DOCSLIB.ORG

Enzyme, Nitrogen, and DNA Concentrations Insarcoma 180

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Enzyme, Nitrogen, and DNA Concentrations Insarcoma 180 Enzyme, Nitrogen, and DNA Concentrations in Sarcoma 180 in Mice Treated with 6-Mercaptopurine* PAULJ. FODOR,DONALDA. CLARKE,ANDOSCARBODANSKY (Division (if Enzymology and Metabolism and Division of Experimental Chemotherapy, Sloan-Kettering Institute for Cancer Research; Department of Biochemistry, Memorial and James Ewing Hospitals; and Sloan-Kettering Divisiion of Cornell University Medical College,New York, N.Y.) SUMMARY The concentrations of homogenate-nitrogen, of DNA, and the activities of various nucleotidases, adenosine deaminase, cathepsin and lactic dehydrogenase have been studied in homogenates of Sarcoma 180 from non treated mice, from mice given injec tions of 6-carboxymethylcellulose in saline, and from mice treated with 6-mercapto- purine suspended in saline containing 6-carboxymethylcellulose. Statistically significant increases in the activities of all the nucleotidases, adenosine deaminase, and cathepsin have been observed in tumor homogenates of mice treated with 6-mercaptopurine. Statistically significant decreases in tumor weight, homo genate-nitrogen, DNA, and lactic dehydrogenase have been observed in the same homogenates. The tumor homogenates of the controls receiving 6-carboxymethylcellulose in saline showed only increases in adenosine deaminase and cathepsin which, however, did not reach the activity levels attained in homogenates of mice treated with 6-mercapto purine. The significance of the findings is discussed. Although the enzymic patterns of tumor growth lism of the regressing tumors (8-10). Within the have been the subject of many investigations (13), past few years the effects of the administration of the processes of regression or arrested growth, alpha peltatin (26), acetylpodophyllotoxin deriva whether spontaneous or induced by chemotherapy, tives (27), chloroethylamine derivatives (11), have received relatively little attention. The study ethyleneimine derivatives (15-18), colchicine (1), of most spontaneously regressing tumors is fraught and of 6-mercaptopurine (21) on glucose utiliza with technical difficulties, since the number of tion, over-all glycolysis, DPN content, and a few such regressions is usually unpredictable, thus other metabolic aspects have been investigated. making unavailable sufficient material for system Among the chemotherapeutic agents studied so atic investigations. Studies on the spontaneously far in their effect on tumor metabolism, 6-mercap regressing Flexner-Jobling carcinoma, which shows topurine occupies an important position because spontaneous regression in about 35 per cent of all of its growth-inhibitory effect on both human and transplants, revealed definite changes in the en- animal tumors (22) with relatively few toxic side zymic pattern and, consequently, in the metabo- effects (4). * This work has been supported in part by the following to This study is the first of a series in which a O.S.: American Cancer Society Grants P-168 and P-164B, systematic effort will be made to elucidate the (irant DRG 332D from the Damon Runyon Memorial Fund metabolic changes induced in tumors by adminis for Cancer Research, and (irant C-4251 (C2S1), from the Na tration of 6-mercaptopurine to the host. Sarcoma tional Cancer Institute, National Institutes of Health, Public Health Service; and to D.A.C. :American Cancer Society Grant 180 has been chosen as the experimental tumor, T-2aB, and Contract SA-43-ph-2445 from The Cancer Chemo since its histology is well known, treatment of the therapy National Service Center, National Cancer Institute, host with 6-mercaptopurine induces no necrosis in National Institutes of Health, U.S. Public Health Service. the tumor, nor do tumors of nontreated hosts con Received for publication August 15, 1960. tain necrotic portions, provided they are collected 232 Downloaded from cancerres.aacrjournals.org on September 30, 2021. © 1961 American Association for Cancer Research. FoDOR et al.