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UCLA UCLA Previously Published Works Title Homotaurine, a safe blood-brain barrier permeable GABAA-R-specific agonist, ameliorates disease in mouse models of multiple sclerosis. Permalink https://escholarship.org/uc/item/7kq6p5tv Journal Scientific reports, 8(1) ISSN 2045-2322 Authors Tian, Jide Dang, Hoa Wallner, Martin et al. Publication Date 2018-11-08 DOI 10.1038/s41598-018-32733-3 Peer reviewed eScholarship.org Powered by the California Digital Library University of California www.nature.com/scientificreports OPEN Homotaurine, a safe blood-brain barrier permeable GABAA-R-specifc agonist, ameliorates disease in Received: 12 April 2018 Accepted: 11 September 2018 mouse models of multiple sclerosis Published: xx xx xxxx Jide Tian, Hoa Dang, Martin Wallner, Richard Olsen & Daniel L. Kaufman There is a need for treatments that can safely promote regulatory lymphocyte responses. T cells express GABA receptors (GABAA-Rs) and GABA administration can inhibit Th1-mediated processes such as type 1 diabetes and rheumatoid arthritis in mouse models. Whether GABAA-R agonists can also inhibit Th17-driven processes such as experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS), is an open question. GABA does not pass through the blood-brain barrier (BBB) making it ill-suited to inhibit the spreading of autoreactivity within the CNS. Homotaurine is a BBB-permeable amino acid that antagonizes amyloid fbril formation and was found to be safe but inefective in long-term Alzheimer’s disease clinical trials. Homotaurine also acts as GABAA-R agonist with better pharmacokinetics than that of GABA. Working with both monophasic and relapsing-remitting mouse models of EAE, we show that oral administration of homotaurine can (1) enhance CD8+CD122+PD-1+ and CD4+Foxp3+ Treg, but not Breg, responses, (2) inhibit autoreactive Th17 and Th1 responses, and (3) efectively ameliorate ongoing disease. -
Structural Diversity in Echinocandin Biosynthesis: the Impact of Oxidation Steps and Approaches Toward an Evolutionary Explanation
Z. Naturforsch. 2017; 72(1-2)c: 1–20 Wolfgang Hüttel* Structural diversity in echinocandin biosynthesis: the impact of oxidation steps and approaches toward an evolutionary explanation DOI 10.1515/znc-2016-0156 can be well applied to parts of the pathway; however, thus Received July 29, 2016; revised July 29, 2016; accepted August 28, far, there is no comprehensive theory that could explain 2016 the entire biosynthesis. Abstract: Echinocandins are an important group of cyclic Keywords: antifungals; gene clusters; metabolic diversity; non-ribosomal peptides with strong antifungal activ- non-ribosomal peptide biosynthesis; secondary meta- ity produced by filamentous fungi from Aspergillaceae bolism; filamentous fungi. and Leotiomycetes. Their structure is characterized by numerous hydroxylated non-proteinogenic amino acids. Biosynthetic clusters discovered in the last years contain up to six oxygenases, all of which are involved in amino 1 Introduction acid modifications. Especially, variations in the oxidation Echinocandins are fungal non-ribosomal cyclic hexapep- pattern induced by these enzymes account for a remark- tides with a fatty acid side chain attached to a dihydroxy- able structural diversity among the echinocandins. This ornithine residue. As they are specific noncompetitive review provides an overview of the current knowledge of inhibitors of the β-1,3-glucan synthase involved in fungal echinocandin biosynthesis with a special focus on diver- cell wall biosynthesis, they have a pronounced antifungal sity-inducing oxidation steps. The emergence of metabolic bioactivity. Although natural echinocandins are not of diversity is further discussed on the basis of a comprehen- clinical use due to their toxicity and low solubility, chemi- sive overview of the structurally characterized echinocan- cal derivatives such as caspofungin, anidulafungin, and dins, their producer strains and biosynthetic clusters. -
Practice Guideline
