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Association Between CYP17A1, CYP19A1, and HSD17B1 Gene Polymorphisms in Hormone Synthesis Pathway with Ovarian Cancer Risk
Association between CYP17A1, CYP19A1, and HSD17B1 Gene Polymorphisms in Hormone Synthesis pathway with Ovarian Cancer Risk Gowtham Kumar G1, Andrea Francis1, Solomon Paul1, Chirag Molia1, Manickavasagam M1, Usha Rani1, Ramya R1, and Nalini Ganesan1 1Sri Ramachandra Institute of Higher Education and Research August 27, 2020 Abstract Objective: To investigate the polymorphisms of genes in the steroidogenesis pathway to understand the etiological mechanisms to OC risk in the South Indian population Design: Case-Control Study Setting and Sample: Ovarian cancer cases (200) and healthy individuals (200) from the South Indian population. Methods: All the cases and controls were genotyped for SNPs by using allelic discrimination assay. Main outcome measures: Genetic distribution of SNPs of Steroidogenesis pathway genes in the South Indian population. Results: The observed results for rs743752, the homozygous CC genotype revealed significant association (OR; 1.68; 95%CI, 1.25-2.26; p =<0.05) and the dominant model, recessive model and additive model showed a significant association with an OR of 1.62; 95%CI, 1.09 { 2.42; p = 0.015, OR of 0.29, 95%CI, 0.14 { 0.60; p = <0.001 and OR of 1.68, 95%CI, 1.25 { 2.26); p = <0.001 respectively in cases and controls for OC risk. In rs10046, the heterozygous CT genotype (OR; 1.61; 95%CI 1.06 { 2.43; p = 0.023), the dominant (OR; 1.65; 95%CI, 1.11 { 2.45; p = 0.012) and the additive (OR; 1.46; 95%CI, 1.07 - 1.98; p = 0.015) models were found to be statistically significant. -
Hsd17b1) Inhibitor for Endometriosis
DEVELOPMENT OF HYDROXYSTEROID (17-BETA) DEHYDROGENASE TYPE 1 (HSD17B1) INHIBITOR FOR ENDOMETRIOSIS Niina Saarinen1,2, Tero Linnanen1, Jasmin Tiala1, Camilla Stjernschantz1, Leena Hirvelä1, Taija Heinosalo2, Bert Delvoux3, Andrea Romano3, Gabriele Möller4, Jerzy Adamski4, Matti Poutanen2, Pasi Koskimies1 1Forendo Pharma Ltd, Finland; 2Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, Finland; 3Department of Obstetrics and Gynaecology; GROW, School for Oncology and Developmental Biology; Maastricht University Medical Centre, The Netherlands; 4Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, Germany BACKGROUND OBJECTIVE Local activation of estrogens in endometriosis tissue The main objective of the present work was to assess is considered important for growth of the lesions. the preclinical efficacy of the novel HSD17B1 inhibitor, Hydroxysteroid (17-beta) dehydrogenase type 1 FOR-6219 (HSD17B1) is expressed in endometriosis tissue and converts the biologically low-active estrogen, estrone (E1), to the highly active estradiol (E2), while hydroxysteroid (17-beta) dehydrogenase type 2 (HSD17B2), catalyzes the opposite reaction. In contrast to eutopic endometrium, in endometriotic lesions the HSD17B1/HSD17B2 expression ratio is increased and E2 levels are higher than those of E1 throughout the menstrual cycle. Thus, inhibition of HSD17B1 is considered as a feasible strategy for lowering local E2 production in endometriosis. MAIN RESULTS FOR-6219 inhibits human HSD17B1 Ø FOR-6219 is a potent and FOR-6219 does not trigger estrogenic fully selective inhibitor of response in immature rat uterine human HSD17B1 over growth assay HSD17B2 Ø FOR-6219 does not bind to estrogen receptor α or β, and exhibits no estrogen-like response in immature rat uterotrophic assay Ø FOR-6219 inhibits HSD17B1 in cynomolgus monkey, dog and rabbit i.e. -
The Role of Genetic Variation in Predisposition to Alcohol-Related Chronic Pancreatitis
