University of Alberta

Total Page:16

File Type:pdf, Size:1020Kb

University of Alberta University of Alberta The Effect of Caffeine on the Neurobehavioral and Neuropathological Outcome of the Newborn Rat By Omar Abu-Sa’da A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE in Medical Sciences Department of Paediatrics © OMAR ABU-SA’DA Spring 2010 Edmonton, Alberta Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission. Library and Archives Bibliothèque et Canada Archives Canada Published Heritage Direction du Branch Patrimoine de l’édition 395 Wellington Street 395, rue Wellington Ottawa ON K1A 0N4 Ottawa ON K1A 0N4 Canada Canada Your file Votre référence ISBN: 978-0-494-60602-5 Our file Notre référence ISBN: 978-0-494-60602-5 NOTICE: AVIS: The author has granted a non- L’auteur a accordé une licence non exclusive exclusive license allowing Library and permettant à la Bibliothèque 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 télécommunication ou par l’Internet, prêter, telecommunication or on the Internet, distribuer et vendre des thèses partout dans le loan, distribute and sell theses monde, à des fins commerciales ou autres, sur worldwide, for commercial or non- support microforme, papier, électronique et/ou commercial purposes, in microform, autres formats. paper, electronic and/or any other formats. The author retains copyright L’auteur conserve la propriété du droit d’auteur ownership and moral rights in this et des droits moraux qui protège cette thèse. Ni thesis. Neither the thesis nor la thèse ni des extraits substantiels de celle-ci substantial extracts from it may be ne doivent être imprimés ou autrement printed or otherwise reproduced reproduits sans son autorisation. without the author’s permission. In compliance with the Canadian Conformément à la loi canadienne sur la Privacy Act some supporting forms protection de la vie privée, quelques may have been removed from this formulaires secondaires ont été enlevés de thesis. cette thèse. While these forms may be included Bien que ces formulaires aient inclus dans in the document page count, their la pagination, il n’y aura aucun contenu removal does not represent any loss manquant. of content from the thesis. EXAMINING COMMITTEE Dr. Jerome Y. Yager, Department of Paediatrics, Supervisor. Dr. Po-Yin Cheung, Department of Paediatrics, Co-Supervisor. Dr. Gregory D. Funk, Department of Physiology, Supervisory Committee Member. DEDICATION I dedicate my thesis to my parents who reared me to be a good person and encouraged me to be a good physician, to my loving and devoted wife, to my children who have made my life full with happiness and hope and to my teachers and colleagues. THESIS ABSTRACT Caffeine is used for the treatment of apnea of prematurity. The objective of this study was to determine the long term neuropathological and neurobehavioral effects of caffeine on the immature rat brain. Newborn rats were injected with either caffeine, or normal saline from postnatal days 3 to 7, equivalent to the human premature infant of 28-36 weeks. Behavioral tests revealed no abnormality in caffeine treated animals compared to controls. Fluro- Jade B stain of P4 rat brains showed that caffeine caused significant neuronal cell death in some areas of the brain, compared to controls, but this alteration was transient and not present at P8. Anti-NeuN stain at P21 showed significant neuronal cell loss in CA1 and hypothalamus regions in the caffeine group, but not at P160. Anti-Neurofilament M stain at