The Antimycobacterial Activity of Hypericum Perforatum Herb and the Effects of Surfactants

Total Page:16

File Type:pdf, Size:1020Kb

The Antimycobacterial Activity of Hypericum Perforatum Herb and the Effects of Surfactants Utah State University DigitalCommons@USU All Graduate Theses and Dissertations Graduate Studies 8-2012 The Antimycobacterial Activity of Hypericum perforatum Herb and the Effects of Surfactants Shujie Shen Utah State University Follow this and additional works at: https://digitalcommons.usu.edu/etd Part of the Engineering Commons Recommended Citation Shen, Shujie, "The Antimycobacterial Activity of Hypericum perforatum Herb and the Effects of Surfactants" (2012). All Graduate Theses and Dissertations. 1322. https://digitalcommons.usu.edu/etd/1322 This Thesis is brought to you for free and open access by the Graduate Studies at DigitalCommons@USU. It has been accepted for inclusion in All Graduate Theses and Dissertations by an authorized administrator of DigitalCommons@USU. For more information, please contact [email protected]. i THE ANTIMYCOBACTERIAL ACTIVITY OF HYPERICUM PERFORATUM HERB AND THE EFFECTS OF SURFACTANTS by Shujie Shen A thesis submitted in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE in Biological Engineering Approved: Charles D. Miller, PhD Ronald C. Sims, PhD Major Professor Committee Member Marie K. Walsh, PhD Mark R. McLellan, PhD Committee Member Vice President for Research and Dean of the School of Graduate Studies UTAH STATE UNIVERSITY Logan, Utah 2012 ii Copyright © Shujie Shen 2012 All Rights Reserved iii ABSTRACT The Antimycobacterial Activity of Hypericum perforatum Herb and the Effects of Surfactants by Shujie Shen, Master of Science Utah State University, 2012 Major Professor: Dr. Charles D. Miller Department: Biological Engineering Due to the essential demands for novel anti-tuberculosis treatments for global tuberculosis control, this research investigated the antimycobacterial activity of Hypericum perforatum herb (commonly known as St. John’s wort, SJW), including a SJW methanol extract, purified major bioactive constituents of SJW: hypericin (Hpn), pseudohypericin (Phn) and hyperforin (Hfn). The SJW acidified methanol extract showed bactericidal activity against Mycobacterium JLS at 0.05 mg/ml culture. Purified compounds were tested at similar concentrations contained in the SJW methanol extract treatment. Among three purified bioactive compounds, only Hfn was bactericidal at 12 µg/ml. The other two compounds Phn and Hpn were not inhibitory or bactericidal at concentrations corresponding to the SJW methanol extract treatments. iv The Polysorbate surfactant Tween 80, which is commonly added to the mycobacterial cultures to prevent cell clumping, was found to have inhibitory effects on the antimycobacterial activities of SJW extract and hyperforin. The addition of Tween 80 (0.05% v/v) increased the minimum bactericidal concentration (MIC) of SJW methanol extract from 0.05 to 0.33mg /ml and from 12 to 80 µg/ml for Hfn. This inhibitory effect of Tween 80 on SJW is opposite to the effect of Tween 80 on the antimycobacterial activity of rifampin and isoniazid. These observations are also in conflict with the existing permeability barrier hypothesis. A hypothesis that hyperforin molecules were sequestered in the core of Tween 80 micelles was given out to explain the repression effect of Tween 80 on hyperforin activity. The effectiveness of Tween 60, Tween 40 and Tween 20 on SJW activity was also tested. Tween 60 and Tween 40 showed the similar dose-dependent inhibitory effect on SJW extract activity with Tween 80, while the inhibitory effect of Tween 20 is much weaker. A preliminary test was performed to detect the activity of SJW acidified MeOH extract and hyperforin on M. tuberculosis H37Rv strain. Results showed the MIC was 0.67mg SJW