DOCSLIB.ORG

FRCR. Thesis Submit

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

2807400880 CLINICAL AND PHARMACOLOGICAL ASPECTS OF THE USE OF MORPHINE IN ADVANCED CANCER Peter John Hoskin B.Sc., M.B.,B.S., MRCP(UK), FRCR. Thesis submitted for the degree of Doctor of Medicine in the University of London 1 ProQuest Number: U553630 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 U553630 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 ABSTRACT The pharmacology of morphine has been studied with particular reference to Its use In chronic dosage In patients with advanced cancer and to explore the hypothesis that one of Its metabolites, norphine-6 ^ 1ucurcnide, which is a highly potent analgesic in animal models, may play an Important part In the analgesic action of morphine. In this work two different assays for morphine, morphine-3- glucuronlde (M3G) and marphlne-6 -glucuronide (M6G) have been compared; radioimmunoassay (RIA) and high performance liquid chromatography (HPLC). Basic pharmacokinetic parameters for morphine and morphine-6 - glucurcnlde have been established In healthy volunteers. Changes in both morphine and M 6G plasma concentrations were found to reflect changes in scores for drowsiness, relaxation and dry mouth after oral and intravenous adniinistration. In cancer patients receiving regular doses of oral morphine there was a mean absolute bioavailability of 34% which was not significantly different from that in healthy volunteers. No influence of impaired hepatic function due to metastases was seen on this or plasma clearance. A ratio of morphine:M6 G of between 1:6 and 1:9 was found (compared to a ratio of 1 : 1 1 in healthy volunteers), and the ratio of morphine:M3G was 1:55. The pharmacology of controlled release morphine tablets (MST- Ocntinus) has been investigated. No difference in bioavailability relative to aqueous morphine solution was found and when changing from oral morphine solution to MST no advantage in using a loading dose of aqueous morphine when initiating treatment with controlled release tablets was found. 2 Morphine, M3G and M 6G have been demonstrated In CSF, pleural fluid and ascitic fluid from cancer patients. Evidence for an enterohepatic circulation of morphine has been obtained by the demonstration of these substances in bile from cancer patients receiving regular morphine. Patterns of use of morphine in patients with cancer pain have been studied by both a retrospective review of drug use in a continuing care unit and a postal questionnaire to a cross section of medical practitioners. 3 CONTENTS Page ABSTRACT 2 ACKNCWLEJX3EMENTS 18 CHAPTER 1 INTRODUCTION 21 l.a) Morphine Pharmaceutical preparations l.a.l Morphine Sulphate 24 l.a. 2 Nepenthe 24 l.a.3 Controlled Release Preparations 25 l.a.4 Parenteral Preparations 25 l.a.5 Others 25 Clinical use l.a.6 General Aspects 26 l.a.7 Oral Administration 29 l.a.8 Rectal Administration 30 l.a.9 Parenteral Administration 30 1. a. 10 Equivalent parenteral:oral dose ratios 31 l.a. 11 Spinal Administration 32 l.a. 12 Buccal Administration 34 l.a. 13 Tolerance and Addiction 34 l.a. 14 Morphine Intolerance 38 4 Pharmacokinetics Page l.a.15 General Considerations 39 1. a. 16 Absorption 3 9 1. a. 17 Distribution 40 1. a. 18 Metabolism 42 l.a. 19 Excretion 47 l.a.20 Summary of Published Pharmacokinetic Parameters 49 Pharmacodynamics l.a.21 Clinical Efects of Morphine 55 l.a.22 Opioid Receptors 55 l.a.23 Active Metabolites 57 l.b Objectives 61 CHAPTER 2 METHODS 2.a Review of Morphine Assay Methods 2.a.l Early Methods 63 2.a.2 Radioisotope Tracer Methods 64 2.a.3 Fluorometric Assay 64 2.a.4 Gas Liquid Chromatography 65 2. a. 5 Radioimmunoassay 65 2.a .6 High Performance Liquid 68 Chromatography 5 2.b HPLC Assay for Morphine and Morphine Metabolites Page 2.b.l Extraction Technique 70 2.b.2 Chromatography 72 2.b.3 Development of Assay 78 2.c RIA Assay for Morphine 82 2.d RIA Assay for Morphine Metabolites 87 2.e Comparison of RIA with HPLC 2.e.l Introduction 92 2.e.2 HPLC vs HPLC 93 2.e.3 HPLC vs RIA 95 2.e.4 HPLC vs HPLC vs RIA 98 2.e.5 Differential RIA 100 2.e.6 Discussion 103 2.f Method of Blood Sampling 2.f .1 Introduction 104 2.f .2 Materials and Method 106 (i ) Sample Collection (ii) Assay Technique (iii) Statistical Analysis 2.f .3 Results 108 2.f.4 Discussion 111 6 CHAPTER 3 PHARMACOKINETIC AND PHARMACODYNAMIC STUDIES WITH MORPHINE IN HEALTHY VOLUNTEERS Page a) Pharmacokinetics of Morphine after (i) IV Injection (ii) Oral Elixir, (iii) Controlled Release Tablet (MST), (iv) Buccal Tablet. 