P8, P21 and P160 showed no differences between the control and caffeine groups. We conclude that use of caffeine has no significant effect on the behavioral tests measured in our newborn rat pups. While caffeine caused neuronal cell death at P4, and neuronal cell loss in CA1 and hypothalamus regions at P21, there was no long-lasting effect on neuropathological outcome. However, given these latter findings, the use of caffeine in the premature infant must still be done with caution. ACKNOWLEDGEMENTS No research is a solo effort. I would like to thank Dr. Jerome Y. Yager, who has been not only a valuable adviser through this research and thesis project, but also a great role model, a caring mentor and a truly wise supervisor. My special appreciation goes to Dr. Po-Yin Cheung for being a co-supervisor, for supervising me during the course “Directed Reading in Clinical Medicine”, and for his continuous support and advice. I would also like to thank Dr. Gregory D. Funk for being a member of the supervising committee and for many varied ways of demonstrating support and advice. My thanks go also to Arlene Figley for her excellent administrative help and to Dr. Richard Schulz for his chairing the examining committee. To my colleagues in Dr.Yager's laboratory: Edward Armstrong, Dr. Alireza Karimi Pour, Keqin Shen, and Amy M. Black, I appreciate your patience, wisdom and your great contributions to my research and thesis. Thanks Ed for your advice, teaching and patience all through my research. My heartfelt thanks are due to my parents for their continuous support and praying, and to all my brothers and sisters. To my lovely daughters - Mais, Lujein and Layan- thank you for all the joy and endless light and happiness you bring to my life. Finally, my sincere thanks go to my love, my heart and my best friend: my wife; Nabeela. Thank you for the talking, listening, laughing and sharing your life with me. You are the best gift from GOD. I will continue to be grateful to you, my love, forever. TABLE OF CONTENTS PAGE Introduction:...................................................................................................... 1 References:..............................................................................................................3 Chapter 1: Apnea of Prematurity and Its Treatment:………………4 1.1. Apnea of Prematurity:………………………………………………………4 1.1.1. Background:……………………………………………………………4 1.1.2. Pathophysiologic Mechanisms of Apnea of Prematurity:........................7 1.1.3. Apnea of Prematurity and Neurodevelopmental Outcome in Very Low Birth Weight Infants:………………………………………11 1.1.4. Apnea of Prematurity and Gastroesophageal Reflux Disease in Very Low Birth Weight Infants:……………………………………14 1.1.5. Apnea of Prematurity and Feeding in Very Low Birth Weight Infants:………………………………………………………………...15 1.1.6. Apnea of Prematurity and Sudden Infant Death Syndrome in Very Low Birth Weight Infants:………………………………………16 1.2. Treatment of Apnea of Prematurity:……………………………………..17 1.2.1. Non-Pharmacological Treatment of Apnea of Prematurity:........................17 1.2.2. Pharmacological Treatment of Apnea of Prematurity:..........................21 1.2.2.1. Methylxanthines:................................................................21 1.2.2.2. Doxapram:………………………………………………..22 1.2.2.3. Carnitine:…………………………………………………23 1.2.2.4. Creatine:………………………………………………….23 References:………………………………………………………………………25 Chapter Two: Caffeine as Treatment of Apnea of Prematurity:...29 Introduction:…………………………………………………………………….29 2.1. Structure & Pharmacodynamic Properties of Caffeine:………………...29 2.2. Systemic Effects of Caffeine:………………………………………………30 2.3. Physiologic Effects of Caffeine:...