extract/ml and 200 µg Hfn /ml. In all, M. tuberculosis H37Rv stain is not that sensitive to SJW and hyperforin as other non-pathogenic strains tested in the present and previous studies. (95 pages) v PUBLIC ABSTRACT The Antimycobacterial Activity of Hypericum Perforatum Herb and the Effects of Surfactants Shujie Shen Tuberculosis is a stubborn and lethal infectious disease. The world-wide tuberculosis surveillance reports that the new TB cases ranges from seven to eight million per year and deaths ranges from 1.3 to 1.6 million every year. The treatment of tuberculosis mainly depends on antituberculosis drugs, such as isoniazid, rifampin, pyrazinamide and ethambutol. However, drug-resistance acquisition is an inevitable process during tuberculosis treatment. Today, multi-drug resistant and the extensively drug-resistant TB cases have been widely reported around the world. Thus, the discovery of novel antituberculosis drugs is essential to effective TB treatment. Hypericum perforatum, also called St. John’s Wort, is a perennial herb. This research investigated St. John’s Wort’s potential use as an antituberculosis drug. In this study, we demonstrated the effectiveness of St. John’s wort methanol extract and three main bioactive constitutes against mycobacterial strains, including Mycobacterial tuberculosis, which is the pathogenic bacteria causing tuberculosis. We also investigated the effect of surfactants, which are commonly used in pharmaceutical and food industry, on the activity of St. John’s. The results of this study offer substantial information on the antituberculosis potential of St. John’s Wort. vi ACKNOWLEDGMENTS This project would not have been performed successfully without the support from faculty and staff of the Biological Engineering Department. I would like to express my gratitude to all of them. Particularly, I would like to thank my advisor, Dr. Charles Miller, for the continuous support to my M.S. study and research, for his patience, motivation, enthusiasm and immense knowledge, and for his sincere encouragement. Besides my advisor, I would like to thank my thesis committee, Dr. Ronald Sims and Dr. Marie Walsh, who helped me a lot and gave me a lot of useful suggestions with this project. I also would like to thank the previous master student, Trent W. Mortensen, whose previous research work greatly contributed to the development of this project. I would also like to thank my fellow labmates, for all the favors they did for me and for all the fun we had in the past three years. At last, I would like to thank my family, whose support and encouragement made this possible. Shujie Shen vii CONTENTS Page ABSTRACT…………………….……………………………………………………. iii PUBLIC ABSTRACT………………………………………………………………… v ACKNOWLEDGMENTS…………………………………………………………… vi LIST OF TABLES…………………………………………………………………… ix LIST OF FIGURES…………………………………………………………………… x LIST OF ABBREVIATIONS……………………………………………………….. xii CHAPTER 1. INTRODUCTION…………………………………………………………….. 1 The Needs for Novel Anti-Tuberculosis Drug………………………. 1 Hypothesis………………………………………………………………. 3 Objectives……………………………………………………………….. 3 2. REVIEW OF LITERATURE……………………………………………… 4 Mycobacteria……………………………………………………………. 4 Tuberculosis………………………………………………………….... 6 Hypericum Perforatum (St. John’s Wort)…………………………… 11 Permeability Battier Theory…………………………………………. 17 The Effect of Polysorbates…………………………………………… 19 Previous Studies……………………………………………………… 25 Summary……………………………………………………………… 25 3. EFFECT OF HYPERICUM PERFORATUM ON MYCOBACTERIA VIABILITY……………………………………… 26 Introduction………………………………………………………… 26 Materials and Methods……………………………………………… 27 Results and Discussion………………………………………………. 29 viii Conclusion……………………………………………………………. 35 4. EFFECT OF SURFACTANT ON ANTIMYCOBACTERIA ACTIVITY OF HYPERICUM PERFORATUM…………………………… 36 Introduction…………………………………………………………….. 36 Material and Method………………………………………………….. 