DOCSLIB.ORG

Download (4MB)

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Download (4MB) https://theses.gla.ac.uk/ Theses Digitisation: https://www.gla.ac.uk/myglasgow/research/enlighten/theses/digitisation/ This is a digitised version of the original print thesis. Copyright and moral rights for this work are retained by the author A copy can be downloaded for personal non-commercial research or study, without prior permission or charge This work cannot be reproduced or quoted extensively from without first obtaining permission in writing from the author The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the author When referring to this work, full bibliographic details including the author, title, awarding institution and date of the thesis must be given Enlighten: Theses https://theses.gla.ac.uk/ research-enlighten@glasgow.ac.uk Natural and synthetic factors which influence the calcium sensitivity of chemically-skinned rat cardiac muscle A thesis submitted for the degree of Doctor of Philosophy © D. S. Steele 1990 Institute of Physiology, Glasgow University ProQuest Number: 11003372 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a com plete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest ProQuest 11003372 Published by ProQuest LLC(2018). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States C ode Microform Edition © ProQuest LLC. ProQuest LLC. 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106- 1346 Contents Page number List of contents................................................................................................. (i-v) List of figures.................................................................................................. (vi-viii) List of tables................................................................................................... (ix) Abbreviations................................................................................................... (x) Acknowledgements........................................................................................ (xi) Summary............................................................................................................ (xii-xv) Chapter 1: General Introduction Excitation contraction coupling in striated muscle........................ 2 The regulation of force in striated muscle.......................................... 4 Changes in contractile force with length............................................. 4 Physical factors and the length-tension relationship...................... 5 Changes in activation with muscle length.......................................... 5 Endogenous modulators of Ca-sensitivity............................................ 6 Ca-sensitivity and the hydrolysis of A TP............................................ 7 Ionic strength................................................................................................... 7 a and /3-receptor stimulation................................................................... 8 Endogenous imidazoles............................................................................... 10 Taurine................................................................................................................ 10 Synthetic Ca-sensitisers................................................................................ 11 Mechanisms underlying changes in Ca-sensitivity. Length-dependent changes in Ca-sensitivity..................................... 12 Ionic strength and pH................................................................................. 14 Caffeine and related compounds........................................................... 15 Inorganic phosphate...................................................................................... 18 Conclusions....................................................................................................... 18 Chapter 2: Materials and Methods General protocol............................................................................................ 21 Preparation mounting and force measurement............................... The microscope system and measurement of ..............................s.l 22 Solution exchange.......................................................................................... 24 Chemical supplies.......................................................................................... 25 Solution Composition.................................................................................. 25 p H ........................................................................................................................ 26 Ionic strength................................................................................................... 28 Calculation of free metal concentrations.............................................. 28 The chemical skinning procedure......................................................... 29 Data Handling................................................................................................. 31 Data analysis.................................................................................................... 32 The Hill Equation......................................................................................... 33 Chapter 3 Caffeine contractures in saponin-skinned trabeculae Introduction Protocol for caffeine-induced contractures........................................ 36 Effects of caffeine on intact tissue........................................................ 37 Experiments on isolated s.r....................................................................... 39 Experiments on selectively-skinned cardiac muscle....................... 