…………………………………………30 2.4. Pharmacokinetic Properties of Caffeine:...……………………………….35 TABLE OF CONTENTS PAGE 2.5. Caffeine Dosage and Interactions:...………………………………………37 2.6. Therapeutic Efficacy of Caffeine:...……………………………………….39 2.7. Adenosine:...………………………………………………………………...39 2.8. The Effects of Caffeine and Adenosine on the Developing Brain:...……………………………………………………………………...41 2.8.1. Breathing:...……………………………………………………………41 2.8.2. Sleep and the Level of Arousal:...……………………………………..43 2.8.3. Anxiety and Pain:...……………………………………………………44 2.8.4. Cognition and Memory:...……………………………………………..44 2.8.5. Neuronal Protection, Injury and Maturation:...………………………..45 2.8.6. Seizure: ...…………………………………………………………….48 2.8.7. Cerebral Blood Flow:...………………………………………………..49 2.8.8. Pituitary Gland:...……………………………………………………...50 2.10. The Effects of Caffeine on Pregnancy:...………………………………...51 2.11. Caffeine and Lactation:...………………………………...........................53 2.12. Conclusion:...………………………………...............................................54 References:...……………………………….........................................................58 Chapter 3: Methodology and Experimental Protocols:...…………..68 3.1. Hypothesis:……………………………......………………………………...68 3.2. Rat Model:……………………………......………………………………...68 3.3. Study Design:……………………………......……………………………...69 3.3.1. The Period of Giving Caffeine Treatment:………………………70 3.3.2. The Dosage of Caffeine Treatment:……...………………………71 3.4. Animal Neurobehavioral Tests:…………………...………………………71 3.4.1. Early Behavioural Testing: Neonatal (P4-P9), Post-Neonatal, Infantile and Pre-Juvenile
Recommended publications
  • Additions and Deletions to the Drug Product List
    Prescription and Over-the-Counter Drug Product List 40TH EDITION Cumulative Supplement Number 09 : September 2020 ADDITIONS/DELETIONS FOR PRESCRIPTION DRUG PRODUCT LIST ACETAMINOPHEN; BUTALBITAL; CAFFEINE TABLET;ORAL BUTALBITAL, ACETAMINOPHEN AND CAFFEINE >A> AA STRIDES PHARMA 325MG;50MG;40MG A 203647 001 Sep 21, 2020 Sep NEWA ACETAMINOPHEN; CODEINE PHOSPHATE SOLUTION;ORAL ACETAMINOPHEN AND CODEINE PHOSPHATE >D> AA WOCKHARDT BIO AG 120MG/5ML;12MG/5ML A 087006 001 Jul 22, 1981 Sep DISC >A> @ 120MG/5ML;12MG/5ML A 087006 001 Jul 22, 1981 Sep DISC TABLET;ORAL ACETAMINOPHEN AND CODEINE PHOSPHATE >A> AA NOSTRUM LABS INC 300MG;15MG A 088627 001 Mar 06, 1985 Sep CAHN >A> AA 300MG;30MG A 088628 001 Mar 06, 1985 Sep CAHN >A> AA ! 300MG;60MG A 088629 001 Mar 06, 1985 Sep CAHN >D> AA TEVA 300MG;15MG A 088627 001 Mar 06, 1985 Sep CAHN >D> AA 300MG;30MG A 088628 001 Mar 06, 1985 Sep CAHN >D> AA ! 300MG;60MG A 088629 001 Mar 06, 1985 Sep CAHN ACETAMINOPHEN; HYDROCODONE BITARTRATE TABLET;ORAL HYDROCODONE BITARTRATE AND ACETAMINOPHEN >A> @ CEROVENE INC 325MG;5MG A 211690 001 Feb 07, 2020 Sep CAHN >A> @ 325MG;7.5MG A 211690 002 Feb 07, 2020 Sep CAHN >A> @ 325MG;10MG A 211690 003 Feb 07, 2020 Sep CAHN >D> AA VINTAGE PHARMS 300MG;5MG A 090415 001 Jan 24, 2011 Sep DISC >A> @ 300MG;5MG A 090415 001 Jan 24, 2011 Sep DISC >D> AA 300MG;7.5MG A 090415 002 Jan 24, 2011 Sep DISC >A> @ 300MG;7.5MG A 090415 002 Jan 24, 2011 Sep DISC >D> AA 300MG;10MG A 090415 003 Jan 24, 2011 Sep DISC >A> @ 300MG;10MG A 090415 003 Jan 24, 2011 Sep DISC >D> @ XIROMED 325MG;5MG A 211690
    [Show full text]
  • Neonatal Intensive Care Drug Therapy Update: a Bibliography