36 Results…………………………………………………………………. 39 Discussion…………………………………………………………….. 41 Conclusion…………………………………………………………….. 45 5. EFFECT OF HYPERICUM PERFORATUM ON MYCOBACTERIUM TUBERCULOSIS VIABILITY…………………. 51 Introduction……………………………………………………………. 51 Materials and Methods………………………………………………… 51 Results and Discussion……………………………………………….. 53 Conclusion…………………………………………………………… 55 6. ENGINEERING APPLICATIONS AND FUTURE WORK……………… 56 Engineering Applications and Considerations……………………....... 56 Future Work Recommendations………………………………………. 58 REFERENCES……………………………………………………………………… 60 APPENDICES………………………………………………………………………… 72 ix LIST OF TABLES Table Page 2.1 Uses of surfactant based on the hydrophilic-lipophilic balance (HLB)………. 22 2.2 Physicochemical parameters of polysorbates…………………………………. 22 4.1 The tested polysorbate concentration…………………………………………. 38 4.2 Effect of Tween 80 on antimycobacterial activity of isoniazid and rifampin Against Mycobacterium JLS….................................. 41 5.1 The tested acidified SJW MeOH extract and hyperforin concentrations…………………………………………………. 53 5.2 SJW acidified MeOH extract MIC test against M. tuberculosis ……………………………………………………… 53 A.1 Statistic analysis of in the absence of Tween 80 SJW MeOH extract against M. JLS test……………………………………….. 74 A.2 Statistic analysis of in the presence of Tween 80 hyperforin against M. JLS test…………………………………………………. 75 A.3 Statistic analysis of in the absence of Tween 80 hyperforin against M. JLS test………………………………………………… 76 A.4 Statistic analysis of in the presence of various Tween 80 concentrations SJW MeOH extract against M. JLS test………………………………………. 77 A.5 Statistic analysis of in the presence of various Tween 60 concentrations SJW MeOH extract against M. JLS test………………………………………. 78 A.6 Statistic analysis of in the presence of various Tween 40 concentrations SJW MeOH extract against M. JLS test………………………………………. 79 A.7 Statistic analysis of in the presence of various Tween 20 concentrations SJW MeOH extract against M. JLS test………………………………………. 80 A.8 Statistic analysis
Recommended publications
  • Revised Use-Function Classification (2007)
    INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY IPCS INTOX Data Management System (INTOX DMS) Revised Use-Function Classification (2007) The Use-Function Classification is used in two places in the INTOX Data Management System: the Communication Record and the Agent/Product Record. The two records are linked: if there is an agent record for a Centre Agent that is the subject of a call, the appropriate Intended Use-Function can be selected automatically in the Communication Record. The Use-Function Classification is used when generating reports, both standard and customized, and for searching the case and agent databases. In particular, INTOX standard reports use the top level headings of the Intended Use-Functions that were selected for Centre Agents in the Communication Record (e.g. if an agent was classified as an Analgesic for Human Use in the Communication Record, it would be logged as a Pharmaceutical for Human Use in the report). The Use-Function classification is very important for ensuring harmonized data collection. In version 4.4 of the software, 5 new additions were made to the top levels of the classification provided with the system for the classification of organisms (items XIV to XVIII). This is a 'convenience' classification to facilitate searching of the Communications database. A taxonomic classification for organisms is provided within the INTOX DMS Agent Explorer. In May/June 2006 INTOX users were surveyed to find out whether they had made any changes to the Use-Function Classification. These changes were then discussed at the 4th and 5th Meetings of INTOX Users. Version 4.5 of the INTOX DMS includes the revised pesticides classification (shown in full below).