39 The effect of caffeine on isolated s.r. channels.............................. 40 The aim of this chapter............................................................................. 40 R esults Oscillations in saponin-skinned trabeculae........................................ 43 Caffeine and relaxations from submaximal activation................. 46 The effect of caffeine on the relaxation from Cmax.................... 46 Mitochondria and the caffeine contractures..................................... 47 D iscussion Oscillating and steady-state tension production....................... 49 The effect of caffeine on the rate of relaxation............................. 52 The relevance of these results to the current study..................... 54 ii Chapter 4: The effect of cAMP on skinned trabeculae. Introduction Catecholamines, cyclic nucleotides and contractility...................... 58 The effect of cAMP sarcolemmal channels...................................... 58 The effect of cAMP on the sarcoplasmic reticulum..................... 59 Cyclic nucleotides and the contractile proteins 59 Phosphodiesterase......................................................................................... 62 Saponin-treated trabeculae........................................................................ 64 The aim of this chapter.............................................................................. 65 R esults Adenylate cyclase and forskolin toxin................................................ 66 Exogenous cAMP and the caffeine contracture............................ 67 The variability of the phenomenon....................................................... 68 The effect of PDE inhibition on the cAMP response................. 69 cGMP on the caffeine contracture........................................................ 71 Cyclic nucleotides and Ca-sensitivity..................................................... 71 D iscussion Forskolin Toxin and the activity of adenylate cyclase.................. 74 cAMP and the caffeine contracture...................................................... 75 Phosphodiesterase and the caffeine response................................. 77 Cyclic nucleotides and Ca-sensitivity................................................... 78 Conclusions....................................................................................................... 81 Chapter 5: Caffeine and sulmazole: comparative aspects. Introduction Sulmazole and the contractile proteins............................................... 83 Effects on cardiac sarcoplasmic reticulum......................................... 84 The aim of this study.................................................................................. 84 R esults Protocol to determine s.r. Ca-release.................................................. 86 Caffeine, sulmazole and s.r. [Ca] release.......................................... 86 Accumulated data.......................................................................................... 87 Increased Ca-sensitivity and contracture amplitude...................... 88 Effect of caffeine and sulmazole on CICR oscillations............... 90 Effects on maximum Ca-activated force............................................. 90 iii D iscussion Effects on the sarcoplasmic reticulum................................................ 92 Effects on submaximal force production.......................................... 93 Effects on maximum Ca-activated force........................................... 94
Load more

Recommended publications
  • Acute Hemodynamics of Pimobendan in Chronic Heart Failure SUMMARY
    Acute Hemodynamics of Pimobendan in Chronic Heart Failure A Comparative Crossover Study of Captopril and Pimobendan Takashi TSUDA, M.D., Tohru IZUMI, M.D., Makoto KODAMA, M.D., Haruo HANAWA, M.D., Minoru TAKAHASHI, M.D., Masataka SUZUKI, M.D., Toshiya AIZAKI, M.D., Hirohide UCHIYAMA, M.D., Hirohiko KUWANO, M.D., and Akira SHIBATA, M.D. SUMMARY Acute hemodynamics of pimobendan were compared to captopril in a crossover trial in patients with chronic heart failure (NYHA II-III). Heart failure had been stabilized by conventional therapy with diuretics and digitalis for more than 2 weeks. Patients receiving vasodilators were excluded. The hemodynamics were analyzed using a Swan-Ganz cath- eter at the bedside during drug administration. Following an intravenous injection of 2.5mg of pimobendan, there was a significant increase in heart rate and decrease in mean pulmonary artery pressure, total pulmonary resistance, mean arterial pressure, sys- temic vascular resistance and mean right atrial pressure 2 hours after the injection. Captopril (12.5mg, orally) significantly decreased mean ar- terial pressure, systemic vascular resistance and double product 2 hours after administration. In this study, the inotropic effect was evaluated through the relation between the stroke volume index and diastolic pul- monary artery pressure, and also between the stroke volume index and mean arterial pressure. Although decreases of diastolic pulmonary artery pressure and mean arterial pressure were seen with both drugs, the dif- ferences in stroke volume index were not significant. In comparison with captopril, the acute hemodynamics of pimoben- dan are characterized as follows: 1) the systemic arteriovasodilating ef- fects of the two drugs were equal, 2) the pulmonary arteriovasodilating effect of pimobendan was marked, 3) a venodilating effect, documented through a decrease of mean right atrial pressure, was seen only with pi- mobendan.
