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Endothelin System and Therapeutic Application of Endothelin Receptor
xperim ACCESS Freely available online & E en OPEN l ta a l ic P in h l a C r m f o a c l a o n l o r g u y o J Journal of ISSN: 2161-1459 Clinical & Experimental Pharmacology Research Article Endothelin System and Therapeutic Application of Endothelin Receptor Antagonists Abebe Basazn Mekuria, Zemene Demelash Kifle*, Mohammedbrhan Abdelwuhab Department of Pharmacology, School of Pharmacy, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia ABSTRACT Endothelin is a 21 amino acid molecule endogenous potent vasoconstrictor peptide. Endothelin is synthesized in vascular endothelial and smooth muscle cells, as well as in neural, renal, pulmonic, and inflammatory cells. It acts through a seven transmembrane endothelin receptor A (ETA) and endothelin receptor B (ETB) receptors belongs to G protein-coupled rhodopsin-type receptor superfamily. This peptide involved in pathogenesis of cardiovascular disorder like (heart failure, arterial hypertension, myocardial infraction and atherosclerosis), renal failure, pulmonary arterial hypertension and it also involved in pathogenesis of cancer. Potentially endothelin receptor antagonist helps the treatment of the above disorder. Currently, there are a lot of trails both per-clinical and clinical on endothelin antagonist for various cardiovascular, pulmonary and cancer disorder. Some are approved by FAD for the treatment. These agents are including both selective and non-selective endothelin receptor antagonist (ETA/B). Currently, Bosentan, Ambrisentan, and Macitentan approved -
(12) Patent Application Publication (10) Pub. No.: US 2012/0190743 A1 Bain Et Al
US 2012O190743A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2012/0190743 A1 Bain et al. (43) Pub. Date: Jul. 26, 2012 (54) COMPOUNDS FOR TREATING DISORDERS Publication Classification OR DISEASES ASSOCATED WITH (51) Int. Cl NEUROKININ 2 RECEPTORACTIVITY A6II 3L/23 (2006.01) (75) Inventors: Jerald Bain, Toronto (CA); Joel CD7C 69/30 (2006.01) Sadavoy, Toronto (CA); Hao Chen, 39t. ii; C Columbia, MD (US); Xiaoyu Shen, ( .01) Columbia, MD (US) A6IPI/00 (2006.01) s A6IP 29/00 (2006.01) (73) Assignee: UNITED PARAGON A6IP II/00 (2006.01) ASSOCIATES INC., Guelph, ON A6IPI3/10 (2006.01) (CA) A6IP 5/00 (2006.01) A6IP 25/00 (2006.01) (21) Appl. No.: 13/394,067 A6IP 25/30 (2006.01) A6IP5/00 (2006.01) (22) PCT Filed: Sep. 7, 2010 A6IP3/00 (2006.01) CI2N 5/071 (2010.01) (86). PCT No.: PCT/US 10/48OO6 CD7C 69/33 (2006.01) S371 (c)(1) (52) U.S. Cl. .......................... 514/552; 554/227; 435/375 (2), (4) Date: Apr. 12, 2012 (57) ABSTRACT Related U.S. Application Data Compounds, pharmaceutical compositions and methods of (60) Provisional application No. 61/240,014, filed on Sep. treating a disorder or disease associated with neurokinin 2 4, 2009. (NK) receptor activity. Patent Application Publication Jul. 26, 2012 Sheet 1 of 12 US 2012/O190743 A1 LU 1750 15OO 1250 OOO 750 500 250 O O 20 3O 40 min SampleName: EM2OO617 Patent Application Publication Jul. 26, 2012 Sheet 2 of 12 US 2012/O190743 A1 kixto CFUgan <tro CFUgan FIG.2 Patent Application Publication Jul. -
THELIN, INN-Sitaxentan Sodium
European Medicines Agency Evaluation of Medicines for Human Use London, 17 December 2009 Doc. Ref EMA/831836/2009 ASSESSMENT REPORT FOR Thelin International non-proprietary name/Common name: sitaxentan sodium EMEA/H/C/000679/II/0018 Variation Assessment Report as adopted by theauthorised CHMP with all information of a commercially confidential nature deleted longer no product Medicinal 7 Westferry Circus, Canary Wharf, London, E14 4HB, UK Tel. (44-20) 74 18 84 00 Fax (44-20) 74 18 86 13 E-mail: [email protected] http://www.ema.europa.eu European Medicines Agency, 2009. Reproduction is authorised provided the source is acknowledged. I. SCIENTIFIC DISCUSSION 