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Sample records for boehringer ingelheim promeco

  1. Boehringer Ingelheim Promeco contemplates the benefits of cogeneration in its new plant; Boehringer Ingelheim Promeco contempla beneficios de la cogeneracion para su nueva planta

    Energy Technology Data Exchange (ETDEWEB)

    Ruiz Esparza, R. [Instituto de Investigaciones Electricas, Cuernavaca (Mexico); Khouri Solis, A. [Boehringer Ingelheim Promeco, Mexico, D. F. (Mexico)

    1997-12-31

    This paper presents the results of the feasibility study performed in BOEHRINGER INGELHEIM PROMECO to determine the benefits that a cogeneration system could render in satisfying the energy demand of its plant currently being expanded. The results showed that in accordance with the operation mode of the already expanded plant, the highest benefits could be obtained of a cogeneration system with a capacity of 1,600 Kw that would partially satisfy the thermal and electrical demands of BOEHRINGER INGELHEIM PROMECO. [Espanol] El presente articulo presenta los resultados de factibilidad que se realizo en Boehringer Ingelheim Promeco para determinar los beneficios que podria rendir un sistema de cogeneracion al satisfacer las demandas energeticas de su planta actualmente en ampliacion. Los resultados mostraron que de acuerdo al modo de operacion de la planta ya ampliada, los beneficios mas altos se obtendrian de un sistema de cogeneracion con capacidad de 1,600 kW que satisfaria parcialmente las demandas termicas y electricas de Boehringer Ingelheim Promeco.

  2. Computer-aided drug design at Boehringer Ingelheim

    Science.gov (United States)

    Muegge, Ingo; Bergner, Andreas; Kriegl, Jan M.

    2016-09-01

    Computer-Aided Drug Design (CADD) is an integral part of the drug discovery endeavor at Boehringer Ingelheim (BI). CADD contributes to the evaluation of new therapeutic concepts, identifies small molecule starting points for drug discovery, and develops strategies for optimizing hit and lead compounds. The CADD scientists at BI benefit from the global use and development of both software platforms and computational services. A number of computational techniques developed in-house have significantly changed the way early drug discovery is carried out at BI. In particular, virtual screening in vast chemical spaces, which can be accessed by combinatorial chemistry, has added a new option for the identification of hits in many projects. Recently, a new framework has been implemented allowing fast, interactive predictions of relevant on and off target endpoints and other optimization parameters. In addition to the introduction of this new framework at BI, CADD has been focusing on the enablement of medicinal chemists to independently perform an increasing amount of molecular modeling and design work. This is made possible through the deployment of MOE as a global modeling platform, allowing computational and medicinal chemists to freely share ideas and modeling results. Furthermore, a central communication layer called the computational chemistry framework provides broad access to predictive models and other computational services.

  3. 78 FR 64016 - Importer of Controlled Substances, Notice of Registration, Boehringer Ingelheim Chemicals

    Science.gov (United States)

    2013-10-25

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF JUSTICE Drug Enforcement Administration Importer of Controlled Substances, Notice of Registration, Boehringer Ingelheim Chemicals By Notice dated June 18, 2013, and published in the Federal Register on July 1, 2013, 78 FR...

  4. 78 FR 64018 - Manufacturer of Controlled Substances; Notice of Registration; Boehringer Ingelheim Chemicals, Inc.

    Science.gov (United States)

    2013-10-25

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances; Notice of Registration; Boehringer Ingelheim Chemicals, Inc. By Notice dated June 18, 2013, and published in the Federal Register on July 1, 2013, 78...

  5. 77 FR 67397 - Importer Of Controlled Substances; Notice of Registration; Boehringer Ingelheim Chemicals, Inc.

    Science.gov (United States)

    2012-11-09

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF JUSTICE Drug Enforcement Administration Importer Of Controlled Substances; Notice of Registration; Boehringer Ingelheim Chemicals, Inc. By Notice dated July 17, 2012, and published in the Federal Register on July 26, 2012, 77...

  6. 77 FR 70188 - Manufacturer of Controlled Substances; Notice of Registration; Boehringer Ingelheim Chemicals, Inc.

    Science.gov (United States)

    2012-11-23

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances; Notice of Registration; Boehringer Ingelheim Chemicals, Inc. By Notice dated July 17, 2012, and published in the Federal Register on July 26, 2012, 77...

  7. The Epidemiological Boehringer Ingelheim Employee Study—Part I: Impact of Overweight and Obesity on Cardiometabolic Risk

    Directory of Open Access Journals (Sweden)

    Kerstin Kempf

    2013-01-01

    Full Text Available Objective. Obesity-dependent diseases cause economic burden to companies. Large-scale data for working populations are lacking. Prevalence of overweight and obesity in the Boehringer Ingelheim (BI Employee cohort and the relationship between body mass index (BMI and cardiometabolic risk factors and diseases were estimated. Design and Methods. Employees (≥38 years, employed in Ingelheim ≥2 years; n=3151 of BI Pharma GmbH & Co. KG were invited by the medical corporate department to participate in intensive health checkups. Cross-sectional analysis of baseline data collected through 2006–2011 was performed. Results. 90% of eligible subjects participated (n=2849. Prevalences of overweight and obesity were 40% and 18% and significantly higher in men and participants ≥50 years. Cardiometabolic risk factor levels and prevalences of cardiometabolic diseases significantly increased with BMI and were higher in overweight and obese participants. Cut-points for increased risk estimated from ROC curves were ≈25 kg/m2 for hypertension, hypercholesterolemia, arteriosclerosis, and hypertriglyceridemia and 26.7–28.0 kg/m2 for the metabolic syndrome, insulin resistance, hyperinsulinemia, increased intima media thickness, and type 2 diabetes. Conclusion. This is the first large-scale occupational health care cohort from a single company. Cardiometabolic risk factors and diseases accumulate with increasing BMI. Occupational weight reduction programs seem to be reasonable strategies.

  8. 2 obras de F. J. Barba Corsini: Edificio de los Laboratorios Boehringer Sohn Ingelheim, S. A. B., en San Juan Despí, Barcelona; Cine Victoria, en Hospitalet de Llobregat

    Directory of Open Access Journals (Sweden)

    Barba Corsini, F. J.