THE AMERICAN ASSOCIATION PSYCHIATRIC PRACTICE GUIDELINE FOR THE PHARMACOLOGICAL TREATMENT WITH OF ALCOHOL PATIENTS USE DISORDER lcohol use disorder (AUD) is a major public health problem in the United States. The estimated 12-month and lifetime prevalence values for AUD are 13.9% and THE AMERICAN PSYCHIATRIC ASSOCIATION A 29.1%, respectively, with approximately half of individuals with lifetime AUD having a severe disorder. AUD and its sequelae also account for significant excess mortality and cost the United States more than $200 billion annually. Despite its high prevalence and numerous negative consequences, AUD remains undertreated. In fact, fewer than 1 in 10 individuals in the United States with a 12-month diagnosis of AUD PRACTICE GUIDELINE receive any treatment. Nevertheless, effective and evidence-based interventions are available, and treatment is associated with reductions in the risk of relapse and AUD- FOR THE associated mortality. The American Psychiatric Association Practice Guideline for the Pharmacological Pharmacological Treatment of Treatment of Patients With Alcohol Use Disorder seeks to reduce these substantial psychosocial and public health consequences of AUD for millions of affected individu- Patients With Alcohol Use Disorder als. The guideline focuses specifically on evidence-based pharmacological treatments for AUD in outpatient settings and includes additional information on assessment and treatment planning, which are an integral part of using pharmacotherapy to treat AUD. In addition to reviewing the available evidence on the use of AUD pharmacotherapy, the guideline offers clear, concise, and actionable recommendation statements, each of which is given a rating that reflects the level of confidence that potential benefits of an intervention outweigh potential harms. -
Taurine and Its Analogs in Neurological Disorders Focus On
Redox Biology 24 (2019) 101223 Contents lists available at ScienceDirect Redox Biology journal homepage: www.elsevier.com/locate/redox Review article Taurine and its analogs in neurological disorders: Focus on therapeutic T potential and molecular mechanisms Md. Jakariaa, Shofiul Azama, Md. Ezazul Haquea, Song-Hee Joa, Md. Sahab Uddinb, In-Su Kima,c, ∗ Dong-Kug Choia,c, a Department of Applied Life Sciences and Integrated Bioscience, Graduate School, Konkuk University, Chungju, South Korea b Department of Pharmacy, Southeast University, Dhaka, Bangladesh c Department of Integrated Bioscience and Biotechnology, College of Biomedical and Health Sciences, and Research Institute of Inflammatory Diseases (RID), Konkuk University, Chungju, South Korea ARTICLE INFO ABSTRACT Keywords: Taurine is a sulfur-containing amino acid and known as semi-essential in mammals and is produced chiefly by Taurine the liver and kidney. It presents in different organs, including retina, brain, heart and placenta and demonstrates Analogs extensive physiological activities within the body. In the several disease models, it attenuates inflammation- and Therapeutic oxidative stress-mediated injuries. Taurine also modulates ER stress, Ca2+ homeostasis and neuronal activity at Molecular role the molecular level as part of its broader roles. Different cellular processes such as energy metabolism, gene Clinical study and Neurological disorders expression, osmosis and quality control of protein are regulated by taurine. In addition, taurine displays po- tential ameliorating effects against different neurological disorders such as neurodegenerative diseases, stroke, epilepsy and diabetic neuropathy and protects against injuries and toxicities of the nervous system. Several findings demonstrate its therapeutic role against neurodevelopmental disorders, including Angelman syndrome, Fragile X syndrome, sleep-wake disorders, neural tube defects and attention-deficit hyperactivity disorder. -
Design, Development, and Characterization of Novel Antimicrobial Peptides for Pharmaceutical Applications Yazan H
University of Arkansas, Fayetteville ScholarWorks@UARK Theses and Dissertations 8-2013 Design, Development, and Characterization of Novel Antimicrobial Peptides for Pharmaceutical Applications Yazan H. Akkam University of Arkansas, Fayetteville Follow this and additional works at: http://scholarworks.uark.edu/etd Part of the Biochemistry Commons, Medicinal and Pharmaceutical Chemistry Commons, and the Molecular Biology Commons Recommended Citation Akkam, Yazan H., "Design, Development, and Characterization of Novel Antimicrobial Peptides for Pharmaceutical Applications" (2013). Theses and Dissertations. 908. http://scholarworks.uark.edu/etd/908 This Dissertation is brought to you for free and open access by ScholarWorks@UARK. