Antibiotic Resistance Threats in the United States, 2019
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Mechanisms and Strategies to Overcome Multiple Drug Resistance in Cancer
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector FEBS Letters 580 (2006) 2903–2909 Minireview Mechanisms and strategies to overcome multiple drug resistance in cancer Tomris Ozben* Akdeniz University, Faculty of Medicine, Department of Biochemistry, 07070 Antalya, Turkey Received 30 January 2006; accepted 9 February 2006 Available online 17 February 2006 Edited by Horst Feldmann The cytotoxic drugs that are most frequently associated with Abstract One of the major problems in chemotherapy is multi- drug resistance (MDR) against anticancer drugs. ATP-binding MDR are hydrophobic, amphipathic natural products, such as cassette (ABC) transporters are a family of proteins that medi- the taxanes (paclitaxel and docetaxel), vinca alkaloids (vinorel- ate MDR via ATP-dependent drug efflux pumps. Many MDR bine, vincristine, and vinblastine), anthracyclines (doxorubicin, inhibitors have been identified, but none of them have been pro- daunorubicin, and epirubicin), epipodophyllotoxins (etoposide ven clinically useful without side effects. Efforts continue to dis- and teniposide), antimetabolites (methorexate, fluorouracil, cover not toxic MDR inhibitors which lack pharmacokinetic cytosar, 5-azacytosine, 6-mercaptopurine, and gemcitabine) interactions with anticancer drugs. Novel approaches have also topotecan, dactinomycin, and mitomycin C [4,6–8]. been designed to inhibit or circumvent MDR. In this review, Overexpression of ATP-binding cassette (ABC) transporters the structure and function of ABC transporters and development has been shown to be responsible for MDR [5]. Therefore eluci- of MDR inhibitors are described briefly including various ap- dation of the structure and function for each ABC transporter is proaches to suppress MDR mechanisms. -
Infectious Disease
INFECTIOUS DISEASE Infectious diseases are caused by germs that are transmitted directly from person to NOTE: person; animal to person (zoonotic The following symbols are used throughout this Community Health Assessment Report to serve only as a simple and quick diseases); from mother to unborn child; or reference for data comparisons and trends for the County. indirectly, such as when a person touches Further analysis may be required before drawing conclusions about the data. a surface that some germs can linger on. The NYSDOH recommends several The apple symbol represents areas in which Oneida County’s status or trend is FAVORABLE or COMPARABLE to its effective strategies for preventing comparison (i.e., NYS, US) or areas/issues identified as infectious diseases,, including: ensuring STRENGTHS. procedures and systems are in place in The magnifying glass symbols represent areas in which Oneida County’s status or trend is UNFAVORABLE to its communities for immunizations to be up to comparison (i.e., NYS, US) or areas/issues of CONCERN date; enabling sanitary practices by or NEED that may warrant further analysis. conveniently located sinks for washing DATA REFERENCES: hands; influencing community resources • All References to tables are in Attachment A – Oneida County Data Book. and cultures to facilitate abstinence and • See also Attachment B – Oneida County Chart Book for risk reduction practices for sexual behavior additional data. and injection drug use, and setting up support systems to ensure medicines are taken as prescribed.453 The reporting of suspect or confirmed communicable diseases is mandated under the New York State Sanitary Code (10NYCRR 2.10). -
Chapter 12 Antimicrobial Therapy Antibiotics