    [Show full text]
  • Antimycobacterial Natural Products – an Opportunity for the Colombian Biodiversity
    Review Juan Bueno1, Ericsson David Coy2, Antimycobacterial natural products – an Elena Stashenko3 opportunity for the Colombian biodiversity 1Grupo Micobacterias, Subdirección Red Nacional de Laboratorios, Instituto Nacional de Salud, Bogotá, D.C., Centro Colombiano de Investigación en Tuberculosis CCITB, Bogotá, Colombia. 2Laboratorio de Investigación en Productos Naturales Vegetales, Departamento de Química, Facultad de Ciencias, Universidad Nacional de Colombia, Bogotá, Colombia. 3Laboratorio de Cromatografía, Centro de Investigación en Biomoléculas, CIBIMOL, CENIVAM, Universidad Industrial de Santander, Bucaramanga, Colombia. ABSTRACT centaje de los individuos afectados desarrollará clínicamente la enfermedad, cada año esta ocasiona aproximadamente ocho It is estimated that one-third part of the world population millones de nuevos casos y dos millones de muertes. Mycobac- is infected with the tubercle bacillus. While only a small per- terium tuberculosis es el agente infeccioso que produce la ma- centage of infected individuals will develop clinical tuberculo- yor mortalidad humana, comparado con cualquier otra especie sis, each year there are approximately eight million new cases microbiana. Los objetivos de los distintos programas para el and two million deaths. Mycobacterium tuberculosis is thus control de la tuberculosis son la cura y diagnóstico de la infec- responsible for more human mortality than any other single ción activa, la prevención de recaídas, la reducción de trans- microbial species. The goals of tuberculosis control are focused misión y evitar la aparición de la resistencia a los medicamen- to cure active disease, prevent relapse, reduce transmission tos. Por más de 50 años, los productos naturales han sido útiles and avert the emergence of drug-resistance. For over 50 years, en combatir bacterias y hongos patógenos.
    [Show full text]
  • Against the Plasmodium Falciparum Apicoplast
    A Systematic In Silico Search for Target Similarity Identifies Several Approved Drugs with Potential Activity against the Plasmodium falciparum Apicoplast Nadlla Alves Bispo1, Richard Culleton2, Lourival Almeida Silva1, Pedro Cravo1,3* 1 Instituto de Patologia Tropical e Sau´de Pu´blica/Universidade Federal de Goia´s/Goiaˆnia, Brazil, 2 Malaria Unit/Institute of Tropical Medicine (NEKKEN)/Nagasaki University/ Nagasaki, Japan, 3 Centro de Mala´ria e Doenc¸as Tropicais.LA/IHMT/Universidade Nova de Lisboa/Lisboa, Portugal Abstract Most of the drugs in use against Plasmodium falciparum share similar modes of action and, consequently, there is a need to identify alternative potential drug targets. Here, we focus on the apicoplast, a malarial plastid-like organelle of algal source which evolved through secondary endosymbiosis. We undertake a systematic in silico target-based identification approach for detecting drugs already approved for clinical use in humans that may be able to interfere with the P. falciparum apicoplast. The P. falciparum genome database GeneDB was used to compile a list of <600 proteins containing apicoplast signal peptides. Each of these proteins was treated as a potential drug target and its predicted sequence was used to interrogate three different freely available databases (Therapeutic Target Database, DrugBank and STITCH3.1) that provide synoptic data on drugs and their primary or putative drug targets. We were able to identify several drugs that are expected to interact with forty-seven (47) peptides predicted to be involved in the biology of the P. falciparum apicoplast. Fifteen (15) of these putative targets are predicted to have affinity to drugs that are already approved for clinical use but have never been evaluated against malaria parasites.
