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The Effects of Targeted Deletion of the Aromatase Enzyme on Prostatic Contractile Responses to Noradrenaline in Mice
495 The effects of targeted deletion of the aromatase enzyme on prostatic contractile responses to noradrenaline in mice Katherine T Gray, Jennifer L Short, Evan R Simpson1 and Sabatino Ventura Prostate Research Co-operative, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia 1Prince Henry’s Institute of Medical Research, Monash Medical Centre, 246 Clayton Road, Clayton, Victoria 3168, Australia (Correspondence should be addressed to S Ventura; Email: [email protected]) Abstract This investigation aimed to see whether a change in the concentration-dependent contractions. Prazosin (0.3 mM) oestrogen to androgen ratio alters prostate contractility. Isolated attenuated the responses induced by noradrenaline and EFS in organ bath studies using prostates from aromatase knockout all mice (P%0.019, nZ5–7), while cocaine (10 mM) attenuated (ArKO) mice which were homozygous (ArKOK/K)and the responses evoked by tyramine (P!0.001, nZ6). There were heterozygous (ArKOC/K) for the disrupted aromatase cyp19 no genotype differences in EFS- and noradrenaline-induced gene and wild-type littermates (ArKOC/C) were conducted. responses (PR0.506, nZ10–13). Prostates from ArKOK/K The distribution of noradrenergic nerves was visualized using and ArKOC/K mice were more sensitive to tyramine than the sucrose–potassium phosphate–glyoxylic acid method. prostates from ArKOC/C mice (P!0.001, nZ11–13). Dense ArKOK/K mice had increased prostate weights compared adrenergic innervation of the prostate was similar in all mice. with ArKOC/C mice. Frequency–response curves to electrical These results suggest that although the absence of aromatase field stimulation (EFS; 0.5 ms pulse duration, 60 V,0.1–20 Hz) increases prostatic growth, this translates only to a subtle and yielded frequency-dependent contractions, while noradrenaline selective increase in contractility in mature mice. -
Three-Dimensional Structure of Holo 3A,20J3-Hydroxysteroid
Proc. Nati. Acad. Sci. USA Vol. 88, pp. 10064-10068, November 1991 Biochemistry Three-dimensional structure of holo 3a,20j3-hydroxysteroid dehydrogenase: A member of a short-chain dehydrogenase family (x-ray crystaflography/steroid-metabolizing enzyme/dinucleotide-linked oxldoreductase/sterold-protein interaction/sequence and folding homologies) DEBASHIS GHOSH*t, CHARLES M. WEEKS*, PAWEL GROCHULSKI*t, WILLIAM L. DUAX*, MARY ERMAN*, ROBERT L. RIMSAY§, AND J. C. ORR§ *Medical Foundation of Buffalo, 73 High Street, Buffalo, NY 14203; and Memorial University of Newfoundland, St. John's, Newfoundland, Canada AlB 3V6 Communicated by Herbert A. Hauptman, July 18, 1991 (receivedfor review May 14, 1991) ABSTRACT The x-ray structure of a short-chain dehy- the substrate binding regions, offers further insight concern- drogenase, the bacterial holo 3a,20/3-hydroxysteroid dehydro- ing the significance of conserved residues and their possible genase (EC 1.1.1.53), is described at 2.6 A resolution. This roles in substrate specificity and overall enzyme function. enzyme is active as a tetramer and crystallizes with four identical subunits in the asymmetric unit. It has the a/( fold characteristic ofthe dinucleotide binding region. The fold ofthe MATERIALS AND METHODS rest of the subunit, the quarternary structure, and the nature The crystals, grown in the presence of 4 mM NADH, belong ofthe cofactor-enzyme interactions are, however, significantly to the space group P43212 having unit cell dimensions a = different from those observed in the long-chain dehydrogena- 106.2 A and c = 203.8 A and contain one full tetramer (106 ses. The architecture of the postulated active site is consistent kDa) in the asymmetric unit (13). -