Chapter 12 Antimicrobial Therapy Topics: • Ideal drug - Antimicrobial Therapy - Selective Toxicity • Terminology - Survey of Antimicrobial Drug • Antibiotics - Microbial Drug Resistance - Drug and Host Interaction An ideal antimicrobic: Chemotherapy is the use of any chemical - soluble in body fluids, agent in the treatment of disease. - selectively toxic , - nonallergenic, A chemotherapeutic agent or drug is any - reasonable half life (maintained at a chemical agent used in medical practice. constant therapeutic concentration) An antibiotic agent is usually considered to - unlikely to elicit resistance, be a chemical substance made by a - has a long shelf life, microorganism that can inhibit the growth or - reasonably priced. kill microorganisms. There is no ideal antimicrobic An antimicrobic or antimicrobial agent is Selective Toxicity - Drugs that specifically target a chemical substance similar to an microbial processes, and not the human host’s. antibiotic, but may be synthetic. Antibiotics Spectrum of antibiotics and targets • Naturally occurring antimicrobials – Metabolic products of bacteria and fungi – Reduce competition for nutrients and space • Bacteria – Streptomyces, Bacillus, • Molds – Penicillium, Cephalosporium * * 1 The mechanism of action for different 5 General Mechanisms of Action for antimicrobial drug targets in bacterial cells Antibiotics - Inhibition of Cell Wall Synthesis - Disruption of Cell Membrane Function - Inhibition of Protein Synthesis - Inhibition of Nucleic Acid Synthesis - Anti-metabolic activity Antibiotics -
National Antibiotic Consumption for Human Use in Sierra Leone (2017–2019): a Cross-Sectional Study
Tropical Medicine and Infectious Disease Article National Antibiotic Consumption for Human Use in Sierra Leone (2017–2019): A Cross-Sectional Study Joseph Sam Kanu 1,2,* , Mohammed Khogali 3, Katrina Hann 4 , Wenjing Tao 5, Shuwary Barlatt 6,7, James Komeh 6, Joy Johnson 6, Mohamed Sesay 6, Mohamed Alex Vandi 8, Hannock Tweya 9, Collins Timire 10, Onome Thomas Abiri 6,11 , Fawzi Thomas 6, Ahmed Sankoh-Hughes 12, Bailah Molleh 4, Anna Maruta 13 and Anthony D. Harries 10,14 1 National Disease Surveillance Programme, Sierra Leone National Public Health Emergency Operations Centre, Ministry of Health and Sanitation, Cockerill, Wilkinson Road, Freetown, Sierra Leone 2 Department of Community Health, Faculty of Clinical Sciences, College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone 3 Special Programme for Research and Training in Tropical Diseases (TDR), World Health Organization, 1211 Geneva, Switzerland; [email protected] 4 Sustainable Health Systems, Freetown, Sierra Leone; [email protected] (K.H.); [email protected] (B.M.) 5 Unit for Antibiotics and Infection Control, Public Health Agency of Sweden, Folkhalsomyndigheten, SE-171 82 Stockholm, Sweden; [email protected] 6 Pharmacy Board of Sierra Leone, Central Medical Stores, New England Ville, Freetown, Sierra Leone; [email protected] (S.B.); [email protected] (J.K.); [email protected] (J.J.); [email protected] (M.S.); [email protected] (O.T.A.); [email protected] (F.T.) Citation: Kanu, J.S.; Khogali, M.; 7 Department of Pharmaceutics and Clinical Pharmacy & Therapeutics, Faculty of Pharmaceutical Sciences, Hann, K.; Tao, W.; Barlatt, S.; Komeh, College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown 0000, Sierra Leone 8 J.; Johnson, J.; Sesay, M.; Vandi, M.A.; Directorate of Health Security & Emergencies, Ministry of Health and Sanitation, Sierra Leone National Tweya, H.; et al. -
Novel Antimicrobial Agents Inhibiting Lipid II Incorporation Into Peptidoglycan Essay MBB
27 -7-2019 Novel antimicrobial agents inhibiting lipid II incorporation into peptidoglycan Essay MBB Mark Nijland S3265978 Supervisor: Prof. Dr. Dirk-Jan Scheffers Molecular Microbiology University of Groningen Content Abstract..............................................................................................................................................2 1.0 Peptidoglycan biosynthesis of bacteria ........................................................................................3 2.0 Novel antimicrobial agents ...........................................................................................................4 2.1 Teixobactin ...............................................................................................................................4 2.2 tridecaptin A1............................................................................................................................7 2.3 Malacidins ................................................................................................................................8 2.4 Humimycins ..............................................................................................................................9 2.5 LysM ........................................................................................................................................ 10 3.0 Concluding remarks .................................................................................................................... 11 4.0 references ................................................................................................................................. -