    1967-11-01

    Full Text Available Building for the Boehringer Sohn Ingelheim, S. A. E. Laboratories, at San Juan Despí – Barcelona The semibasement houses the services, including dressing rooms, dining hall, central air conditioning, stores, and other technical services. The ground floor comprises the main entrance hall and also some of the laboratories, whilst the rest of the building is mostly devoted to the functional purpose of the firm, i. e., laboratory work. The manager's office and council chamber are located on the second floor. The external aspect of the building reflects its function and is an outstanding example of impressive simplicity. Victoria Cinema, at Hospitalet de Llobregat – Barcelona The design of the building takes specifically into account the poor features of the site, the greater cost efficiency of reinforced concrete and the saving in construction time associated with metallic construction. Hence a compound design was adopted. All the external walls are built with unfaced brick, and «Durisol» has been adopted for the ceilings. The choice of illumination and colouring give the walls a fine quality, and emphasize their plastic texture. A restful quality and an indication of its commercial purpose are the fundamental features reflected by the external aspect of the building.Edificio de los Laboratorios Boehringer Sohn Ingelheim, S. A. E., en San Juan Despí- Barcelona La planta semisótano del edificio está dedicada a servicios: vestuario, comedor, central de acondicionamiento de aire, almacenes de utillaje, y servicios técnicos en general. En la planta baja se ha dispuesto el vestíbulo principal de acceso; y tanto en el resto de esta planta como en las superiores, se desarrollan todas las funciones de laboratorios. En la planta segunda se han instalado los despachos de Dirección, Sala de Juntas, etc. La expresión arquitectónica exterior del edificio responde a su utilidad y resalta por su elegante sencillez. Cine Victoria, en Hospitalet de

  9. 78 FR 39340 - Manufacturer of Controlled Substances; Notice of Application; Boehringer Ingelheim Chemicals, Inc.

    Science.gov (United States)

    2013-07-01

    ... [Federal Register Volume 78, Number 126 (Monday, July 1, 2013)] [Notices] [Page 39340] [FR Doc No: 2013-15604] DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances..., Office of Diversion Control, Drug Enforcement Administration. [FR Doc. 2013-15604 Filed 6-28-13; 8:45...

  10. 78 FR 39337 - Importer of Controlled Substances, Notice of Application, Boehringer Ingelheim Chemicals

    Science.gov (United States)

    2013-07-01

    ... [Federal Register Volume 78, Number 126 (Monday, July 1, 2013)] [Notices] [Page 39337] [FR Doc No... Federal Register on September 23, 1975, 40 FR 43745-46, all applicants for registration to import a basic..., Deputy Assistant Administrator, Office of Diversion Control, Drug Enforcement Administration. [FR...

  11. Laboratory evaluation of the Boehringer Mannheim "Hitachi 705" automatic analyzer.

    Science.gov (United States)

    Kineiko, R W; Floering, D A; Morrissey, M

    1983-04-01

    We evaluated a new multi-channel chemistry analyzer, the Hitachi 705 Automatic Analyzer, marketed by Boehringer Mannheim Diagnostics, Inc. The instrument is a computer-controlled discrete analyzer, which can be run in a combination profile mode and single-test mode. Sixteen different tests per sample may be performed at the rate of 180 tests per hour. The Hitachi 705 is especially suitable for use in hospitals that do not perform profile testing. Precision and linearity were excellent and the instrument was relatively trouble-free, with little operator attention required during operation. The Hitachi 705 was easily interfaced to our laboratory computer. We compared the performance of the instrument with that of the Du Pont aca; the two instruments compared favorably.

  12. Laboratory evaluation of the Boehringer Mannheim "Diagnostic M" automated discrete analyzer.

    Science.gov (United States)

    Robinson, C A; Proelss, H; Stabler, T V

    1982-01-01

    We evaluated a new multiple-channel chemistry analyzer, the Boehringer Mannheim "Diagnostic M." This instrument can perform 25 tests at the rate of 120 1.3-mL serum samples per hour. The instrument may be run in either a profile mode or single-test mode. In the single-test mode only the necessary reagent is pumped. the instrument is computer controlled. We compared it with the Technicon SMAC, SMA 12/60, and SMA 6/60. It demonstrated excellent precision, linearity, lack of interference, ease of operation, and satisfactory comparison with values obtained by the Technicon methods.

  13. Ⅲ期试验结果支持Boehringer Ingelheim公司的flibanserin

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    根据德国Boehringer Ingelheim公司最新公布的一项研究结果,女性性欲问题有望得到自己的治疗药物——一种相当于制药巨头Pfizer公司治疗男性勃起功能障碍药Viagra(sildenafil,西地那非)的药物,一名发言人称该药物可能在18个月内获准上市。

  14. Atrial fibrillation and vascular disease-a bad combination

    DEFF Research Database (Denmark)

    Bjerring Olesen, Jonas; Gislason, Gunnar Hilmar; Torp-Pedersen, Christian;

    2012-01-01

    served as a consultant for Bayer, Astellas, Merck, AstraZeneca, Sanofi, BMS/Pfizer, Biotronik, Portola and Boehringer Ingelheim and has been on the speakers bureau for Bayer, BMS/Pfizer, Boehringer Ingelheim, and Sanofi-Aventis. Drs. Gislason and Torp-Pedersen disclose no conflicts of interest....

  15. Die Pseudoskorpion-Fauna (Arachnida: Pseudoscorpiones eines Auwaldes bei Ingelheim am Rhein, unter besonderer Berücksichtigung der Auswirkungen des trocken-warmen Winters 2006/2007

    Directory of Open Access Journals (Sweden)

    Marx, Michael T.

    2008-07-01

    Full Text Available From the beginning of May 2005 to September 2007 the pseudoscorpion fauna in a hardwood floodplain forest of the Rhine valley near Ingelheim was investigated. Altogether 587 individuals representing two species from two families were captured using pitfall traps, trunk eclectors and by litter sieving. The warm, dry winter 2006/2007 exhibited a strong influence upon the activity of Neobisium carcinoides (Hermann, 1804. This winter event was followed by an extreme drought in April 2007, which affected the activity maximum of the corticolous species Chernes hahnii (C.L. Koch, 1839. In 2005 and 2006 the activity maximum of C. hahnii was observed in July, whereas in 2007 maturity was achieved earlier in May. Furthermore 31 individuals of N. carcinoides were captured in trunk eclectors. This climbing behaviour correlates with the presence of Lepidocyrtus lignorum (Collembola: Entomobryidae on the trunks.