United States Patent Office 3,350,427 Patented Oct
United States Patent Office 3,350,427 Patented Oct. 31, 1967 1. 2 3,358,427 By lower alkyl is contemplated hydrocarbon radicals PROCESS FOR THE DEHYDROHALOGENATION having preferably up to four carbon atoms including CF SEROADS methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, and WilliamOrange, H. N.J., Gebert, assignors Morris to ScheringPaias, and Corporation, Nathaniel Murrill, Bloom tertiary butyl. field, N.Y., a corporation of New Jersey Our process is particularly valuable when it is desired No Drawing. Fied Jan. 28, 1966, Ser. No. 523,573 to dehydrobrominate a 17-bromo-20-keto-steroid having 10 Claims. (C. 260-397.4) at least one hydrogen at C-16, e.g. 16oz - methyl - 17 oz bromo-5-pregnen-3,6-ol-20-one or the 3-acetate thereof to This invention relates to a novel improved process for the corresponding 16-dehydro-20-keto-steroid, e.g. 5, 16 dehydrohalogenating organic compounds. O pregnadien-36-ol-20-one or the 3-acetate thereof, which In general, the invention sought to be patented is de are known, valuable intermediates in the preparation of scribed as residing in the concept of treating an o-bromo other known therapeutically valuable compounds. For ketone having a hydrogen on the beta carbon with a example, 16-methyl - 5, 16 - pregnadien-3 (3-ol-20-one may dehydrchalogenating agent selected from the group con be catalytically hydrogenated to provide 166-methyl-5- sisting of an alkaline earth oxide, an alkaline earth hy 5 pregnen-36 - ol - 20-one which may be oxidized to 16,3- droxide, and mixtures thereof in a solvent Selected from methylprogesterone. -
T 1635/09 T 1635/09 T 1635/09 (Verfahrenssprache) (Translation) (Traduction)
542 Amtsblatt EPA Official Journal EPO Journal officiel OEB 11/2011 Entscheidung der Technischen Decision of Technical Board Décision de la Chambre de Beschwerdekammer 3.3.02 of Appeal 3.3.02 dated recours technique 3.3.02 en date vom 27. Oktober 2010 27 October 2010 du 27 octobre 2010 T 1635/09 T 1635/09 T 1635/09 (Verfahrenssprache) (Translation) (Traduction) Zusammensetzung der Kammer: Composition of the Board: Composition de la Chambre : Vorsitzender: Chairman: Président : U. Oswald U. Oswald U. Oswald Mitglieder: Members: Membres : A. Lindner, L. Bühler A. Lindner, L. Bühler A. Lindner, L. Bühler Patentinhaber/Beschwerdeführer: Patent proprietor/Appellant: Titulaire/requérant : Bayer Schering Pharma Bayer Schering Pharma Bayer Schering Pharma Aktiengesellschaft Aktiengesellschaft Aktiengesellschaft Einsprechender 01/ Opponent 01/Appellant: Opposant 01/requérant : Beschwerdeführer: STRAGEN PHARMA SA STRAGEN PHARMA SA STRAGEN PHARMA SA Einsprechender 02/ Opponent 02/Appellant: Opposant 02/requérant : Beschwerdeführer: Laboratorios Léon Farma, S.A. Laboratorios Léon Farma, S.A. Laboratorios Léon Farma, S.A. Einsprechender 03/ Opponent 03/Appellant: Opposant 03/requérant : Beschwerdeführer: Sandoz AG Sandoz AG Sandoz AG Einsprechender 04/ Opponent 04/Party to the Opposant 04/partie à la procédure : Verfahrensbeteiligter: proceedings: Helm AG Helm AG Helm AG Stichwort: Headword: Référence : Zusammensetzung für Empfängnisver- Composition for contraception/BAYER Composition contraceptive/BAYER hütung/BAYER SCHERING PHARMA AG SCHERING PHARMA -