    [Show full text]
  • Pimobendan Possibilities
    Pimobendan Possibilities Rob Sanders DVM, DACVIM (Cardiology) Associate Prof Cardiology Department of Small Animal Clinical Sciences College of Veterinary Medicine Veterinary Medical Center, D212 Michigan State University East Lansing, MI 48824-1314 When should I start using pimobendan in a dog with mitral valve disease? Okay we have all heard about the EPIC study(J Vet Intern Med. 2016 Nov;30(6):1765- 1779). Here are the conclusions (I have added the bolding)… ” The conclusions of this study are only relevant to dogs with cardiac enlargement secondary to preclinical MMVD (stage B2) as all dogs entering the study met or exceeded 3 different heart size criteria (LA/Ao ≥ 1.6, LVIDDN ≥ 1.7, and VHS > 10.5) and no dogs without cardiac enlargement were recruited to the study. Similarly, the conclusions are only relevant to dogs with a murmur of at least a grade 3/6 in intensity. Treatment with pimobendan of all dogs that have a murmur compatible with the presence of MMVD would not be justified on the basis of the findings of this study.” I like evidence to base my clinical decisions upon. For the moment lets accept the results as presented. Based on the presented results of the EPIC study dogs with preclinical degenerative valve disease should start getting pimobendan when all of the following criteria have been met… 1. Have at least a grade 3 murmur 2. Meet or exceed ALL three different heart size criteria a. LA/Ao ≥ 1.6 by echocardiography b. LVIDDN ≥ 1.7 by echocardiograpy c. VHS > 10.5 by radiography Ok…so you have to do an auscultation (easy), you have to do rads (easy) and you have to get an echo done and calculate LVIDDN (normalized end diastolic left ventricular diameter).
    [Show full text]
  • Phosphodiesterase (PDE)
    Phosphodiesterase (PDE) Phosphodiesterase (PDE) is any enzyme that breaks a phosphodiester bond. Usually, people speaking of phosphodiesterase are referring to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below. However, there are many other families of phosphodiesterases, including phospholipases C and D, autotaxin, sphingomyelin phosphodiesterase, DNases, RNases, and restriction endonucleases, as well as numerous less-well-characterized small-molecule phosphodiesterases. The cyclic nucleotide phosphodiesterases comprise a group of enzymes that degrade the phosphodiester bond in the second messenger molecules cAMP and cGMP. They regulate the localization, duration, and amplitude of cyclic nucleotide signaling within subcellular domains. PDEs are therefore important regulators ofsignal transduction mediated by these second messenger molecules. www.MedChemExpress.com 1 Phosphodiesterase (PDE) Inhibitors, Activators & Modulators (+)-Medioresinol Di-O-β-D-glucopyranoside (R)-(-)-Rolipram Cat. No.: HY-N8209 ((R)-Rolipram; (-)-Rolipram) Cat. No.: HY-16900A (+)-Medioresinol Di-O-β-D-glucopyranoside is a (R)-(-)-Rolipram is the R-enantiomer of Rolipram. lignan glucoside with strong inhibitory activity Rolipram is a selective inhibitor of of 3', 5'-cyclic monophosphate (cyclic AMP) phosphodiesterases PDE4 with IC50 of 3 nM, 130 nM phosphodiesterase. and 240 nM for PDE4A, PDE4B, and PDE4D, respectively. Purity: >98% Purity: 99.91% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 1 mg, 5 mg Size: 10 mM × 1 mL, 10 mg, 50 mg (R)-DNMDP (S)-(+)-Rolipram Cat. No.: HY-122751 ((+)-Rolipram; (S)-Rolipram) Cat. No.: HY-B0392 (R)-DNMDP is a potent and selective cancer cell (S)-(+)-Rolipram ((+)-Rolipram) is a cyclic cytotoxic agent. (R)-DNMDP, the R-form of DNMDP, AMP(cAMP)-specific phosphodiesterase (PDE) binds PDE3A directly.