—Sarcoma 180 and 6-Mercaptopurine 233 not later than the 9th day after transplanta tumors that were removed between the 4th tion (5).1 and 5th day after implantation. The average weight of these younger tumors approximated that MATERIALS AND METHODS of the tumors from the 6-MP-treated mice at the Randomly selected female Swiss albino mice end of 7 days of treatment. The younger tumors (HalCR)2 weighing between 18 and 29 gm. served were studied to assess the influence of tumor as experimental animals and also as carriers of the weight on the various parameters. tumor line. The tumor line was maintained by bi Preparation of tumors homogenates.—The ani lateral implantation of tumor fragments of equal mals were killed by cervical dislocation: the tu size; the site of implantation was the subcutaneous mors were excised, weighed, washed briefly in ice- ventro-lateral region of the host mice. It was cus cold saline, and dissected to remove macroscopi- tomary to harvest these tumors on the 7th day cally visible blood vessels. The tumor slices were after implantation. Twenty-six fragments, each again briefly washed in saline, freed quickly from approximately 5 mg. wet weight, were regularly any adhering moisture by being pressed between prepared from one tumor and transplanted into filter paper, weighed on a torsion balance to with the right ventro-lateral region of as many animals. in 1 mg., and immediately transferred to glass Thirteen of the tumor-bearing mice received homogenizing tubes immersed in crushed ice. daily treatment with 6-MP for 7 successive days, Homogenization was effected in saline in a poly- beginning at 24 hours after tumor implantation tetrafluoroethylene (Teflon) homogenizer. The (Group 3). The daily dose was 75 mg/kg of body time required for homogenization did not exceed weight, suspended in 1.0 ml. of saline containing 1 minute. The homogenates were then filtered 0.5 per cent of CMC.3 This dose was divided into through a thin layer of glass wool to remove 2 parts of 0.5 ml.; one was injected regularly in macroscopicaJly visible pieces of nonhomogeniz- the morning of each day and the other 7-8 hours able material, mostly connective tissue.4 The ho later. A second group of thirteen mice (Group 2), mogeneity of the filtrates was ascertained by the serving as controls to the 6-MP-treated group, re fact that aliquots were found to contain equal ceived comparable injections of CMC in saline amounts of nitrogen estimated as described below. only. The tumors from all mice were harvested The time lapse between homogenization and incu regularly between the 7th and 9th day following bation with the substrate was not allowed to ex implantation. Three tumors from each group were ceed 15 minutes. selected at random for histologie examination; the Assay of enzyme activity.—Catheptic activity remainder were employed for the biochemical as was estimated by determination of tyrosine as sessments of the present study. Another control sayed in the NPN fraction after incubation of the group consisted of mice given implants of tumor. homogenates with a preparation of purified horse These mice received no injections of any kind blood hemoglobin. The method of assay and the (Group 1). These animals were also sacrificed preparation of the hemoglobin solution have been between the 7th and 9th day after implanta described (8). Two ml. of hemoglobin were mixed tion and their tumors removed to ascertain with 2 ml. of acetate buffer, pH 3.5, and 1 ml. of that the various parameters under study did homogenate was added. The incubation time was not vary significantly from normal values es 15 minutes for homogenates of Groups 2 and 3 and tablished for Sarcoma 180 as a preliminary was extended to 30 minutes for those of Group 1 study to the present one. A final control group and la. Homogenates were prepared of 1 part tis (Group la) consisted of nontreated mice with sue (wet weight) and 30 volumes of saline. 