3.a.l Introduction 114 3.a.2 Patients and Method 115 3.a.3 Assay Method 117 3.a.4 Statistical Analysis 117 3.a.5 Results 118 3.a .6 Discussion 124 b) Pharmacokinetics of M6G after (i) IV Injection (ii) Oral Elixir (iii) Controlled Release Tablet (MST) (iv) Buccal Tablet 3.b.l Introduction 126 3.b.2 Patients and Method 126 3.b.3 Assay Method 126 3.b.4 Statistical Analysis 126 3.b.5 Results 129 3.b.6 Discussion 133 7 c) Concentration ^ Effect Relationships Page (i) Morphine (ii) M6G 3.C.1 Introduction 135 3.C.2 Method 135 3.C.3 Results 138 3.C.4 Discussion 141 CHAPTER 4 STUDIES ON THE BIQAVAILABILITY AND PHARMACOKINETICS OF MORPHINE IN PATIENTS WITH ADVANCED CANCER 4.a Bioavailability of Morphine in patients with advanced cancer: (i) Normal hepatic function (ii) Impaired hepatic function 4.a.l Introduction 143 4.a.2 Patients and method 144 4.a.3 Sanple analysis 145 4.a.4 Statistical analysis 145 4.a.5 Results 146 4.a .6 Discussion 156 8 4.b The relative bioavailability of oral Morphine Elixir and Controlled Release Morphine Tablets (MST-Continus) Page 4.b.l Introduction 159 4.b.2 Patients and Method 160 4.b.3 Sample analysis 161 4.b.4 Statistical Analysis 162 4.b.5 Results 163 (i) Patient Population 163 (ii) Individual profiles 163 (iii) Relative Bioavailability of Morphine 165 Snax anc* *max far Morphine 168 (v) Metabolite Data 170 (vi) Pain Scores 175 (vii) Steady State Samples 177 4.b.6 Discussion 179 4.c Evaluation of the use of a loading dose of morphine when starting Controlled Release Morphine Tablets. 4.C.1 Introduction 183 4.C.2 Method 184 4.C.3 Sample analysis 186 4.C.4 Statistical analysis 186 4.C.5 Results 187 4.C.6 Discussion 196 9 CHAPTER 5 STUDIES INTO THE DISTRIBUTION OF MORPHINE AND MORPHINE-6 -GLUCURONIDE IN PATIENTS WITH ADVANCED CANCER Page 5.a Evidence fear enterohepatic circulation of Morphine in man 5.a.l Introduction 199 5.a.2 Patients and Method 199 5.a.3 Analysis 2 0 0 5.a.4 Results 2 0 0 5.a.5 Discussion 203 5.b The passage of Morphine and M 6G across the blood-brain barrier into CSF 5.b.l Introduction 205 5.b.2 Patients and Method 206 5.b.3 Analysis 206 5.b.4 Results 206 5.b.5 Discussion 2 1 1 5.c The passage of morphine and M 6 G into malignant effusions 5.C.1 Introduction 214 5.C.2 Patients and Method 214 5.C.3 Analysis 215 5.C.4 Results 215 5.C.5 Discussion 217 10 CHAPTER 6 CLINICAL STUDIES ON THE USE OF OPIOID DRUGS IN PATIENTS WITH ADVANCED CANCER Page 6 .a Questionnaire study into the use and attitudes of medical staff to opioid drugs in advanced cancer. 6 .a.l Introduction 219 6 .a .2 Subjects and method 2 2 0 6 .a.3 Statistical analysis 2 2 1 6 .a.4 Results 2 2 2 6 .a.5 Discussion 238 6 .b Retrospective review of treatment patterns in a continuing care unit. 6 .b.l Introduction 242 6.b.2 Patients and Methods 242 6.b.3 Results 243 (i) Analgesic Use 243 (ii) Coanalgesic Use 250 (iii) Antiemetic Use 251 (iv) Antitumour Therapy 254 (v) Other Therapies 256 6.b.4 Discussion 257 11 CHAPTER 7 OONCLUSICNS Page 7.a Assay Methods 262 7.b Pharmacokinetics of morphine 263 7.c Morphine metabolites 264 7.b Controlled release morphine tablets 265 7.e Enterohepatic circulation of morphine 265 7.f Clinical use of opioid drugs in patients with advanced cancer. 266 7.g Future Studies 267 REFERENCES 270 APPENDIX 1 Raw data 284 APPENDIX 2 Questionnaire from Chapter 6 .a 303 APPENDIX 3 PUBLICATIONS 308 12 LIST OF TABLES Page l.a.l Alternative strong opioid drugs and analgesic equivalents 27 1.a.2 Published pharmaookinetic parameters of morphine 50 2.C.1 Cross reactivity of specific morphine antiserum 83 2.C.2 Recovery of morphine added to drug-free serum 8 6 2.d.l Cross reactivity of rabbit antiserum G/R/ 6 8 8 2.d.2 Cross reactivity of goat antiserum G/G/l 90 2.e. 1 Comparison of HPLC (Barts) with HPLC (Hackney) for morphine and M6G 94 2.e.2 Comparison of HPLC and RIA using the mean difference over two series of 150 samples 97 2.e.3 Comparison of values for M6G by differential RIA 101 2.e.4 Recovery data for RIA 102 2.f.1 Details of sample preparation in published reports 1975-1987 105 2.f.2 Details of sample preparation 107 2.f.3 Details of morphine administration in patients entered in to sampling study 109 3.a.l Pharmaookinetic parameters for morphine after IV administration 1 2 0 3.a.2 AUC and absolute bioavailability for morphine in healthy volunteers 1 2 1 3.a.3 C^ax and for morphine in healthy volunteers 122 3.a.4 Subject acceptability of the buccal morphine tablet 123 3.b.l AUC for M 6G and morphine:M6G ratios in healthy volunteers 130 3.b.2 and tmax for M6G in healthy volunteers
Recommended publications
  • List of Narcotic Drugs Under International Control