    [Show full text]
  • Cardiovascular Effect of Pyridazine Derivative Pimobedan and Other Related Compounds Mohammad Asif*
    American Journal of Pharmacology and Pharmacotherapeutics Review Article Cardiovascular Effect of Pyridazine Derivative Pimobedan and Other Related Compounds Mohammad Asif* Department of Pharmacy, GRD (PG) IMT, Dehradun, 248009 Uttarakhand, India *Corresponding author e-mail: aasif321@gmail.com A B S T R A C T The pyridazine ring is present in various biologically active compounds and some pyridazine compounds have been reported as valuable cardiovascular agents. Benzimidazole-pyridazinone compound, 4,5-dihydro-6-[2-(4-methoxyphenyl)-1H-benzimidazole-5-yl]-5-methyl-3(2H)- pyridazinone (pimobedan or vetmedin) is a potent cardiovascular agent. It is a non adrenergic, non-glycoside inotropic drug with vasodilator activities and exerts a stimulatory myocardial activity by a dual mechanism of action with raise in calcium sensitivity of cardiac myofilaments and inhibition of phosphodiesterase. Pyridazine is an attractive compound for designing and development of novel pyridazine compounds as cardiotonic agents in future. Keywords: Pimobendan, cardiovascular, vasodilatative, phosphodiesterase, calcium sensitiser. INTRODUCTION Nowadays cardiovascular diseases and dyspnoea3. This results from myocardial (CVD) are major public health problem ischaemia (MI), arrhythmias, non- wordwide, in this regards ischemic heart compliance with treatment or intercurrent disease (IHD) or coronary heart disease infections. Acute heart failure (AHF) may (CHD) is more common.1 The prevalence is also arise suddenly following a cardiac increasingly occurs in the elderly insult in a patient without previous evidence population.2 The common cause is coronary of overt CVD. About 15% of worldwide artery disease (CAD), either alone or in mortality is attributable to heart disease combination with hypertension. Other (HD)4. It is estimated that HD will be the factors, likes hypercholesterolaemia, biggest cause of disease burden worldwide diabetes mellitus, obesity and smoking may By 20205,6.
    [Show full text]
  • Pimobendan Use in Cats PHARMACOLOGY
    CLINICAL RESOURCE FOCUS ON Pimobendan Use in Cats PHARMACOLOGY Although pimobendan is not labeled for use in cats, several retrospective studies have reported the use of pimobendan in cats with congestive heart failure (CHF) secondary to a variety of cardiomyopathies and other forms of heart disease (TABLE 1), with and without ventricular systolic dysfunction (SEE CASE SCENARIO).1-3 A retrospective case-control study of cats in heart failure with hypertrophic cardiomyopathy (HCM) that did receive versus did not receive pimobendan reported a survival benefit (103 days compared with 626 days, in favor of pimobendan).3 DOSING Pimobendan dosing for cats is similar to that for dogs (0.25 to 0.3 mg/kg PO q12h). INDICATIONS In cats, the predominate type of cardiomyopathy is hypertrophic with preserved or normal ventricular systolic function. The rationale for using a positive inotrope in cats with HCM is not entirely clear; however, it may be associated with improved ventricular relaxation via phosphodiesterase III (PDEIII) inhibition, enhanced atrial and auricular contraction and emptying, and/or reduced platelet aggregation.4,5 Cats with hypertrophic obstructive cardiomyopathy have HCM with evidence of left ventricular outflow tract obstruction. Obstruction in cats with HCM is often intermittent, variable in severity, and exacerbated by elevated heart rates. Because outflow tract obstruction is a relative contraindication for pimobendan use in cats with cardiomyopathy, an echocardiogram is recommended before administrating it to cats with CHF that are stable or easily stabilized with conventional therapy (stage C). However, in cats with refractory CHF (stage D), pimobendan can be considered as rescue therapy without first performing echocardiography.