    LWW/JPNN AS310-13 July 28, 2004 23:11 Char Count= 0 J Perinat Neonat Nurs Vol. 18, No. 3, pp. 292–306 c 2004 Lippincott Williams & Wilkins, Inc. Neonatal Intensive Care Drug Therapy Update: A Bibliography Jason Sauberan, PharmD BIBLIOGRAPHY I. Overview A. Clark RH, Bloom BT, Gerstmann DR Medications Used in Neonatal Intensive Care Units—A Descriptive Study [abstract 3047]. In: Program and abstracts of the 2004 Pediatric Academic Societies’ Annual Meeting, San Francisco, CA. B. Barr J, Brenner-Zada G, Heiman E, Pareth G, Bulkowstein M, Greenberg R, Berkovitch M. Unlicensed and off-label medication use in a neonatal intensive care unit: a prospective study. Am J Perinatol. 2002 Feb;19(2):67–72. C. O’Donnell CP, Stone RJ, Morley CJ. Unlicensed and off-label drug use in an Australian neonatal intensive care unit. Pediatrics. 2002 Nov;110(5):e52. D. Committee on Drugs. American Academy of Pediatrics. Uses of drugs not described in the package insert (off-label uses). Pediatrics. 2002 Jul;110(1 Pt 1):181–3. II. Anti-infectives A. Linezolid 1. Deville JG, Adler S, Azimi PH, Jantausch BA, Morfin MR, Beltran S, Edge-Padbury B, Naberhuis-Stehouwer S, Bruss JB. Linezolid versus vancomycin in the treatment of known or suspected resistant gram-positive infections in neonates. Pediatr Infect Dis J. 2003 Sep;22(9 Suppl):S158–63. 2. Vo M, Cirincione BB, Rubino CM, Jungbluth GL. Pharmacokinetics of Linezolid in Neonates and Young Infants [abstract A-1409]. In: Program and abstracts of the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, CA.
    [Show full text]
  • Application and Review of Pediatric Pharmacotherapy, Sample Chapter
    Application and Review of Pediatric Pharmacotherapy Chapter No. 1 Dated: 29/7/2010 At Time: 16:16:4 Section 1 Neonatal intensive care “Luck is where preparation meets opportunity.” This section consists of 16 medication orders followed by corresponding patient profiles representing pharmacotherapy associated with patients admit- ted to a neonatal intensive care unit. Each patient profile is followed by multiple-choice questions pertaining to the medication order and profile infor- mation. Choose the one best-lettered response to each item. The correct answers are provided at the end of this section. The reader is encouraged to attempt all questions for each case or for the entire section prior to referring to the answers. Moreover, where appropriate, the answer key provides a thor- ough explanation of the correct response and should serve as an additional learning tool for the reader. Application and Review of Pediatric Pharmacotherapy Chapter No. 1 Dated: 29/7/2010 At Time: 16:16:4 2 | Application and Review of Pediatric Pharmacotherapy Medication orders Physician order Patient weight: 2.5 kg Aminophylline 10 mg iv load, then begin 2.5 mg iv q 12 h Obtain theophylline concentration 1 h postinfusion of loading dose Date/time: 12/01/2100 Patient name: Baby Boy Turner Physician: John Craver Patient ID: 111222 Medical profile Patient: Baby Boy Turner Patient weight: 2.5 kg Age: 1d/o Present illness: Apneic episodes Allergies: None Medical history: 33 weeks gestation, Apgar 7 and 9 Labs: pending Medication profile Questions Q1 Which of the following is an acceptable definition of apnea of prematurity? 1 o cessation of breathing for less than 20 s 2 o cessation of breathing for at least 20 s 3 o cessation of breathing for less than 20 s when accompanied by bradycardia A o 1 only B o 3 only C o 1 and 3 only Application and Review of Pediatric Pharmacotherapy Chapter No.