Study Protocol: LPCN 1021-18-001
Oral Testosterone Undecanoate Protocol No. LPCN 1021-18-001 Lipocine Inc. TU, LPCN 1021 675 Arapeen Drive, Suite 202 Salt Lake City, UT-84108 1.0 TITLE PAGE Clinical Study Protocol: LPCN 1021-18-001 Ambulatory Blood Pressure Monitoring in Oral Testosterone Undecanoate (TU, LPCN 1021) Treated Hypogonadal Men. Investigational Product : Testosterone Undecanoate (TU, LPCN 1021) Date of Protocol : 19 February 2019 FDA IND No. : 106476 Development Phase : Phase 3 Testosterone replacement therapy in adult, 18 years or older, males for conditions associated with a deficiency or absence of endogenous Indication : testosterone – primary hypogonadism (congenital or acquired) or secondary hypogonadism (congenital or acquired) Investigator : Multi-Center, US Sponsor : Lipocine Inc. 675 Arapeen Drive, Suite 202, Salt Lake City, Utah – 84108 Tel: +1-801-994-7383 Fax: +1-801-994-7388 Sponsor / : Nachiappan Chidambaram Emergency Contact 675 Arapeen Drive, Suite 202, Salt Lake City, Utah – 84108 Tel: +1-801-994-7383, Ext 2188 Fax: +1-801-994-7388 Email: [email protected] Protocol Version : 06 Confidentiality Statement This document is a confidential communication of Lipocine Inc. Acceptance of this document signifies agreement by the recipient that no unpublished information contained within will be published or disclosed to a third party without prior written approval, except that this document may be disclosed to an Institutional Review Board under the same conditions of confidentiality. Date: 19 February 2019 Confidential Page 1 of 50 Oral Testosterone Undecanoate Protocol No. LPCN 1021-18-001 Lipocine Inc. TU, LPCN 1021 675 Arapeen Drive, Suite 202 Salt Lake City, UT-84108 2.0 SUMMARY OF CHANGES TO PROTOCOL VERSION 2 Version 02 of the LPCN 1021-18-001 study protocol was developed to make the following changes to the study: • Added sexual desire and sexual distress questions to pre-treatment and post-treatment phases of the study. -
NINDS Custom Collection II
ACACETIN ACEBUTOLOL HYDROCHLORIDE ACECLIDINE HYDROCHLORIDE ACEMETACIN ACETAMINOPHEN ACETAMINOSALOL ACETANILIDE ACETARSOL ACETAZOLAMIDE ACETOHYDROXAMIC ACID ACETRIAZOIC ACID ACETYL TYROSINE ETHYL ESTER ACETYLCARNITINE ACETYLCHOLINE ACETYLCYSTEINE ACETYLGLUCOSAMINE ACETYLGLUTAMIC ACID ACETYL-L-LEUCINE ACETYLPHENYLALANINE ACETYLSEROTONIN ACETYLTRYPTOPHAN ACEXAMIC ACID ACIVICIN ACLACINOMYCIN A1 ACONITINE ACRIFLAVINIUM HYDROCHLORIDE ACRISORCIN ACTINONIN ACYCLOVIR ADENOSINE PHOSPHATE ADENOSINE ADRENALINE BITARTRATE AESCULIN AJMALINE AKLAVINE HYDROCHLORIDE ALANYL-dl-LEUCINE ALANYL-dl-PHENYLALANINE ALAPROCLATE ALBENDAZOLE ALBUTEROL ALEXIDINE HYDROCHLORIDE ALLANTOIN ALLOPURINOL ALMOTRIPTAN ALOIN ALPRENOLOL ALTRETAMINE ALVERINE CITRATE AMANTADINE HYDROCHLORIDE AMBROXOL HYDROCHLORIDE AMCINONIDE AMIKACIN SULFATE AMILORIDE HYDROCHLORIDE 3-AMINOBENZAMIDE gamma-AMINOBUTYRIC ACID AMINOCAPROIC ACID N- (2-AMINOETHYL)-4-CHLOROBENZAMIDE (RO-16-6491) AMINOGLUTETHIMIDE AMINOHIPPURIC ACID AMINOHYDROXYBUTYRIC ACID AMINOLEVULINIC ACID HYDROCHLORIDE AMINOPHENAZONE 3-AMINOPROPANESULPHONIC ACID AMINOPYRIDINE 9-AMINO-1,2,3,4-TETRAHYDROACRIDINE HYDROCHLORIDE AMINOTHIAZOLE AMIODARONE HYDROCHLORIDE AMIPRILOSE AMITRIPTYLINE HYDROCHLORIDE AMLODIPINE BESYLATE AMODIAQUINE DIHYDROCHLORIDE AMOXEPINE AMOXICILLIN AMPICILLIN SODIUM AMPROLIUM AMRINONE AMYGDALIN ANABASAMINE HYDROCHLORIDE ANABASINE HYDROCHLORIDE ANCITABINE HYDROCHLORIDE ANDROSTERONE SODIUM SULFATE ANIRACETAM ANISINDIONE ANISODAMINE ANISOMYCIN ANTAZOLINE PHOSPHATE ANTHRALIN ANTIMYCIN A (A1 shown) ANTIPYRINE APHYLLIC -
