DOCSLIB.ORG

Intensive Care Muscle Wasting and Weakness

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Intensive Care Muscle Wasting and Weakness Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 862 Intensive care Muscle Wasting and Weakness Underlying Mechanisms, Muscle Specific Differences and a Specific Intervention Strategy GuiLLAumE RENAud ACTA UNIVERSITATIS UPSALIENSIS ISSN 1651-6206 UPPSALA ISBN 978-91-554-8586-3 2013 urn:nbn:se:uu:diva-192531 Dissertation presented at Uppsala University to be publicly examined in Hedstrandsalen, Ingång 70, bv, Akademiska sjukhuset, Uppsala, Friday, March 8, 2013 at 13:15 for the degree of Doctor of Philosophy (Faculty of Medicine). The examination will be conducted in English. Abstract Renaud, G. 2013. Intensive care Muscle Wasting and Weakness: Underlying Mechanisms, Muscle Specific Differences and a Specific Intervention Strategy. Acta Universitatis Upsaliensis. Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 862. 57 pp. Uppsala. ISBN 978-91-554-8586-3. The intensive care unit (ICU) condition, i.e., immobilisation, sedation and mechanical ventilation, often results in severe muscle wasting and weakness as well as a specific acquired myopathy, i.e., Acute Quadriplegic Myopathy (AQM). The exact mechanisms underlying AQM remain incomplete, but this myopathy is characterised a preferential myosin loss and a decreased muscle membrane leading to a delayed recovery from the primary disease, increased mortality and morbidity and altered quality of life of survivors. This project aims at improving our understanding of the mechanisms underlying the muscle wasting and weakness associated with AQM and explore the effects of a specific intervention strategy. Time-resolved analyses have been undertaken using a unique experimental rodent ICU model and specifically studying the muscle wasting and weakness in limb and diaphragm muscles over a two week period. Further, we used passive mechanical loading in an attempt to alleviate the impaired muscle function and wasting associated with the ICU condition. Subsequently, the knowledge gained from the animal model was translated into a clinical study. Mechanical silencing (absence of external and internal strain) due to immobilisation, pharmacological neuromuscular blockade and sedation, was identified as a key factor triggering the muscle wasting and weakness associated with AQM in limb muscles. In addition, MuRF1, a member of the ubiquitin proteasome degradation pathway is playing a major role in the contractile protein degradation observed in both the diaphragm and limb muscles offering a potential candidate for future therapeutic approaches. Moreover, passive mechanical loading resulted in significant positive effects on muscle structure and function in the rodent ICU model, decreasing muscle atrophy and the loss of force generating capacity. In ICU patients passive mechanical loading improved the muscle fibre force generating capacity but did not affect muscle wasting. Nevertheless, this work strongly supports the importance of early physical therapy and mobilization in deeply sedated and mechanically ventilated ICU patients. Furthermore, we observed significant differences in the phenotype and mechanism underlying the loss of force generating capacity between the diaphragm and limb muscles in response to controlled mechanical ventilation (CMV) and immobilisation. This knowledge will have to be taken into account when designing intervention strategies to alleviate the muscle wasting and weakness that occurs in mechanically ventilated and immobilized ICU patients. Guillaume Renaud, Uppsala University, Department of Neuroscience, Clinical Neurophysiology, Akademiska sjukhuset, SE-751 85 Uppsala, Sweden. © Guillaume Renaud 2013 ISSN 1651-6206 ISBN 978-91-554-8586-3 urn:nbn:se:uu:diva-192531 (http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-192531) A mes Neveux et Nièces List of Papers This thesis is based on the following papers, which are referred to in the text by their Roman numerals. I Ochala J, Gustafson AM, Diez ML, Renaud G, Li M, Aare S, Qaisar R, Banduseela VC, Hedstrom Y, Tang X, Dworkin B, Ford GC, Nair KS, Perera S, Gautel M, and Larsson L. Prefer- ential skeletal muscle myosin loss in response to mechanical si- lencing in a novel rat intensive care unit model: Underlying mechanisms. J Physiol 589: 2007-2026, 2011. II Renaud† G, Diez† ML, Ravar B, Gorza L, Feng HZ, Jin JP, Cacciani N, Gustafson AM, Ochala J, Corpeño R, Li M, Hed- ström Y, Ford GC, Nair KS, Larsson L. Sparing of muscle mass and function by passive loading in an experimental intensive care unit model. J physiol. In press. III Diez† ML, Renaud† G, Andersson M, Gonzales Marrero H, Cacciani N, Engquist H, Corpeño R, Artemenko K, Bergquist J, and Larsson L. Intensive care unit muscle wasting: mechanisms and intervention strategies. Crit Care, 16:R209, 2012 IV Renaud G, Corpeño R, Gorza L, Jin JP, Gustafson AM, Iwa- moto H, Yagi N, and Larsson L. Time-course analysis of me- chanical ventilation-induced diaphragm contractile muscle dys- function. In manuscript. † Contributed equally to the study Reprints were made with permission from the respective publishers. Contents Introduction ................................................................................................... 