    [Show full text]
  • Caffeine in the Treatment of Pain
    Rev Bras Anestesiol ARTIGOS DE REVISÃO 2012; 62: 3: 387-401 ARTIGOS DE REVISÃO Cafeína para o Tratamento de Dor Cristiane Tavares, TSA 1, Rioko Kimiko Sakata, TSA 2 Resumo: Tavares C, Sakata RK – Cafeína para o Tratamento de Dor. Justificativa e objetivos: A cafeína é uma substância amplamente consumida com efeitos em diversos sistemas e que apresenta farmacoci- nética e farmacodinâmica características, causando interações com diversos medicamentos. O objetivo deste estudo é fazer uma revisão sobre os efeitos da cafeína. Conteúdo: Nesta revisão, são abordados a farmacologia da cafeína, os mecanismos de ação, as indicações, as contraindicações, as doses, as interações e os efeitos adversos. Conclusões: Faltam estudos controlados, randomizados e duplos-cegos para avaliar a eficácia analgésica da cafeína nas diversas síndromes dolorosas. Em pacientes com dor crônica, é necessário ter cautela em relação ao desenvolvimento de tolerância, abstinência e interação medi- camentosa no uso crônico de cafeína. Unitermos: ANALGESIA; DOR; DROGAS, Alcaloide/cafeína. ©2012 Elsevier Editora Ltda. Todos os direitos reservados. INTRODUÇÃO Estrutura química A cafeína foi isolada em 1820, mas a estrutura correta des- A cafeína é um alcaloide presente em mais de 60 espécies ta metilxantina foi estabelecida na última década do século de plantas 4. Sua estrutura molecular pertence a um grupo XIX. Os efeitos não foram claramente reconhecidos até 1981, de xantinas trimetiladas que incluem seus compostos inti- quando o bloqueio de receptores adenosina foi correlacio- mamente relacionados: teobromina (presente no cacau) e nado às propriedades estimulantes da cafeína e de seus teofilina (presente no chá) 1. Quimicamente, esses alcaloides análogos 1. Provavelmente a cafeína é uma das substâncias são semelhantes a purinas, xantinas e ácido úrico, que são psicoativas mais utilizadas no mundo, promovendo efeitos compostos metabolicamente importantes 4.
    [Show full text]
  • Pharmacy and Poisons (Third and Fourth Schedule Amendment) Order 2017
    Q UO N T FA R U T A F E BERMUDA PHARMACY AND POISONS (THIRD AND FOURTH SCHEDULE AMENDMENT) ORDER 2017 BR 111 / 2017 The Minister responsible for health, in exercise of the power conferred by section 48A(1) of the Pharmacy and Poisons Act 1979, makes the following Order: Citation 1 This Order may be cited as the Pharmacy and Poisons (Third and Fourth Schedule Amendment) Order 2017. Repeals and replaces the Third and Fourth Schedule of the Pharmacy and Poisons Act 1979 2 The Third and Fourth Schedules to the Pharmacy and Poisons Act 1979 are repealed and replaced with— “THIRD SCHEDULE (Sections 25(6); 27(1))) DRUGS OBTAINABLE ONLY ON PRESCRIPTION EXCEPT WHERE SPECIFIED IN THE FOURTH SCHEDULE (PART I AND PART II) Note: The following annotations used in this Schedule have the following meanings: md (maximum dose) i.e. the maximum quantity of the substance contained in the amount of a medicinal product which is recommended to be taken or administered at any one time. 1 PHARMACY AND POISONS (THIRD AND FOURTH SCHEDULE AMENDMENT) ORDER 2017 mdd (maximum daily dose) i.e. the maximum quantity of the substance that is contained in the amount of a medicinal product which is recommended to be taken or administered in any period of 24 hours. mg milligram ms (maximum strength) i.e. either or, if so specified, both of the following: (a) the maximum quantity of the substance by weight or volume that is contained in the dosage unit of a medicinal product; or (b) the maximum percentage of the substance contained in a medicinal product calculated in terms of w/w, w/v, v/w, or v/v, as appropriate.