    [Show full text]
  • Ah-Gwah-Ching Sanatorium (Minnesota State Sanatorium)
    AH-GWAH-CHING SANATORIUM (MINNESOTA STATE SANATORIUM). Superintendent’s files. Box list. Location Box 1. 1907-1908: Numerical file “indexes.” 2 folders. 106.I.6.5B Labeled Business, 1913-1918, and Medical, 1907-1918; are actually numerical file lists. The files that correspond to these numerical lists have been placed chronologically within this record series; the numbers are noted in square brackets following each file title. 1907: Business correspondence. Mainly between Supt. W. J. Marclay and the State Board of Control. 1907-1908: Downer Mullen, State Board of Control. [48] 1907-1910: Massachusetts State Sanatorium. [70] 1908: Business correspondence. 1909: Business correspondence. 2 folders. Medical correspondence. M. C. Cutter, State Board of Control, Agent. [56] 1909-1910: Downer Mullen, State Board of Control, Accountant. 2 folders. [48] 1909-1911: Minnesota state institutions. [84] 1910: Business correspondence. 1910-1911: Dr. E. L. Touhy and Dr. Wm. M. Hart. [31] Physicians. [36] Future buildings. [147B] 1911: Business correspondence. Dr. W. J. Marclay. [28] H. L. Haylov. [32] Ramsey County Board of Control. [43] Institution monthly reports, 1911-1916. [43A] Auditors and treasurers, Minnesota counties. [43A] Hennepin County Board of Control. [43 1/2] Misc. charities and tuberculosis committees. [44] Misc. business. [47] Misc. medical. [48] Inquiries and requests (misc.). [50] Water supply. [53B] Minnesota Board of Health. [83] agc02.lst AH-GWAH-CHING SANATORIUM (MINNESOTA STATE SANATORIUM). Superintendent’s files. Box list. p. 2 Location Box 1. Superintendent’s cottage. [147A] 106.I.6.5B (cont.) New buildings. [147D] Misc. examiners. [150] Instruction and amusement. [352] Re-union of ex-patients at Minnesota State Fair.
    [Show full text]
  • Hospitals, Asylums and Sanitariums”
    “Finding Missing Ancestors in Institutional Records, Part I: Hospitals, Asylums and Sanitariums” Madeline Yanov I. HOSPITALS 1. General information: A hospital is a healthcare institution providing treatment with specialized nursing and medical staff and medical equipment. The term was also used for sanitoriums or asylums for the mentally ill. “State hospitals” – historic euphemism for “mental hospitals” or “insane asylums”. 2. History of American Hospitals Births, deaths and illnesses mostly occurred at home Concept emerged from almshouses, providing care for the ailing poor First hospital co-founded by Benjamin Franklin in Philadelphia in 1751 Modern concept of hospital emerged after the Civil War. Hospitals were historically run by religious or charitable organizations. 3. HIPPA Health Insurance Portability & Accountability Act – 1996 o Access to own medical records o Permission needed to view your records o Upon death – records sealed forever Revised in 2013 o Other restrictions from 1996 Act still apply except o Limits period of protection of deceased to 50 years after death Even though you meet federal guidelines you STILL have to satisfy State and Local Laws. 4. How to find out if hospital records are available No law says how long records must be kept - old records are often destroyed. If hospital doesn’t exist, check state libraries, archives, and local genealogical societies. If hospital exists – check website and catalog for digitized records. If there are no digitized records, then you or a representative has to go in person. State and hospital rules determine WHO gets access to records. 5. Other records containing medical information Death certificates Cemetery and burial records Court records Newspaper articles National Home for Disabled Volunteer Soldiers – precursor to VA hospital.
    [Show full text]
  • 1, 4-Dihydropyridine Calcium Channel Blockers: Homology Modeling Of
    Hindawi Publishing Corporation ISRN Medicinal Chemistry Volume 2014, Article ID 203518, 14 pages http://dx.doi.org/10.1155/2014/203518 Research Article 1,4-Dihydropyridine Calcium Channel Blockers: Homology Modeling of the Receptor and Assessment of Structure Activity Relationship Moataz A. Shaldam, Mervat H. Elhamamsy, Eman A. Esmat, and Tarek F. El-Moselhy Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt Correspondence should be addressed to Tarek F. El-Moselhy; [email protected] Received 28 September 2013; Accepted 5 December 2013; Published 10 February 2014 Academic Editors: R. B. de Alencastro, P. L. Kotian, O. A. Santos-Filho, L. Soulere,` and S. Srichairatanakool Copyright © 2014 Moataz A. Shaldam et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. +2 1,4-Dihydropyridine (DHP), an important class of calcium antagonist, inhibits the influx of extracellular Ca through L-type voltage-dependent calcium channels. Three-dimensional (3D) structure of calcium channel as a receptor for 1,4-dihydropyridine is a step in understanding its mode of action. Protein structure prediction and modeling tools are becoming integral parts of the standard toolkit in biological and biomedical research. So, homology modeling (HM) of calcium channel alpha-1C subunit as DHP receptor model was achieved. The 3D structure of potassium channel was used as template for HM process. The resulted dihydropyridine receptor model was checked by different means to assure stereochemical quality and structural integrity of the model.