The Role of Genetic Variation in Predisposition to Alcohol-related Chronic Pancreatitis Thesis submitted in accordance with the requirements of the University of Liverpool for the degree of Doctor in Philosophy by Marianne Lucy Johnstone April 2015 The Role of Genetic Variation in Predisposition to Alcohol-related Chronic Pancreatitis 2015 Abstract Background Chronic pancreatitis (CP) is a disease of fibrosis of the pancreas for which alcohol is the main causative agent. However, only a small proportion of alcoholics develop chronic pancreatitis. Genetic polymorphism may affect pancreatitis risk. Aim To determine the factors required to classify a chronic pancreatic population and identify genetic variations that may explain why only some alcoholics develop chronic pancreatitis. Methods The most appropriate method of diagnosing CP was assessed using a systematic review. Genetics of different populations of alcohol-related chronic pancreatitics (ACP) were explored using four different techniques: genome-wide association study (GWAS); custom arrays; PCR of variable nucleotide tandem repeats (VNTR) and next generation sequencing (NGS) of selected genes. Results EUS and sMR were identified as giving the overall best sensitivity and specificity for diagnosing CP. GWAS revealed two associations with CP (identified and replicated) at PRSS1-PRSS2_rs10273639 (OR 0.73, 95% CI 0.68-0.79) and X-linked CLDN2_rs12688220 (OR 1.39, 1.28-1.49) and the association was more pronounced in the ACP group (OR 0.56, 0.48-0.64)and OR 2.11, 1.84-2.42). The previously identified VNTR in CEL was shown to have a lower frequency of the normal repeat in ACP than alcoholic liver disease (ALD; OR 0.61, 0.41-0.93). -
Genes in Eyecare Geneseyedoc 3 W.M
Genes in Eyecare geneseyedoc 3 W.M. Lyle and T.D. Williams 15 Mar 04 This information has been gathered from several sources; however, the principal source is V. A. McKusick’s Mendelian Inheritance in Man on CD-ROM. Baltimore, Johns Hopkins University Press, 1998. Other sources include McKusick’s, Mendelian Inheritance in Man. Catalogs of Human Genes and Genetic Disorders. Baltimore. Johns Hopkins University Press 1998 (12th edition). http://www.ncbi.nlm.nih.gov/Omim See also S.P.Daiger, L.S. Sullivan, and B.J.F. Rossiter Ret Net http://www.sph.uth.tmc.edu/Retnet disease.htm/. Also E.I. Traboulsi’s, Genetic Diseases of the Eye, New York, Oxford University Press, 1998. And Genetics in Primary Eyecare and Clinical Medicine by M.R. Seashore and R.S.Wappner, Appleton and Lange 1996. M. Ridley’s book Genome published in 2000 by Perennial provides additional information. Ridley estimates that we have 60,000 to 80,000 genes. See also R.M. Henig’s book The Monk in the Garden: The Lost and Found Genius of Gregor Mendel, published by Houghton Mifflin in 2001 which tells about the Father of Genetics. The 3rd edition of F. H. Roy’s book Ocular Syndromes and Systemic Diseases published by Lippincott Williams & Wilkins in 2002 facilitates differential diagnosis. Additional information is provided in D. Pavan-Langston’s Manual of Ocular Diagnosis and Therapy (5th edition) published by Lippincott Williams & Wilkins in 2002. M.A. Foote wrote Basic Human Genetics for Medical Writers in the AMWA Journal 2002;17:7-17. A compilation such as this might suggest that one gene = one disease. -
The Effects of Antipsychotic Treatment on Metabolic Function: a Systematic Review and Network Meta-Analysis
The effects of antipsychotic treatment on metabolic function: a systematic review and network meta-analysis Toby Pillinger, Robert McCutcheon, Luke Vano, Katherine Beck, Guy Hindley, Atheeshaan Arumuham, Yuya Mizuno, Sridhar Natesan, Orestis Efthimiou, Andrea Cipriani, Oliver Howes ****PROTOCOL**** Review questions 1. What is the magnitude of metabolic dysregulation (defined as alterations in fasting glucose, total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, and triglyceride levels) and alterations in body weight and body mass index associated with short-term (‘acute’) antipsychotic treatment in individuals with schizophrenia? 2. Does baseline physiology (e.g. body weight) and demographics (e.g. age) of patients predict magnitude of antipsychotic-associated metabolic dysregulation? 3. Are alterations in metabolic parameters over time associated with alterations in degree of psychopathology? 1 Searches We plan to search EMBASE, PsycINFO, and MEDLINE from inception using the following terms: 1 (Acepromazine or Acetophenazine or Amisulpride or Aripiprazole or Asenapine or Benperidol or Blonanserin or Bromperidol or Butaperazine or Carpipramine or Chlorproethazine or Chlorpromazine or Chlorprothixene or Clocapramine or Clopenthixol or Clopentixol or Clothiapine or Clotiapine or Clozapine or Cyamemazine or Cyamepromazine or Dixyrazine or Droperidol or Fluanisone or Flupehenazine or Flupenthixol or Flupentixol or Fluphenazine or Fluspirilen or Fluspirilene or Haloperidol or Iloperidone -
