for biomaterial and implant bioengineers. References: [1] O. Reifschneider, C.L. Schutz, C. Brochhausen, G. Hampel, T. Ross, M. Sperling, U. Karst, Quantitative bioimaging of p-boronophenylalanine in thin liver tissue sections as a tool for treatment planning in boron neutron capture therapy, Anal Bioanal Chem, DOI 10.1007/s00216- 014-8012-4(2014). [2] A. Wittig, J. Michel, R.L. Moss, F. Stecher-Rasmussen, H.F. Arlinghaus, P. Bendel, P.L. Mauri, S. Altieri, R. Hilger, P.A. Salvadori, L. Menichetti, R. Zamenhof, W.A. Sauerwein, Boron analysis and boron imaging in biological materials for Boron Neutron Capture Therapy (BNCT), Crit Rev Oncol Hematol, 68 (2008) 66-90.
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Design, synthesis and evaluation of benzofuran-acetamide scaffold as potential anticonvulsant agent Ashok K. Shakya1,* Mehnaz Kamal2, Vishal M. Balaramnavar3, Sana’a K. Bardaweel4, 1 3 2 Rajashri R. Naik , Anil K. Saxena , H. H. Siddiqui
1Faculty of Pharmacy and Medical Sciences, Al-Ahliyya Amman University, Amman, 19328, Jordan; email: [email protected]; 2Faculty of Pharmacy, Integral University, Kursi Road, Lucknow 226026 (U. P.), India; email:[email protected]; 3Medicinal and Process Chemistry Division, Central Drug Research Institute, Lucknow-226001 (U. P.), India; email:[email protected]; 4Faculty of Pharmacy, The University of Jordan, Amman, Jordan; email: [email protected].
Abstract A series of N-(2-(benzoyl/4-chlorobenzoyl)-benzofuran-3-yl)-2-(substituted) acetamide derivatives (4-5 a-l) was synthesized in good yield and evaluated for possible anticonvulsant activity, neurotoxicity and acute toxicity studies. All the synthesized compounds were in agreement with elemental and spectral data. Majority of the compounds exhibited anticonvulsant activity at a dose of 30 mg/kg body weight at 0.5-4h interval; indicating their ability to prevent seizure spread at low doses. Relative to phenytoin, compound 5i (N-(2-(4- chlorobenzoyl)-benzofuran-3-yl)-2-(cyclohexyl(methyl)amino)-acetamide) and 5c (N-(2-(4- chlorobenzoyl)-benzofuran-3-yl)-2-(4-methylpiperidin-1-yl)acetamide) demonstrated comparable anticonvulsant potency of 0.74 and 0.72, respectively, whereas compound 5f ((N-(2-(4- chlorobenzoyl)-benzofuran-3-yl)-2-(4-(furan-2-carbonyl)-piperazin-1-yl) acetamide) exhibited the lowest relative potency of 0.16. The ALD50 of the test compounds were 681 mg/kg body weight. The ED50 of the synthesized compounds ranged from 0.055-0.259 mM (~23.4 to 127.6 mg/kg) body weight. Molecular modeling studies (Fig.1 a-c) suggest that these compounds have strong interaction with the GABA-AT which is responsible for the activity.
a b c
Fig. 1. Docking predicted poses and interactions between (a) compound 5c, (b) compound 5i and (c) Phenytoin, and amino acids in the active site of 4-aminobutyrate-aminotransferase (GABA-AT) (PDB code 1OHV). Acknowledgement
The authors are thankful to Dean, Faculty of Pharmacy and Medical Sciences, Amman 19328, Jordan and Dean, Faculty of Pharmacy, Integral University, Lucknow 226026 (U.P.), India for providing necessary facilities. Authors are also thankful to SAIF, CDRI, Lucknow, India and The University of Jordan, Amman, Jordan for elemental and spectral analyses.