Globalization and Infectious Diseases: a Review of the Linkages
TDR/STR/SEB/ST/04.2 SPECIAL TOPICS NO.3 Globalization and infectious diseases: A review of the linkages Social, Economic and Behavioural (SEB) Research UNICEF/UNDP/World Bank/WHO Special Programme for Research & Training in Tropical Diseases (TDR) The "Special Topics in Social, Economic and Behavioural (SEB) Research" series are peer-reviewed publications commissioned by the TDR Steering Committee for Social, Economic and Behavioural Research. For further information please contact: Dr Johannes Sommerfeld Manager Steering Committee for Social, Economic and Behavioural Research (SEB) UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) World Health Organization 20, Avenue Appia CH-1211 Geneva 27 Switzerland E-mail: [email protected] TDR/STR/SEB/ST/04.2 Globalization and infectious diseases: A review of the linkages Lance Saker,1 MSc MRCP Kelley Lee,1 MPA, MA, D.Phil. Barbara Cannito,1 MSc Anna Gilmore,2 MBBS, DTM&H, MSc, MFPHM Diarmid Campbell-Lendrum,1 D.Phil. 1 Centre on Global Change and Health London School of Hygiene & Tropical Medicine Keppel Street, London WC1E 7HT, UK 2 European Centre on Health of Societies in Transition (ECOHOST) London School of Hygiene & Tropical Medicine Keppel Street, London WC1E 7HT, UK TDR/STR/SEB/ST/04.2 Copyright © World Health Organization on behalf of the Special Programme for Research and Training in Tropical Diseases 2004 All rights reserved. The use of content from this health information product for all non-commercial education, training and information purposes is encouraged, including translation, quotation and reproduction, in any medium, but the content must not be changed and full acknowledgement of the source must be clearly stated. -
Brilacidin First-In-Class Defensin-Mimetic Drug Candidate
Brilacidin First-in-Class Defensin-Mimetic Drug Candidate Mechanism of Action, Pre/Clinical Data and Academic Literature Supporting the Development of Brilacidin as a Potential Novel Coronavirus (COVID-19) Treatment April 20, 2020 Page # I. Brilacidin: Background Information 2 II. Brilacidin: Two Primary Mechanisms of Action 3 Membrane Disruption 4 Immunomodulatory 7 III. Brilacidin: Several Complementary Ways of Targeting COVID-19 10 Antiviral (anti-SARS-CoV-2 activity) 11 Immuno/Anti-Inflammatory 13 Antimicrobial 16 IV. Brilacidin: COVID-19 Clinical Development Pathways 18 Drug 18 Vaccine 20 Next Steps 24 V. Brilacidin: Phase 2 Clinical Trial Data in Other Indications 25 VI. AMPs/Defensins (Mimetics): Antiviral Properties 30 VII. AMPs/Defensins (Mimetics): Anti-Coronavirus Potential 33 VIII. The Broader Context: Characteristics of the COVID-19 Pandemic 36 Innovation Pharmaceuticals 301 Edgewater Place, Ste 100 Wakefield, MA 01880 978.921.4125 [email protected] Innovation Pharmaceuticals: Mechanism of Action, Pre/Clinical Data and Academic Literature Supporting the Development of Brilacidin as a Potential Novel Coronavirus (COVID-19) Treatment (April 20, 2020) Page 1 of 45 I. Brilacidin: Background Information Brilacidin (PMX-30063) is Innovation Pharmaceutical’s lead Host Defense Protein (HDP)/Defensin-Mimetic drug candidate targeting SARS-CoV-2, the virus responsible for COVID-19. Laboratory testing conducted at a U.S.-based Regional Biocontainment Laboratory (RBL) supports Brilacidin’s antiviral activity in directly inhibiting SARS-CoV-2 in cell-based assays. Additional pre-clinical and clinical data support Brilacidin’s therapeutic potential to inhibit the production of IL-6, IL-1, TNF- and other pro-inflammatory cytokines and chemokines (e.g., MCP-1), identified as central drivers in the worsening prognoses of COVID-19 patients. -