'The following abbreviations will be used: 6-MP for 6- Determination of A TPase.—ATPase was de mercaptopurine; CMC for 6-carboxymethylcellulose; ATP termined as previously described (9), but EDTA and ATPase, respectively, for adenosine triphosphate and was added to a final concentration of 0.001 M,and adenosine triphosphatase; DNA for deoxyribonucleic acid; the MgCl2 concentration increased to 0.2 ml. NPX for nonprotein nitrogen; homogenate-N for homogenate nitrogen; P¡for orthophosphate; EDTA for ethylendiamino- of a 0.0984 M solution in a total of 3.2 ml. of tetraacetic acid. The term "CMC-treated" implies I.P. injec reaction mixture.6 Homogenates were prepared of tions of 6-carboxyinethylcellulose in saline; the term "6-MP- 1It was not possible to prepare stable dispersions of the treated" indicates that the mice received I.P. injections of tumor connective tissue; treatment of the tissue in an ultra 6-mercaptopurine in saline containing 6-carboxymethylcellu sonic disintegrator at maximum number of oscillations for 45 lose. minutes, (M.S.E. Ultrasonic Disintegrator, Measuring & 2Millerton Research Farm, Inc. Scientific Equipment, Ltd.) resulted only in coarse, unstable 36-MP in the dose administered is insoluble at, or near, suspensions. neutrality. CMC has been used to stabilize the finely dispersed *In all instances where EDTA was added the optimum suspensions of the compound. "concentration was established. Downloaded from cancerres.aacrjournals.org on September 30, 2021. © 1961 American Association for Cancer Research. 234 Cancer Research Vol. 21, February 1961 1 part tissue (wet weight) in 40 volumes of saline. concentration has been expressed as /ig DNA/ml Determination of adenosine-o'-phosphatase,— of glass wool-filtered homogenate.6 Adenosine-5'-phosphatase was determined by as Determination of nitrogen.—Nitrogen was as say of the PÃŒliberated in a mixture consisting of sayed in aliquots of the glass wool-filtered ho- 20 Amólesof adenosine-5'-phosphoric acid (Sigma) mogenates used for enzyme assays by micro- disolved in 0.6 ml. of water and adjusted to pH digestion with sulfuric acid and HjOs followed by 7.5; 1.20 ml. of 0.038 M diethyl barbiturate buffer, nesslerization of aliquots.
Load more

Recommended publications
  • (12) United States Patent (10) Patent No.: US 8,993,581 B2 Perrine Et Al
    US00899.3581B2 (12) United States Patent (10) Patent No.: US 8,993,581 B2 Perrine et al. (45) Date of Patent: Mar. 31, 2015 (54) METHODS FOR TREATINGVIRAL (58) Field of Classification Search DSORDERS CPC ... A61K 31/00; A61K 31/166; A61K 31/185: A61K 31/233; A61K 31/522: A61K 38/12: (71) Applicant: Trustees of Boston University, Boston, A61K 38/15: A61K 45/06 MA (US) USPC ........... 514/263.38, 21.1, 557, 565, 575, 617; 424/2011 (72) Inventors: Susan Perrine, Weston, MA (US); Douglas Faller, Weston, MA (US) See application file for complete search history. (73) Assignee: Trustees of Boston University, Boston, (56) References Cited MA (US) U.S. PATENT DOCUMENTS (*) Notice: Subject to any disclaimer, the term of this 3,471,513 A 10, 1969 Chinn et al. patent is extended or adjusted under 35 3,904,612 A 9/1975 Nagasawa et al. U.S.C. 154(b) by 0 days. (Continued) (21) Appl. No.: 13/915,092 FOREIGN PATENT DOCUMENTS (22) Filed: Jun. 11, 2013 CA 1209037 A 8, 1986 CA 2303268 A1 4f1995 (65) Prior Publication Data (Continued) US 2014/OO45774 A1 Feb. 13, 2014 OTHER PUBLICATIONS Related U.S. Application Data (63) Continuation of application No. 12/890,042, filed on PCT/US 10/59584 Search Report and Written Opinion mailed Feb. Sep. 24, 2010, now abandoned. 11, 2011. (Continued) (60) Provisional application No. 61/245,529, filed on Sep. 24, 2009, provisional application No. 61/295,663, filed on Jan. 15, 2010. Primary Examiner — Savitha Rao (74) Attorney, Agent, or Firm — Nixon Peabody LLP (51) Int.
