Sodium Channel Na Channels;Na+ Channels
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Crowdsourcing Analysis of Off-Label Intervention Usage in Amyotrophic Lateral Sclersosis
CROWDSOURCING ANALYSIS OF OFF-LABEL INTERVENTION USAGE IN AMYOTROPHIC LATERAL SCLERSOSIS A Thesis Presented to The Academic Faculty by Benjamin I. Mertens In Partial Fulfillment of the Requirements for the Degree B.S. in Biomedical Engineering with the Research Option in the Wallace H. Coulter School of Biomedical Engineering Georgia Institute of Technology Spring 2017 1 ACKNOWLEDGEMENTS I would like to thank my research advisor, Dr. Cassie Mitchell, first and foremost, for helping me through this long process of research, analysis, writing this thesis and the corresponding article to be submitted for peer-reviewed journal publication. There is no way I could have done this, or written it as eloquently without her. Next, I would like to acknowledge Grant Coan, Gloria Bowen, and Nathan Neuhart for all helping me on the road to writing this paper. Lastly, I would like to thank Dr. Lena Ting for her consultation as the faculty reader. 2 TABLE OF CONTENTS Page ACKNOWLEDGEMENTS 2 LIST OF TABLES 4 LIST OF FIGURES 5 LIST OF ABBREVIATIONS 6 SUMMARY 7 CHAPTERS 1 Philosophy 9 2 Crowdsourced Off-label Medications to Extend ALS Disease Duration 12 Introduction 12 Methodology 15 Results 18 Discussion 25 Tables 33 Figures 38 APPENDIX A: All Table 2 Appearance in Patients and Visits 44 APPENDIX B: All Table 3 Appearance in Patients and Visits 114 REFERENCES 129 3 LIST OF TABLES Page Table 1: Database Overview 33 Table 2: Ontology of Individual Medications 34 Table 3: Ontology of Intervention Groups 36 4 LIST OF FIGURES Page Figure 1: Relational circle -
In Silico Methods for Drug Repositioning and Drug-Drug Interaction Prediction
In silico Methods for Drug Repositioning and Drug-Drug Interaction Prediction Pathima Nusrath Hameed ORCID: 0000-0002-8118-9823 Submitted in total fulfilment of the requirements for the degree of Doctor of Philosophy Department of Mechanical Engineering THE UNIVERSITY OF MELBOURNE May 2018 Copyright © 2018 Pathima Nusrath Hameed All rights reserved. No part of the publication may be reproduced in any form by print, photoprint, microfilm or any other means without written permission from the author. Abstract Drug repositioning and drug-drug interaction (DDI) prediction are two fundamental ap- plications having a large impact on drug development and clinical care. Drug reposi- tioning aims to identify new uses for existing drugs. Moreover, understanding harmful DDIs is essential to enhance the effects of clinical care. Exploring both therapeutic uses and adverse effects of drugs or a pair of drugs have significant benefits in pharmacology. The use of computational methods to support drug repositioning and DDI prediction en- able improvements in the speed of drug development compared to in vivo and in vitro methods. This thesis investigates the consequences of employing a representative training sam- ple in achieving better performance for DDI classification. The Positive-Unlabeled Learn- ing method introduced in this thesis aims to employ representative positives as well as reliable negatives to train the binary classifier for inferring potential DDIs. Moreover, it explores the importance of a finer-grained similarity metric to represent the pairwise drug similarities. Drug repositioning can be approached by new indication detection. In this study, Anatomical Therapeutic Chemical (ATC) classification is used as the primary source to determine the indications/therapeutic uses of drugs for drug repositioning. -