Chuanxiong Rhizoma Compound on HIF-VEGF Pathway and Cerebral Ischemia-Reperfusion Injury’S Biological Network Based on Systematic Pharmacology
ORIGINAL RESEARCH published: 25 June 2021 doi: 10.3389/fphar.2021.601846 Exploring the Regulatory Mechanism of Hedysarum Multijugum Maxim.-Chuanxiong Rhizoma Compound on HIF-VEGF Pathway and Cerebral Ischemia-Reperfusion Injury’s Biological Network Based on Systematic Pharmacology Kailin Yang 1†, Liuting Zeng 1†, Anqi Ge 2†, Yi Chen 1†, Shanshan Wang 1†, Xiaofei Zhu 1,3† and Jinwen Ge 1,4* Edited by: 1 Takashi Sato, Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of 2 Tokyo University of Pharmacy and Life Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, China, Galactophore Department, The First 3 Sciences, Japan Hospital of Hunan University of Chinese Medicine, Changsha, China, School of Graduate, Central South University, Changsha, China, 4Shaoyang University, Shaoyang, China Reviewed by: Hui Zhao, Capital Medical University, China Background: Clinical research found that Hedysarum Multijugum Maxim.-Chuanxiong Maria Luisa Del Moral, fi University of Jaén, Spain Rhizoma Compound (HCC) has de nite curative effect on cerebral ischemic diseases, *Correspondence: such as ischemic stroke and cerebral ischemia-reperfusion injury (CIR). However, its Jinwen Ge mechanism for treating cerebral ischemia is still not fully explained. [email protected] †These authors share first authorship Methods: The traditional Chinese medicine related database were utilized to obtain the components of HCC. The Pharmmapper were used to predict HCC’s potential targets. Specialty section: The CIR genes were obtained from Genecards and OMIM and the protein-protein This article was submitted to interaction (PPI) data of HCC’s targets and IS genes were obtained from String Ethnopharmacology, a section of the journal database. -
Partial Agreement in the Social and Public Health Field
COUNCIL OF EUROPE COMMITTEE OF MINISTERS (PARTIAL AGREEMENT IN THE SOCIAL AND PUBLIC HEALTH FIELD) RESOLUTION AP (88) 2 ON THE CLASSIFICATION OF MEDICINES WHICH ARE OBTAINABLE ONLY ON MEDICAL PRESCRIPTION (Adopted by the Committee of Ministers on 22 September 1988 at the 419th meeting of the Ministers' Deputies, and superseding Resolution AP (82) 2) AND APPENDIX I Alphabetical list of medicines adopted by the Public Health Committee (Partial Agreement) updated to 1 July 1988 APPENDIX II Pharmaco-therapeutic classification of medicines appearing in the alphabetical list in Appendix I updated to 1 July 1988 RESOLUTION AP (88) 2 ON THE CLASSIFICATION OF MEDICINES WHICH ARE OBTAINABLE ONLY ON MEDICAL PRESCRIPTION (superseding Resolution AP (82) 2) (Adopted by the Committee of Ministers on 22 September 1988 at the 419th meeting of the Ministers' Deputies) The Representatives on the Committee of Ministers of Belgium, France, the Federal Republic of Germany, Italy, Luxembourg, the Netherlands and the United Kingdom of Great Britain and Northern Ireland, these states being parties to the Partial Agreement in the social and public health field, and the Representatives of Austria, Denmark, Ireland, Spain and Switzerland, states which have participated in the public health activities carried out within the above-mentioned Partial Agreement since 1 October 1974, 2 April 1968, 23 September 1969, 21 April 1988 and 5 May 1964, respectively, Considering that the aim of the Council of Europe is to achieve greater unity between its members and that this -
Copyrighted Material