  16. Diffusion-weighted magnetic resonance imaging in ileocolonic Crohn's disease

    DEFF Research Database (Denmark)

    Juel, Mie A; Rafaelsen, Søren Rafael; Nathan, Torben

    protocol contained coronal e-thrive and SShT2 with free-breathing and a factor b fixed at 800 s/mm2. Patients were examined in the prone position before and after intravenous administration of 20 mg Hyoscin Butylbromide (Buscopan®, Boehringer Ingelheim, Basel, Switzerland). Ileocolonoscopy with Simple...

  17. Ettevõttel lasub ühiskondlik vastutus / Karen Schmidt

    Index Scriptorium Estoniae

    Schmidt, Karen

    2011-01-01

    Terve Eesti SA algatusel Eesti ettevõtete poolt moodustatud koalitsioonist "Ettevõtted HIV vastu", kuhu kuuluvad Hill & Knowlton, Nordecon, Swedbank, TNS Emor, Coca-Cola, Johnson & Johnson, Rimi Eesti Food, DHL Estonia, Boehringer Ingelheim, Radisson BLU Hotell Tallinn ja TBWA/Guvatrak. Koalitsiooni töös osales kolm aastat ka Statoil

  18. "Partners in Science": A Model Cooperative Program Introducing High School Teachers and Students to Leading-Edge Pharmaceutical Science

    Science.gov (United States)

    Woska, Joseph R., Jr.; Collins, Danielle M.; Canney, Brian J.; Arcario, Erin L.; Reilly, Patricia L.

    2005-01-01

    "Partners in Science" is a cooperative program between Boehringer Ingelheim Pharmaceuticals, Inc. and area high schools in the community surrounding our Connecticut campus. It is a two-phase program that introduces high school students and teachers to the world of drug discovery and leading-edge pharmaceutical research. Phase 1 involves…

  19. Availability, affordability, and consumption of fruits and vegetables in 18 countries across income levels: findings from the Prospective Urban Rural Epidemiology (PURE study

    Directory of Open Access Journals (Sweden)

    Victoria Miller, BSc

    2016-10-01

    Funding: Population Health Research Institute, the Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, AstraZeneca (Canada, Sanofi-Aventis (France and Canada, Boehringer Ingelheim (Germany and Canada, Servier, GlaxoSmithKline, Novartis, King Pharma, and national or local organisations in participating countries.

  20. 75 FR 71016 - Intramammary Dosage Form New Animal Drugs; Cloxacillin Benzathine

    Science.gov (United States)

    2010-11-22

    ... approval of a supplementary new animal drug application (NADA) filed by Boehringer Ingelheim Vetmedica, Inc... Highway, St. Joseph, MO 64506-2002 has filed a supplement to NADA 55-058 for DRY-CLOX (cloxacillin benzathine) Intramammary Infusion for dry dairy cattle. The supplemental NADA provides for various...

  1. Initiation of triple therapy maintenance treatment among patients with COPD in the US

    OpenAIRE

    Simeone JC; Luthra R; Kaila S; Pan X; Bhagnani TD; Liu J; Wilcox TK

    2016-01-01

    Jason C Simeone,1 Rakesh Luthra,2 Shuchita Kaila,2 Xiaoyun Pan,1 Tarun D Bhagnani,1 Jieruo Liu,1 Teresa K Wilcox1 1Real-World Evidence, Evidera, Waltham, MA, 2HEOR Value Demonstration Team, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA Background: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends triple therapy (long-acting muscarinic receptor antagonists, long-acting beta-2 agonists, and inhaled corticosteroids) for patients with only the most s...

  2. Are adults with bipolar disorder active? Objectively measured physical activity and sedentary behavior using accelerometry

    OpenAIRE

    Janney, Carol A; Fagiolini, Andrea; Swartz, Holly A.; Jakicic, John M.; Holleman, Robert G.; Richardson, Caroline R

    2013-01-01

    Carol A Janney has received research support from Actigraph, Inc for this study. Andrea Fagiolini is/has been a consultant and/or speaker and/or has received grants from: Angelini, Astra Zeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Pfizer, Eli Lilly, Janssen, Lundbeck, Novartis, Otsuka, Roche and Sigma Tau. Holly A. Swartz has received honoraria from Servier, Astra Zeneca, SciMed, Bristol-Myers Squibb, Eli Lilly, and Sanofi. She has received royalties from UpToDate. John M. Ja...

  3. 勃林格殷格翰的外姓掌门人

    Institute of Scientific and Technical Information of China (English)

    刘莉莉

    2002-01-01

    @@ 罗尔夫·克莱伯(Rolf Krebs)教授有着儒雅的外貌和内敛的行事方式,在药理学专家和顶级经理人--世界最大的私人制药集团勃林格殷格翰(Boehringer Ingelheim)的执行董事会主席这两重身份中,他的气质似乎更近于前者.

  4. Estudio de la Cualificación Operacional y de la Instalación de un reactor en una Planta de Producción Química-Farmacéutica

    OpenAIRE

    Ferrer Ponce, Gemma

    2006-01-01

    Este proyecto se ha desarrollado en el marco de la empresa químico–farmacéutica Boehringer Ingelheim, situada en Malgrat de Mar. Se ha realizado la Cualificación de la Instalación (IQ) y la Cualificación Operacional (OQ) de un reactor de producción multipropósito. La cualificación consta de un conjunto de pruebas destinadas a demostrar que el equipo cumple con las especificaciones y requerimientos de usuario definidos por el Departamento de Producción. Esta cualificación surge de la ...

  5. Cualificación de equipos auxiliares de producción de una planta químico-farmacéutica

    OpenAIRE

    Rodiera i Forroll, Francesc

    2008-01-01

    Este proyecto se basó en la cualificación de los equipos auxiliares de producción de la planta químico-farmacéutica que Boehringer Ingelheim tiene en Malgrat de Mar (Barcelona) con el fin de establecer una evidencia documental, mediante la ejecución de pruebas, de que los equipos y sus componentes poseen los atributos requeridos para obtener un producto con una calidad determinada de forma consistente y continuada. Para ello se elaboró toda la documentación necesaria para la co...