Antibiotic Resistance: from the Bench to Patients
antibiotics Editorial Antibiotic Resistance: From the Bench to Patients Márió Gajdács 1,* and Fernando Albericio 2,3 1 Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Dóm tér 10., 6720 Szeged, Hungary 2 School of Chemistry, University of KwaZulu-Natal, Durban 4001, South Africa 3 Department of Organic Chemistry, University of Barcelona, CIBER-BBN, 08028 Barcelona, Spain * Correspondence: [email protected]; Tel.: +36-62-341-330 Received: 20 August 2019; Accepted: 26 August 2019; Published: 27 August 2019 The discovery and subsequent clinical introduction of antibiotics is one of the most important game-changers in the history of medicine [1]. These drugs have saved millions of lives from infections that would previously have been fatal, and later, they allowed for the introduction of surgical interventions, organ transplantation, care of premature infants, and cancer chemotherapy [2]. Nevertheless, the therapy of bacterial infections is becoming less and less straightforward due to the emergence of multidrug resistance (MDR) in these pathogens [3]. Direct consequences of antibiotic resistance include delays in the onset of the appropriate (effective) antimicrobial therapy, the need to use older, more toxic antibiotics (e.g., colistin) with a disadvantageous side-effect profile, longer hospital stays, and an increasing burden on the healthcare infrastructure; overall, a decrease in the quality-of-life (QoL) and an increase in the mortality rate of the affected patients [4,5]. To highlight the severity of the issue, several international declarations have been published to call governments around the globe to take action on antimicrobial resistance [6–9]. Since the 1980s, pharmaceutical companies have slowly turned away from antimicrobial research and towards the drug therapy of chronic non-communicable diseases [10,11]. -
Chlamydia-English
URGENT and PRIVATE IMPORTANT INFORMATION ABOUT YOUR HEALTH DIRECTIONS FOR SEX PARTNERS OF PERSONS WITH CHLAMYDIA PLEASE READ THIS VERY CAREFULLY Your sex partner has recently been treated for chlamydia. Chlamydia is a sexually transmitted disease (STD) that you can get from having any kind of sex (oral, vaginal, or anal) with a person who already has it. You may have been exposed. The good news is that it’s easily treated. You are being given a medicine called azithromycin (sometimes known as “Zithromax”) to treat your chlamydia. Your partner may have given you the actual medicine, or a prescription that you can take to a pharmacy. These are instructions for how to take azithromycin. The best way to take care of this infection is to see your own doctor or clinic provider right away. If you can’t get to a doctor in the next several days, you should take the azithromycin. Even if you decide to take the medicine, it is very important to see a doctor as soon as you can, to get tested for other STDs. People can have more than one STD at the same time. Azithromycin will not cure other sexually transmitted infections. Having STDs can increase your risk of getting HIV, so make sure to also get an HIV test. SYMPTOMS Some people with chlamydia have symptoms, but most do not. Symptoms may include pain in your testicles, pelvis, or lower part of your belly. You may also have pain when you urinate or when having sex. Many people with chlamydia do not know they are infected because they feel fine. -
Clinical Pharmacology 1: Phase 1 Studies and Early Drug Development
Clinical Pharmacology 1: Phase 1 Studies and Early Drug Development Gerlie Gieser, Ph.D. Office of Clinical Pharmacology, Div. IV Objectives • Outline the Phase 1 studies conducted to characterize the Clinical Pharmacology of a drug; describe important design elements of and the information gained from these studies. • List the Clinical Pharmacology characteristics of an Ideal Drug • Describe how the Clinical Pharmacology information from Phase 1 can help design Phase 2/3 trials • Discuss the timing of Clinical Pharmacology studies during drug development, and provide examples of how the information generated could impact the overall clinical development plan and product labeling. Phase 1 of Drug Development CLINICAL DEVELOPMENT RESEARCH