Index Note: page numbers in italics refer to figures; those in bold to tables or boxes. abacavir 686 tolerability 536–537 children and adolescents 461 acamprosate vascular dementia 549 haematological 798, 805–807 alcohol dependence 397, 397, 402–403 see also donepezil; galantamine; hepatic impairment 636 eating disorders 669 rivastigmine HIV infection 680 re‐starting after non‐adherence 795 acetylcysteine (N‐acetylcysteine) learning disability 700 ACE inhibitors see angiotensin‐converting autism spectrum disorders 505 medication adherence and 788, 790 enzyme inhibitors obsessive compulsive disorder 364 Naranjo probability scale 811, 812 acetaldehyde 753 refractory schizophrenia 163 older people 525 acetaminophen, in dementia 564, 571 acetyl‐L‐carnitine 159 psychiatric see psychiatric adverse effects acetylcholinesterase (AChE) 529 activated partial thromboplastin time 805 renal impairment 647 acetylcholinesterase (AChE) acute intoxication see intoxication, acute see also teratogenicity inhibitors 529–543, 530–531 acute kidney injury 647 affective disorders adverse effects 537–538, 539 acutely disturbed behaviour 54–64 caffeine consumption 762 Alzheimer’s disease 529–543, 544, 576 intoxication with street drugs 56, 450 non‐psychotropics causing 808, atrial fibrillation 720 rapid tranquillisation 54–59 809, 810 clinical guidelines 544, 551, 551 acute mania see mania, acute stupor 107, 108, 109 combination therapy 536 addictions 385–457 see also bipolar disorder; depression; delirium 675 S‐adenosyl‐l‐methionine 275 mania dosing 535 ADHD -
United States Patent (10 ) Patent No.: US 10,660,887 B2 Javitt (45 ) Date of Patent: *May 26 , 2020
US010660887B2 United States Patent (10 ) Patent No.: US 10,660,887 B2 Javitt (45 ) Date of Patent : *May 26 , 2020 (54 ) COMPOSITION AND METHOD FOR (56 ) References Cited TREATMENT OF DEPRESSION AND PSYCHOSIS IN HUMANS U.S. PATENT DOCUMENTS 6,228,875 B1 5/2001 Tsai et al. ( 71 ) Applicant : Glytech , LLC , Ft. Lee , NJ (US ) 2004/0157926 A1 * 8/2004 Heresco - Levy A61K 31/198 514/561 (72 ) Inventor: Daniel C. Javitt , Ft. Lee , NJ (US ) 2005/0261340 Al 11/2005 Weiner 2006/0204486 Al 9/2006 Pyke et al . 2008/0194631 Al 8/2008 Trovero et al. ( 73 ) Assignee : GLYTECH , LLC , Ft. Lee , NJ (US ) 2008/0194698 A1 8/2008 Hermanussen et al . 2010/0069399 A1 * 3/2010 Gant CO7D 401/12 ( * ) Notice : Subject to any disclaimer, the term of this 514 / 253.07 patent is extended or adjusted under 35 2010/0216805 Al 8/2010 Barlow 2011/0207776 Al 8/2011 Buntinx U.S.C. 154 ( b ) by 95 days . 2011/0237602 A1 9/2011 Meltzer This patent is subject to a terminal dis 2011/0306586 Al 12/2011 Khan claimer . 2012/0041026 A1 2/2012 Waizumi ( 21 ) Appl. No.: 15 /650,912 FOREIGN PATENT DOCUMENTS CN 101090721 12/2007 ( 22 ) Filed : Jul. 16 , 17 KR 2007 0017136 2/2007 WO 2005/065308 7/2005 (65 ) Prior Publication Data WO 2005/079756 9/2005 WO 2011044089 4/2011 US 2017/0312275 A1 Nov. 2 , 2017 WO 2012/104852 8/2012 WO 2005/000216 9/2013 WO 2013138322 9/2013 Related U.S. Application Data (63 ) Continuation of application No. -
A Challenge for Medicinal Chemistry by the 17Β-Hydroxysteroid Dehydro
Send Orders of Reprints at [email protected] 1164 Current Topics in Medicinal Chemistry, 2013, 13, 1164-1171 A Challenge for Medicinal Chemistry by the 17-hydroxysteroid Dehydro- genase Superfamily: An Integrated Biological Function and Inhibition Study S.-X. Lina,b, D. Poiriera and J. Adamskic,d.e aLaboratory of Molecular Endocrinology and Oncology, Centre Hospitalier Universitaire (CHU) de Quebec Research Center (CHUL) and Laval University, Québec City, Québec, G1V4G2, Canada; bWHO Collaborating Center for Re- search in Human Reproductive Health, Shanghai, 200031, China; cHelmholtz Zentrum München, Institute of Experi- mental Genetics, Genome Analysis Center, 85764 Neuherberg, Germany; dLehrstuhl für Experimentelle Genetik, Tech- nische Universität München, 85350 Freising-Weihenstephan, Germany; eGerman Center for Diabetes Research (DZD), 85764 Neuherberg, Germany Abstract: Members of the 17-hydroxysteroid dehydrogenase (17-HSD) superfamily perform distinct multiple catalyses by the same enzyme, apparently contradictory to the long-held beliefs regarding the high specificity of enzymes. Surpris- ingly, these multi-catalyses can combine synergistically in vitro and in vivo and their dysfunction may result in the stimu- lation of breast or prostate cancer. 17-HSD1 possesses high estrogen activation activity, while its androgen inactivation is significant for decreasing the week concentration of dihydrotestosterone (DHT) in breast cancer cells, an important fac- tor for cell proliferation. 17-HSD5 can also carry out multiple catalyses in hormone-dependent cancer cells. In addition to 17-HSDs 1 and 5 some other family members possess such dual-activity as well, and their inhibition decreases hor- mone-dependent cancer proliferation. The multi-specificity of 17-HSD1 is structurally based on the pseudo-symmetric androgens that can accommodate the narrow enzyme substrate tunnel by both normal and alternative binding. -