  6. ▼Olodaterol--another LABA for COPD.

    Science.gov (United States)

    2015-04-01

    ▼Olodaterol solution for inhalation (Striverdi Respimat-Boehringer Ingelheim) is a long-acting beta2 agonist (LABA) licensed for once-daily use as maintenance bronchodilator therapy for chronic obstructive pulmonary disease (COPD). This is the third LABA to be licensed in the UK for once-daily use for patients with COPD. DTB has previously reviewed the use of indacaterol and vilanterol in combination with fluticasone furoate (▼Relvar Ellipta).1,2 In this article we consider the evidence for olodaterol and whether it offers any advantages in the management of COPD.

  7. Once-daily long-acting beta-agonists for chronic obstructive pulmonary disease: an indirect comparison of olodaterol and indacaterol

    Directory of Open Access Journals (Sweden)

    Roskell NS

    2014-07-01

    Full Text Available Neil S Roskell,1 Antonio Anzueto,2 Alan Hamilton,3 Bernd Disse,4 Karin Becker5 1Statistics, Bresmed Health Solutions Ltd, Sheffield, UK; 2School of Medicine, University of Texas Health Science Center, San Antonio, TX, USA; 3Medical Department, Boehringer Ingelheim (Canada Ltd, Burlington, ON, Canada; 4Medical Department, Boehringer Ingelheim GmbH, Ingelheim am Rhein, Germany; 5Global Health Economics and Outcomes Research, Boehringer Ingelheim GmbH, Ingelheim am Rhein, Germany Purpose: In the absence of head-to-head clinical trials comparing the once-daily, long-acting beta2-agonists olodaterol and indacaterol for the treatment of chronic obstructive pulmonary disease (COPD, an indirect treatment comparison by systematic review and synthesis of the available clinical evidence was conducted. Methods: A systematic literature review of randomized, controlled clinical trials in patients with COPD was performed to evaluate the efficacy and safety of olodaterol and indacaterol. Network meta-analysis and adjusted indirect comparison methods were employed to evaluate treatment efficacy, using outcomes based on trough forced expiratory volume in 1 second (FEV1, Transition Dyspnea Index, St George’s Respiratory Questionnaire total score and response, rescue medication use, and proportion of patients with exacerbations. Results: Eighteen trials were identified for meta-analysis (eight, olodaterol; ten, indacaterol. Olodaterol trials included patients of all severities, whilst indacaterol trials excluded patients with very severe COPD. Concomitant maintenance bronchodilator use was allowed in most olodaterol trials, but not in indacaterol trials. When similarly designed trials/data were analyzed for change from baseline in trough FEV1 (liters, the following mean differences (95% confidence interval were observed: trials excluding concomitant bronchodilator: indacaterol 75 mcg versus olodaterol 5 mcg, –0.005 (–0.077 to 0.067, and indacaterol 150 mcg

  8. Conception through build of an automated liquids processing system for compound management in a low-humidity environment.

    Science.gov (United States)

    Belval, Richard; Alamir, Ab; Corte, Christopher; DiValentino, Justin; Fernandes, James; Frerking, Stuart; Jenkins, Derek; Rogers, George; Sanville-Ross, Mary; Sledziona, Cindy; Taylor, Paul

    2012-12-01

    Boehringer Ingelheim's Automated Liquids Processing System (ALPS) in Ridgefield, Connecticut, was built to accommodate all compound solution-based operations following dissolution in neat DMSO. Process analysis resulted in the design of two nearly identical conveyor-based subsystems, each capable of executing 1400 × 384-well plate or punch tube replicates per batch. Two parallel-positioned subsystems are capable of independent execution or alternatively executed as a unified system for more complex or higher throughput processes. Primary ALPS functions include creation of high-throughput screening plates, concentration-response plates, and reformatted master stock plates (e.g., 384-well plates from 96-well plates). Integrated operations included centrifugation, unsealing/piercing, broadcast diluent addition, barcode print/application, compound transfer/mix via disposable pipette tips, and plate sealing. ALPS key features included instrument pooling for increased capacity or fail-over situations, programming constructs to associate one source plate to an array of replicate plates, and stacked collation of completed plates. Due to the hygroscopic nature of DMSO, ALPS was designed to operate within a 10% relativity humidity environment. The activities described are the collaborative efforts that contributed to the specification, build, delivery, and acceptance testing between Boehringer Ingelheim Pharmaceuticals, Inc. and the automation integration vendor, Thermo Scientific Laboratory Automation (Burlington, ON, Canada).

  9. Higher lung deposition with Respimat® Soft Mist™ Inhaler than HFA-MDI in COPD patients with poor technique

    Directory of Open Access Journals (Sweden)

    Peter Brand

    2008-08-01

    Full Text Available Peter Brand1, Bettina Hederer2, George Austen3, Helen Dewberry3, Thomas Meyer41RWTH, Aachen, Germany; 2Boehringer Ingelheim, Ingelheim, Germany; 3Boehringer Ingelheim, Bracknell, UK; 4Inamed Research, Gauting, GermanyAbstract: Aerosols delivered by Respimat® Soft Mist™ Inhaler (SMI are slower-moving and longer-lasting than those from pressurized metered-dose inhalers (pMDIs, improving the efficiency of pulmonary drug delivery to patients. In this four-way cross-over study, adults with chronic obstructive pulmonary disease (COPD and with poor pMDI technique received radiolabelled Berodual® (fenoterol hydrobromide 50 µg/ipratropium bromide 20 µg via Respimat® SMI or hydrofluoroalkane (HFA-MDI (randomized order on test days 1 and 2, with no inhaler technique training. The procedure was repeated on test days 3 and 4 after training. Deposition was measured by gamma scintigraphy. All 13 patients entered (9 males, mean age 62 years; FEV1 46% of predicted inhaled too fast at screening (peak inspiratory flow rate [IF]: 69–161 L/min. Whole lung deposition was higher with Respimat® SMI than with pMDI for untrained (37% of delivered dose vs 21% of metered dose and trained patients (53% of delivered vs 21% of metered dose (pSign-Test = 0.15; pANOVA< 0.05. Training also improved inhalation profiles (slower average and peak IF as well as longer breath-hold time. Drug delivery to the lungs with Respimat® SMI is more efficient than with pMDI, even with poor inhaler technique. Teaching patients to hold their breath as well as to inhale slowly and deeply increased further lung deposition using Respimat® SMI.Keywords: chronic obstructive pulmonary disease, drug delivery, inhalation, metered-dose inhaler, poor inhalation technique, training