Part I Biopharmaceuticals
1 Part I Biopharmaceuticals Translational Medicine: Molecular Pharmacology and Drug Discovery First Edition. Edited by Robert A. Meyers. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2018 by Wiley-VCH Verlag GmbH & Co. KGaA. 3 1 Analogs and Antagonists of Male Sex Hormones Robert W. Brueggemeier The Ohio State University, Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Columbus, Ohio 43210, USA 1Introduction6 2 Historical 6 3 Endogenous Male Sex Hormones 7 3.1 Occurrence and Physiological Roles 7 3.2 Biosynthesis 8 3.3 Absorption and Distribution 12 3.4 Metabolism 13 3.4.1 Reductive Metabolism 14 3.4.2 Oxidative Metabolism 17 3.5 Mechanism of Action 19 4 Synthetic Androgens 24 4.1 Current Drugs on the Market 24 4.2 Therapeutic Uses and Bioassays 25 4.3 Structure–Activity Relationships for Steroidal Androgens 26 4.3.1 Early Modifications 26 4.3.2 Methylated Derivatives 26 4.3.3 Ester Derivatives 27 4.3.4 Halo Derivatives 27 4.3.5 Other Androgen Derivatives 28 4.3.6 Summary of Structure–Activity Relationships of Steroidal Androgens 28 4.4 Nonsteroidal Androgens, Selective Androgen Receptor Modulators (SARMs) 30 4.5 Absorption, Distribution, and Metabolism 31 4.6 Toxicities 32 Translational Medicine: Molecular Pharmacology and Drug Discovery First Edition. Edited by Robert A. Meyers. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2018 by Wiley-VCH Verlag GmbH & Co. KGaA. 4 Analogs and Antagonists of Male Sex Hormones 5 Anabolic Agents 32 5.1 Current Drugs on the Market 32 5.2 Therapeutic Uses and Bioassays -
Development of a Human 3D Prostate Microtissue Assay for Anti
Development of a Human 3D Prostate Microtissue Assay for Anti-androgen Screening Chad Deisenroth1, Joshua Harrill1, Cassandra Brinkman1, Menghang Xia2, Kevin Crofton1, Russell Thomas1 1 National Center for Computational Toxicology, ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 2 National Center for Advancing Translational Sciences, National Institute of Health, Rockville, MD 20850 Altered androgen hormone biosynthesis and metabolism can modulate androgen levels, contributing to endocrine disruption that may result in impaired reproductive and sexual development. Steroid 5α-reductase isozymes are expressed in key peripheral tissues and catalyze the conversion of testosterone into the more potent androgen 5α - dihydrotestosterone (DHT). Activation of maximal androgen signaling requires conversion of testosterone to DHT to bind to the androgen receptor (AR) and induce transactivation of downstream gene signaling. The evaluation of chemical-mediated disruption of androgen signaling is typically performed through a combination of in vitro and in vivo tests that interrogate both receptor and non-receptor events including accessory sex organ (ASO) development. Chemical-mediated disruption of ASO development may occur via inhibition of 5α-reductase, or direct disruption of AR signaling. The objective here was to establish a higher- tier human-based, in vitro assay of ASO growth using a multiplexed 3D prostate epithelial cell microtissue model. The androgen-sensitive LNCaP cell line was seeded in a 96-well hanging drop culture model to evaluate microtissue growth over a period of 11 days. Prostate Specific Antigen (PSA) secretion, a biomarker for AR signaling, yielded a wide dynamic range with a Positive/Negative control (P/N) ratio of 3,326 and Z’ of 0.78. -