11 Skeletal Muscle ........................................................................................ 11 Contractile proteins .................................................................................. 13 Actin .................................................................................................... 13 Myosin ................................................................................................. 13 Muscle Contraction .................................................................................. 15 Regulation of muscle mass ....................................................................... 17 Oxidative stress ........................................................................................ 18 Acute Quadriplegic Myopathy ................................................................. 21 Characteristics ..................................................................................... 22 Diagnosis ............................................................................................. 22 Risk factors .......................................................................................... 23 Interventions ........................................................................................ 24 Aims of the present investigation.................................................................. 25 Materials and methods .................................................................................. 26 Animals (I, II and IV) .......................................................................... 26 Human patients (III) ............................................................................ 26 Muscle biopsy and muscle fibre membrane permeabilization (I, II, III and IV) ............................................................................................ 27 Contractile measurements of single muscle fibres (I, II, III and IV) ... 27 Enzyme-histochemistry and immunocytochemistry (I and III) ........... 28 Myosin heavy chain isoform expression (I, II, III and IV) .................. 28 Actin, myosin and total protein quantification (I, II, III and IV) ......... 28 Western blots (I, II and IV) .................................................................. 28 Total RNA isolation and quantification (I, II, III and IV) ................... 29 Quantitative RT-PCR (I, II, III and IV) ............................................... 29 Protein oxidation detection (II and IV) ................................................ 29 Fractional synthesis rate (I, II) ............................................................. 29 Ultrasound measurements (III) ............................................................ 29 Electrophysiological measurements (III) ............................................. 30 Gene expression profiling (II) ............................................................. 30 Post-translational modifications (III) ................................................... 30 X-ray diffraction (IV) .......................................................................... 30 Statistics (I, II, III and IV) ................................................................... 31 Results and Discussion ................................................................................. 32 A rodent model that mimics ICU conditions (I) ....................................... 32 Mechanical silencing is key for triggering AQM (I) ................................ 33 MuRF1 is a key factor underlying muscle proteolysis (I and IV) ............ 33 Passive mechanical loading is beneficial on skeletal muscle (II and III) . 34 Passive mechanical loading reduces the oxidative stress associated with mechanical silencing (II) .................................................................. 35 ICU condition induces specific myosin post-translational modifications (III) ........................................................................................................... 36 Controlled mechanical ventilation causes early contractile dysfunction in the diaphragm (IV) ............................................................................... 37 Diaphragm atrophy differs from the one observed in limb muscles (IV) 37 Mechanical ventilation induces a severe oxidative stress (IV) ................ 38 Conclusions ..................................................................................................