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Index
Baldemir · 69 Çubuk · 69 A Baltaci · 85 Baradan · 32 Abdelhamid · 55 Bardaweel · 126 D Abdelhedi · 117, 118 BAY · 87 ACAR · 116 Bayramoglu · 89 Dalila · 55 Adibkia · 112, 113 Bazargan · 57 Daoud · 55 Adiguzel · 85 BEN DBIBIS M · 107 DEDEOĞLU · 33 Agar · 74, 75, 77, 78, 80, 81, 82, 83, BEN HADJ MOHAMED M · 107 Değim · 15 86 Benahmad M · 65 DEMİR · 62 AKIN · 97, 111 Berashvili · 49 Demirci · 119 Akkal S · 65 BERINDAN-NEAGOE · 47 Demirezer · 31 Akpinar · 90 BERKTAS · 122 Demirkan · 27 Aksu · 88 Bernkop-Schnürch · 39 Demirkaya Miloglu · 40, 98, 99, AKSU · 8 BEYTUR · 59 100 ALBAYRAK · 59 BEYTUT · 96 Dijoux-Franca M-G · 65 Alikhodjaeva M.I. · 91 Bikiaris · 123 Dilek · 76 ALKAN · 59 Boşgelmez · 69 DİNÇ · 24, 64 Altaani · 58 Bozhadze · 49 Divar · 63 Altınöz · 120 BOZKURT · 111 Djarri L · 65 Anar · 74, 75, 77, 78, 80, 81, 82, BRAICU · 47 DÖLEK · 70 83, 86, 110 Bryant · 10 Dursunoğlu · 41, 102 Anil · 84 Budak · 110 Arpa · 26 BUDAK · 111 Ascı · 108 BUĞA · 97 E AŞKIN · 87 Aslan · 77, 78, 82, 83, 89 Eken · 69 Asvadi · 37 C Ekinci · 92, 93, 94 ATALAY · 122 EL OUAR · 47 Atasever · 101, 106 Cadirci · 125 Ensafi · 17 ATICI · 36 Çağlar · 26 ERDOĞAN · 103, 121 ATILA · 124, 125 Çaglayan · 29 Erim · 22 Ay · 125 CAN · 111 Erkekoglu · 108 AYDIN · 70, 115, 116 ÇANKAYA · 111 EROL · 111 AYDOĞDU · 97 CANPOLAT · 97 ERTEKİN · 64 Aygül · 92, 93, 94 Çelebier · 120 ESEN · 97 AYGÜN · 115, 116 Çermik · 69 Esenbuga · 100 Ayromlou · 50 Cevher · 88 ESSADI R · 107 Azza · 117, 118 CEYLAN · 103, 121 CHAHED H · 107 Chekib-Arslane · 55 F B Cherkasova A.V. · 35 Ciftci · 110 Faghih · 56, 95 Bakan · 89, 90, 101, 106, 125 Çığır · 104, 105 FERCHICHI S · 107 Bakuridze · 49 Çil · 41, 102 Fereidoonnezhad · 56, 95 Balaramnavar · 126 CİVAŞ · 97 Flisjuk E.V · 35 Balbay · 12 ÇOBAN · 111 Balci · 108 ÇOLAK · 36
126
G K M
Gebisa · 73 KADIOGLU · 43, 44, 70, 124 Mangunwidjaja · 38 Genc · 85 Kalaycıoğlu · 22 Medjroubi K · 65 Godekli · 40 Kamal · 126 Meral · 80, 81 Gökdag · 74, 75 Kara · 41, 90, 102 MERAL · 116 Gözcü · 102 Karabiber · 84 MERCANTEPE · 111 GÖZCÜ · 70 Karadayı · 31 MILED A · 107 Gul · 89, 90 Karakus · 125 Miraghaec · 57 Gül · 28 KARAKUŞ · 121 Moawad · 54 Güler · 69 Karaoglu · 119 Mohammad · 58 Güllüce · 31 Karasulu · 26 Mohammed · 51, 73 Günaydın · 22 KARDAŞ · 59 Mojaddami · 56 Gunes · 89 KART · 96 Mshvildadz · 49 GÜRSOY-KOL · 59 Kasap · 84 Muhitdinov C · 91 Güvenalp · 31, 41, 102 Kavrakovski · 61, 66, 67, 