    [Show full text]
  • Finding Missing Ancestors in Institutional Records, Part I: Hospitals, Asylums and Sanitariums”
    “Finding Missing Ancestors in Institutional Records, Part I: Hospitals, Asylums and Sanitariums” Madeline Yanov 18 October 2019 I. HOSPITALS 1. General information: • A hospital is a healthcare institution providing treatment with specialized nursing and medical staff and medical equipment. • Term also used for sanitoriums or asylums for the mentally ill • “State hospitals” – euphemism for “mental hospitals” or “insane asylums” 2. History of American Hospitals • Births, deaths and illnesses mostly occurred at home • Concept emerged from almshouses, providing care for the ailing poor • First hospital co-founded by Benjamin Franklin in Philadelphia in 1751 • Modern concept of hospital emerges after the Civil War • Historically run by religious or charitable organizations 3. HIPPA • Health Insurance Portability & Accountability Act – 1996 o Access to own medical records o Permission needed to view your records o Upon death – records sealed forever • Revised in 2013 o Other restrictions from 1996 Act still apply except o Limits period of protection of deceased to 50 years after death • Even though you meet federal guidelines you STILL have to satisfy State and Local Laws. 4. How to find out if hospital records are available • No law says how long records must be kept - old records are often destroyed • If hospital doesn’t exist, check state libraries, archives, and local genealogical societies • If hospital exists – check website and catalog for digitized records. If there are no digitized records, then you or a representative has to go in person • State and hospital rules determine WHO gets access to records 5. Other records containing medical information • Death certificates • Cemetery and burial records • Court records • Newspaper articles • National Home for Disabled Volunteer Soldiers – precursor to VA hospital.
    [Show full text]
  • Antimycobacterial Activity of Cinnamaldehyde in a Mycobacterium Tuberculosis(H37ra) Model
    molecules Article Antimycobacterial Activity of Cinnamaldehyde in a Mycobacterium tuberculosis(H37Ra) Model Rafal Sawicki 1,* , Joanna Golus 1, Agata Przekora 1, Agnieszka Ludwiczuk 2 , Elwira Sieniawska 2 and Grazyna Ginalska 1 1 Chair and Department of Biochemistry and Biotechnology, Medical University of Lublin, Chodzki 1, PL-20093 Lublin, Poland; [email protected] (J.G.); [email protected] (A.P.); [email protected] (G.G.) 2 Medical Plant Unit, Chair and Department of Pharmacognosy, Medical University of Lublin, Chodzki 1, PL-20093 Lublin, Poland; [email protected] (A.L.); [email protected] (E.S.) * Correspondence: [email protected]; Tel.: +48-60631-2059 Academic Editors: Simone Carradori, Maria Daglia and Annabella Vitalone Received: 20 August 2018; Accepted: 16 September 2018; Published: 18 September 2018 Abstract: The purpose of the study was to evaluate the antimycobacterial activity and the possible action mode of cinnamon bark essential oil and its main constituent—cinnamaldehyde—against the Mycobacterium tuberculosis ATCC 25177 strain. Cinnamaldehyde was proved to be the main bioactive compound responsible for mycobacterial growth inhibition and bactericidal effects. The antimycobacterial activity of cinnamaldehyde was found to be comparable with that of ethambutol, one of the first-line anti-TB antibiotics. The selectivity index determined using cell culture studies in vitro showed a high biological potential of cinnamaldehyde. In M. tuberculosis cells exposed to cinnamaldehyde the cell membrane stress sensing and envelope preserving system are activated. Overexpression of clgR gene indicates a threat to the stability of the cell membrane and suggests a possible mechanism of action. No synergism was detected with the basic set of antibiotics used in tuberculosis treatment: ethambutol, isoniazid, streptomycin, rifampicin, and ciprofloxacin.