    [Show full text]
  • Review of Sezary Syndrome
    REVIEWS Sezary syndrome: Immunopathogenesis, literature review of therapeutic options, and recommendations for therapy by the United States Cutaneous Lymphoma Consortium (USCLC) EliseA.Olsen,MD,a Alain H. Rook, MD,b John Zic, MD,c Youn Kim, MD,d PierluigiPorcu,MD,e Christiane Querfeld, MD,f Gary Wood, MD,g Marie-France Demierre, MD,h Mark Pittelkow, MD,i Lynn D. Wilson, MD, MPH,j Lauren Pinter-Brown, MD,k Ranjana Advani, MD,d Sareeta Parker, MD,l Ellen J. Kim, MD,b Jacqueline M. Junkins-Hopkins, MD,m Francine Foss, MD,j Patrick Cacchio, BS,a and Madeleine Duvic, MDn Durham, North Carolina; Philadelphia, Pennsylvania; Nashville, Tennessee; Palo Alto and Los Angeles, California; Columbus, Ohio; Chicago, Illinois;Madison,Wisconsin;Boston,Massachusetts; Rochester, Minnesota; New Haven, Connecticut; Atlanta, Georgia; Baltimore, Maryland; and Houston, Texas Sezary syndrome (SS) has a poor prognosis and few guidelines for optimizing therapy. The US Cutaneous Lymphoma Consortium, to improve clinical care of patients with SS and encourage controlled clinical trials of promising treatments, undertook a review of the published literature on therapeutic options for SS. An overview of the immunopathogenesis and standardized review of potential current treatment options for SS including metabolism, mechanism of action, overall efficacy in mycosis fungoides and SS, and common or concerning adverse effects is first discussed. The specific efficacy of each treatment for SS, both as monotherapy and combination therapy, is then reported using standardized criteria for both SS and response to therapy with the type of study defined by a modification of the US Preventive Services guidelines for evidence-based medicine.
    [Show full text]
  • The Phytochemistry of Cherokee Aromatic Medicinal Plants
    medicines Review The Phytochemistry of Cherokee Aromatic Medicinal Plants William N. Setzer 1,2 1 Department of Chemistry, University of Alabama in Huntsville, Huntsville, AL 35899, USA; [email protected]; Tel.: +1-256-824-6519 2 Aromatic Plant Research Center, 230 N 1200 E, Suite 102, Lehi, UT 84043, USA Received: 25 October 2018; Accepted: 8 November 2018; Published: 12 November 2018 Abstract: Background: Native Americans have had a rich ethnobotanical heritage for treating diseases, ailments, and injuries. Cherokee traditional medicine has provided numerous aromatic and medicinal plants that not only were used by the Cherokee people, but were also adopted for use by European settlers in North America. Methods: The aim of this review was to examine the Cherokee ethnobotanical literature and the published phytochemical investigations on Cherokee medicinal plants and to correlate phytochemical constituents with traditional uses and biological activities. Results: Several Cherokee medicinal plants are still in use today as herbal medicines, including, for example, yarrow (Achillea millefolium), black cohosh (Cimicifuga racemosa), American ginseng (Panax quinquefolius), and blue skullcap (Scutellaria lateriflora). This review presents a summary of the traditional uses, phytochemical constituents, and biological activities of Cherokee aromatic and medicinal plants. Conclusions: The list is not complete, however, as there is still much work needed in phytochemical investigation and pharmacological evaluation of many traditional herbal medicines. Keywords: Cherokee; Native American; traditional herbal medicine; chemical constituents; pharmacology 1. Introduction Natural products have been an important source of medicinal agents throughout history and modern medicine continues to rely on traditional knowledge for treatment of human maladies [1]. Traditional medicines such as Traditional Chinese Medicine [2], Ayurvedic [3], and medicinal plants from Latin America [4] have proven to be rich resources of biologically active compounds and potential new drugs.