1.1. Introduction Thelin contains sitaxentan sodium, which is an endothelin receptor antagonist, with higher selectivity for the ETA receptor than the ETB receptor subtype. Endothelin-1 (ET-1) is a potent vascular paracrine and autocrine peptide in the lung, and can also promote fibrosis, cell proliferation, cardiac hypertrophy and remodeling, and is pro-inflammatory. ET-1 concentrations are elevated in plasma and lung tissue of patients with pulmonary arterial hypertension (PAH), as well as other cardiovascular disorders and connective tissue diseases, including scleroderma, acute and chronic heart failure, myocardial ischaemia, systemic hypertension, and atherosclerosis, suggesting a pathogenic role of ET- 1 in these diseases. In PAH and heart failure, in the absence of endothelin receptor antagonism, elevated ET-1 concentrations are strongly correlated with the severity and prognosis of these diseases. Additionally, PAH is also characterised by reduced nitric oxide activity. ET-1 actions are mediated through endothelin A receptors (ETA), present on smooth muscle cells, and endothelin B receptors (ETB), present on endothelial cells. -
Corrigendum Doi:10.1093/Eurheartj/Ehr046
Corrigendum doi:10.1093/eurheartj/ehr046 ............................................................................................................................................................................. Corrigendum to: ‘Guidelines for the diagnosis and treatment of pulmonary hypertension’ [European Heart Journal (2009) 30, 2493–2537]. The Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). Authors/Task Force Members: Nazzareno Galie` (Chairperson) (Italy); Marius M. Hoeper (Germany); Marc Humbert (France); Adam Torbicki (Poland); Jean-Luc Vachiery (France); Joan Albert Barbera (Spain); Maurice Beghetti (Switzerland); Paul Corris (UK); Sean Gaine (Ireland); J. Simon Gibbs (UK); Miguel Angel Gomez-Sanchez (Spain); Guillaume Jondeau (France); Walter Klepetko (Austria) Christian Opitz (Germany); Andrew Peacock (UK); Lewis Rubin (USA); Michael Zellweger (Switzerland); Gerald Simonneau (France). Withdrawal of sitaxentan in the treatment of pulmonary arterial hypertension The 2009 ESC Practice Clinical Guidelines for the diagnosis and treatment of pulmonary hypertension included the endothelin receptor antag- onist sitaxentan in an algorithm of evidence-based treatment for pulmonary arterial hypertension. Sitaxentan was recommended with a Class I/Level A grade of evidence in WHO functional class III patients and Class IIa/Level C grade of evidence -
Classification Decisions Taken by the Harmonized System Committee from the 47Th to 60Th Sessions (2011
CLASSIFICATION DECISIONS TAKEN BY THE HARMONIZED SYSTEM COMMITTEE FROM THE 47TH TO 60TH SESSIONS (2011 - 2018) WORLD CUSTOMS ORGANIZATION Rue du Marché 30 B-1210 Brussels Belgium November 2011 Copyright © 2011 World Customs Organization. All rights reserved. Requests and inquiries concerning translation, reproduction and adaptation rights should be addressed to [email protected]. D/2011/0448/25 The following list contains the classification decisions (other than those subject to a reservation) taken by the Harmonized System Committee ( 47th Session – March 2011) on specific products, together with their related Harmonized System code numbers and, in certain cases, the classification rationale. Advice Parties seeking to import or export merchandise covered by a decision are advised to verify the implementation of the decision by the importing or exporting country, as the case may be. HS codes Classification No Product description Classification considered rationale 1. Preparation, in the form of a powder, consisting of 92 % sugar, 6 % 2106.90 GRIs 1 and 6 black currant powder, anticaking agent, citric acid and black currant flavouring, put up for retail sale in 32-gram sachets, intended to be consumed as a beverage after mixing with hot water. 2. Vanutide cridificar (INN List 100). 3002.20 3. Certain INN products. Chapters 28, 29 (See “INN List 101” at the end of this publication.) and 30 4. Certain INN products. Chapters 13, 29 (See “INN List 102” at the end of this publication.) and 30 5. Certain INN products. Chapters 28, 29, (See “INN List 103” at the end of this publication.) 30, 35 and 39 6. Re-classification of INN products. -