    [Show full text]
  • Marrakesh Agreement Establishing the World Trade Organization
    No. 31874 Multilateral Marrakesh Agreement establishing the World Trade Organ ization (with final act, annexes and protocol). Concluded at Marrakesh on 15 April 1994 Authentic texts: English, French and Spanish. Registered by the Director-General of the World Trade Organization, acting on behalf of the Parties, on 1 June 1995. Multilat ral Accord de Marrakech instituant l©Organisation mondiale du commerce (avec acte final, annexes et protocole). Conclu Marrakech le 15 avril 1994 Textes authentiques : anglais, français et espagnol. Enregistré par le Directeur général de l'Organisation mondiale du com merce, agissant au nom des Parties, le 1er juin 1995. Vol. 1867, 1-31874 4_________United Nations — Treaty Series • Nations Unies — Recueil des Traités 1995 Table of contents Table des matières Indice [Volume 1867] FINAL ACT EMBODYING THE RESULTS OF THE URUGUAY ROUND OF MULTILATERAL TRADE NEGOTIATIONS ACTE FINAL REPRENANT LES RESULTATS DES NEGOCIATIONS COMMERCIALES MULTILATERALES DU CYCLE D©URUGUAY ACTA FINAL EN QUE SE INCORPOR N LOS RESULTADOS DE LA RONDA URUGUAY DE NEGOCIACIONES COMERCIALES MULTILATERALES SIGNATURES - SIGNATURES - FIRMAS MINISTERIAL DECISIONS, DECLARATIONS AND UNDERSTANDING DECISIONS, DECLARATIONS ET MEMORANDUM D©ACCORD MINISTERIELS DECISIONES, DECLARACIONES Y ENTEND MIENTO MINISTERIALES MARRAKESH AGREEMENT ESTABLISHING THE WORLD TRADE ORGANIZATION ACCORD DE MARRAKECH INSTITUANT L©ORGANISATION MONDIALE DU COMMERCE ACUERDO DE MARRAKECH POR EL QUE SE ESTABLECE LA ORGANIZACI N MUND1AL DEL COMERCIO ANNEX 1 ANNEXE 1 ANEXO 1 ANNEX
    [Show full text]
  • Inotropic Effects of a Single Intravenous Recommended Dose of Pimobendan in Healthy Dogs
    NOTE Internal Medicine Inotropic effects of a single intravenous recommended dose of pimobendan in healthy dogs Yasutomo HORI1)*, Hiroto TAIRA1), Yuji NAKAJIMA1), Yusyun ISHIKAWA1), Yuki YUMOTO1), Yuya MAEKAWA1) and Akiko OSHIRO1) 1)School of Veterinary Medicine, Rakuno Gakuen University, 582 Midori-machi, Bunkyodai, Ebetsu, Hokkaido 069-8501, Japan ABSTRACT. We investigated the effects of an injectable pimobendan solution (0.15 mg/kg) on J. Vet. Med. Sci. cardiac function in healthy dogs. Fifteen dogs were divided into placebo, intravenous pimobendan 81(1): 22–25, 2019 injection, and subcutaneous pimobendan injection groups. In the placebo, the heart rate, systolic and end-diastolic left ventricular pressure (LVPs and LVEDP), and peak positive (max dP/dt) and doi: 10.1292/jvms.18-0185 negative (min dP/dt) first derivatives of the left ventricular pressure did not change for 60 min. After the intravenous pimobendan injection, LVEDP decreased significantly within 5 min, while the max dP/dt increased, and the effects continued until 60 min. In comparison, there were no Received: 3 April 2018 hemodynamic changes after the subcutaneous pimobendan injection. This study demonstrates Accepted: 29 October 2018 that injectable pimobendan induced a rapid inotropic effect and decreased the LVEDP in dogs. Published online in J-STAGE: 8 November 2018 KEY WORDS: canine, heart failure, phosphodiesterase inhibitor, pimobendan, systolic function There are eleven families of hydrolytic enzymes called cyclic nucleotide phosphodiesterases (PDE), and PDE3 is a cGMP- inhibited cAMP PDE; hydrolase of cAMP and cGMP phosphodiester bonds [12]. PDE3 is abundant in cardiomyocytes and vascular smooth muscle and regulates cardiac and vascular smooth muscle contractility [8, 12].
    [Show full text]
  • Drug Schedules Regulation B.C
    Pharmacy Operations and Drug Scheduling Act DRUG SCHEDULES REGULATION B.C. Reg. 9/98 Deposited and effective January 9, 1998 Last amended June 28, 2018 by B.C. Reg. 137/2018 Consolidated Regulations of British Columbia This is an unofficial consolidation. Point in time from June 28 to December 6, 2018 B.C. Reg. 9/98 (O.C. 35/98), deposited and effective January 9, 1998, is made under the Pharmacy Operations and Drug Scheduling Act, S.B.C. 2003, c. 77, s. 22. This is an unofficial consolidation provided for convenience only. This is not a copy prepared for the purposes of the Evidence Act. This consolidation includes any amendments deposited and in force as of the currency date at the bottom of each page. See the end of this regulation for any amendments deposited but not in force as of the currency date. Any amendments deposited after the currency date are listed in the B.C. Regulations Bulletins. All amendments to this regulation are listed in the Index of B.C. Regulations. Regulations Bulletins and the Index are available online at www.bclaws.ca. See the User Guide for more information about the Consolidated Regulations of British Columbia. The User Guide and the Consolidated Regulations of British Columbia are available online at www.bclaws.ca. Prepared by: Office of Legislative Counsel Ministry of Attorney General Victoria, B.C. Point in time from June 28 to December 6, 2018 Pharmacy Operations and Drug Scheduling Act DRUG SCHEDULES REGULATION B.C. Reg. 9/98 Contents 1 Alphabetical order 2 Sale of drugs 3 [Repealed] SCHEDULES Alphabetical order 1 (1) The drug schedules are printed in an alphabetical format to simplify the process of locating each individual drug entry and determining its status in British Columbia.