208135Orig1s000
CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 208135Orig1s000 STATISTICAL REVIEW(S) U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research Office of Translational Sciences Office of Biostatistics S TATISTICAL R EVIEW AND E VALUATION CLINICAL STUDIES NDA/BLA #: 208135 Drug Name: Tetracaine Hydrochloride Ophthalmic Solution 0.5% (STERI-UNIT®) Indication(s): For procedures requiring a rapid and short acting ophthalmic anesthetic Applicant: Alcon research ltd Date(s): Stamp date: April 30, 2015 PDUFA date: February 29, 2016 Review Priority: Standard Biometrics Division: DBIV Statistical Reviewer: Abel Tilahun Eshete Concurring Reviewers: Yan Wang Medical Division: Ophthalmology Clinical Team: Medical Reviewer: Jennifer Harris Project Manager: Michael Puglisi Keywords: Topical anesthesia, Pain scores, Tetracaine . Reference ID: 3875889 Table of Contents 1 EXECUTIVE SUMMARY............................................................................................................................... 4 2 INTRODUCTION............................................................................................................................................. 6 2.1 OVERVIEW ................................................................................................................................................... 6 2.2 SUBMISSION HISTORY .................................................................................................................................. 6 2.3 -
Summary Analgesics Dec2019
Status as of December 31, 2019 UPDATE STATUS: N = New, A = Advanced, C = Changed, S = Same (No Change), D = Discontinued Update Emerging treatments for acute and chronic pain Development Status, Route, Contact information Status Agent Description / Mechanism of Opioid Function / Target Indication / Other Comments Sponsor / Originator Status Route URL Action (Y/No) 2019 UPDATES / CONTINUING PRODUCTS FROM 2018 Small molecule, inhibition of 1% diacerein TWi Biotechnology / caspase-1, block activation of 1 (AC-203 / caspase-1 inhibitor Inherited Epidermolysis Bullosa Castle Creek Phase 2 No Topical www.twibiotech.com NLRP3 inflamasomes; reduced CCP-020) Pharmaceuticals IL-1beta and IL-18 Small molecule; topical NSAID Frontier 2 AB001 NSAID formulation (nondisclosed active Chronic low back pain Phase 2 No Topical www.frontierbiotech.com/en/products/1.html Biotechnologies ingredient) Small molecule; oral uricosuric / anti-inflammatory agent + febuxostat (xanthine oxidase Gout in patients taking urate- Uricosuric + 3 AC-201 CR inhibitor); inhibition of NLRP3 lowering therapy; Gout; TWi Biotechnology Phase 2 No Oral www.twibiotech.com/rAndD_11 xanthine oxidase inflammasome assembly, reduced Epidermolysis Bullosa Simplex (EBS) production of caspase-1 and cytokine IL-1Beta www.arraybiopharma.com/our-science/our-pipeline AK-1830 Small molecule; tropomyosin Array BioPharma / 4 TrkA Pain, inflammation Phase 1 No Oral www.asahi- A (ARRY-954) receptor kinase A (TrkA) inhibitor Asahi Kasei Pharma kasei.co.jp/asahi/en/news/2016/e160401_2.html www.neurosmedical.com/clinical-research; -
Proxymetacaine Hydrochloride Ropivacaine Hydrochloride