    [Show full text]
  • View/Download
    Research Article Research Article Dermatology Research Therapy with Pegylated Interferon or Combined with Cryosurgery in Condyloma Acuminata. Phase III Clinical Trial Israel Alfonso Trujillo*, Tomás Tabilo Bocic, Ángela Rosa Gutiérrez Rojas, Hugo Nodarse Cuní, María Elena Flores Andrade, and María del Carmen Toledo García *Correspondence: Israel Alfonso-Trujillo, Calzada of Managua # 1133 e/Caimán and Quemados. Las Guásimas. Arroyo Naranjo, Havana, Cuba, E-mail: Surgical Clinical Hospital: "Hermanos Ameijeiras", Cuba. [email protected] Received: 04 January 2019; Accepted: 18 February 2019 Citation: Israel Alfonso Trujillo, Tomás Tabilo Bocic, Ángela Rosa Gutiérrez Rojas, et al. Therapy with Pegylated Interferon or Combined with Cryosurgery in Condyloma Acuminata. Phase III Clinical Trial. Dermatol Res. 2019; 1(1); 1-8. ABSTRACT Background: The continuous recurrence of condyloma acuminata makes the constant search for necessary therapeutic alternatives. Patients and method: To evaluate the therapeutic efficacy and safety of pegylated interferon, alone or adjuvant for cryosurgery, in the condyloma acuminata an open clinical trial was carried out on 30 patients of the "Hermanos Ameijeiras" hospital, who were randomized to receive for 6 weeks (group A) only fortnightly cryosurgery, (group B) subcutaneous pegylated interferon, once a week, associated with fortnightly cryosurgery application or (group C) only subcutaneous pegylated interferon, once a week. The main variable was the percentage of recurrence at one year of follow-up, evaluated quarterly. There was also a rigorous control of adverse events. Results: At the end of the treatment 8/10 (80%) patients from group A, 10/10 (100%) from group B and 9/10 (90%) from group C were left without injuries.
    [Show full text]
  • Belayachi Et Al., Afr J Tradit Complement Altern Med. (2017) 14(2):356-373 Doi:10.21010/Ajtcam.V14i2.37
    Belayachi et al., Afr J Tradit Complement Altern Med. (2017) 14(2):356-373 doi:10.21010/ajtcam.v14i2.37 INDUCTION OF CELL CYCLE ARREST AND APOPTOSIS BY ORMENIS ERIOLEPIS A MORROCAN ENDEMIC PLANT IN VARIOUS HUMAN CANCER CELL LINES Lamiae Belayachia,b*, Clara Aceves-Luquerob, Nawel Merghoubd, Silvia Fernández de Mattosb,c, Saaïd a b,c a Amzazi , Priam Villalonga ,Youssef Bakri a Biochemistry-Immunology Laboratory, Faculty of Sciences, Mohammed V-Agdal University, Rabat, Morocco, b Cancer Cell Biology Group, Institut Universitari d’Investigació en Ciències de la Salut (IUNICS), c Departament de Biologia Fonamental, Universitat de les Illes Balears, Illes Balears, Spain, Green Biotechnology Center. MAScIR (Moroccan Foundation for Advanced Science, Innovation & Research)- Rabat Design Center, Rabat - Morocco. *Corresponding author E-mail: [email protected] Abstract Background: Ormenis eriolepis Coss (Asteraceae) is an endemic Moroccan subspecies, traditionally named “Hellala” or “Fergoga”. It’s usually used for its hypoglycemic effect as well as for the treatment of stomacal pain. As far as we know, there is no scientific exploration of anti tumoral activity of Ormenis eriolepis extracts. Materials and Methods: In this regard, we performed a screening of organic extracts and fractions in a panel of both hematological and solid cancer cell lines, to evaluate the potential in vitro anti tumoral activity and to elucidate the respective mechanisms that may be responsible for growth arrest and cell death induction. The plant was extracted using organic solvents, and four different extracts were screened on Jurkat, Jeko-1, TK-6, LN229, SW620, U2OS, PC-3 and NIH3T3 cells. Results: Cell viability assays revealed that, the IC50 values were (11,63±5,37µg/ml) for Jurkat, (13,33±1,67µg/ml) for Jeko-1, (41,67±1,98µg/ml) for LN229 and (19,31±4,88µg/ml) for PC-3 cells upon treatment with Oe-DF and Oe-HE respectively.