WSAVA List of Essential Medicines for Cats and Dogs
The World Small Animal Veterinary Association (WSAVA) List of Essential Medicines for Cats and Dogs Version 1; January 20th, 2020 Members of the WSAVA Therapeutic Guidelines Group (TGG) Steagall PV, Pelligand L, Page SW, Bourgeois M, Weese S, Manigot G, Dublin D, Ferreira JP, Guardabassi L © 2020 WSAVA All Rights Reserved Contents Background ................................................................................................................................... 2 Definition ...................................................................................................................................... 2 Using the List of Essential Medicines ............................................................................................ 2 Criteria for selection of essential medicines ................................................................................. 3 Anaesthetic, analgesic, sedative and emergency drugs ............................................................... 4 Antimicrobial drugs ....................................................................................................................... 7 Antibacterial and antiprotozoal drugs ....................................................................................... 7 Systemic administration ........................................................................................................ 7 Topical administration ........................................................................................................... 9 Antifungal drugs ..................................................................................................................... -
The Effects of Osaterone Acetate on Clinical Signs and Prostate Volume in Dogs with Benign Prostatic Hyperplasia
Polish Journal of Veterinary Sciences Vol. 21, No. 4 (2018), 797–802 DOI 10.24425/pjvs.2018.125601 Original article The effects of osaterone acetate on clinical signs and prostate volume in dogs with benign prostatic hyperplasia P. Socha, S. Zduńczyk, D. Tobolski, T. Janowski Department of Animal Reproduction with Clinic, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Oczapowskiego 14, 10-719 Olsztyn, Poland Abstract A clinical trial was performed to evaluate the therapeutic efficacy of osaterone acetate (OSA) in the treatment of benign prostatic hyperplasia (BPH) in dogs. Osaterone acetate (Ypozane, Virbac) was administered orally at a dose of 0.25 mg/kg body weight once a day for seven days to 23 dogs with BPH. During the 28-day trial, the dogs were monitored five times for their clinical signs and prostate volume. The OSA treatment promoted rapid reduction of clinical scores to 73.2% on day 7 and to 5.9% on day 28 (p<0.05). Osaterone acetate induced the complete clinical remission in approximately 83.0% of the dogs on day 28. The prostate volume regressed to 64.3% of the pretreatment volume after two weeks of the treatment (p<0.05) and to 54.7% at the end of the trial (p<0.05). In conclusion, OSA quickly reduced clinical signs and volume of the prostate glands in dogs with BPH. Key words: dogs, benign prostatic hyperplasia, osaterone acetate, prostate volume Introduction hyperplasia and subsequently transforms to cystic hyperplasia with the formation of multiple small cysts Benign prostatic hyperplasia (BPH) is the most within the prostatic parenchyma. -