    List of Narcotic Drugs Under International Control

    International Narcotics Control Board Yellow List Annex to Forms A, B and C 59th edition, July 2020 LIST OF NARCOTIC DRUGS UNDER INTERNATIONAL CONTROL Prepared by the INTERNATIONAL NARCOTICS CONTROL BOARD* Vienna International Centre P.O. Box 500 A-1400 Vienna, Austria Internet address: http://www.incb.org/ in accordance with the Single Convention on Narcotic Drugs, 1961** Protocol of 25 March 1972 amending the Single Convention on Narcotic Drugs, 1961 * On 2 March 1968, this organ took over the functions of the Permanent Central Narcotics Board and the Drug Supervisory Body, r etaining the same secretariat and offices. ** Subsequently referred to as “1961 Convention”. V.20-03697 (E) *2003697* Purpose The Yellow List contains the current list of narcotic drugs under international control and additional relevant information. It has been prepared by the International Narcotics Control Board to assist Governments in completing the annual statistical reports on narcotic drugs (Form C), the quarterly statistics of imports and exports of narcotic drugs (Form A) and the estimates of annual requirements for narcotic drugs (Form B) as well as related questionnaires. The Yellow List is divided into four parts: Part 1 provides a list of narcotic drugs under international control in the form of tables and is subdivided into three sections: (1) the first section includes the narcotic drugs listed in Schedule I of the 1961 Convention as well as intermediate opiate raw materials; (2) the second section includes the narcotic drugs listed in Schedule II of the 1961 Convention; and (3) the third section includes the narcotic drugs listed in Schedule IV of the 1961 Convention.
  • BY Aaron J. Gottschalk