    [Show full text]
  • Estonian Statistics on Medicines 2016 1/41
    Estonian Statistics on Medicines 2016 ATC code ATC group / Active substance (rout of admin.) Quantity sold Unit DDD Unit DDD/1000/ day A ALIMENTARY TRACT AND METABOLISM 167,8985 A01 STOMATOLOGICAL PREPARATIONS 0,0738 A01A STOMATOLOGICAL PREPARATIONS 0,0738 A01AB Antiinfectives and antiseptics for local oral treatment 0,0738 A01AB09 Miconazole (O) 7088 g 0,2 g 0,0738 A01AB12 Hexetidine (O) 1951200 ml A01AB81 Neomycin+ Benzocaine (dental) 30200 pieces A01AB82 Demeclocycline+ Triamcinolone (dental) 680 g A01AC Corticosteroids for local oral treatment A01AC81 Dexamethasone+ Thymol (dental) 3094 ml A01AD Other agents for local oral treatment A01AD80 Lidocaine+ Cetylpyridinium chloride (gingival) 227150 g A01AD81 Lidocaine+ Cetrimide (O) 30900 g A01AD82 Choline salicylate (O) 864720 pieces A01AD83 Lidocaine+ Chamomille extract (O) 370080 g A01AD90 Lidocaine+ Paraformaldehyde (dental) 405 g A02 DRUGS FOR ACID RELATED DISORDERS 47,1312 A02A ANTACIDS 1,0133 Combinations and complexes of aluminium, calcium and A02AD 1,0133 magnesium compounds A02AD81 Aluminium hydroxide+ Magnesium hydroxide (O) 811120 pieces 10 pieces 0,1689 A02AD81 Aluminium hydroxide+ Magnesium hydroxide (O) 3101974 ml 50 ml 0,1292 A02AD83 Calcium carbonate+ Magnesium carbonate (O) 3434232 pieces 10 pieces 0,7152 DRUGS FOR PEPTIC ULCER AND GASTRO- A02B 46,1179 OESOPHAGEAL REFLUX DISEASE (GORD) A02BA H2-receptor antagonists 2,3855 A02BA02 Ranitidine (O) 340327,5 g 0,3 g 2,3624 A02BA02 Ranitidine (P) 3318,25 g 0,3 g 0,0230 A02BC Proton pump inhibitors 43,7324 A02BC01 Omeprazole
    [Show full text]
  • Triterpenoid–PEG Ribbons Targeting Selectivity in Pharmacological Effects
    biomedicines Article Triterpenoid–PEG Ribbons Targeting Selectivity in Pharmacological Effects Zulal Özdemir 1,2,† , Uladzimir Bildziukevich 1,2,†, Martina Capkovˇ á 1,† , Petra Lovecká 3, Lucie Rárová 4,‡ , David Šaman 5, Michala Zgarbová 5,‡, Barbora Lapuníková 5,‡, Jan Weber 5, Oxana Kazakova 6 and ZdenˇekWimmer 1,2,* 1 Department of Chemistry of Natural Compounds, University of Chemistry and Technology in Prague, Technická 5, 16628 Prague 6, Czech Republic; [email protected] (Z.Ö.); [email protected] (U.B.); [email protected] (M.C.)ˇ 2 Isotope Laboratory, Institute of Experimental Botany of the Czech Academy of Sciences, Vídeˇnská 1083, 14220 Prague 4, Czech Republic 3 Department of Biochemistry and Microbiology, University of Chemistry and Technology in Prague, Technická 5, 16628 Prague 6, Czech Republic; [email protected] 4 Department of Experimental Biology, Faculty of Science, Palacký University, Šlechtitel ˚u27, 78371 Olomouc, Czech Republic; [email protected] 5 Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo námˇestí 2, 16610 Prague 6, Czech Republic; [email protected] (D.Š.); [email protected] (M.Z.); [email protected] (B.L.); [email protected] (J.W.) 6 Ufa Institute of Chemistry of the Ufa Federal Research Centre of the Russian Academy of Sciences, 71, pr. Oktyabrya, 450054 Ufa, Russia; [email protected] * Correspondence: [email protected] or [email protected] † Z.Ö., U.B. and M.C.ˇ contributed equally. Citation: Özdemir, Z.; Bildziukevich, ‡ L.R., cytotoxicity screening tests; M.Z. and B.L., antiviral tests. U.; Capková,ˇ M.; Lovecká, P.; Rárová, L.; Šaman, D.; Zgarbová, M.; Abstract: (1) Background: To compare the effect of selected triterpenoids with their structurally Lapuníková, B.; Weber, J.; Kazakova, resembling derivatives, designing of the molecular ribbons was targeted to develop compounds with O.; et al.