Huidige Situatie En Toekomstverkenning
Stichting Laka: Documentatie- en onderzoekscentrum kernenergie De Laka-bibliotheek The Laka-library Dit is een pdf van één van de publicaties in This is a PDF from one of the publications de bibliotheek van Stichting Laka, het in from the library of the Laka Foundation; the Amsterdam gevestigde documentatie- en Amsterdam-based documentation and onderzoekscentrum kernenergie. research centre on nuclear energy. Laka heeft een bibliotheek met ongeveer The Laka library consists of about 8,000 8000 boeken (waarvan een gedeelte dus ook books (of which a part is available as PDF), als pdf), duizenden kranten- en tijdschriften- thousands of newspaper clippings, hundreds artikelen, honderden tijdschriftentitels, of magazines, posters, video's and other posters, video’s en ander beeldmateriaal. material. Laka digitaliseert (oude) tijdschriften en Laka digitizes books and magazines from the boeken uit de internationale antikernenergie- international movement against nuclear beweging. power. De catalogus van de Laka-bibliotheek staat The catalogue of the Laka-library can be op onze site. De collectie bevat een grote found at our website. The collection also verzameling gedigitaliseerde tijdschriften uit contains a large number of digitized de Nederlandse antikernenergie-beweging en magazines from the Dutch anti-nuclear power een verzameling video's. movement and a video-section. Laka speelt met oa. haar informatie- Laka plays with, amongst others things, its voorziening een belangrijke rol in de information services, an important role in the Nederlandse anti-kernenergiebeweging. Dutch anti-nuclear movement. Appreciate our work? Feel free to make a small donation. Thank you. www.laka.org | [email protected] | Ketelhuisplein 43, 1054 RD Amsterdam | 020-6168294 | L.P. -
Regulation and Relevance for Chronic Lung Diseases
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Springer - Publisher Connector Purinergic Signalling (2006) 2:399–408 DOI 10.1007/s11302-006-9001-7 ORIGINAL ARTICLE E-NTPDases in human airways: Regulation and relevance for chronic lung diseases Lauranell H. Burch & Maryse Picher Received: 11 January 2005 /Accepted: 21 December 2005 / Published online: 30 May 2006 # Springer Science + Business Media B.V. 2006 Abstract Chronic obstructive lung diseases are char- are characterized by higher rates of nucleotide elimi- acterized by the inability to prevent bacterial infection nation, azide-sensitive E-NTPDase activities and ex- and a gradual loss of lung function caused by recurrent pression. This review integrates the biphasic regulation inflammatory responses. In the past decade, numerous of airway E-NTPDases with the function of purine studies have demonstrated the importance of nucleo- signaling in lung diseases. During acute insults, a tide-mediated bacterial clearance. Their interaction transient reduction in E-NTPDase activities may be with P2 receptors on airway epithelia provides a rapid beneficial to stimulate ATP-mediated bacterial clear- Fon-and-off_ signal stimulating mucus secretion, cilia ance. In chronic lung diseases, elevating E-NTPDase beating activity and surface hydration. On the other activities may represent an attempt to prevent P2 hand, abnormally high ATP levels resulting from receptor desensitization and nucleotide-mediated lung damaged epithelia and bacterial lysis may cause lung damage. edema and exacerbate inflammatory responses. Air- way ATP concentrations are regulated by ecto nucle- Keywords apyrase . bacterial clearance . CD39 . oside triphosphate diphosphohydrolases (E-NTPDases) chronic obstructive lung diseases . -