PRE POST AND CLINICAL APPROVAL 1 DISCOVERY DEVELOPMENT 2 3 PHASE e e e s s s a a a h h h P P P Clinical Pharmacology Studies Initial IND (first in human) NDA/BLA SUBMISSION Phase 1 – studies designed mainly to investigate the safety/tolerability (if possible, identify MTD), pharmacokinetics and pharmacodynamics of an investigational drug in humans Clinical Pharmacology • Study of the Pharmacokinetics (PK) and Pharmacodynamics (PD) of the drug in humans – PK: what the body does to the drug (Absorption, Distribution, Metabolism, Excretion) – PD: what the drug does to the body • PK and PD profiles of the drug are influenced by physicochemical properties of the drug, product/formulation, administration route, patient’s intrinsic and extrinsic factors (e.g., organ dysfunction, diseases, concomitant medications, -
Structure of a Penicillin Binding Protein Complexed with a Cephalosporin-Peptidoglycan Mimic M.A
Structure of a Penicillin Binding Protein Complexed with a Cephalosporin-Peptidoglycan Mimic M.A. McDonough1, W. Lee2, N.R. Silvaggi1, L.P. Kotra 2, Z-H. Li2, Y. Takeda2, S .O. Mobashery2, and J.A. Kelly1 1Department of Molecular and Cell Biology and Institute for Materials Science, Univ. of Connecticut, Storrs, CT 2Institute for Drug Design and the Department of Chemistry, Wayne State Univ., Detroit, MI Many bacteria that are responsible for causing dis- lactams. Also, one questions why ß-lactamases hydro- eases in humans are rapidly developing mutant strains lyze ß-lactams and release them rapidly but they do resistant to existing antibiotics. Proliferation of these not react with peptide substrates. mutant strains is likely to be a serious health-care prob- To help answer these questions, structural studies lem of increasing proportions. Almost sixty percent of of the Streptomyces sp. R61 D-Ala-D-Ala-peptidase all clinically used antibiotics are beta-lactams, which have been undertaken to investigate how the enzyme stop the growth of bacteria by interfering with their cell- wall biosynthesis. The cell walls are made of glycan chains that polymerize to form a structure that gives strength and shape to the bacteria. An understanding of the process how the cell wall is synthesized may help in designing more potent antibiotics. D-Ala-D-Ala-carboxypeptidase/transpeptidases (DD-peptidases) are penicillin-binding proteins (PBPs), the targets of ß-lactam antibiotics such as penicillins and cephalosporins (Figure 1A). These enzymes cata- lyze the final cross-linking step of bacterial cell wall bio- synthesis. In vivo inhibition of PBPs by ß-lactams re- sults in the cessation of bacterial growth. -
Getting to Grips with Unix and the Linux Family
Getting to grips with Unix and the Linux family David Chiappini, Giulio Pasqualetti, Tommaso Redaelli Torino, International Conference of Physics Students August 10, 2017 According to the booklet At this end of this session, you can expect: • To have an overview of the history of computer science • To understand the general functioning and similarities of Unix-like systems • To be able to distinguish the features of different Linux distributions • To be able to use basic Linux commands • To know how to build your own operating system • To hack the NSA • To produce the worst software bug EVER According to the booklet update At this end of this session, you can expect: • To have an overview of the history of computer science • To understand the general functioning and similarities of Unix-like systems • To be able to distinguish the features of different Linux distributions • To be able to use basic Linux commands • To know how to build your own operating system • To hack the NSA • To produce the worst software bug EVER A first data analysis with the shell, sed & awk an interactive workshop 1 at the beginning, there was UNIX... 2 ...then there was GNU 3 getting hands dirty common commands wait till you see piping 4 regular expressions 5 sed 6 awk 7 challenge time What's UNIX • Bell Labs was a really cool place to be in the 60s-70s • UNIX was a OS developed by Bell labs • they used C, which was also developed there • UNIX became the de facto standard on how to make an OS UNIX Philosophy • Write programs that do one thing and do it well.