    [Show full text]
  • Caffeine Citrate 10Mg/Ml Oral Solution Maintenance Doses
    PACKAGE LEAFLET: INFORMATION FOR THE PATIENT doctor or nurse may give one more higher • changes in blood tests (reduced levels dose, before continuing to the lower of haemoglobin after prolonged Caffeine Citrate 10mg/ml Oral Solution maintenance doses. treatment) Duration of treatment • reduced thyroid hormone at the start Equivalent to Caffeine 5mg/ml Your baby’s doctor will decide exactly of treatment with other medicines given at the same Please read all of this leaflet carefully how long your newborn must continue Reporting of side effects time. A premature baby may need many before your baby is given this therapy with Caffeine Citrate 10mg/ml If your newborn gets any side effects, medicines, and any problems with caffeine medicine. Oral Solution. If your baby has 5 to 7 days talk to your baby’s doctor. This includes are likely to be minor, but tell the doctor • Keep this leaflet. You may need to read without apnoea attacks, the doctor will any possible side effects not listed in this about any other medication they may it again. stop treatment. leaflet. You can also report side effects D04359 not know about, particularly any other • If you have further questions, please The doctor may decide to check the directly via Yellow Card Scheme. medicine (for example theophylline) given ask the hospital doctor who is looking levels of caffeine in a blood sample Website: www.mhra.gov.uk/yellowcard to your baby to help it breathe. after your baby. as a precaution, or if your baby is not or search for MHRA Yellow Card in the If your newborn gets any side effects, Medications containing phenobarbitone responding to treatment as expected.
    [Show full text]
  • Nevada Medicaid Formulary
    Nevada Medicaid-Approved Preferred Drug List Effective August 15, 2021 Legend In each class, drugs are listed alphabetically by either brand name or generic name. Brand name drug: Uppercase in bold type Generic drug: Lowercase in plain type AL: Age Limit Restrictions DO: Dose Optimization Program GR: Gender Restriction OTC: Over the counter medication available with a prescription. (Prescribers please indicate OTC on the prescription) PA: Prior authorization is required. Prior authorization is the process of obtaining approval of benefits before certain prescriptions are filled. QL: Quantity limits; certain prescription medications have specific quantity limits per prescription or per month. SP: Specialty Pharmacy ST: Step therapy is required. You may need to use one medication before benefits for the use of another medication can be authorized. Drug Name Reference Notes *ADHD/ANTI-NARCOLEPSY/ANTI- OBESITY/ANOREXIANTS* *ADHD AGENT - SELECTIVE ALPHA ADRENERGIC AGONISTS*** clonidine hcl er oral tablet extended release Kapvay AL; QL 12 hour *ADHD AGENT - SELECTIVE NOREPINEPHRINE REUPTAKE INHIBITOR*** atomoxetine hcl oral capsule Strattera DO; AL; QL *AMPHETAMINE MIXTURES*** amphetamine-dextroamphet er oral capsule extended release 24 hour 10 mg, 15 mg, 5 Adderall XR DO; AL; QL mg amphetamine-dextroamphet er oral capsule extended release 24 hour 20 mg, 25 mg, 30 Adderall XR AL; QL mg amphetamine-dextroamphetamine oral Adderall DO; AL; QL tablet 10 mg, 12.5 mg, 15 mg, 5 mg, 7.5 mg amphetamine-dextroamphetamine oral Adderall AL tablet 20 mg,
    [Show full text]
  • Acetylsalicylic Acid (375 Mg), Codeine Phosphate (15 Mg), Caffeine (15 Mg*) Tablets
    Prescribing Information INCLUDING PATIENT MEDICATION INFORMATION N.282® Acetylsalicylic Acid (375 mg), Codeine Phosphate (15 mg), Caffeine (15 mg*) Tablets *equivalent to 30 mg caffeine citrate N.292® Acetylsalicylic acid (375 mg), Codeine Phosphate (30 mg), Caffeine (15 mg*) Tablets *equivalent to 30 mg caffeine citrate ANALGESIC - ANTIPYRETIC PENDOPHARM, Division of Pharmascience Inc. Date of Revision: 6111 Royalmount Ave., Suite 100 Montréal, Québec November 23, 2016 H4P 2T4 Submission Control No.: 195437 282 and 292 are registered trademarks of Pharmascience Inc. TABLE OF CONTENT PART I: HEALTH PROFESSIONAL INFORMATION ......................................................... 3 SUMMARY PRODUCT INFORMATION ........................................................................ 3 INDICATIONS AND CLINICAL USE .............................................................................. 3 CONTRAINDICATIONS ................................................................................................... 4 WARNINGS AND PRECAUTIONS .................................................................................. 5 ADVERSE REACTIONS ................................................................................................. 12 DRUG INTERACTIONS .................................................................................................. 14 DOSAGE AND ADMINISTRATION .............................................................................. 15 OVERDOSAGE ...............................................................................................................