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of ScholarWorks@UARK. For more information, please contact [email protected], [email protected]. Design, Development, and Characterization of Novel Antimicrobial Peptides for Pharmaceutical Applications Design, Development, and Characterization of Novel Antimicrobial Peptides for Pharmaceutical Applications A Dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Cell and Molecular Biology by Yazan H. Akkam Jordan University of Science and Technology Bachelor of Science in Pharmacy, 2001 Al-Balqa Applied University Master of Science in Biochemistry and Chemistry of Pharmaceuticals, 2005 August 2013 University of Arkansas This dissertation is approved for recommendation to the Graduate Council. Dr. David S. McNabb Dissertation Director Professor Roger E. Koeppe II Professor Gisela F. Erf Committee Member Committee Member Professor Ralph L. Henry Dr. Suresh K. Thallapuranam Committee Member Committee Member ABSTRACT Candida species are the fourth leading cause of nosocomial infection. The increased incidence of drug-resistant Candida species has emphasized the need for new antifungal drugs. -
Treatment of Patients with Substance Use Disorders Second Edition
PRACTICE GUIDELINE FOR THE Treatment of Patients With Substance Use Disorders Second Edition WORK GROUP ON SUBSTANCE USE DISORDERS Herbert D. Kleber, M.D., Chair Roger D. Weiss, M.D., Vice-Chair Raymond F. Anton Jr., M.D. To n y P. G e o r ge , M .D . Shelly F. Greenfield, M.D., M.P.H. Thomas R. Kosten, M.D. Charles P. O’Brien, M.D., Ph.D. Bruce J. Rounsaville, M.D. Eric C. Strain, M.D. Douglas M. Ziedonis, M.D. Grace Hennessy, M.D. (Consultant) Hilary Smith Connery, M.D., Ph.D. (Consultant) This practice guideline was approved in December 2005 and published in August 2006. A guideline watch, summarizing significant developments in the scientific literature since publication of this guideline, may be available in the Psychiatric Practice section of the APA web site at www.psych.org. 1 Copyright 2010, American Psychiatric Association. APA makes this practice guideline freely available to promote its dissemination and use; however, copyright protections are enforced in full. No part of this guideline may be reproduced except as permitted under Sections 107 and 108 of U.S. Copyright Act. For permission for reuse, visit APPI Permissions & Licensing Center at http://www.appi.org/CustomerService/Pages/Permissions.aspx. AMERICAN PSYCHIATRIC ASSOCIATION STEERING COMMITTEE ON PRACTICE GUIDELINES John S. McIntyre, M.D., Chair Sara C. Charles, M.D., Vice-Chair Daniel J. Anzia, M.D. Ian A. Cook, M.D. Molly T. Finnerty, M.D. Bradley R. Johnson, M.D. James E. Nininger, M.D. Paul Summergrad, M.D. Sherwyn M. -
Pneumocystis Jiroveci Pneumonia Following Kidney Transplantation: a Retrospective Analysis of 22 Cases
Int J Clin Exp Med 2017;10(1):1234-1242 www.ijcem.com /ISSN:1940-5901/IJCEM0025412 Original Article Comparison of caspofungin and trimethoprim-sulfamethoxazole combination therapy with standard monotherapy in patients with Pneumocystis jiroveci pneumonia following kidney transplantation: a retrospective analysis of 22 cases Bo Yu1, Yu Yang1, Linyang Ye1, Xiaowei Xie2, Jiaxiang Guo1 Departments of 1Urology, 2Pulmonology, The First Affiliated Hospital of PLA’s General Hospital, Fu Cheng Road 51#, Haidian District, Beijing 100048, China Received February 1, 2016; Accepted April 27, 2016; Epub January 15, 2017; Published January 30, 2017 Abstract: Pneumocystis jiroveci pneumonia (PCP) is one of the most common and fatal opportunistic infections of renal transplant recipients. The objective of this retrospective study was to compare the therapeutic effect and safety of caspofungin and trimethoprim-sulfamethoxazole (TMP-SMZ) combination therapy with standard TMP- SMZ monotherapy in 22 patients with severe PCP following kidney transplantation. The presence of P. jiroveci was determined by direct fluorescence staining, PCR analysis, detection of beta-1, 3-glucan and serum lactate dehy- drogenase levels. Thirteen patients received combination therapy, and nine patients received standard TMP-SMZ monotherapy for PCP. There were no significant differences in the baseline demographics and clinical characteris- tics were detected. Patients in the combination therapy group experienced better overall outcomes characterized by reduced duration of increased body temperature (P < 0.001), respiratory intensive care unit stay (P < 0.001), less requirement for mechanical ventilation (P = 0.005) and shorter high dosage TMP-SMZ treatment course (P < 0.01). 44.4% of patients receiving standard TMP-SMZ progressed to acute respiratory distress syndrome (ARDS), none of the patients in the combination therapy group experienced ARDS (P = 0.017). -