    [Show full text]
  • Public Health Reviews
    Public Health Reviews Treatment of tuberculosis: present status and future prospects Philip Onyebujoh,1 Alimuddin Zumla,2 Isabella Ribeiro,1 Roxana Rustomjee,3 Peter Mwaba,4 Melba Gomes,1 & John M. Grange 2 Abstract Over recent years, tuberculosis (TB) and disease caused by human immunodeficiency virus (HIV) have merged in a synergistic pandemic. The number of new cases of TB is stabilizing and declining, except in countries with a high prevalence of HIV infection. In these countries, where HIV is driving an increase in the TB burden, the capacity of the current tools and strategies to reduce the burden has been exceeded. This paper summarizes the current status of TB management and describes recent thinking and strategy adjustments required for the control of TB in settings of high HIV prevalence. We review the information on anti-TB drugs that is available in the public domain and highlight the need for continued and concerted efforts (including financial, human and infrastructural investments) for the development of new strategies and anti-TB agents. Keywords Tuberculosis, Multidrug-resistant/drug therapy; Antitubercular agents/administration and dosage/adverse effects; Directly observed therapy; Drug therapy/trends; Drug combinations; Quinolones; Quinoline; Nitroimidazoles; Quinolizines; HIV infections/drug therapy; Evaluation studies (source: MeSH, NLM). Mots clés Tuberculose résistante à la polychimiothérapie /chimiothérapie; Antituberculeux/administration et posologie/effets indésirables; Thérapie sous observation directe; Chimiothérapie/orientations;
    [Show full text]
  • Smokejumper Magazine, January 2021
    Eastern Washington University EWU Digital Commons Smokejumper and Static Line Magazines Smokejumper Digital Archive January 2021 Smokejumper Magazine, January 2021 National Smokejumper Association Follow this and additional works at: https://dc.ewu.edu/smokejumper_mag Part of the Forest Management Commons Recommended Citation National Smokejumper Association, "Smokejumper Magazine, January 2021" (2021). Smokejumper and Static Line Magazines. 127. https://dc.ewu.edu/smokejumper_mag/127 This Book is brought to you for free and open access by the Smokejumper Digital Archive at EWU Digital Commons. It has been accepted for inclusion in Smokejumper and Static Line Magazines by an authorized administrator of EWU Digital Commons. For more information, please contact [email protected]. The National Smokejumper Quarterly Magazine Association January 2021 Smokejumper Me and Vietnam ................................................................................................... 4 Birth of a Tree Farmer ........................................................................................ 10 John McDaniel Retires ...................................................................................... 15 CONTENTS Message from Message from the President ....................................2 Me and Vietnam ......................................................4 the President Birth of a Tree Farmer ..........................................10 Sounding Off from the Editor ................................14 major fires in Oregon. Across John McDaniel Retires
    [Show full text]
  • Synthesis and Antimycobacterial and Antiprotozoal Activities of Some Novel Nitrobenzylated Heterocycles