    BY Aaron J. Gottschalk

    BIOCHEMICAL AND DEVELOPMENTAL CHARACTERIZATION OF A SNF2-LIKE ATPASE AMPLIFIED IN LIVER CANCER 1 (ALC1) BY Aaron J. Gottschalk Submitted to the graduate degree program in Biochemistry and Molecular Biology and the Graduate faculty of the University of Kansas Medical Center in partial fulfillment for the degree of Doctor of Philosophy. _______________________ Chairperson Committee members* _______________________* _______________________* _______________________* _______________________* Date defended: ________________ The Dissertation Committee for Aaron J. Gottschalk certifies that this is the approved version of the following dissertation: BIOCHEMICAL AND DEVELOPMENTAL CHARACTERIZATION OF A SNF2-LIKE ATPASE AMPLIFIED IN LIVER CANCER 1 (ALC1) Committee: _______________________ Chairperson* _______________________ _______________________ _______________________ _______________________ Date defended: ________________ 2 ACKNOWLEDGEMENTS First and foremost, I would like to express my deepest thanks and gratitude to my mentors Joan and Ron Conaway. During my tenure in their lab as a graduate student I have been afforded an amazing opportunity to learn and grow as a scientist while independently developing this project. It is their extreme kindness, steadfast encouragement, guidance, and humor that have made even the toughest of problems both scientific and in life seem very surmountable, and for that I thank them profoundly. Next, I would like to thank my committee members Drs. Glen Andrews, Jennifer Gerton, Leslie Heckert, and Ken Peterson for all their useful advice and suggestions throughout the course of my graduate career. Not only did my committee members provide great scientific direction but they also made bi-annual meetings fun and engaging. I would like to thank all of the members of the Conaway Lab including: Charles Banks, Margaret Banks, Yong Cai, Jingji Jin, Stephanie Kong, Nawel Mahrour, Ana Pedraza, Chieri Sato, Shigeo Sato, Henrietta Szutorisz, Hide Takahashi, Tingting Yao, Dotan Sela, Lu Chen, and Merry McClaird.
  • Opioid Analgesics

    Opioid Analgesics

    14 Opioid Analgesics Maree T. Smith1,2 and Wei H. Goh1 1Centre for Integrated Preclinical Drug Development, The University of Queensland, St Lucia Campus, Brisbane, Queensland 2School of Pharmacy, The University of Queensland, St Lucia Campus, Brisbane, Queensland Australia 1. Introduction Intensive research on the neurobiology of pain over the past two decades has revealed many receptors, ion channels and enzymes with potential as novel targets for development of a new generation of analgesic agents. However, despite large investment in preclinical and clinical development of small molecules and biologics as potential novel pain therapeutics, very few have reached the clinic. Hence, drugs used in the clinical setting for the pharmacological management of pain continue to be those that were first recommended in 1986 by the World Health Organisation (WHO) for the management of chronic cancer pain (WHO, 1986). Twenty-five years on, the WHO 3-step Analgesic Ladder (Figure 1) is still used widely to guide the pharmacological management of pain and opioid analgesics are the mainstay for alleviation of moderate to severe nociceptive pain. Fig. 1. World Health Organisation 3-Step Analgesic Ladder (WHO, 1986) www.intechopen.com 288 Pain Management – Current Issues and Opinions 2. WHO Analgesic Ladder The WHO Analgesic Ladder provides a succinct encapsulation of the guidelines for the management of chronic pain according to intensity (WHO, 1986). Specifically, for mild pain, non-opioid analgesics on Step 1 of the Analgesic Ladder including acetaminophen, aspirin and nonsteroidal anti-inflammatory drugs such as ibuprofen, are recommended. When the pain has a neuropathic component, addition of an adjuvant agent such as a tricyclic antidepressant, anticonvulsant or anti-arrhythmic agent, is recommended.
  • 1 the Maternal and Neonatal Disposition of Pethidine And