Drug Discovery and Development with Plant-Derived Compounds
Progress in Drug Research Founded by Ernst Jucker Series Editors Prof. Dr. Paul L. Herrling Alex Matter, M.D., Director Novartis International AG Novartis Institute for Tropical Diseases CH-4002 Basel 10 Biopolis Road, #05-01 Chromos Switzerland Singapore 138670 Singapore Progress in Drug Research Natural Compounds as Drugs Volume I Vol. 65 Edited by Frank Petersen and René Amstutz Birkhäuser Basel • Boston • Berlin Editors Frank Petersen René Amstutz Novartis Pharma AG Lichtstrasse 35 4056 Basel Switzerland Library of Congress Control Number: 2007934728 Bibliographic information published by Die Deutsche Bibliothek Die Deutsche Bibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data is available in the internet at http://dnb.ddb.de ISBN 978-3-7643-8098-4 Birkhäuser Verlag AG, Basel – Boston – Berlin The publisher and editor can give no guarantee for the information on drug dosage and administration contained in this publication. The respective user must check its accuracy by consulting other sources of reference in each individual case. The use of registered names, trademarks etc. in this publication, even if not identified as such, does not imply that they are exempt from the relevant protective laws and regulations or free for general use. This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, re-use of illustrations, recitation, broad- casting, reproduction on microfilms or in other ways, and storage in data banks. For any kind of use, permission of the copyright owner must be obtained. © 2008 Birkhäuser Verlag AG Basel · Boston · Berlin P.O. -
Echinocandins: a Promising New Antifungal Group G
Educational Forum Echinocandins: A promising new antifungal group G. K. Randhawa, G. Sharma Department of ABSTRACT Pharmacology, Echinocandins are a new option for fungal infections. They are fungicidal and less toxic to the host Government Medical β College, Amritsar, by virtue of their novel mechanism of action. They are -1, 3-glucan synthase inhibitors. FDA, USA Punjab, India. has approved caspofungin for treatment of invasive aspergillosis in patients who fail to respond or are unable to tolerate other antifungals. Two other agents are in phase III clinical trials – micafungin Received: 31.3.2003 and anidulafungin. Caspofungin among echinocandins has been studied vastly and offers apparent Revised: 4.8.2003 exciting advantages of a broad spectrum of activity including strains of fungi resistant to other Accepted: 29.9.2003 antifungal agents, tolerability profile, with no nephrotoxicity and hepatotoxicity as compared to azole and macrolide antifungals. It may be effective in AIDS-related candidal esophagitis, oropha- Correspondence to: ryngeal candidiasis, fungal pneumonia and nonmeningeal coccidioidomycosis. Clinical trials are G. K. Randhawa required to ascertain their safety in special groups—pediatric, pregnant and nursing mothers. 338-‘D’ Block, Echinocandins provide an exciting option for combination therapy with other antifungals in fulmi- Ranjit Avenue, Amritsar - 143001, India. nant fungal infections. E-mail: [email protected] KEY WORDS: Caspofungin, glucan synthase inhibitor, fungal infections. Introduction Cell wall-acting -
Fungal Cell Wall Disruption by Alkamides from Echinacea
Fungal cell wall disruption by alkamides from Echinacea By Isabel Maria Linhares Cruz, B.Sc. A thesis submitted to The Faculty of Graduate Studies and Research in partial fulfilment of the degree requirements of (Master of Science) Department of Biology Carleton University Ottawa, Ontario, Canada (August 2011) Copyright © 2011-Isabel Cruz Library and Archives Bibliotheque et 1*1 Canada Archives Canada Published Heritage Direction du Branch Patrimoine de I'edition 395 Wellington Street 395, rue Wellington OttawaONK1A0N4 OttawaONK1A0N4 Canada Canada Your file Votre r4f6rence ISBN: 978-0-494-83172-4 Our file Notre r6f6rence ISBN: 978-0-494-83172-4 NOTICE: AVIS: The author has granted a non L'auteur a accorde une licence non exclusive exclusive license allowing Library and permettant a la Bibliotheque et Archives Archives Canada to reproduce, Canada de reproduire, publier, archiver, publish, archive, preserve, conserve, sauvegarder, conserver, transmettre au public communicate to the public by par telecommunication