    [Show full text]
  • Physiological Effects of Caffeine and Its Congeners Present in Tea And
    Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 2 August 2018 doi:10.20944/preprints201808.0032.v1 1 Type of the paper: Review 2 3 Physiological effects of caffeine and its congeners 4 present in tea and coffee beverages 5 6 I. Iqbal1, M. N. Aftab2, M. A. Safer3, M. Menon4, M. Afzal5⌘ 7 1Department of Life Sciences, Lahore College for Women, Lahore, Pakistan 8 2Institute of Biochemistry and Biotechnology, Government College University, 9 Lahore 54000, Pakistan 10 3Department of Biological Sciences, Faculty of Science, Kuwait University, Kuwait 11 4Plamer University (West Campus) San Jose, CA 12 5Department of Biological Sciences, Faculty of Science, Kuwait University, Kuwait 13 ⌘ Correspondence: [email protected], Tel. +1 352 681 7347 14 15 16 Running title: Caffeine 17 18 19 20 21 22 23 Corresponding author: 24 M. Afzal, 25 10547 NW 14th PL. 26 Gainesville, FL. USA 27 email: [email protected] 28 Tel. +1 352 681 7347 29 30 1 © 2018 by the author(s). Distributed under a Creative Commons CC BY license. Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 2 August 2018 doi:10.20944/preprints201808.0032.v1 31 Abstract: Tea and coffee are the most commonly used beverages throughout the 32 world. Both decoctions are rich in small organic molecules such as 33 phenolics/polyphenolics, purine alkaloids, many methylxanthines, substituted 34 benzoic and cinnamic acids. Many of these molecules are physiologically 35 chemopreventive and chemoprotective agents against many severe conditions such 36 as cancer, Alzheimer, Parkinsonism, inflammation, sleep apnea, cardiovascular 37 disorders, bradycardia, fatigue, muscular relaxation, and oxidative stress.
    [Show full text]
  • CPT / HCPCS Code Drug Description Approximate Cost Share
    The information listed here is for our most prevalent plan. The amount you pay for a covered drug will depend on your plan’s coverage. Please refer to your Medical Plan GTB for more information. To find out the cost of your drugs, please contact HMSA Customer Service at 1-800-776-4672. If you receive services from a nonparticipating provider, you are responsible for a copayment plus any difference between the actual charge and the eligible charge. Legend $0 = no cost share $ = $100 and under $$ = over $100 to $250 $$$ = over $250 to $500 $$$$ = over $500 to $1000 $$$$$ = over $1000 1 = Please call HMSA Customer Service 1-800-776-4672 for cost share information. 2 = The cost share for this drug is dependent upon the diagnosis. Please call HMSA Customer Service at 1-800-772-4672 for more information. 3 = Cost share information for these drugs is dependent upon the dose prescribed. Please call HMSA Customer Service at 1- 800-772-4672 for more information. CPT / HCPCS approximate Code Drug Description cost share J0129 Abatacept Injection $$$$ J0130 Abciximab Injection 3 J0131 Acetaminophen Injection $ J0132 Acetylcysteine Injection $ J0133 Acyclovir Injection $ J0135 Adalimumab Injection $$$$ J0153 Adenosine Inj 1Mg $ J0171 Adrenalin Epinephrine Inject $ J0178 Aflibercept Injection $$$ J0180 Agalsidase Beta Injection 3 J0200 Alatrofloxacin Mesylate 3 J0205 Alglucerase Injection 3 J0207 Amifostine 3 J0210 Methyldopate Hcl Injection 3 J0215 Alefacept 3 J0220 Alglucosidase Alfa Injection 3 J0221 Lumizyme Injection 3 J0256 Alpha 1 Proteinase Inhibitor
    [Show full text]
  • Scanned Using Fujitsu 6670 Scanner and Scandall Pro Ver 1.7 Software