    1 the Maternal and Neonatal Disposition of Pethidine And

    1 THE MATERNAL AND NEONATAL DISPOSITION OF PETHIDINE AND BUPIVACAINE ADMINISTERED IN CHILDBIRTH Submitted by Lidia Josephine Notarianni M.Sc. for the degree of Doctor of Philosophy of the University of London 1979 Department of Biochemical Pharmacology St. Mary's Hospital Medical School Paddington, London W.2 COPYRIGHT "Attention is drawn to the fact that copyright of this thesis rests with its author. This copy of the thesis has been supplied on condition that anyone who consults it is understood to recognise that its copyright rests with its author and that no quotation from the thesis and no information derived from it may be published without the prior consent of the author." This thesis may be photocopied, microfilmed or lent to other libraries for the purpose of consultation 2 To my parents with love and gratitude "Let it, then be distinctly understood, that the popular unprofessional use of ether and chloroform is both immoral and injurious; that it is highly dangerous and may produce death." (W. Charming; in 'A Treatise on Etherization in Childbirth' 1848). 4 CONTENTS Page Abstract 10 Acknowledgements 12 List of figures 13 List of tables 18 Chapter One. Perinatal pharmacology and obstetric analgesia 1.1 Introduction 23 1.1.1 Historical background 23 1.1.2 Analgesic drugs used in obstetric practice 25 1.2 The passage of maternally administered drugs to 26 the fetus 26 1.2.1 Drugs and the fetus 27 1.2.2 Placental structure and transplacental transfer 35 1.2.3 Drug distribution in the fetus 41 1.2.4 Pharmacokinetics of placental transfer at term 46 1.3 Perinatal drug metabolism 52 1.3.1 General metabolism 52 1.3.2 Drug metabolism during pregnancy 54 1.3.3 Drug retabolism by the placenta 58 1.3.4 Drug metabolism by the fetus 60 1.3.5 Drug metabolism by the neonate 63 1.4 Obstetric analgesia 69 1.4.1 Pethidine 70 1.4.2 Xylidide local anaesthetics 75 1.5 Scope of the present work 89 5 Page Chapter Two.
  • (12) Patent Application Publication (10) Pub. No.: US 2016/0186168 A1 Konieczka Et Al

    (12) Patent Application Publication (10) Pub. No.: US 2016/0186168 A1 Konieczka Et Al

    US 2016O1861 68A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2016/0186168 A1 Konieczka et al. (43) Pub. Date: Jun. 30, 2016 (54) PROCESSES AND HOST CELLS FOR Related U.S. Application Data GENOME, PATHWAY. AND BIOMOLECULAR (60) Provisional application No. 61/938,933, filed on Feb. ENGINEERING 12, 2014, provisional application No. 61/935,265, - - - filed on Feb. 3, 2014, provisional application No. (71) Applicant: ENEVOLV, INC., Cambridge, MA (US) 61/883,131, filed on Sep. 26, 2013, provisional appli (72) Inventors: Jay H. Konieczka, Cambridge, MA cation No. 61/861,805, filed on Aug. 2, 2013. (US); James E. Spoonamore, Publication Classification Cambridge, MA (US); Ilan N. Wapinski, Cambridge, MA (US); (51) Int. Cl. Farren J. Isaacs, Cambridge, MA (US); CI2N 5/10 (2006.01) Gregory B. Foley, Cambridge, MA (US) CI2N 15/70 (2006.01) CI2N 5/8 (2006.01) (21) Appl. No.: 14/909, 184 (52) U.S. Cl. 1-1. CPC ............ CI2N 15/1082 (2013.01); C12N 15/81 (22) PCT Filed: Aug. 4, 2014 (2013.01); C12N 15/70 (2013.01) (86). PCT No.: PCT/US1.4/49649 (57) ABSTRACT S371 (c)(1), The present disclosure provides compositions and methods (2) Date: Feb. 1, 2016 for genomic engineering. Patent Application Publication Jun. 30, 2016 Sheet 1 of 4 US 2016/O186168 A1 Patent Application Publication Jun. 30, 2016 Sheet 2 of 4 US 2016/O186168 A1 &&&&3&&3&&**??*,º**)..,.: ××××××××××××××××××××-************************** Patent Application Publication Jun. 30, 2016 Sheet 3 of 4 US 2016/O186168 A1 No.vaegwzºkgwaewaeg Patent Application Publication Jun. 30, 2016 Sheet 4 of 4 US 2016/O186168 A1 US 2016/01 86168 A1 Jun.
  • WO 2015/112750 Al 30 July 2015 (30.07.2015) P O P C T