    [Show full text]
  • Mohformulary Drug List Table of Content
    MOHFormulary Drug List Table of Content Introdaction Message of Minister of Health ...................................................................5 Deputy Minister of Health for Supply and Engineering Affairs ..............7 Use of Formulary ........................................................................................9 Drug Control Policies and Guidelines .....................................................10 Reporting of Adverse Drug Reaction (ADR) Policy ................................20 Medication Error Policy ............................................................................26 Drug Product Quality Reporting Policy ...................................................43 New Changes and Addition to The Formulary ........................................46 Deleted Items .............................................................................................48 Crash Cart Drugs for Pediatrics ...............................................................50 Crash Cart Medication to Maintain Cardiac Output and for Post Resuscitation Stabilization for Pediatric .................................................51 Crash Cart Drugs for Adults .....................................................................51 Adults Supplementary Drugs (Available in The Ward) .........................53 Therapeutic Listing of Drugs ....................................................................54 Drugs used as Antidotes..........................................................................143 Primary Health Care Centers
    [Show full text]
  • Virus-Host Interactomics: New Insights and Opportunities for Antiviral Drug Discovery
    de Chassey et al. Genome Medicine 2014, 6:115 http://genomemedicine.com/content/6/11/115 REVIEW Virus-host interactomics: new insights and opportunities for antiviral drug discovery Benoît de Chassey1, Laurène Meyniel-Schicklin1, Jacky Vonderscher1, Patrice André2,3,4 and Vincent Lotteau3,4* Abstract The current therapeutic arsenal against viral infections remains limited, with often poor efficacy and incomplete coverage, and appears inadequate to face the emergence of drug resistance. Our understanding of viral biology and pathophysiology and our ability to develop a more effective antiviral arsenal would greatly benefit from a more comprehensive picture of the events that lead to viral replication and associated symptoms. Towards this goal, the construction of virus-host interactomes is instrumental, mainly relying on the assumption that a viral infection at the cellular level can be viewed as a number of perturbations introduced into the host protein network when viral proteins make new connections and disrupt existing ones. Here, we review advances in interactomic approaches for viral infections, focusing on high-throughput screening (HTS) technologies and on the generation of high-quality datasets. We show how these are already beginning to offer intriguing perspectives in terms of virus-host cell biology and the control of cellular functions, and we conclude by offering a summary of the current situation regarding the potential development of host-oriented antiviral therapeutics. Introduction the virus life-cycle. These proteins
    [Show full text]
  • The Anti-Cancer Properties of Podophyllotoxin Analogues
    The Anti-cancer Properties of Podophyllotoxin Analogues By Francisco Oliva A thesis submitted in partial fulfillment of the requirements for the Master of Science Biological Sciences Program Youngstown State University December 2019 The Anti-cancer Properties of Podophyllotoxin Analogues Francisco Oliva I hereby release this thesis to the public. I understand that this thesis will be made available from the OhioLINK ETD Center and the Maag Library Circulation Desk for public access. I also authorize the University or other individuals to make copies of this thesis as needed for scholarly research. Signature: Francisco Oliva Student Date Approvals: Dr. Gary R. Walker Thesis Advisor Date Dr. Séverine Van slambrouck Thesis Committee Date Dr. Wim Steelant Thesis Committee Date Dr. Salvatore Sanders Dean of Graduate Studies Date Abstract Cancer is one of the major causes of death in the United States resulting in over 20% of annual deaths. Over the last decade the interest of natural products derived from medicinal plants as potential sources of new anti-cancer drugs has increased greatly. Now, the critical role of medicinal plants through the discovery of their ‘mechanisms of action’ is being widely recognized in the biomedical and pharmaceutical industry. Podophyllotoxin has been extensively used as a lead agent in the development of new anticancer drugs. This study focused on the screening of several podophyllotoxin analogues to determine their effects on cell viability, the induction of apoptosis and cell cycle control on A549, MCF7, Jurkat, MDA-MB-231, and SK-Mel-21 cells. Several of the podophyllotoxin analogues, such as compounds 5.2 were shown to have a potent effect on cell viability, especially on Jurkat T cell Leukemia cells.