1870 Local Anaesthetics Preparations pore: Alcaine; Switz.: Alcaine; Turk.: Alcaine; Opticaine; USA: Ak-Taine; Alcaine; Ocu-Caine; Ophthetic; Parcaine; Venez.: Alcaine; Oftaine†; Poen- (details are given in Part 3) caina. Proprietary Preparations CH3 Multi-ingredient: Spain: Detraine. O Multi-ingredient: Canad.: Fluoracaine†; USA: Fluoracaine; Fluorocaine. N CH3 O Quinisocaine Hydrochloride (BANM, rINNM) H3C Propipocaine (rINN) O Chinisocainum Hydrochloride; Dimethisoquin Hydrochloride Propipocaína; Propipocaïne; Propipocainum; Propoxypipero- (USAN); Dimethisoquinium Chloride; Hidrocloruro de quinisocaí- NH2 caine. 3-Piperidino-4′-propoxypropiophenone. na; Quinisocaïne, Chlorhydrate de; Quinisocaini Hydrochlori- (proxymetacaine) dum. 2-(3-Butyl-1-isoquinolyloxy)-NN-dimethylethylamine hy- Пропипокаин drochloride. C17H25NO2 = 275.4. Хинизокаина Гидрохлорид CAS — 3670-68-6. NOTE. PROX is a code approved by the BP 2008 for use on single unit doses of eye drops containing proxymetacaine hydrochlo- C17H24N2O,HCl = 308.8. ride where the individual container may be too small to bear all CAS — 86-80-6 (quinisocaine); 2773-92-4 (quinisocaine the appropriate labelling information. PROXFLN is a similar hydrochloride). O code approved for eye drops containing proxymetacaine hydro- ATC — D04AB05. chloride and fluorescein sodium. ATC Vet — QD04AB05. N Pharmacopoeias. In Br. and US. BP 2008 (Proxymetacaine Hydrochloride). A white or almost H3C CH3 white, odourless or almost odourless, crystalline powder. Soluble O in water and in chloroform; very soluble in dehydrated alcohol; N practically insoluble in ether. A 1% solution in water has a pH of O CH Profile 5.7 to 6.4. Protect from light. 3 Propipocaine is a local anaesthetic (p.1850) that has been used USP 31 (Proparacaine Hydrochloride). A white to off-white, or for surface anaesthesia. -
NINDS Custom Collection II
ACACETIN ACEBUTOLOL HYDROCHLORIDE ACECLIDINE HYDROCHLORIDE ACEMETACIN ACETAMINOPHEN ACETAMINOSALOL ACETANILIDE ACETARSOL ACETAZOLAMIDE ACETOHYDROXAMIC ACID ACETRIAZOIC ACID ACETYL TYROSINE ETHYL ESTER ACETYLCARNITINE ACETYLCHOLINE ACETYLCYSTEINE ACETYLGLUCOSAMINE ACETYLGLUTAMIC ACID ACETYL-L-LEUCINE ACETYLPHENYLALANINE ACETYLSEROTONIN ACETYLTRYPTOPHAN ACEXAMIC ACID ACIVICIN ACLACINOMYCIN A1 ACONITINE ACRIFLAVINIUM HYDROCHLORIDE ACRISORCIN ACTINONIN ACYCLOVIR ADENOSINE PHOSPHATE ADENOSINE ADRENALINE BITARTRATE AESCULIN AJMALINE AKLAVINE HYDROCHLORIDE ALANYL-dl-LEUCINE ALANYL-dl-PHENYLALANINE ALAPROCLATE ALBENDAZOLE ALBUTEROL ALEXIDINE HYDROCHLORIDE ALLANTOIN ALLOPURINOL ALMOTRIPTAN ALOIN ALPRENOLOL ALTRETAMINE ALVERINE CITRATE AMANTADINE HYDROCHLORIDE AMBROXOL HYDROCHLORIDE AMCINONIDE AMIKACIN SULFATE AMILORIDE HYDROCHLORIDE 3-AMINOBENZAMIDE gamma-AMINOBUTYRIC ACID AMINOCAPROIC ACID N- (2-AMINOETHYL)-4-CHLOROBENZAMIDE (RO-16-6491) AMINOGLUTETHIMIDE AMINOHIPPURIC ACID AMINOHYDROXYBUTYRIC ACID AMINOLEVULINIC ACID HYDROCHLORIDE AMINOPHENAZONE 3-AMINOPROPANESULPHONIC ACID AMINOPYRIDINE 9-AMINO-1,2,3,4-TETRAHYDROACRIDINE HYDROCHLORIDE AMINOTHIAZOLE AMIODARONE HYDROCHLORIDE AMIPRILOSE AMITRIPTYLINE HYDROCHLORIDE AMLODIPINE BESYLATE AMODIAQUINE DIHYDROCHLORIDE AMOXEPINE AMOXICILLIN AMPICILLIN SODIUM AMPROLIUM AMRINONE AMYGDALIN ANABASAMINE HYDROCHLORIDE ANABASINE HYDROCHLORIDE ANCITABINE HYDROCHLORIDE ANDROSTERONE SODIUM SULFATE ANIRACETAM ANISINDIONE ANISODAMINE ANISOMYCIN ANTAZOLINE PHOSPHATE ANTHRALIN ANTIMYCIN A (A1 shown) ANTIPYRINE APHYLLIC -
Rodgers 693..696