  10. Boehringer Ingelheim公司计划在日本提出Pradaxa的申请

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    B Ingelheim公司正计划于明年第一季度在日本提出Pradaxa(dabigatran)用于房颤病人卒中预防的批准申请。涉及全球18,000例病人比较这种口服直接凝血酶抑制剂与华法林的RE—LY研究预计于今年晚些时候出结果,而第一次申请将于2009年底提出。在日本有326例病人参与了RE—LY研究,其治疗方案与全球其他参与者相同。这个产品也在日本等待批准用于全膝置换术后静脉血栓形成(VTE)事件预防。

  11. Efficacy and safety of the long-acting β2-agonist olodaterol over 4 weeks in Japanese patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Ichinose M

    2015-08-01

    Full Text Available Masakazu Ichinose,1 Ayako Takizawa,2 Toshiyasu Izumoto,2 Yusuke Tadayasu,2 Alan L Hamilton,3 Christina Kunz,4 Yoshinosuke Fukuchi51Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; 2Nippon Boehringer Ingelheim Co. Ltd, Tokyo, Japan; 3Boehringer Ingelheim, Burlington, Ontario, Canada; 4Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riß, Germany; 5Juntendo University School of Medicine, Tokyo, JapanBackground: Olodaterol is a novel long-acting β2-agonist with proven ≥24-hour duration of action in preclinical and clinical studies.Objective: This randomized, double-blind, placebo-controlled, parallel-group study evaluated the dose response of once-daily (QD olodaterol based on bronchodilator efficacy, safety, and pharmacokinetics over 4 weeks in Japanese patients with chronic obstructive pulmonary disease (COPD.Methods: All eligible patients were randomized to receive 2 µg, 5 µg, or 10 µg of olodaterol or placebo for 4 weeks via the Respimat® Soft Mist™ inhaler. The primary end point was the change from baseline in trough forced expiratory volume in 1 second (FEV1 after 4 weeks of olodaterol treatment. Secondary end points included trough FEV1 after 1 week and 2 weeks of treatment, FEV1 area under the curve from 0 hour to 3 hours (AUC0–3, peak FEV1 from 0 hour to 3 hours (peak FEV1, and corresponding forced vital capacity (FVC responses. Rescue medication use, COPD symptoms, physician global evaluation, pharmacokinetics, and safety were also assessed.Results: A total of 328 patients with COPD were randomized to receive treatment. All olodaterol doses assessed in the study showed statistically significant increases in trough FEV1 compared to placebo at Day 29 (P<0.0001. Mean increases in peak FEV1 and FEV1 AUC0–3 compared to placebo were also significant (P<0.0001. A clear dose–response relationship was observed across all treatment groups. FVC responses (trough

  12. Precautions to be taken by radiologists and radiographers when prescribing hyoscine-N-butylbromide

    Energy Technology Data Exchange (ETDEWEB)

    Dyde, R. [Department of Radiology, Leeds Teaching Hospitals NHS Trust, Leeds (United Kingdom); Chapman, A.H. [Department of Radiology, Leeds Teaching Hospitals NHS Trust, Leeds (United Kingdom)], E-mail: tony_chapman@ntlworld.com; Gale, R. [Department of Opthalmology, University of Leeds, Leeds (United Kingdom); Mackintosh, A. [Department of Cardiology, Leeds Teaching Hospitals NHS Trust, Leeds (United Kingdom); Tolan, D.J.M. [Department of Radiology, Leeds Teaching Hospitals NHS Trust, Leeds (United Kingdom)

    2008-07-15

    Hyoscine-N-butylbromide (Buscopan, Boehringer Ingelheim) is a widely used antispasmodic in radiological practice. There seems to be no consensus as to best practice within radiology regarding the precautions that need to be taken when prescribing Buscopan. We have performed a thorough review of the available literature and make the following recommendations to those administering Buscopan: (1) enquire whether there is an allergic history; (2) ensure patient literature warns that 'in the rare event that following the examination you develop painful, blurred vision in one or both eyes, you must attend hospital immediately for assessment'; (3) warn patients to expect blurred vision and not to drive until this has worn off; (4) remind clinicians that special consideration needs to be given as to the method of investigating patients with cardiac instability, such as those recently admitted with acute coronary syndrome, recurrent cardiac pain at rest, uncontrolled left ventricular failure and recent ventricular arrhythmias.

  13. Unexpected anterograde amnesia associated with Buscopan used as a predmedication for endocscopy

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    It has been known that peripheral adverse event is caused by peripheral antimuscarinic action, from hyoscine butylbromide (Buscopan; Boehringer Ingelheim, Germany)used as a premedication for endoscopy. However,symptoms or signs associated with the central nervous system are rarely reported in the field of anesthesiology and peripartum labor. This central anticholinergic syndrome is likely caused by blockade of muscarinic cholinergic receptors in the central nervous system. There is no report on Buscopan-induced central anticholinergic syndrome in endoscopy room so far. Three middle-aged females unexpectedly suffered from anterograde amnesia after intramuscular injection of hyoscine butylbromide as an antispasmodic premedication for endoscopy at our endoscopy unit in the Health Promotion Center.

  14. Designing Multi-target Compound Libraries with Gaussian Process Models.

    Science.gov (United States)

    Bieler, Michael; Reutlinger, Michael; Rodrigues, Tiago; Schneider, Petra; Kriegl, Jan M; Schneider, Gisbert

    2016-05-01

    We present the application of machine learning models to selecting G protein-coupled receptor (GPCR)-focused compound libraries. The library design process was realized by ant colony optimization. A proprietary Boehringer-Ingelheim reference set consisting of 3519 compounds tested in dose-response assays at 11 GPCR targets served as training data for machine learning and activity prediction. We compared the usability of the proprietary data with a public data set from ChEMBL. Gaussian process models were trained to prioritize compounds from a virtual combinatorial library. We obtained meaningful models for three of the targets (5-HT2c , MCH, A1), which were experimentally confirmed for 12 of 15 selected and synthesized or purchased compounds. Overall, the models trained on the public data predicted the observed assay results more accurately. The results of this study motivate the use of Gaussian process regression on public data for virtual screening and target-focused compound library design.