Load more

Recommended publications
  • Irina Nicoleta Cimalla Algan/Gan Sensors for Direct Monitoring Of
    Irina Nicoleta Cimalla AlGaN/GaN sensors for direct monitoring of fluids and bioreactions AlGaN/GaN sensors for direct monitoring of fluids and bioreactions Irina Nicoleta Cimalla Universitätsverlag Ilmenau 2011 Impressum Bibliografische Information der Deutschen Nationalbibliothek Die Deutsche Nationalbibliothek verzeichnet diese Publikation in der Deutschen Nationalbibliografie; detaillierte bibliografische Angaben sind im Internet über http://dnb.d-nb.de abrufbar. Diese Arbeit hat der Fakultät für Elektrotechnik und Informationstechnik der Technischen Universität Ilmenau als Dissertation vorgelegen. Tag der Einreichung: 23. November 2009 1. Gutachter: PD Dr. rer. nat. habil. Andreas Schober (Technische Universität Ilmenau) 2. Gutachter: Univ.-Prof. Dr. rer. nat. habil. Oliver Ambacher (Fraunhofer Institut für Angewandte Festkörperphysik Freiburg) 3. Gutachter: PD Dr.-Ing. habil. Frank Schwierz (Technische Universität Ilmenau) Tag der Verteidigung: 15. Juli 2010 Technische Universität Ilmenau/Universitätsbibliothek Universitätsverlag Ilmenau Postfach 10 05 65 98684 Ilmenau www.tu-ilmenau.de/universitaetsverlag Herstellung und Auslieferung Verlagshaus Monsenstein und Vannerdat OHG Am Hawerkamp 31 48155 Münster www.mv-verlag.de ISBN 978-3-86360-003-7 (Druckausgabe) URN urn:nbn:de:gbv:ilm1-2010000519 Titelfoto: photocase.com | AlexFlint „Unde dragoste nu e, nimic nu e” „Wo Liebe nicht ist, ist gar nichts“ Marin Preda: „Cel mai iubit dintre pamanteni“ 5 6 Abstract In this thesis, AlGaN/GaN heterostructures, which have shown to be reliable pH sensors, have been characterized and further developed for the in situ monitoring of cell reactions. For this reason, NG108-15 nerve cells were cultivated on sensor surfaces and their response on different neuroinhibitors was clearly monitored. First, a measurement setup for extracellular recording was designed in connection with an improved chip design and sensor technology.
    [Show full text]
  • Families and the Structural Relatedness Among Globular Proteins
    Protein Science (1993), 2, 884-899. Cambridge University Press. Printed in the USA. Copyright 0 1993 The Protein Society -~~ ~~~~ ~ Families and the structural relatedness among globular proteins DAVID P. YEE AND KEN A. DILL Department of Pharmaceutical Chemistry, University of California, San Francisco, California94143-1204 (RECEIVEDJanuary 6, 1993; REVISEDMANUSCRIPT RECEIVED February 18, 1993) Abstract Protein structures come in families. Are families “closely knit” or “loosely knit” entities? We describe a mea- sure of relatedness among polymer conformations. Based on weighted distance maps, this measure differs from existing measures mainly in two respects: (1) it is computationally fast, and (2) it can compare any two proteins, regardless of their relative chain lengths or degree of similarity. It does not require finding relative alignments. The measure is used here to determine the dissimilarities between all 12,403 possible pairs of 158 diverse protein structures from the Brookhaven Protein Data Bank (PDB). Combined with minimal spanning trees and hier- archical clustering methods,this measure is used to define structural families. It is also useful for rapidly searching a dataset of protein structures for specific substructural motifs.By using an analogy to distributions of Euclid- ean distances, we find that protein families are not tightly knit entities. Keywords: protein family; relatedness; structural comparison; substructure searches Pioneering work over the past 20 years has shown that positions after superposition. RMS is a useful distance proteins fall into families of related structures (Levitt & metric for comparingstructures that arenearly identical: Chothia, 1976; Richardson, 1981; Richardson & Richard- for example, when refining or comparing structures ob- son, 1989; Chothia & Finkelstein, 1990).