Copyright #ERS Journals Ltd 1999 Eur Respir J 1999; 14: 693±696 European Respiratory Journal Printed in UK ± all rights reserved ISSN 0903-1936 The effect of topical benzamil and amiloride on nasal potential difference in cystic fibrosis H.C. Rodgers, A.J. Knox The effect of topical benzamil and amiloride on nasal potential difference in cystic fibrosis. Respiratory Medicine Unit, City Hospital, H.C. Rodgers, A.J. Knox. #ERS Journals Ltd 1999. Hucknall Road, Nottingham, NG5 IPB. ABSTRACT: The electrochemical defect in the bronchial epithelium in cystic fibrosis (CF) consists of defective chloride secretion and excessive sodium reabsorption. The Correspondence: A.J. Knox Respiratory Medicine Unit sodium channel blocker, amiloride, has been shown to reversibly correct the sodium Clinical Sciences Building reabsorption in CF subjects, but long term studies of amiloride have been disap- City Hospital pointing due to its short duration of action. Benzamil, a benzyl substituted amiloride Hucknall Road analogue, has a longer duration of action than amiloride in cultured human nasal Nottingham NG5 lPB epithelium. The results of the first randomized, placebo controlled, double blind, UK crossover study are reported here comparing the effects of benzamil and amiloride on Fax: 0115 9602140 nasal potential difference (nasal PD) in CF. Ten adults with CF attended on three occasions. At each visit baseline nasal PD was Keywords: Amiloride -3 -3 benzamil recorded, the drug (amiloride 1610 M, benzamil 1.7610 M, or 0.9% sodium cystic fibrosis chloride) was administered topically via a nasal spray, and nasal PD was measured at nasal potential difference 15, 30 min, 1, 2, 4 and 8 h. -
Classification Decisions Taken by the Harmonized System Committee from the 47Th to 60Th Sessions (2011
CLASSIFICATION DECISIONS TAKEN BY THE HARMONIZED SYSTEM COMMITTEE FROM THE 47TH TO 60TH SESSIONS (2011 - 2018) WORLD CUSTOMS ORGANIZATION Rue du Marché 30 B-1210 Brussels Belgium November 2011 Copyright © 2011 World Customs Organization. All rights reserved. Requests and inquiries concerning translation, reproduction and adaptation rights should be addressed to [email protected]. D/2011/0448/25 The following list contains the classification decisions (other than those subject to a reservation) taken by the Harmonized System Committee ( 47th Session – March 2011) on specific products, together with their related Harmonized System code numbers and, in certain cases, the classification rationale. Advice Parties seeking to import or export merchandise covered by a decision are advised to verify the implementation of the decision by the importing or exporting country, as the case may be. HS codes Classification No Product description Classification considered rationale 1. Preparation, in the form of a powder, consisting of 92 % sugar, 6 % 2106.90 GRIs 1 and 6 black currant powder, anticaking agent, citric acid and black currant flavouring, put up for retail sale in 32-gram sachets, intended to be consumed as a beverage after mixing with hot water. 2. Vanutide cridificar (INN List 100). 3002.20 3. Certain INN products. Chapters 28, 29 (See “INN List 101” at the end of this publication.) and 30 4. Certain INN products. Chapters 13, 29 (See “INN List 102” at the end of this publication.) and 30 5. Certain INN products. Chapters 28, 29, (See “INN List 103” at the end of this publication.) 30, 35 and 39 6. Re-classification of INN products. -
4 Supplementary File