Wipf Group І University of Pittsburgh
Wipf Group І University of Pittsburgh Serene Tai Research Topic Seminar 1st April 2017 Serene Tai @ Wipf Group Page 1 of 44 4/15/2017 v Prostate - compound tubuloalveolar exocrine gland of the male reproductive system - about the size of a walnut v Prostate cancer - uncontrolled growth of cells in the prostate gland - prostate adenocarcinoma is the major cancer type - 1 in 7 men will be diagnosed with prostate cancer in their lifetime - average age 66; rare before 40 v Symptoms - no symptoms in the early stage - pain and blood in urination, frequent urination, pain in bones and other areas occur in advanced stages American Cancer Society, Cancer Facts & Figures 2017 2 Serene Tai @ Wipf Group Page 2 of 44 4/15/2017 3 Serene Tai @ Wipf Group Page 3 of 44 4/15/2017 v AR is a ligand-dependent nuclear transcription factor that belongs to the steroid hormone receptor superfamily v AR gene encodes a protein of 919 amino acids (110 kDa) v Consists of 4 major functional domains: - N-terminal domain (NTD) - DNA binding domain (DBD) - Hinge region - Ligand binding domain (LBD) v Structure of full length AR has not been solved Acta Pharmacologica Sinica. 2015, 36, 3-23 J. Carcinog. 2011, 10, 20 ACS Chem. Biol. 2016, 11, 2499−2505 4 Serene Tai @ Wipf Group Page 4 of 44 4/15/2017 v Accounts for more than half the size of AR v Contains transactivation function (AF1) v The polyglutamine (polyQ - CAG) and polyglycine (polyG - GGC) tracts affect AR transactivation activity v A combination of experimental and computational analysis suggest that the NTD exists as partially folded protein intermediate (neither full random coil nor stable globular comformation) v Flexible for binding with multiple structurally diverse protein partners Biochem. -
(12) United States Patent (10) Patent No.: US 7,723,320 B2 Bunschoten Et Al
US007723320B2 (12) United States Patent (10) Patent No.: US 7,723,320 B2 Bunschoten et al. (45) Date of Patent: May 25, 2010 (54) USE OF ESTROGEN COMPOUNDS TO DE 23,36434. A 4, 1975 INCREASE LIBDO IN WOMEN WO WO96 O3929 A 2, 1996 (75) Inventors: Evert Johannes Bunschoten, Heesch OTHER PUBLICATIONS (NL); Herman Jan Tijmen Coelingh Bennink, Driebergen (NL); Christian Holinka CF et al: “Comparison of Effects of Estetrol and Taxoxifen Franz Holinka, New York, NY (US) with Those of Estriol and Estradiol on the Immature Rat Uterus'; Biology of Reproduction; 1980; pp. 913-926; vol. 22, No. 4. (73) Assignee: Pantarhei Bioscience B.V., Al Zeist Holinka CF et al; "In-Vivo Effects of Estetrol on the Immature Rat (NL) Uterus'; Biology of Reproduction; 1979: pp. 242-246; vol. 20, No. 2. Albertazzi Paola et al.; "The Effect of Tibolone Versus Continuous Combined Norethisterone Acetate and Oestradiol on Memory, (*) Notice: Subject to any disclaimer, the term of this Libido and Mood of Postmenopausal Women: A pilot study': Data patent is extended or adjusted under 35 base Biosis "Online!; Oct. 31, 2000: pp. 223-229; vol. 36, No. 3; U.S.C. 154(b) by 1072 days. Biosciences Information Service.: Philadelphia, PA, US. Visser et al., “In vitro effects of estetrol on receptor binding, drug (21) Appl. No.: 10/478,264 targets and human liver cell metabolism.” Climacteric (2008) 11(1) Appx. II: 1-5. (22) PCT Filed: May 17, 2002 Visser et al., “First human exposure to exogenous single-dose oral estetrol in early postmenopausal women.” Climacteric (2008) 11(1): (86).