    [Show full text]
  • Report from the 26Th Meeting on Toxinology,“Bioengineering Of
    toxins Meeting Report Report from the 26th Meeting on Toxinology, “Bioengineering of Toxins”, Organized by the French Society of Toxinology (SFET) and Held in Paris, France, 4–5 December 2019 Pascale Marchot 1,* , Sylvie Diochot 2, Michel R. Popoff 3 and Evelyne Benoit 4 1 Laboratoire ‘Architecture et Fonction des Macromolécules Biologiques’, CNRS/Aix-Marseille Université, Faculté des Sciences-Campus Luminy, 13288 Marseille CEDEX 09, France 2 Institut de Pharmacologie Moléculaire et Cellulaire, Université Côte d’Azur, CNRS, Sophia Antipolis, 06550 Valbonne, France; [email protected] 3 Bacterial Toxins, Institut Pasteur, 75015 Paris, France; michel-robert.popoff@pasteur.fr 4 Service d’Ingénierie Moléculaire des Protéines (SIMOPRO), CEA de Saclay, Université Paris-Saclay, 91191 Gif-sur-Yvette, France; [email protected] * Correspondence: [email protected]; Tel.: +33-4-9182-5579 Received: 18 December 2019; Accepted: 27 December 2019; Published: 3 January 2020 1. Preface This 26th edition of the annual Meeting on Toxinology (RT26) of the SFET (http://sfet.asso.fr/ international) was held at the Institut Pasteur of Paris on 4–5 December 2019. The central theme selected for this meeting, “Bioengineering of Toxins”, gave rise to two thematic sessions: one on animal and plant toxins (one of our “core” themes), and a second one on bacterial toxins in honour of Dr. Michel R. Popoff (Institut Pasteur, Paris, France), both sessions being aimed at emphasizing the latest findings on their respective topics. Nine speakers from eight countries (Belgium, Denmark, France, Germany, Russia, Singapore, the United Kingdom, and the United States of America) were invited as international experts to present their work, and other researchers and students presented theirs through 23 shorter lectures and 27 posters.
    [Show full text]
  • World Journal of Biological Chemistry
    ISSN 1949-8454 (online) World Journal of Biological Chemistry World J Biol Chem 2019 January 7; 10(1): 1-27 Published by Baishideng Publishing Group Inc World Journal of W J B C Biological Chemistry Contents Continuous Volume 10 Number 1 January 7, 2019 EDITORIAL 1 New findings showing how DNA methylation influences diseases Sallustio F, Gesualdo L, Gallone A MINIREVIEWS 7 Autism and carnitine: A possible link Demarquoy C, Demarquoy J 17 Last decade update for three-finger toxins: Newly emerging structures and biological activities Utkin YN WJBC https://www.wjgnet.com I January 7, 2019 Volume 10 Issue 1 World Journal of Biological Chemistry Contents Volume 10 Number 1 January 7, 2019 ABOUT COVER Editor-in-Chief of World Journal of Biological Chemistry, Vsevolod V Gurevich, PhD, Professor, Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, United States AIMS AND SCOPE World Journal of Biological Chemistry (World J Biol Chem, WJBC, online ISSN 1949-8454, DOI: 10.4331) is a peer-reviewed open access academic journal that aims to guide clinical practice and improve diagnostic and therapeutic skills of clinicians. WJBC is to rapidly report the most recent developments in the research by the close collaboration of biologists and chemists in area of biochemistry and molecular biology, including: general biochemistry, pathobiochemistry, molecular and cellular biology, molecular medicine, experimental methodologies and the diagnosis, therapy, and monitoring of human disease. We encourage authors to submit their manuscripts to WJBC. We will give priority to manuscripts that are supported by major national and international foundations and those that are of great basic and clinical significance.
    [Show full text]
  • Proteins, Peptides, and Amino Acids
    Proteins, Peptides, and Amino Acids Chandra Mohan, Ph.D. Calbiochem-Novabiochem Corp., San Diego, CA The Chemical Nature of Amino Acids Peptides and polypeptides are polymers of α-amino acids. There are 20 α-amino acids that make-up all proteins of biological interest. The α-amino acids in peptides and proteins α consist of a carboxylic acid (-COOH) and an amino (-NH2) functional group attached to the same tetrahedral carbon atom. This carbon is known as the -carbon. The type of R- group attached to this carbon distinguishes one amino acid from another. Several other amino acids, also found in the body, may not be associated with peptides or proteins. These non-protein-associated amino acids perform specialized functions. Some of the α-amino acids found in proteins are also involved in other functions in the body. For example, tyrosine is involved in the formation of thyroid hormones, and glutamate and aspartate act as neurotransmitters at fast junctions. R Amino acids exist in either D- or L- enantiomorphs or stereoisomers. The D- and L-refer to the absolute confirmation of optically active compounds. With the exception of glycine, all other amino acids are mirror images that can not be superimposed. Most of the amino acids found in nature are of the L-type. Hence, eukaryotic proteins are always composed of L-amino acids although D-amino acids are found in bacterial cell walls and in some peptide antibiotics. All biological reactions occur in an aqueous phase. Hence, it is important to know how the R-group of any given amino acid dictates the structure-function relationships of peptides and proteins in solution.