    1816 1990/826 THE DRUG TARIFF 1990 PURSUANT to section 99 of the Social Security Act 1964, the Minister of Health hereby gives the following direction. ANALYSIS I. Title and commencement 15. Disputes 2. Interpretation PART I PART III GENERAL RULES AFFECTING DIRECTION MISCELLANEOUS PROVISIONS 3. Scope of direction 16. Claims on Department 4. Standards I 7. Allergy treatment sets 5. Charges for requirements 18. Payment for non·disposable syringes and needles PART 11 19. Payment for plastic syringes RULES FOR PRICING 20. Period and quantity of supply for 6. Calculation of payments doctors' and midwives' prescriptions 7. Application of Pricing Schedules 21. Period and quantity of supply for 8. Computation of selling price prescriptions for oral contraceptives 9. Rounding calculations 22. Period and quantity of supply for 10. Minimum charges dentist's prescriptions 11. Adjustment of dose volumes of oral 23. Original packs, and certain antibiotics liquid requirements 24. Bulk supply orders 12. Water 25. Practitioner's supply orders 13. Payment for bulk supply orders 26. Wholesale supply orders 14. Payment for practitioners' supply 27. Revocations and savings orders Schedule DIRECTION 1. Tide and commencement-(I) This direction may be cited as the Drug Tariff 1990. (2) This direction shall come into force on the 1st day of December 1990. 2. Interpretation-(1) In this direction, unless the context otherwise requires,- "The Act" means the Social Security Act 1964: "Board" means an Area Health Board under the Area Health Boards Act 1983 or a Hospital
    [Show full text]
  • Skin Aging Handbook
    SKIN AGING HANDBOOK An Integrated Approach to Biochemistry and Product Development Edited by Nava Dayan Norwich, NY, USA Copyright © 2008 by William Andrew Inc. No part of this book may be reproduced or utilized in any form or by any means, electronic or me- chanical, including photocopying, recording, or by any information storage and retrieval system, without permission in writing from the Publisher. ISBN: 978-0-8155-1584-5 Library of Congress Cataloging-in-Publication Data Skin aging handbook : an integrated approach to biochemistry and product development / edited by Nava Dayan. p. ; cm. -- (Personal care and cosmetic technology) Includes bibliographical references and index. ISBN 978-0-8155-1584-5 (alk. paper) 1. Skin--Aging. 2. Cosmetics. 3. Dermatologic agents. 4. Cosmetic industry. 5. Dermatologic agents industry. I. Dayan, Nava. II. Series. [DNLM: 1. Skin Physiology--drug effects. 2. Aging--drug effects. 3. Chemistry, Pharmaceutical. 4. Cosmetics--economics. 5. Cosmetics--pharmacology. 6. Cosmetics--therapeutic use. WR 102 S62715 2008] QP88.5.S553 2008 612.7’9--dc22 2008009757 Printed in the United States of America This book is printed on acid-free paper. 10 9 8 7 6 5 4 3 2 1 Published by: William Andrew Inc. 13 Eaton Avenue Norwich, NY 13815 1-800-932-7045 www.williamandrew.com Cover Design by Russell Richardson ENVIRONMENTALLY FRIENDLY This book has been printed digitally because this process does not use any plates, ink, chemicals, or press solutions that are harmful to the environment. The paper used in this book has a 30% recycled content. NOTICE To the best of our knowledge the information in this publication is accurate; however the Publisher does not assume any responsibility or liability for the accuracy or completeness of, or consequences arising from, such information.
    [Show full text]