    WO 2015/112750 Al 30 July 2015 (30.07.2015) 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 2015/112750 Al 30 July 2015 (30.07.2015) P O P C T (51) International Patent Classification: (74) Agents: MCEVOY, Michael T. et al; Wilson Sonsini A24F 47/00 (2006.01) A61M 15/06 (2006.01) Goodrich & Rosati, 650 Page Mill Road, Palo Alto, CA 94304-1050 (US). (21) International Application Number: PCT/US2015/0125 12 (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, (22) Date: International Filing AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, 22 January 2015 (22.01 .2015) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, (25) Filing Language: English DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (26) Publication Language: English KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, (30) Priority Data: MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, 61/930,391 22 January 2014 (22.01.2014) US PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, 61/937,3 13 7 February 2014 (07.02.2014) US SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, 61/949,771 7 March 2014 (07.03.2014) US TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW.
  • Analysis of Nkx3.1 Target Genes in Prostate Cancer

    Analysis of Nkx3.1 Target Genes in Prostate Cancer

    ANALYSIS OF NKX3.1 TARGET GENES IN PROSTATE CANCER By Ashish Popatrao Mogal Dissertation Submitted to the Faculty of the Graduate School of Vanderbilt University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY in Pathology August, 2007 Nashville, Tennessee Approved: Professor Fritz Parl Professor David Head Professor Pampee Young Professor Simon Hayward Professor Zu-Wen Sun To my parents, sisters and lovely wife for their enormous support, love and encouragement ii ACKNOWLEDGEMENTS First and foremost, I would like to thank my mentor, Dr. Sarki Abdulkadir. Dr. Abdulkadir has been a great mentor and I am really fortunate to have a mentor like him who has such a fascination and an enthusiasm for pathology. I am really grateful for the guidance, knowledge and support that I received from him both at the scientific and personal levels. I sincerely feel that he has provided me with a strong scientific foundation that will serve as my one of the greatest assets for my future endeavors. Secondly, I would like to thank the members of my dissertation committee, Dr. Fritz Parl, Dr. David Head, Dr. Pampee Young, Dr. Simon Hayward and Dr. Zu- Wen Sun for their excellent guidance, suggestions and insightful comments about my project throughout my training. I am very grateful for their enormous support and encouragement which really helped me in moving forward with such a challenging project. I would like to thank Dr. Philip Crooke from the Department of Mathematics, Vanderbilt University. Dr. Crooke is an excellent mathematician who has formulated a mathematical model based on our experimental observations.
  • (12) Patent Application Publication (10) Pub. No.: US 2016/0340659 A1 SHOSEYOV Et Al

    (12) Patent Application Publication (10) Pub. No.: US 2016/0340659 A1 SHOSEYOV Et Al

    US 2016.0340659A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2016/0340659 A1 SHOSEYOV et al. (43) Pub. Date: Nov. 24, 2016 (54) ACTIN BINDING PEPTIDES AND (86). PCT No.: PCT/IL2O15/05O108 COMPOSITIONS COMPRISING SAME FOR S 371 (c)(1) INHIBITING ANGOGENESIS AND (2) Date: Jul. 21, 2016 TREATING MEDICAL CONDITIONS ASSOCATED WITH SAME Related U.S. Application Data (71) Applicant: YISSUM RESEARCH AND (60) Provisional application No. 61/933,363, filed on Jan. DEVELOPMENT COMPANY OF 30, 2014. THE HEBREW UNIVERSITY OF Publication Classification JERUSALEM LTD., Jerusalem (IL) (51) Int. Cl. (72) Inventors: Oded SHOSEYOV, Karme Yosef (IL); CI2N 9/22 (2006.01) Betty SCHWARTZ, Rechovot (IL); (52) U.S. Cl Shani DORON, Rechovot (IL): Liron CPC ............... CI2N 9/22 (2013.01); C12Y-301/27 NESIEL, Rechovot (IL); Assaf (2013.01); A6 IK 38/00 (2013.01) FRIEDLER, Mevasseret Zion (IL); s (IL); Levava ROIZ, Kiryat-Ono (IL); Patricia SMIRNOFF, Rehovot (IL); The present invention, in some embodiments thereof, relates Iris LEWIN, Mevaseret Zion (IL) to biologically active peptides and, more particularly, but not exclusively, to peptides from T2 RNase (RNASET2) having (21) Appl. No.: 15/113,187 actin binding, pharmaceutical compositions comprising the same, therapeutic use thereof and methods for their produc (22) PCT Filed: Jan. 29, 2015 tion. Patent Application Publication Nov. 24, 2016 Sheet 1 of 27 US 2016/0340659 A1 Patent Application Publication Nov. 24, 2016 Sheet 2 of 27 US 2016/0340659 A1 º|www.nH Hw Patent Application Publica tion Nov. 24, 2016 Sheet 3 of 27 US 2016/0340659 A1 a rives caves ar, or---------- - in rain rasra in a ra.------------------------- Patent Application Publication US 2016/0340659 A1 Patent Application Publication Nov.
  • Weight Gain During Pregnancy: Reexamining the Guidelines