PHARMACEUTICAL APPENDIX to the TARIFF SCHEDULE 2 Table 1
Harmonized Tariff Schedule of the United States (2020) Revision 19 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2020) Revision 19 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 2 Table 1. This table enumerates products described by International Non-proprietary Names INN which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service CAS registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known. -
Viiith INTERNATIONAL SYMPOSIUM on NUCLEAR MEDICINE
INIS-mf--10949 VIIIth INTERNATIONAL SYMPOSIUM ON NUCLEAR MEDICINE JUNE 2 - 5, 1986 KARLOVY VARY CZECHOSLOVAKIA ABSTRACTS ABSTRACTS The booklet contains all abstracts of papers submitted in time to the Secretariat of the Symposium. The abstracts were reproduced from the original forms sent by the ithors. The responsibilit >r the contents and gram- matical style the. re lies upon the authors. 17 ANTIBODY GUIDED TUMOR DETECTION IN PATIENTS WITH CARCINOMA. P.Riva.G.Paganelli, C.Cacciaguerra,V.Tison5G.Landi, G. Riceputi,G.Moscatelli.M.Agostini. Istituto Oncologico Romagnolo. Servizio di Medicir.a Nucleare Ospedale M.Bufalini 47023 Cesena ITALY. As a unit of a multicenter clinical trial coordi - nated by the National Reserch Council we studied two groups of patients,in the last three years.In the first group of undred patients affected by ma- lignat melanoma with stage I-IV we were able to de tect the 75% of well documented lesions employing a 99mTC labelled F(ab')2 fragments of MoAb raised a- gainst melanoma (HMW MAA)225.28S(TECNEMAB 1-SORIN BIOMEDICA).In addition a certain number of unknown metastases were also detected and confirmed after- wards. The second group consisted of two-undred pa tients with gastro-intestinal,breast and lung carci^ noma.In these cases we used a 111 In and or 131 I labelled F(ab')i) fragments of a MoAb Raised against CEA(clone F023C5-S'?RIN-Biomedica) with best results in patients bearing colon retto carcinoma and lung cancer.More in detail we obtained the 8<~-% and the 91% of positive scans respectively.In order to im- prove the sensitivity and the tumour/BK ratio some patients with G.I. -
Does Your Patient Have Bile Acid Malabsorption?
NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #198 NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #198 Carol Rees Parrish, MS, RDN, Series Editor Does Your Patient Have Bile Acid Malabsorption? John K. DiBaise Bile acid malabsorption is a common but underrecognized cause of chronic watery diarrhea, resulting in an incorrect diagnosis in many patients and interfering and delaying proper treatment. In this review, the synthesis, enterohepatic circulation, and function of bile acids are briefly reviewed followed by a discussion of bile acid malabsorption. Diagnostic and treatment options are also provided. INTRODUCTION n 1967, diarrhea caused by bile acids was We will first describe bile acid synthesis and first recognized and described as cholerhetic enterohepatic circulation, followed by a discussion (‘promoting bile secretion by the liver’) of disorders causing bile acid malabsorption I 1 enteropathy. Despite more than 50 years since (BAM) including their diagnosis and treatment. the initial report, bile acid diarrhea remains an underrecognized and underappreciated cause of Bile Acid Synthesis chronic diarrhea. One report found that only 6% Bile acids are produced in the liver as end products of of British gastroenterologists investigate for bile cholesterol metabolism. Bile acid synthesis occurs acid malabsorption (BAM) as part of the first-line by two pathways: the classical (neutral) pathway testing in patients with chronic diarrhea, while 61% via microsomal cholesterol 7α-hydroxylase consider the diagnosis only in selected patients (CYP7A1), or the alternative (acidic) pathway via or not at all.2 As a consequence, many patients mitochondrial sterol 27-hydroxylase (CYP27A1). are diagnosed with other causes of diarrhea or The classical pathway, which is responsible for are considered to have irritable bowel syndrome 90-95% of bile acid synthesis in humans, begins (IBS) or functional diarrhea by exclusion, thereby with 7α-hydroxylation of cholesterol catalyzed interfering with and delaying proper treatment. -