    [Show full text]
  • The Management of Diycult Anogenital Warts
    192 Sex Transm Inf 1999;75:192–194 The management of diYcult anogenital warts Clinical Sex Transm Infect: first published as 10.1136/sti.75.3.192 on 1 June 1999. Downloaded from A McMillan knots Patients with anogenital warts present the extensive and persistent. As regression often healthcare professional with two major occurs within several weeks of delivery, treat- problems—recurrence and persistence. These ment is usually unnecessary. Occasionally, problems occur because of persistence of however, the warts cause discomfort, and these human papillomavirus in keratinocytes, defec- may be treated with cryotherapy or trichloro- tive immune responses in individuals with per- ethanoic acid (TCA). Conventional therapy is sistence and recurrence of warts, and the lack not uniformly successful in the treatment of of specific antiviral therapy. warts in the immunocompromised patient, In this article, the discussion will be confined including HIV infected individuals, and immu- to the management of lesions visible to the notherapy is generally unsatisfactory; it is not, naked eye and a scheme of management that I however, the purpose of this article to discuss have found useful is shown in figure 1. this issue further. The hyperplastic condylomata acuminata In deciding on treatment of persistent that have been present for less than 3 months, lesions, it is worth considering the following: often clear quickly after treatment with podo- Size and number of the lesions—Many indi- phyllin, podophyllotoxin, or cryotherapy. Podo- viduals have a few warts that are less than 1 mm phyllotoxin appears to be more eVective than in diameter and reassurance that spontaneous podophyllin in clearing warts and it has the regression will eventually occur, together with added advantage that the patient can apply it.
    [Show full text]
  • SEXUALLY TRANSMITTED INFECTIONS GUIDANCE GENERAL POINTS • This Guidance Appli Es to ADULT Pati Ents ONLY • STOP and Think Before You Prescribe Antibiotics
    SEXUALLY TRANSMITTED INFECTIONS GUIDANCE GENERAL POINTS • This guidance appli es to ADULT pati ents ONLY • STOP and think before you prescribe antibiotics. Does your patient actually have an infection that requires treatment? • Normal renal and hepatic function assumed – adj us t dos es i f necessary. • For pregnant patients refer to Pr egna nc y a nd Pos tna tal Antibi oti c Woman • For all other infections refer to Hospital Antibiotic Man or Primary Care Antibiotic Man or Antibiotic Website • Refer to Mi croMan for ‘Anti biotic Rul es of Thumb’ and basic mi crobi ol ogy i nformati on on common infecti ons • Guidance on taking sexual history, testing and referral criteria is available in TSRH Primary Care Guidance p4 (add link) Chlamydia (uncomplicated) Doxycycline 100mg bd (7 days). If intolerant: azithromycin 1g od day 1 then 500mg od for 2 days Gonorrhoea Refer to Sexual and Reproductive Health Service. If patient will not attend contact TSRH team for advice. Gonorrhoea (sexual contacts) A full sexual health screen should be offered but antimicrobial treatment should not be prescribed without testing. Antimicrobial resistance is very high. Vulvovaginal candidiasis Fluconazole 150mg as a single dose plus clotrimazole 1% cream 2-3 times daily or Clotrimazole 500mg FEMALE pessary stat plus clotrimazole 1% cream 2-3 times daily Recurrent : >4 episodes/year - send HVS ma rke d “re cu rrent thrush” to microbiology and consider referral to Genito-Urinary Medicine if need advice on further management. Exclude predisposing factors. Bacterial
    [Show full text]