ou par I'lnternet, preter, telecommunication or on the Internet, distribuer et vendre des theses partout dans le loan, distribute and sell theses monde, a des fins commerciales ou autres, sur worldwide, for commercial or non support microforme, papier, electronique et/ou commercial purposes, in microform, autres formats. paper, electronic and/or any other formats. The author retains copyright L'auteur conserve la propriete du droit d'auteur ownership and moral rights in this et des droits moraux qui protege cette these. Ni thesis. Neither the thesis nor la these ni des extraits substantiels de celle-ci substantial extracts from it may be ne doivent etre imprimes ou autrement printed or otherwise reproduced reproduits sans son autorisation. -
Synthetic Approaches to the Bicyclic Core of Teo3.1, Hamigerone and Embellistatin
SYNTHETIC APPROACHES TO THE BICYCLIC CORE OF TEO3.1, HAMIGERONE AND EMBELLISTATIN A thesis submitted in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Chemistry at the University of Canterbury by Sarah Diane Lundy August 2007 ii iii Acknowledgements I would firstly like to thank Dr Jonathan Morris for the opportunity to undertake this research. Despite being away from the department for the last few years, you have continued to provide excellent supervision, guidance and support. I am also grateful for the many hours you have put into reviewing this thesis. Thank you to Professor Peter Steel for taking on the role as my supervisor after Jonathan’s departure to Adelaide, and for your assistance with proof-reading. I am absolutely indebted to Andrew Muscroft-Taylor, the second to last member of the NZ branch of the Morris group. Your friendship, guidance, advice, support, crazy antics, and ‘bagel Fridays’ were crucial in me getting through this PhD. Thanks also go to the previous members of the Morris Group. Regan and Darby for all their help in the lab in the early days, Jonno and Martin for always keeping me entertained in the office, and especially to Liesl for endless cups of tea, chocolate-chip biscuits and for her continued friendship and encouragement since leaving the department. I am very grateful to Dr Emily Parker for being so supportive, encouraging and willing to welcome me into your group (not that you had much choice since I wasn’t moving!). Thanks to the members of the Parker group, especially Scott and Aidan, for their company in the office and the lab, and Penel, for bringing another female into 858 this year. -
Modulation of Brain Hyperexcitability: Potential New Therapeutic Approaches in Alzheimer’S Disease
International Journal of Molecular Sciences Review Modulation of Brain Hyperexcitability: Potential New Therapeutic Approaches in Alzheimer’s Disease Sofia Toniolo 1,2,*, Arjune Sen 3 and Masud Husain 1,2 1 Cognitive Neurology Group, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK; [email protected] 2 Wellcome Trust Centre for Integrative Neuroimaging, Department of Experimental Psychology, University of Oxford, Oxford OX2 6AE, UK 3 Oxford Epilepsy Research Group, Nuffield Department Clinical Neurosciences, John Radcliffe Hospital, Oxford OX3 9DU, UK; [email protected] * Correspondence: sofi[email protected]; Tel.: +44-1865-271310 Received: 29 October 2020; Accepted: 5 December 2020; Published: 7 December 2020 Abstract: People with Alzheimer’s disease (AD) have significantly higher rates of subclinical and overt epileptiform activity. In animal models, oligomeric Aβ amyloid is able to induce neuronal hyperexcitability even in the early phases of the disease. Such aberrant activity subsequently leads to downstream accumulation of toxic proteins, and ultimately to further neurodegeneration and neuronal silencing mediated by concomitant tau accumulation. Several neurotransmitters participate in the initial hyperexcitable state, with increased synaptic glutamatergic tone and decreased GABAergic inhibition. These changes appear to activate excitotoxic pathways and, ultimately, cause reduced long-term potentiation, increased long-term depression, and increased GABAergic inhibitory remodelling at the network level. Brain hyperexcitability has therefore been identified as a potential target for therapeutic interventions aimed at enhancing cognition, and, possibly, disease modification in the longer term. Clinical trials are ongoing to evaluate the potential efficacy in targeting hyperexcitability in AD, with levetiracetam showing some encouraging effects.