    [Show full text]
  • Triple Therapy for ALL? Current Recommendations in Canine Heart Disease Discussion Agenda Goals of Acute HF Rx
    Triple Therapy for ALL? Current recommendations in canine Discussion Agenda heart disease • Goals of acute v. chronic HF management • Treatment recommendations: – Pimobendan • Digoxin – Diuretics Terri DeFrancesco, DVM, DACVIM (Cardiology), DACVECC • Furosemide, Torsemide, Spironolactone, North Carolina State University College of Veterinary Medicine – Vasodilators Raleigh, NC • ACE‐Inhibitors, Sildenafil, Amlodipine tdefranc@ncsu.edu • Summaries for dog HF treatment Staged Diagnostic and Treatment Strategies Goals of Acute HF Rx: Based on Heart Failure Classification • Restore comfort at rest: – Mechanical removal of life‐threatening fluid accumulations – Oxygen supplementation Breed at risk – Reduce anxiety Screening Programs – Reduce the work of breathing Asymptomatic - B1 - No Therapy B2 - ACEI (MVD + DCM), Pimobendan (DCM) -blockers? • Hemodynamic stabilization Dog - Furosemide, Pimobendan, ACEI, +/-Spironolactone – Assess and optimize preload, afterload, Cat – Furosemide, ACEI +/- Pimobendan, Anti-thrombotic heart rate & rhythm, and contractility REFRACTORY HF – USING HIGHER THAN CONVENTIONAL DOSES • Keep them eating Palliation of all clinical signs using multi-modal therapy 11 Goals of Chronic Rx • Maintain acute hemodynamic gains. Heart Failure Decompensations • Improve quality of life – Exercise tolerance – Appetite / weight • Improve survival • Minimize hospitalizations Functional • Optimize owner & patient compliance Ability • Economic impact • Moderately low salt intake Educated client and scheduled HF rechecks will hopefully
    [Show full text]
  • Lääkealan Turvallisuus- Ja Kehittämiskeskuksen Päätös
    Lääkealan turvallisuus- ja kehittämiskeskuksen päätös N:o xxxx lääkeluettelosta Annettu Helsingissä xx päivänä maaliskuuta 2016 ————— Lääkealan turvallisuus- ja kehittämiskeskus on 10 päivänä huhtikuuta 1987 annetun lääke- lain (395/1987) 83 §:n nojalla päättänyt vahvistaa seuraavan lääkeluettelon: 1 § Lääkeaineet ovat valmisteessa suolamuodossa Luettelon tarkoitus teknisen käsiteltävyyden vuoksi. Lääkeaine ja sen suolamuoto ovat biologisesti samanarvoisia. Tämä päätös sisältää luettelon Suomessa lääk- Liitteen 1 A aineet ovat lääkeaineanalogeja ja keellisessä käytössä olevista aineista ja rohdoksis- prohormoneja. Kaikki liitteen 1 A aineet rinnaste- ta. Lääkeluettelo laaditaan ottaen huomioon lää- taan aina vaikutuksen perusteella ainoastaan lää- kelain 3 ja 5 §:n säännökset. kemääräyksellä toimitettaviin lääkkeisiin. Lääkkeellä tarkoitetaan valmistetta tai ainetta, jonka tarkoituksena on sisäisesti tai ulkoisesti 2 § käytettynä parantaa, lievittää tai ehkäistä sairautta Lääkkeitä ovat tai sen oireita ihmisessä tai eläimessä. Lääkkeeksi 1) tämän päätöksen liitteessä 1 luetellut aineet, katsotaan myös sisäisesti tai ulkoisesti käytettävä niiden suolat ja esterit; aine tai aineiden yhdistelmä, jota voidaan käyttää 2) rikoslain 44 luvun 16 §:n 1 momentissa tar- ihmisen tai eläimen elintoimintojen palauttami- koitetuista dopingaineista annetussa valtioneuvos- seksi, korjaamiseksi tai muuttamiseksi farmako- ton asetuksessa kulloinkin luetellut dopingaineet; logisen, immunologisen tai metabolisen vaikutuk- ja sen avulla taikka terveydentilan
    [Show full text]
  • Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DIX to the HTSUS—Continued