NIH Public Access Author Manuscript J Med Chem
NIH Public Access Author Manuscript J Med Chem. Author manuscript; available in PMC 2012 June 23. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: J Med Chem. 2011 June 23; 54(12): 4018±4033. doi:10.1021/jm101591j. Pyrimidine Nucleotides with 4-Alkyloxyimino and Terminal Tetraphosphate δ-Ester Modifications as Selective Agonists of the P2Y4 Receptor Hiroshi Maruokaa, M.P. Suresh Jayasekaraa, Matthew O. Barrettb, Derek A. Franklinb, Sonia de Castroa, Nathaniel Kima, Stefano Costanzic, T. Kendall Hardenb, and Kenneth A. Jacobsona,* aMolecular Recognition Section, Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-0810 bDepartment of Pharmacology, University of North Carolina, School of Medicine, Chapel Hill, North Carolina 27599-7365 cLaboratory of Biological Modeling, NIDDK, National Institutes of Health, Bethesda, Maryland 20892 Abstract P2Y2 and P2Y4 receptors are G protein-coupled receptors, activated by UTP and dinucleoside tetraphosphates, which are difficult to distinguish pharmacologically for lack of potent and selective ligands. We varied structurally phosphate and uracil moieties in analogues of pyrimidine nucleoside 5′-triphosphates and 5′-tetraphosphate esters. P2Y4 receptor potency in phospholipase C stimulation in transfected 1321N1 human astrocytoma cells was enhanced in N4- alkyloxycytidine derivatives. OH groups on a terminal δ-glucose phosphoester of uridine 5′- tetraphosphate were inverted or substituted with H or F to probe H-bonding effects. N4- 4 (Phenylpropoxy)-CTP 16 (MRS4062), Up4-[1]3′-deoxy-3′-fluoroglucose 34 (MRS2927) and N - (phenylethoxy)-CTP 15 exhibit ≥10-fold selectivity for human P2Y4 over P2Y2 and P2Y6 receptors (EC50 values 23, 62 and 73 nM, respectively). -
付表 ⅠA 指定を受けた医薬の有効成分 Annex ⅠA Designated
付表ⅠA 指定を受けた医薬の有効成分 Annex ⅠA Designated Pharmaceutical Active Ingredients 号(Sub-heading) 品名 Description 2818.30 アルゲルドラート algeldrate 2833.22 アルスルフ alusulf 2842.10 アルマシラート almasilate 2842.10 シマルドラート simaldrate 2842.90 硫酸アルマドラ ート almadrate sulfate 2842.90 アルマガート almagate 2842.90 カルバルドラード carbaldrate 2842.90 ヒドロタルシト hydrotalcite 2842.90 マガルドラート magaldrate 2843.30 オーラノフィン auranofin 2843.30 金チオグリカニド aurothioglycanide 2843.30 金チオりんご酸ナトリウム sodium aurothiomalate 2843.30 金チオ硫酸ナトリウム sodium aurotiosulfate 2843.90 カルボプラチン carboplatin 2843.90 シスプラチン cisplatin 2843.90 デキソルマプラチン dexormaplatin 2843.90 エンロプラチン enloplatin 2843.90 イプロプラチン iproplatin 2843.90 ロバプラチン lobaplatin 2843.90 ミボプラチン miboplatin 2843.90 ネダプラチン nedaplatin 2843.90 オルマプラチン ormaplatin 2843.90 オキサリプラチン oxaliplatin 2843.90 セブリプラチン sebriplatin 2843.90 スピロプラチン spiroplatin 2843.90 ゼニプラチン zeniplatin 2844.40 アルツモマブ altumomab 2844.40 塩化セシウム(131Cs) cesium (131 Cs) chloride 2844.40 クロルメロドリン(197Hg) chlormerodrin (197 Hg) 2844.40 シアノコバラミン(57Co) cyanocobalamin (57 Co) 2844.40 シアノコバラミン(58Co) cyanocobalamin (58 Co) 2844.40 シアノコバラミン(60Co) cyanocobalamin (60 Co) 2844.40 エチオダイズド油(131I) ethiodized oil (131 I) 2844.40 くえん酸第二鉄(59Fe)注射液 ferric (59 Fe) citrate in 2844.40 フィブリノゲン(125I) fibrinogen (125 I) 2844.40 フルデオキシグルコー ス(18F) fludeoxyglucose ( 18 F) 2844.40 フルオロドパ(18F) fluorodopa (18 F) 2844.40 くえん酸ガリウム(67Ga) gallium (67 Ga) citrate 2844.40 金コロイド(198Au) gold (198 Au), colloidal 2844.40 イオベングアン(131I) iobenguane (131 I) 2844.40 よう化人血清アルブミン(125I) iodinated (125 I) human serum albumin 2844.40 よう化人血清アルブミン(131I) iodinated