  15. Tiotropium – what role in asthma?

    Science.gov (United States)

    2015-09-01

    Tiotropium solution for inhalation (Spiriva Respimat - Boehringer Ingelheim) is the first long-acting muscarinic antagonist to be marketed in the UK for the management of asthma. It is licensed as add-on maintenance bronchodilator treatment in adults with asthma who are using an inhaled corticosteroid (≥800μg budesonide/day or equivalent) and a long-acting beta2 agonist, and who have had one or more severe exacerbations in the previous year. This corresponds to use at step 4 of both the British asthma guideline and the Global Initiative for Asthma (GINA) strategy for the treatment of asthma in adults. Here we consider the evidence for tiotropium in the management of asthma and whether it offers any advantages over existing therapeutic options at step 4.

  16. 原发性高血压:控制早晨血压峰值的固定复方%Essenzielle Hypertonie:Fixkombination zur Kontrolle morgentlicher Blutdruckspitzen

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    2002年4月Boehringer Ingelheim 公司收到关于其复方制剂Micardis plus(R)(AT1受体阻滞剂Telmisartan + 利尿剂氢氯噻嗪)在欧洲范围批准上市的批文.这个治疗原发性高血压的制剂,已于2002年5月在德国首次上市.本品适用于单种药物不能有效控制早晨血压的病人和适用复方制剂的严重高血压患者.

  17. On the Relationship between Distribution and Motivation of Citation Based on Citation Frequency and Content Analysis%基于引用频次和内容分析的引文分布与动机关系研究*

    Institute of Scientific and Technical Information of China (English)

    王剑; 高峰; 满芮; 刘茜

    2013-01-01

    为了准确理解和辨识引文动机和引文分布之间的关系,以谷歌学术收录的Boehringer Ingelheim Fonds资助的学术论文为研究样本,借助引文频次和引文内容作为捕获引文动机的载体,利用统计学和认知学的相关技术,设计实验从定量角度研究了引文分布和引文动机的联系。实验结果表明:引文动机和引文分布确实在统计学上存在一定的相关性,即引文分布是作者对引文态度的体现因素之一。%To understand and recognize the relationship between motivation and distribution of citations, we use papers in Google Scholar which were funded by Boehringer Ingelheim Fonds as study samples and the citation frequency and content are utilized as carrier for captu-ring citation motivation. Using statistical and cognitive science related technologies, an experiment for studying the contact between moti-vation and distribution of citations quantitatively is designed. It is showed that there is really a certain correlation between citation distribu-tions and citation motivation, thus citation distribution is an element reflecting the author's attitude towards citations.

  18. Pharmacokinetics and bioequivalence of 2 meloxicam oral dosage formulations in healthy adult horses.

    Science.gov (United States)

    Vivancos, Melanie; Barker, Jessica; Engbers, Sarah; Fischer, Carrie; Frederick, Jami; Friedt, Heather; Rybicka, Joanna M; Stastny, Tereza; Banse, Heidi; Cribb, Alastair E

    2015-07-01

    Meloxicam, a non-steroidal anti-inflammatory drug, is approved for use in horses in several countries, but an equine formulation is not available in North America. However, meloxicam is being used in an extra-label manner in horses in Canada. The purpose of this study, therefore, was to assess the bioequivalence of an approved oral meloxicam suspension (Metacam 15 mg/mL for horses; Boehringer Ingelheim Vetmedica GmBH, Ingelheim, Germany) from the European Union with human meloxicam tablets (Meloxicam 15 mg tablets; TEVA Canada, Toronto, Ontario) compounded with molasses to improve palatability and administration. The geometric mean ratios (GMR test/reference) and the 90% confidence intervals of the pivotal pharmacokinetic parameters (area under the curve and maximum concentration) were within the defined limits of 80% to 125% generally accepted for products to be considered bioequivalent. Therefore, use of human meloxicam tablets compounded with molasses would be expected to produce a similar clinical response in horses as the approved oral product from the European Union.

  19. Daily home-based spirometry during withdrawal of inhaled corticosteroid in severe to very severe chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Rodriguez-Roisin R

    2016-08-01

    Full Text Available Roberto Rodriguez-Roisin,1 Kay Tetzlaff,2,3 Henrik Watz,4 Emiel FM Wouters,5 Bernd Disse,2 Helen Finnigan,6 Helgo Magnussen,4 Peter MA Calverley7 1Respiratory Institute, Servei de Pneumologia, Hospital Clínic IDIBAPS-CIBERES, Universitat de Barcelona, Barcelona, Spain; 2Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany; 3Department of Sports Medicine, University of Tübingen, Tübingen, Germany; 4Pulmonary Research Institute at Lung Clinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany; 5Department of Respiratory Medicine, University Hospital Maastricht, Maastricht University, Maastricht, the Netherlands; 6Department of Biostatistics and Data Sciences, Boehringer Ingelheim, Bracknell, UK; 7Institute of Ageing and Chronic Disease, Aintree University Hospital, Liverpool, UK Abstract: The WISDOM study (NCT00975195 reported a change in lung function following withdrawal of fluticasone propionate in patients with severe to very severe COPD treated with tiotropium and salmeterol. However, little is known about the validity of home-based spirometry measurements of lung function in COPD. Therefore, as part of this study, following suitable training, patients recorded daily home-based spirometry measurements in addition to undergoing periodic in-clinic spirometric testing throughout the study duration. We subsequently determined the validity of home-based spirometry for detecting changes in lung function by comparing in-clinic and home-based forced expiratory volume in 1 second in patients who underwent stepwise fluticasone propionate withdrawal over 12 weeks versus patients remaining on fluticasone propionate for 52 weeks. Bland–Altman analysis of these data confirmed good agreement between in-clinic and home-based measurements, both across all visits and at the individual visits at study weeks 6, 12, 18, and 52. There was a measurable difference between the forced expiratory volume