    [Show full text]
  • 6-Bromohypaphorine from Marine Nudibranch Mollusk Hermissenda Crassicornis Is an Agonist of Human Α7 Nicotinic Acetylcholine Receptor
    Mar. Drugs 2015, 13, 1255-1266; doi:10.3390/md13031255 OPEN ACCESS marine drugs ISSN 1660-3397 www.mdpi.com/journal/marinedrugs Article 6-Bromohypaphorine from Marine Nudibranch Mollusk Hermissenda crassicornis is an Agonist of Human α7 Nicotinic Acetylcholine Receptor Igor E. Kasheverov 1, Irina V. Shelukhina 1, Denis S. Kudryavtsev 1, Tatyana N. Makarieva 2, Ekaterina N. Spirova 1, Alla G. Guzii 2, Valentin A. Stonik 2 and Victor I. Tsetlin 1,* 1 Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Street, 16/10, Moscow 117997, Russia; E-Mails: [email protected] (I.E.K.); [email protected] (I.V.S.); [email protected] (D.S.K.); [email protected] (E.N.S.) 2 G.B. Elyakov Pacific Institute of Bioorganic Chemistry (PIBOC), Russian Academy of Sciences, Prospect 100 let Vladivostoku, 159, Vladivostok 690022, Russia; E-Mails: [email protected] (T.N.M.); [email protected] (A.G.G.); [email protected] (V.A.S.) * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel./Fax: +7-495-335-57-33. Academic Editor: Alejandro M. Mayer Received: 30 December 2014 / Accepted: 15 February 2015 / Published: 12 March 2015 Abstract: 6-Bromohypaphorine (6-BHP) has been isolated from the marine sponges Pachymatisma johnstoni, Aplysina sp., and the tunicate Aplidium conicum, but data on its biological activity were not available. For the nudibranch mollusk Hermissenda crassicornis no endogenous compounds were known, and here we describe the isolation of 6-BHP from this mollusk and its effects on different nicotinic acetylcholine receptors (nAChR).
    [Show full text]
  • Drug and Medication Classification Schedule
    KENTUCKY HORSE RACING COMMISSION UNIFORM DRUG, MEDICATION, AND SUBSTANCE CLASSIFICATION SCHEDULE KHRC 8-020-1 (11/2018) Class A drugs, medications, and substances are those (1) that have the highest potential to influence performance in the equine athlete, regardless of their approval by the United States Food and Drug Administration, or (2) that lack approval by the United States Food and Drug Administration but have pharmacologic effects similar to certain Class B drugs, medications, or substances that are approved by the United States Food and Drug Administration. Acecarbromal Bolasterone Cimaterol Divalproex Fluanisone Acetophenazine Boldione Citalopram Dixyrazine Fludiazepam Adinazolam Brimondine Cllibucaine Donepezil Flunitrazepam Alcuronium Bromazepam Clobazam Dopamine Fluopromazine Alfentanil Bromfenac Clocapramine Doxacurium Fluoresone Almotriptan Bromisovalum Clomethiazole Doxapram Fluoxetine Alphaprodine Bromocriptine Clomipramine Doxazosin Flupenthixol Alpidem Bromperidol Clonazepam Doxefazepam Flupirtine Alprazolam Brotizolam Clorazepate Doxepin Flurazepam Alprenolol Bufexamac Clormecaine Droperidol Fluspirilene Althesin Bupivacaine Clostebol Duloxetine Flutoprazepam Aminorex Buprenorphine Clothiapine Eletriptan Fluvoxamine Amisulpride Buspirone Clotiazepam Enalapril Formebolone Amitriptyline Bupropion Cloxazolam Enciprazine Fosinopril Amobarbital Butabartital Clozapine Endorphins Furzabol Amoxapine Butacaine Cobratoxin Enkephalins Galantamine Amperozide Butalbital Cocaine Ephedrine Gallamine Amphetamine Butanilicaine Codeine
    [Show full text]
  • List Over Prohibited Substances and Withdrawal Times, Valid from January 1St, 2016 A. LIST of PROHIBITED SUBSTANCES