Supplemental Material for High-throughput screening discovers anti-fibrotic properties of Haloperidol by hindering myofibroblast activation Michael Rehman1, Simone Vodret1, Luca Braga2, Corrado Guarnaccia3, Fulvio Celsi4, Giulia Rossetti5, Valentina Martinelli2, Tiziana Battini1, Carlin Long2, Kristina Vukusic1, Tea Kocijan1, Chiara Collesi2,6, Nadja Ring1, Natasa Skoko3, Mauro Giacca2,6, Giannino Del Sal7,8, Marco Confalonieri6, Marcello Raspa9, Alessandro Marcello10, Michael P. Myers11, Sergio Crovella3, Paolo Carloni5, Serena Zacchigna1,6 1Cardiovascular Biology, 2Molecular Medicine, 3Biotechnology Development, 10Molecular Virology, and 11Protein Networks Laboratories, International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano, 34149, Trieste, Italy 4Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste, Italy 5Computational Biomedicine Section, Institute of Advanced Simulation IAS-5 and Institute of Neuroscience and Medicine INM-9, Forschungszentrum Jülich GmbH, 52425, Jülich, Germany 6Department of Medical, Surgical and Health Sciences, University of Trieste, 34149 Trieste, Italy 7National Laboratory CIB, Area Science Park Padriciano, Trieste, 34149, Italy 8Department of Life Sciences, University of Trieste, Trieste, 34127, Italy 9Consiglio Nazionale delle Ricerche (IBCN), CNR-Campus International Development (EMMA- INFRAFRONTIER-IMPC), Rome, Italy This PDF file includes: Supplementary Methods Supplementary References Supplementary Figures with legends 1 – 18 Supplementary Tables with legends 1 – 5 Supplementary Movie legends 1, 2 Supplementary Methods Cell culture Primary murine fibroblasts were isolated from skin, lung, kidney and hearts of adult CD1, C57BL/6 or aSMA-RFP/COLL-EGFP mice (1) by mechanical and enzymatic tissue digestion. Briefly, tissue was chopped in small chunks that were digested using a mixture of enzymes (Miltenyi Biotec, 130- 098-305) for 1 hour at 37°C with mechanical dissociation followed by filtration through a 70 µm cell strainer and centrifugation. -
The Elimination of High Doses of Phenytoin In
THE ELIMINATION OF HIGH DOSES OF PHENYTOIN IN MAN AND THE RABBIT by Peter Chinwah Department of Clinical Pharmacology St. Vincent's Hospital Darlinghurst, 2010, N.S.W. AUSTRALIA A Thesis submitted for the Degree of Master of Science in the University of New South Wales February, 1987 Ul·lilJ:2?.S1TY QF N.S.W. ~ 14 JUN 1988 f L!.:.": --":c_A:_'''"lARY I (i) ACKNOWLEDGEMENTS I wish to thank Professor Denis Wade for the opportunity to undertake this thesis in the Department of Clinical Pharmacology and for his overseeing and supervision of this project. I would like to express my gratitude to Dr Garry Graham, Senior Lecturer in the Department of Physiology and Pharmacology at the University of New South Wales, for his significant contribution in discussion and critical review of this thesis. I also wish to thank my colleagues of the Department of Clinical Pharmacology and Toxicology at St Vincent's Hospital for their assistance during the course of the project. Finally, I am grateful to Dr Ken Williams of the Department of Clinical Pharmacology and Toxicology at St Vincent's Hospital for many hours of discussion, and his admonishment, long suffering and perserverence which have made this thesis possible. (ii) ABSTRACT The pharmacokinetics of phenytoin were studied in twelve patients who presented to casualty with phenytoin toxicity. These patients were divided into 3 groups according to the type of plasma elimination profiles observed. Group 1. consisted of 3 patients who demonstrated first order elimination kinetics with long elimination half lives (70-106 hours). Group 2. consisted of 6 patients who showed saturable elimination kinetics (mean estimated terminal half life 28 hours). -