    Weight Gain During Pregnancy: Reexamining the Guidelines

    Weight Gain During Pregnancy: Reexamining the Guidelines Kathleen M. Rasmussen and Ann L. Yaktine, Editors Committee to Reexamine IOM Pregnancy Weight Guidelines Food and Nutrition Board and Board on Children, Youth, and Families PREPUBLICATION COPY: UNCORRECTED PROOFS THE NATIONAL ACADEMIES PRESS 500 Fifth Street, N.W. Washington, DC 20001 NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance. This study was supported by Contract No. HHSH250200446009I TO HHSH240G5806 between the National Academy of Sciences and U.S. Department of Health and Human Services Health Resources and Services Administration; Contract No. 200-2007-M-21619 between the National Academy of Sciences and Centers for Disease Control and Prevention Division of Nutrition and Physical Activity and Obesity; Contract No. N01-OD-4-2139 TO 192 between the National Academy of Sciences and National Institutes of Health Institute of Child Health and Human Development; Contract No. N01-OD-4-2139 TO 192 between the National Academy of Sciences and National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases; Contract No. HHSP23300700522P between the National Academy of Sciences and U.S. Department of Health and Human Services Office on Women’s Health; Contract No. HHSP23320070071P between the National Academy of Sciences and U.S.
  • List of Narcotic Drugs Under International Control

    List of Narcotic Drugs Under International Control

    International Narcotics Control Board YYeellllooww LLiisstt Annex to Forms A, B and C 50th edition, December 2011 LIST OF NARCOTIC DRUGS UNDER INTERNATIONAL CONTROL Prepared by the INTERNATIONAL NARCOTICS CONTROL BOARD* Vienna International Centre P.O. Box 500 A-1400 Vienna, Austria Internet address: http://www.incb.org/ in accordance with the Single Convention on Narcotic Drugs, 1961** Protocol of 25 March 1972 amending the Single Convention on Narcotic Drugs, 1961 ___________ * On 2 March 1968, this organ took over the functions of the Permanent Central Narcotics Board and the Drug Supervisory Body, retaining the same secretariat and offices. ** Subsequently referred to as “1961 Convention”. Purpose The Yellow List contains the current list of narcotic drugs under international control and additional relevant information. It has been prepared by the International Narcotics Control Board to assist Governments in completing the annual statistical reports on narcotic drugs (Form C), the quarterly statistics of imports and exports of narcotic drugs (Form A) and the estimates of annual requirements for narcotic drugs (Form B) as well as related questionnaires. The Yellow List is divided into four parts: Part 1 provides a list of narcotic drugs under international control in form of tables and is subdivided into three sections: (1) the first section includes the narcotic drugs listed in Schedule I of the 1961 Convention and/or Group I of the 1931 Convention; (2) the second section includes the narcotic drugs listed in Schedule II of the 1961 Convention and/or Group II of the 1931 Convention; and (3) the third section includes the narcotic drugs listed in Schedule IV of the 1961 Convention and/or Group II of the 1931 Convention.
  • Australian Medicines Terminology Editorial Rules