    Reviewed 01.06.16 List over prohibited substances and withdrawal times, valid from January 1st, 2016 This list has been developed in collaboration with the other Nordic countries through NEMAC (Nordic Equine Medication and Anti-doping Committee) and is reviewed yearly by the board of DNT (The Norwegian Trotting Association) (in accordance with DNT’s Doping Regulations 2016 § 3, 1st subsection). The List of prohibited substances and withdrawal times consists of the A-list, listing substances and treatment methods that are absolutely prohibited for horses, and the B-list, listing substances that are prohibited in competition; the withdrawal times for these substances as well as treatment methods with withdrawal times. The list may be reviewed several times per year. This list is valid starting from January 1st, 2016 and is enforced until a new list takes effect. A valid list of withdrawal times can be found at any time on DNT’s official website, www.travsport.no. Withdrawal times given on STC’s official website, www.travsport.se, are also valid in Norway. Health certificate and keeping of medical records The trainer is responsible for ensuring that any treatment that requires a withdrawal time is listed in the horse’s health certificate. The start and end dates of the treatment, the name of the treatment/medication/active substance, amount given, method of administration, withdrawal time as well as the name of the veterinarian or other person responsible for the treatment must all be listed in the health certificate in accordance with DNT’s Doping Regulations 2016 § 4. Passport and health certificate should be brought with the horse at all times.
    [Show full text]
  • Targeting Cannabinoid Receptors: Current Status and Prospects of Natural Products
    International Journal of Molecular Sciences Review Targeting Cannabinoid Receptors: Current Status and Prospects of Natural Products Dongchen An, Steve Peigneur , Louise Antonia Hendrickx and Jan Tytgat * Toxicology and Pharmacology, KU Leuven, Campus Gasthuisberg, O&N 2, Herestraat 49, P.O. Box 922, 3000 Leuven, Belgium; [email protected] (D.A.); [email protected] (S.P.); [email protected] (L.A.H.) * Correspondence: [email protected] Received: 12 June 2020; Accepted: 15 July 2020; Published: 17 July 2020 Abstract: Cannabinoid receptors (CB1 and CB2), as part of the endocannabinoid system, play a critical role in numerous human physiological and pathological conditions. Thus, considerable efforts have been made to develop ligands for CB1 and CB2, resulting in hundreds of phyto- and synthetic cannabinoids which have shown varying affinities relevant for the treatment of various diseases. However, only a few of these ligands are clinically used. Recently, more detailed structural information for cannabinoid receptors was revealed thanks to the powerfulness of cryo-electron microscopy, which now can accelerate structure-based drug discovery. At the same time, novel peptide-type cannabinoids from animal sources have arrived at the scene, with their potential in vivo therapeutic effects in relation to cannabinoid receptors. From a natural products perspective, it is expected that more novel cannabinoids will be discovered and forecasted as promising drug leads from diverse natural sources and species, such as animal venoms which constitute a true pharmacopeia of toxins modulating diverse targets, including voltage- and ligand-gated ion channels, G protein-coupled receptors such as CB1 and CB2, with astonishing affinity and selectivity.