1 Abietic Acid R Abrasive Silica for Polishing DR Acenaphthene M (LC
1 abietic acid R abrasive silica for polishing DR acenaphthene M (LC) acenaphthene quinone R acenaphthylene R acetal (see 1,1-diethoxyethane) acetaldehyde M (FC) acetaldehyde-d (CH3CDO) R acetaldehyde dimethyl acetal CH acetaldoxime R acetamide M (LC) acetamidinium chloride R acetamidoacrylic acid 2- NB acetamidobenzaldehyde p- R acetamidobenzenesulfonyl chloride 4- R acetamidodeoxythioglucopyranose triacetate 2- -2- -1- -β-D- 3,4,6- AB acetamidomethylthiazole 2- -4- PB acetanilide M (LC) acetazolamide R acetdimethylamide see dimethylacetamide, N,N- acethydrazide R acetic acid M (solv) acetic anhydride M (FC) acetmethylamide see methylacetamide, N- acetoacetamide R acetoacetanilide R acetoacetic acid, lithium salt R acetobromoglucose -α-D- NB acetohydroxamic acid R acetoin R acetol (hydroxyacetone) R acetonaphthalide (α)R acetone M (solv) acetone ,A.R. M (solv) acetone-d6 RM acetone cyanohydrin R acetonedicarboxylic acid ,dimethyl ester R acetonedicarboxylic acid -1,3- R acetone dimethyl acetal see dimethoxypropane 2,2- acetonitrile M (solv) acetonitrile-d3 RM acetonylacetone see hexanedione 2,5- acetonylbenzylhydroxycoumarin (3-(α- -4- R acetophenone M (LC) acetophenone oxime R acetophenone trimethylsilyl enol ether see phenyltrimethylsilyl... acetoxyacetone (oxopropyl acetate 2-) R acetoxybenzoic acid 4- DS acetoxynaphthoic acid 6- -2- R 2 acetylacetaldehyde dimethylacetal R acetylacetone (pentanedione -2,4-) M (C) acetylbenzonitrile p- R acetylbiphenyl 4- see phenylacetophenone, p- acetyl bromide M (FC) acetylbromothiophene 2- -5- -
8–16–01 Vol. 66 No. 159 Thursday Aug. 16, 2001 Pages 42929
8–16–01 Thursday Vol. 66 No. 159 Aug. 16, 2001 Pages 42929–43064 VerDate 11-MAY-2000 19:13 Aug 15, 2001 Jkt 194001 PO 00000 Frm 00001 Fmt 4710 Sfmt 4710 E:\FR\FM\16AUWS.LOC pfrm11 PsN: 16AUWS 1 II Federal Register / Vol. 66, No. 159 / Thursday, August 16, 2001 The FEDERAL REGISTER is published daily, Monday through SUBSCRIPTIONS AND COPIES Friday, except official holidays, by the Office of the Federal Register, National Archives and Records Administration, PUBLIC Washington, DC 20408, under the Federal Register Act (44 U.S.C. Subscriptions: Ch. 15) and the regulations of the Administrative Committee of Paper or fiche 202–512–1800 the Federal Register (1 CFR Ch. I). The Superintendent of Assistance with public subscriptions 512–1806 Documents, U.S. Government Printing Office, Washington, DC 20402 is the exclusive distributor of the official edition. General online information 202–512–1530; 1–888–293–6498 Single copies/back copies: The Federal Register provides a uniform system for making available to the public regulations and legal notices issued by Paper or fiche 512–1800 Federal agencies. These include Presidential proclamations and Assistance with public single copies 512–1803 Executive Orders, Federal agency documents having general FEDERAL AGENCIES applicability and legal effect, documents required to be published Subscriptions: by act of Congress, and other Federal agency documents of public interest. Paper or fiche 523–5243 Assistance with Federal agency subscriptions 523–5243 Documents are on file for public inspection in the Office of the Federal Register the day before they are published, unless the issuing agency requests earlier filing.