  20. Nicoboxil/nonivamide cream effectively and safely reduces acute nonspecific low back pain – a randomized, placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Blahova Z

    2016-12-01

    Full Text Available Zuzana Blahova,1 Janina Claudia Holm,1 Thomas Weiser,2 Erika Richter,2 Matthias Trampisch,2 Elena Akarachkova3 1Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria; 2Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim am Rhein, Germany; 3I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation Background/objective: Low back pain affects many patients and has a high socioeconomic impact. Topical capsaicinoids have been used for decades to treat musculoskeletal pain. This study investigated the effects of the fixed dose combination (FDC of nonivamide (a capsaicinoid and nicoboxil (a nicotinic acid ester cream in the treatment of acute nonspecific low back pain.Materials and methods: This phase III randomized, double-blind, placebo-controlled, multinational, multi-center trial investigated efficacy, safety, and tolerability of topical nicoboxil 1.08%/nonivamide 0.17% (Finalgon® cream in treatment of acute nonspecific low back pain with the endpoints: pain intensity (PI difference between pre-dose baseline and 8 hours after first application and the end of treatment, mobility score, and efficacy score.Results: Patients (n=138, 21–65 years of age, were treated for up to 4 days with FDC or placebo cream. Mean baseline PI was 6.8 on a 0–10 point numerical rating scale. After 8 hours, pain was more reduced with the FDC than with placebo (adjusted means: 2.824 vs. 0.975 points; p<0.0001. On the last treatment day, mean pain reduction by the FDC was stronger than with placebo (adjusted means: 5.132 vs. 2.174 points; p<0.0001. Mobility on Day 1 was in favor of the FDC when compared to placebo (odds ratio [95% confidence interval {CI}]: 7.200 [3.609, 14.363], p<0.0001. At the end of treatment, patients treated with the FDC rated efficacy significantly higher than placebo (odds ratio [95% CI]: 11.370 [5.342, 24.199], p<0.0001. Both treatments were tolerated well. No serious adverse events were reported.Conclusion: Nicoboxil

  1. Efficacy and safety of tiotropium Respimat® SMI in COPD in two 1-year randomized studies

    Directory of Open Access Journals (Sweden)

    Eric Bateman

    2010-06-01

    Full Text Available Eric Bateman1, Dave Singh2, David Smith3, Bernd Disse4, Lesley Towse5, Dan Massey5, Jon Blatchford5, Demetri Pavia5, Rick Hodder61Division of Pulmonology, Department of Medicine, University of Cape Town, Cape Town, South Africa; 2University Hospital of South Manchester Foundation Trust, University of Manchester, Manchester, UK; 3North Bristol Lung Centre, Southmead Hospital, Bristol, UK; 4Boehringer Ingelheim, GmbH, Ingelheim, Germany; 5Boehringer Ingelheim, Ltd., Bracknell, Berkshire, UK; 6Divisions of Pulmonary and Critical Care Medicine, University of Ottawa, Ottawa, Ontario, CanadaAbstract: Two 1-year studies evaluated the long-term efficacy and safety of tiotropium 5 or 10 μg versus placebo, inhaled via the Respimat® Soft MistTM Inhaler (SMI. The two studies were combined and had 4 co-primary endpoints (trough FEV1 response, Mahler Transition Dyspnea Index [TDI] and St George’s Respiratory Questionnaire scores all at week 48, and COPD exacerbations per patient-year. A total of 1990 patients with COPD participated (mean FEV1: 1.09 L. The mean trough FEV1 response of tiotropium 5 or 10 μg relative to placebo was 127 or 150 mL, respectively (both P < 0.0001. The COPD exacerbation rate was significantly lower with tiotropium 5 μg (RR = 0.78; P = 0.002 and tiotropium 10 μg (RR = 0.73; P = 0.0008; the health-related quality of life and Mahler TDI co-primary endpoints were significantly improved with both doses (both P < 0.0001. Adverse events were generally balanced except anticholinergic class effects, which were more frequent with active treatment. Fatal events occurred in 2.4% (5 μg, 2.7% (10 μg, and 1.6% (placebo of patients; these differences were not significant. Tiotropium Respimat® SMI 5 μg demonstrated sustained improvements in patients with COPD relative to placebo and similar to the 10 μg dose but with a lower frequency of anticholinergic adverse events.Keywords: COPD, exacerbations, FEV1, quality of life, Respimat

  2. HCVerso1 and 2: faldaprevir with deleobuvir (BI 207127 and ribavirin for treatment-naïve patients with chronic hepatitis C virus genotype-1b infection

    Directory of Open Access Journals (Sweden)

    Sarrazin C

    2016-11-01

    Full Text Available Christoph Sarrazin,1 Francesco Castelli,2 Pietro Andreone,3 Maria Buti,4 Massimo Colombo,5 Stanislas Pol,6 Filipe Calinas,7 Massimo Puoti,8 Antonio Olveira,9 Mitchell Shiffman,10 Jerry O Stern,11 George Kukolj,12 Michael Roehrle,13 Stella Aslanyan,11 Qiqi Deng,11 Richard Vinisko,11 Federico J Mensa,11 David R Nelson,14 on behalf of the HCVerso1 and 2 study groups 1Department of Internal Medicine 1, JW Goethe University Hospital, Frankfurt, Germany; 2Department of Infectious and Tropical Diseases, University of Brescia, Brescia, 3Department of Medical and Surgical Sciences, Università di Bologna and Azienda Ospedaliero-Universitaria, Policlinico Sant‘Orsola-Malpighi, Bologna, Italy; 4Department of Internal Medicine, Hospital Universitari Vall d’Hebron and CIBERehd del Instituto Carlos III, Barcelona, Spain; 5Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy; 6University Paris Descartes, Department of Hepatology, Hospital Cochin, APHP and INSERM UMS-20, Institut Pasteur, Paris, France; 7Department of Gastroenterology, Centro Hospitalar de Lisboa Central, Lisbon, Portugal; 8Department of Infectious Diseases, AO Ospedale Niguarda Cà Granda, Milan, Italy; 9Liver Unit, Hospital Universitario La Paz, CIBERehd, Madrid, Spain; 10Liver Institute of Virginia, Bon Secours Health System, Richmond, VA, USA; 11Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA; 12Boehringer Ingelheim Ltd/Ltée, Burlington, ON, Canada; 13Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany; 14Clinical and Translational Science Institute, University of Florida, Gainesville, FL, USA Abstract: The interferon-free combination of once-daily faldaprevir 120 mg, twice-daily deleobuvir 600 mg, and weight-based ribavirin was evaluated in two Phase III studies (HCVerso1, HCVerso2 in hepatitis C virus genotype-1b-infected, treatment-naïve patients, including