South African National Essential Medicine List Primary Level and Adult Hospital Level Medication Review Process Component: Mental Healthcare Conditions
South African National Essential Medicine List Primary Level and Adult Hospital Level Medication Review Process Component: Mental Healthcare conditions 1. Executive Summary Date: 6 June 2017 Medicine (INN): Clotiapine injection Medicine (ATC): N05AH06 Indication (ICD10 code): Acute aggressive disruptive behaviour (R45.1/4/5/6/F60.3) Patient population: Adults Level of Care: Primary and secondary level Prescriber Level: Medical doctor NNT: n/a Current standard of Care: Chlorpromazine injection / Haloperidol+Promethazine Motivator/reviewer name(s): Dr Lesley Robertson PTC affiliation: Gauteng Provincial PTC 2. Name of author(s)/motivator(s) Dr Lesley Robertson 3. Author affiliation and conflict of interest details Affiliation: University of Witwatersrand; Affiliated to South African Society of Psychiatrists; Committee member of the Adult Hospital Level Expert Review Committee (2017‐2019); Co‐opted to support the Primary Health Expert Review Committee (2016‐2018). Conflicts of interest: Dr Reddy Laboratories annual sponsorship of Public Sector Psychiatry Forum (SASOP); Honararium from Sanofi Aventis (2015) channelled to South African Society of Mental Health and Deafness via SASOP. 4. Introduction/Background As chlorpromazine injection has not been available on contract since 2014 (erratic availability of chlorpromazine from sole supplier) there is a need for an alternative to Haloperidol+Promethazine in the acute management of aggressive and disruptive patients at PHC and hospital level (Adult). (The current Adult Hospital Level STGs and EML, 2015 edition, recommends chlorpromazine injection when haloperidol injection is not available). 5. Purpose/Objective ‐ P: Adults with acute aggressive and disruptive behaviour ‐ I: Chlorpromazine injection ‐ C: Clotiapine injection ‐ O: Rapid tranquilisation, stabilisation 6. Methods Search strategy: The Tripdatabase was searched, using the following search strategy "chlorpromazine AND clotiapine" and articles were restricted to systematic reviews and controlled trials. -
Gianluca BW.Indd
Use and safety of psychotropic drugs in elderly patients Gianluca Trifi rò GGianlucaianluca BBW.inddW.indd 1 225-May-095-May-09 111:22:461:22:46 AAMM Th e work presented in this thesis was conducted both at the Department of Medical Informatics of the Erasmus Medical Center, Rotterdam, Th e Netherlands and the Depart- ment of Clinical and Experimental Medicine and Pharmacology of University of Messina, Messina, Italy. Th e studies reported in chapter 2.2 and 4.3 were respectively supported by grants from the Italian Drug Agency and Pfi zer. Th e contributions of the general practitioners participating in the IPCI, Health Search/ Th ales, and Arianna databases are greatly acknowledged. Financial support for printing and distribution of this thesis was kindly provided by IPCI, SIMG/Health Search, Eli Lilly Nederland BV, Boehringer-Ingelheim B.V., Novartis Pharma B.V. and University of Messina. Cover design by Emanuela Punzo, Antonio Franco e Gianluca Trifi rò. Th e background photo in the cover is a landscape from Santa Lucia del Mela (Sicily) and was kindly pro- vided by Franco Trifi rò. Th e photo of the elderly person is from Antonio Franco Trifi rò. Layout and print by Optima Grafi sche Communicatie, Rotterdam, Th e Netherlands. GGianlucaianluca BBW.inddW.indd 2 225-May-095-May-09 111:22:481:22:48 AAMM Use and Safety of Psychotropic Drugs in Elderly Patients Gebruik en veiligheid van psychotropische medicaties in de oudere patienten Proefschrift ter verkrijging van de graad van doctor aan de Erasmus Universiteit Rotterdam op gezag van de rector magnifi cus Prof.dr.