    20558 Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DEPARMENT OF THE TREASURY Services, U.S. Customs Service, 1301 TABLE 1.ÐPHARMACEUTICAL APPEN- Constitution Avenue NW, Washington, DIX TO THE HTSUSÐContinued Customs Service D.C. 20229 at (202) 927±1060. CAS No. Pharmaceutical [T.D. 95±33] Dated: April 14, 1995. 52±78±8 ..................... NORETHANDROLONE. A. W. Tennant, 52±86±8 ..................... HALOPERIDOL. Pharmaceutical Tables 1 and 3 of the Director, Office of Laboratories and Scientific 52±88±0 ..................... ATROPINE METHONITRATE. HTSUS 52±90±4 ..................... CYSTEINE. Services. 53±03±2 ..................... PREDNISONE. 53±06±5 ..................... CORTISONE. AGENCY: Customs Service, Department TABLE 1.ÐPHARMACEUTICAL 53±10±1 ..................... HYDROXYDIONE SODIUM SUCCI- of the Treasury. NATE. APPENDIX TO THE HTSUS 53±16±7 ..................... ESTRONE. ACTION: Listing of the products found in 53±18±9 ..................... BIETASERPINE. Table 1 and Table 3 of the CAS No. Pharmaceutical 53±19±0 ..................... MITOTANE. 53±31±6 ..................... MEDIBAZINE. Pharmaceutical Appendix to the N/A ............................. ACTAGARDIN. 53±33±8 ..................... PARAMETHASONE. Harmonized Tariff Schedule of the N/A ............................. ARDACIN. 53±34±9 ..................... FLUPREDNISOLONE. N/A ............................. BICIROMAB. 53±39±4 ..................... OXANDROLONE. United States of America in Chemical N/A ............................. CELUCLORAL. 53±43±0
    [Show full text]
  • Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act
    Updated June 07, 2021 Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act Three categories of bulk drug substances: • Category 1: Bulk Drug Substances Under Evaluation • Category 2: Bulk Drug Substances that Raise Significant Safety Risks • Category 3: Bulk Drug Substances Nominated Without Adequate Support Updates to Categories of Substances Nominated for the 503B Bulk Drug Substances List1 • Add the following entry to category 2 due to serious safety concerns of mutagenicity, cytotoxicity, and possible carcinogenicity when quinacrine hydrochloride is used for intrauterine administration for non- surgical female sterilization: 2,3 o Quinacrine Hydrochloride for intrauterine administration • Revision to category 1 for clarity: o Modify the entry for “Quinacrine Hydrochloride” to “Quinacrine Hydrochloride (except for intrauterine administration).” • Revision to category 1 to correct a substance name error: o Correct the error in the substance name “DHEA (dehydroepiandosterone)” to “DHEA (dehydroepiandrosterone).” 1 For the purposes of the substance names in the categories, hydrated forms of the substance are included in the scope of the substance name. 2 Quinacrine HCl was previously reviewed in 2016 as part of FDA’s consideration of this bulk drug substance for inclusion on the 503A Bulks List. As part of this review, the Division of Bone, Reproductive and Urologic Products (DBRUP), now the Division of Urology, Obstetrics and Gynecology (DUOG), evaluated the nomination of quinacrine for intrauterine administration for non-surgical female sterilization and recommended that quinacrine should not be included on the 503A Bulks List for this use. This recommendation was based on the lack of information on efficacy comparable to other available methods of female sterilization and serious safety concerns of mutagenicity, cytotoxicity and possible carcinogenicity in use of quinacrine for this indication and route of administration.
    [Show full text]