    Synthesis and Antimycobacterial and Antiprotozoal Activities of Some Novel Nitrobenzylated Heterocycles Agata G´orskaa, Lidia Chomiczb, Justyna Zebrowska˙ b, Przemysław Myjakc, Ewa Augustynowicz-Kope´cd, Zofia Zwolskad, Janusz Piekarczyke, Henryk Rebandelf, and Zygmunt Kazimierczuka,g a Institute of Chemistry, Agricultural University, 159C Nowoursynowska St., 02-787 Warsaw, Poland b Department of Medical Biology, Medical University of Warsaw, 73 Nowogrodzka St., 02-018 Warsaw, Poland c Department of Tropical Parasitology, Medical University of Gdansk, 9b Powstania Styczniowego St. 81-106 Gdynia, Poland d National Tuberculosis and Lung Diseases Research Institute, 26 Płocka St., 01-138 Warsaw, Poland e 2nd Department of Maxillofacial Surgery, Medical University of Warsaw, 4 Lindleya St., 02-005 Warsaw, Poland f Department of Teaching and Effects of Education, Medical University of Warsaw, 4 Oczki St., 02-007 Warsaw, Poland g Laboratory of Experimental Pharmacology, Polish Academy of Sciences Medical Research Center, 5 Pawinskiego St., 02-106 Warsaw, Poland Reprint requests to Prof. Z. Kazimierczuk. E-mail: [email protected] Z. Naturforsch. 61b, 101 – 107 (2006); received October 7, 2005 A series of N-, S-, and O-mononitro- and dinitrobenzyl derivatives of heterocycles was synthe- sized by alkylation of heterocyclic bases with the respective nitrobenzyl chlorides. Of the newly syn- thesized compounds, dinitrobenzylsulfanyl derivatives of 1-methyl-2-mercaptoimidazole (2c) and of 5-nitro- and 5,6-dichloro-2-mercaptobenzimidazole (8b and 8c, and 8e and 8f, respectively) showed considerable antimycobacterial activity. On a molar basis, nine of the novel compounds showed also a considerably higher antiprotozoal efficacy than metronidazole that reduced T. hominis viability to 73.5% at 8 µg/ml.
    [Show full text]
  • Antimycobacterial Activity of DNA Intercalator Inhibitors of Mycobacterium Tuberculosis Primase Dnag
    HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author J Antibiot Manuscript Author (Tokyo). Author Manuscript Author manuscript; available in PMC 2017 November 15. Published in final edited form as: J Antibiot (Tokyo). 2015 March ; 68(3): 153–157. doi:10.1038/ja.2014.131. Antimycobacterial activity of DNA intercalator inhibitors of Mycobacterium tuberculosis primase DnaG Chathurada Gajadeeraa,#, Melisa J. Willbyb,#, Keith D. Greena, Pazit Shaulc, Micha Fridmanc, Sylvie Garneau-Tsodikovaa,*, James E. Poseyb,*, and Oleg V. Tsodikova,* aDepartment of Pharmaceutical Sciences, University of Kentucky, Lexington, KY, 40536-0596, USA bDivision of Tuberculosis Elimination, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA cSchool of Chemistry, Tel Aviv University, Tel Aviv, 66978, Israel Abstract Due to the rise in drug resistance in tuberculosis combined with the global spread of its causative pathogen, Mycobacterium tuberculosis (Mtb), innovative anti-mycobacterial agents are urgently needed. Recently, we developed a novel primase-pyrophosphatase assay and used it to discover inhibitors of an essential Mtb enzyme, primase DnaG (Mtb DnaG), a promising and unexplored potential target for novel anti-tuberculosis chemotherapeutics. Doxorubicin, an anthracycline antibiotic used as an anticancer drug, was found to be a potent inhibitor of Mtb DnaG. In this study, we investigated both inhibition of Mtb DnaG and the inhibitory activity against in vitro growth of Mtb and M. smegmatis (Msm) by other anthracyclines, daunorubicin and idarubicin, as well as by less cytotoxic DNA intercalators: aloe-emodin, rhein, and a mitoxantrone derivative. Generally, low-μM inhibition of Mtb DnaG by the anthracyclines was correlated with their low- μM minimum inhibitory concentrations.
    [Show full text]