    [Show full text]
  • Natural Neurotoxins with Targeting T0 Cholinergic Nervous System (Cholinotoxins)
    22 VOJENSKÉ ZDRAVOTNICKÉ LISTY - SUPLEMENTUM VOLUME LXVII, 1998, no. 2 NATURAL NEUROTOXINS WITH TARGETING T0 CHOLINERGIC NERVOUS SYSTEM (CHOLINOTOXINS) Jiří PATOČKA Department of Toxicology, Purkyně Military Medical Academy, Hradec Králové Summary Cholinergic nervous system plays an important røle in many physiological and behavioral functions in all animals. The activity of central and peripheral nervous system depends on the production and fate of acetylcholine and all compounds influenced its biosynthesis, storage, release, hydrolysis, and interactions with different subtypes of acetylcholine both muscarinic and nicotinic receptors. Many natural neurotoxins also interact with different parts of cholinergic nervous system and these compounds are the aim of this review. KEY WORDS: Cholinergic nervous system; Alkaloids; Animal venoms; Neurotoxins. 1. Introduction purposes by native civilizations in all continents. Toxins of venomous animals as for instance snakes, Natural toxins are chemical agents of biological scorpions, spiders, bees etc., have fascinated origin, present in the bodies of some organisms or mankind because of their dramatic toxic effect on in the special glands which product venom. Toxins other animals. These poisons are used by the have evolved in microorganisms, fungi, plants and animals for protection against predators or for animals over many thousands of years to have capturing prey and very often affect their nervous specific and unique effects. Venoms from different system (neurotoxins). Many venoms have multiple toxic plants are known and used for different components or toxins that lead toa complicated VOLUME LXVII, 1998, no. 2 VOJENSKE ZDRAVOTNICKÉ LISTY - SUPLEMENTUM › 23 clinical picture. The toxicity of many toxins is very Arecoline high, very often comparable with chemical warfare agents, and they may be dangerous for humans.
    [Show full text]
  • Drug/Substance Trade Name(S)
    A B C D E F G H I J K 1 Drug/Substance Trade Name(s) Drug Class Existing Penalty Class Special Notation T1:Doping/Endangerment Level T2: Mismanagement Level Comments Methylenedioxypyrovalerone is a stimulant of the cathinone class which acts as a 3,4-methylenedioxypyprovaleroneMDPV, “bath salts” norepinephrine-dopamine reuptake inhibitor. It was first developed in the 1960s by a team at 1 A Yes A A 2 Boehringer Ingelheim. No 3 Alfentanil Alfenta Narcotic used to control pain and keep patients asleep during surgery. 1 A Yes A No A Aminoxafen, Aminorex is a weight loss stimulant drug. It was withdrawn from the market after it was found Aminorex Aminoxaphen, Apiquel, to cause pulmonary hypertension. 1 A Yes A A 4 McN-742, Menocil No Amphetamine is a potent central nervous system stimulant that is used in the treatment of Amphetamine Speed, Upper 1 A Yes A A 5 attention deficit hyperactivity disorder, narcolepsy, and obesity. No Anileridine is a synthetic analgesic drug and is a member of the piperidine class of analgesic Anileridine Leritine 1 A Yes A A 6 agents developed by Merck & Co. in the 1950s. No Dopamine promoter used to treat loss of muscle movement control caused by Parkinson's Apomorphine Apokyn, Ixense 1 A Yes A A 7 disease. No Recreational drug with euphoriant and stimulant properties. The effects produced by BZP are comparable to those produced by amphetamine. It is often claimed that BZP was originally Benzylpiperazine BZP 1 A Yes A A synthesized as a potential antihelminthic (anti-parasitic) agent for use in farm animals.
    [Show full text]
  • WO 2016/079553 Al 26 May 2016 (26.05.2016) P O P C T
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2016/079553 Al 26 May 2016 (26.05.2016) P O P C T (51) International Patent Classification: HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, A61K 36/889 (2006.01) A61P 39/02 (2006.01) KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, (21) International Application Number: PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, PCT/IB20 14/002463 SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, (22) International Filing Date: TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. 17 November 2014 (17.1 1.2014) (84) Designated States (unless otherwise indicated, for every (25) Filing Language: English kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, (26) Publication Language: English TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, (71) Applicant: UMM-AL-QURA UNIVERSITY [SA/SA]; TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, Alaabdeya District, P.O. Box 715, Makkah 21955 (SA). DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, (72) Inventor: ALGHAMDI, Saeed Saeed; P.O. Box 795 1, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, Awali, Makkah 21955 (SA).
    [Show full text]