    Australian Medicines Terminology Editorial Rules

    Australian Medicines Terminology Editorial Rules 30 April 2021 v2.9 Approved for external information Document ID: DH-3447:2021 Australian Digital Health Agency ABN 84 425 496 912, Level 25, 175 Liverpool St, Sydney, NSW 2000 Telephone 1300 901 001 or email [email protected] www.digitalhealth.gov.au Acknowledgements Council of Australian Governments The Australian Digital Health Agency is jointly funded by the Australian Government and all state and territory governments. IHTSDO (SNOMED CT) This material includes SNOMED Clinical TermsTM (SNOMED CT®) which is used by permission of the International Health Terminology Standards Development Organisation (IHTSDO). All rights reserved. SNOMED CT® was originally created by The College of American Pathologists. “SNOMED” and “SNOMED CT” are registered trademarks of the IHTSDO. Disclaimer The Australian Digital Health Agency (“the Agency”) makes the information and other material (“Information”) in this document available in good faith but without any representation or warranty as to its accuracy or completeness. The Agency cannot accept any responsibility for the consequences of any use of the Information. As the Information is of a general nature only, it is up to any person using or relying on the Information to ensure that it is accurate, complete and suitable for the circumstances of its use. Document control This document is maintained in electronic form and is uncontrolled in printed form. It is the responsibility of the user to verify that this copy is the latest revision. Copyright © 2021 Australian Digital Health Agency This document contains information which is protected by copyright. All Rights Reserved. No part of this work may be reproduced or used in any form or by any means – graphic, electronic, or mechanical, including photocopying, recording, taping, or information storage and retrieval systems – without the permission of the Australian Digital Health Agency.
  • T.C. Selçuk Üniversitesi Fen Bilimleri Enstitüsü

    T.C. Selçuk Üniversitesi Fen Bilimleri Enstitüsü

    T.C. SELÇUK ÜNİVERSİTESİ FEN BİLİMLERİ ENSTİTÜSÜ UYUŞTURUCU TİPİ KENEVİR GENOTİPLERİNİN RAPD-PCR METODU İLE KARAKTERİZASYONU VE KULLANILAN İSTATİSTİKİ YÖNTEMLERİN DEĞERLENDİRİLMESİ Emine PINARKARA YÜKSEK LİSANS TEZİ ZOOTEKNİ ANA BİLİM DALI KONYA, 2007 ÖZET Yüksek Lisans Tezi UYUŞTURUCU TİPİ KENEVİR GENOTİPLERİNİN RAPD-PCR METODU İLE KARAKTERİZASYONU VE KULLANILAN İSTATİSTİKİ YÖNTEMLERİN DEĞERLENDİRİLMESİ Emine PINARKARA Selçuk Üniversitesi Fen Bilimleri Enstitüsü Zootekni Ana Bilim Dalı Danışman: Yrd. Doç. Dr. Seyit Ali KAYIŞ 2007, Sayfa: 103 Jüri: Yrd. Doç. Dr. Seyit Ali KAYIŞ Prof. Dr. Saim BOZTEPE Yrd. Doç. Dr. Erdoğan Eşref HAKKI Bu çalışmada, Türkiye’nin farklı coğrafik bölgelerinden kaçak ekimler sonucu ele geçirilerek, İstanbul Adli Tıp Kurumu tarafından fakültemize teslim edilen kenevir tohumları arasında akrabalık bulunup bulunmadığı RAPD dominant markörleri kullanılarak araştırılmıştır. Dominant markörlerin istatistiki analizlerinde kullanılan temel koordinatlar analizi, kümeleme analizi, kümelerin güven sınırları, Mantel testi ve Nei ve Li genetik mesafesi tanıtılmış ve elde edilen veriler üzerinde bu metotlar uygulanmıştır. Bu çalışmada 29 kenevir aksesyonu sera saksı ortamında DNA izolasyonu için yaprak örnekleri alınıncaya kadar yetiştirilmiştir. Moleküler genetik çalışmalarda tek birey DNA (SET1) ve bulk DNA (SET2) setleri kullanılmıştır. PCR amplifikasyonları sonucunda SET1’de 264, SET2’de 241 DNA bantı skorlanmıştır. Elde edilen verilerin istatistiki analizleri sonucunda SET1’de kullanılan aksesyonlar arasında belirgin