68 GÜZELGÖZ · 97 Kazaz · 41 Khabnadideh · 63 N Khalafi-Nezhad · 95 H Khanfar · 58 Nadia · 117, 118 KHELIL S · 107 Naik · 126 Halici · 125 Khlifi L · 109 NAIMI · 47 HALICI · 111 KILBOZ · 48 Narkevich I.A. · 23, 35 Hamed · 54 KILIÇ · 70, 71, 72, 79, 97 Hasan · 38 Kilic Baygutalp · 89, 90, 101, 106 Hauptstein · 39 Kır · 120 O Hay AE · 65 Kirillova E.N · 23, 35 Hetta · 51, 54 Kizil · 77, 78, 82, 83 ODABASI · 70 Hind · 117, 118 KIZILTUNÇ ÖZMEN · 87 Odabasoglu · 122 Hosseinzadeh · 57 Koca · 84 Okur · 26 Koçak · 120 Onur ŞENOL · 43 Kocer Gumusel · 108 Oral · 108 I KORKMAZ · 79 ÖREN · 64 Koşar · 69 Osma · 104, 105 Ibis · 10 Koyuncu · 29 Owis · 51 İNAM · 62 KÜÇÜK TUNCA · 53 Özbek · 41 İnce · 104, 105 Kumbhat · 45 ÖZBEY · 111 Iqbal · 39 KUTLU · 122 ÖZÇELIK · 97 IRIMIE · 47 Özdoğan · 25 Islambulchilar · 37, 39, 50 Özer · 25 Ismail · 51, 54 L Ozgencli · 110 Özsoy · 88 Laffleur · 39 Ozturk · 89, 90, 101, 106 J Langer · 10 Ozyürek · 84 Laouer H · 65 Jabbalah A · 107 Latifa · 117, 118 Jahangiri · 112, 113 Lefahal M · 65 P Jana Simonovska · 67 leithner · 39 Javadirad · 57 Lilia · 55 Palabiyik · 125 Javed Ansari · 34 Polat · 89, 90, 101, 106 Jeridi · 117, 118 Polatdemir · 40, 99, 100 Jokhadze · 49 Popovska · 61, 66, 67, 68
127
R Souheyla · 55 W Söyüt · 92 SÖZGEN · 97 Rafajlovska · 61, 66, 67, 68 Wieder · 10 Sunar · 74, 75, 86 Reçber · 120 Sunarti · 38 Rezaei · 56, 95 SUNGUR · 48 Rixsibaeva M.O. · 91 Y Suparno · 38 Supuran · 76 Yaman · 108 S YAMAN · 44 T YAPAR · 9 Şahin · 13, 14 Yaşar · 52 SAHLI S · 109 YAŞAR · 97 TALAZ · 115 Şahne · 30 Yassin · 51 Tanrıverdi · 25 Salama · 51 Yeğen · 88 Tas · 99 Saliha · 55 Yeğenoğlu · 30 TİMİRLİ ZURNACI · 53 Salima · 117, 118 Yerdelen · 84 TLILI H · 107 Saruhan · 40, 98, 99, 100 Yildirim · 85 Tohma · 42 Sattari · 37, 50 Yıldızhan · 69 TOPRAK · 115 Saxena · 126 YILDIZTEKİN · 70 Trajkoska-Bojadziska · 61, 66, 67, Sayıt · 25 Yıldıztekin · 108 68 Schneider · 11 Yilmaz · 125 Türkoğlu · 104, 105 Seidel · 10 YILMAZ · 97, 124 Sengul · 86 Yılmaz · 52 SENOL · 44 U YÖNET · 97 Şentürk · 92, 93, 94 Yuca · 102 Setiyon · 38 Yücel · 69 ULUKOYLU · 53 Sevindik · 31, 102 YÜKSEK · 59 Ulutaş · 30 Sezen Karaoglan E · 114 YÜREKLİ · 79 Unal · 29 Shakya · 32, 126 YÜZGÜLLÜ · 97 Üstündağ Okur · 123 Shenkute · 73 Uzun · 99 Shokoohinia · 57 Siafaka · 123 Z Siddiqui · 126 V Simonovska · 61, 66, 68 Zaabat N · 65 Sisecioglu · 85 ZINE EL ABEDINE A · 107 Vachnadze · 49 SÖNMEZ · 97
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