  3. Comorbidities of patients in tiotropium clinical trials: comparison with observational studies of patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Miravitlles M

    2015-03-01

    Full Text Available Marc Miravitlles,1 David Price,2 Klaus F Rabe,3,7 Hendrik Schmidt,4 Norbert Metzdorf,5 Bartolome Celli6 1Pneumology Department, Hospital Universitari Vall d’Hebron, Ciber de Enfermedades Respiratorias (CIBERES, Barcelona, Spain; 2Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 3Department of Medicine, Christian-Albrechts-Universität zu Kiel (CAU, Großhansdorf, Germany; 4Global Biometrics and Clinical Applications, Boehringer Ingelheim Pharma GmbH and Co KG, Ingelheim am Rhein, Germany; 5TA Respiratory Diseases, Boehringer Ingelheim Pharma GmbH and Co KG, Ingelheim am Rhein, Germany; 6Pulmonary Division, Brigham and Women’s Hospital, Boston, MA, USA; 7LungenClinic Grosshansdorf, Großhansdorf, Germany Background: There is an ongoing debate on whether patients with chronic obstructive pulmonary disease (COPD seen in real-life clinical settings are represented in randomized controlled trials (RCTs of COPD. It is thought that the stringent inclusion and exclusion criteria of RCTs may prevent the participation of patients with specific characteristics or risk factors.Methods: We surveyed a database of patients recruited into 35 placebo-controlled tiotropium RCTs and also conducted a systematic literature review of large-scale observational studies conducted in patients with a documented diagnosis of COPD between 1990 and 2013. Patient demographics and comorbidities with a high prevalence in patients with COPD were compared between the two patient populations at baseline. Using the Medical Dictionary for Regulatory Activities (MedDRA; v 14.0, patient comorbidities in the pooled tiotropium RCTs were classified according to system organ class, pharmacovigilance (PV endpoints, and Standardised MedDRA Queries to enable comparison with the observational studies.Results: We identified 24,555 patients in the pooled tiotropium RCTs and 61,361 patients among the 13 observational studies that met our

  4. A Comparative Pharmacokinetics Study of the Anti-Parkinsonian Drug Pramipexole

    Directory of Open Access Journals (Sweden)

    Ratih S. I. Putri

    2016-11-01

    Full Text Available The present study aimed to compare pharmacokinetic parameters of two pramipexole 0.25 mg formulations in order to show bioequivalence. The study was conducted in a randomized, open-label, two-period, two-sequence, and crossover design, involving 23 healthy volunteers. One of the 0.25 mg formulations of pramipexole evaluated in the study was manufactured by PT Dexa Medica, Palembang, Indonesia, the other, used as the reference, by Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany. All eligible subjects were required to fast before each drug administration period, which was separated by a one-week washout period. Pramipexole concentrations in plasma were assayed using a validated ultra performance liquid chromatography with mass spectrometry (UPLC-MS/MS detector. The evaluated pharmacokinetic parameters included the area under the plasma concentration curve from time zero to the last observed measurable concentration (AUC0-t, the area under the plasma concentration curve extrapolated to infinite time (AUC0-∞, the maximum plasma concentration (Cmax, the time to reach Cmax (tmax, and the plasma concentration half-life (t1/2. To evaluate the bioequivalence of those two pramipexole formulations, 90% confidence intervals (CIs for geometric mean ratios of both formulations were calculated for AUC and Cmax parameters, while tmax and t1/2 differences were analyzed on the non-transformed data using Wilcoxon matched-pairs and a Student’s paired t-test, respectively. The 90% CIs for the geometric mean ratios of the two pramipexole formulations were 95.89% (90.73%–101.34%, 95.53% (89.75%–101.68%, and 92.11% (84.35%–100.58% for AUC0-t, AUC0-∞, and Cmax, respectively. There were no statistically significant differences for tmax and t1/2 between the two pramipexole formulations. It is concluded that two pramipexole formulations in this study were bioequivalent.

  5. Development and implementation of treadmill exercise testing protocols in COPD

    Directory of Open Access Journals (Sweden)

    Christopher B Cooper

    2010-10-01

    Full Text Available Christopher B Cooper1, Marlon Abrazado1, Daniel Legg2, Steven Kesten21David Geffen School of Medicine, University of California, Los Angeles, CA, USA; 2Boehringer Ingelheim Pharmaceuticals Inc., Ingelheim, GermanyBackground: Because treadmill exercise testing is more representative of daily activity than cycle testing, we developed treadmill protocols to be used in various clinical settings as part of a two-year, multicenter, chronic obstructive pulmonary disease (COPD trial evaluating the effect of tiotropium on exercise.Methods: We enrolled 519 COPD patients aged 64.6 ± 8.3 years with a postbronchodilator forced expiratory volume in one second (FEV1 of 1.25 ± 0.42 L, 44.3% ± 11.9% predicted. The patients performed symptom-limited treadmill tests where work rate (W was increased linearly using speed and grade adjustments every minute. On two subsequent visits, they performed constant W tests to exhaustion at 90% of maximum W from the incremental test.Results: Mean incremental test duration was 522 ± 172 seconds (range 20–890, maximum work rate 66 ± 34 watts. For the first and second constant W tests, both at 61 ± 33 watts, mean endurance times were 317 ± 61 seconds and 341 ± 184 seconds, respectively. The mean of two tests had an intraclass correlation coefficient of 0.85 (P < 0.001. During the second constant W test, 88.2% of subjects stopped exercise because of breathing discomfort; 87.1% for Global Initiative for Chronic Obstructive Lung Disease (GOLD Stage II, 88.5% for GOLD Stage III, and 90.2% for GOLD Stage IV.Conclusion: The symptom-limited incremental and constant work treadmill protocol was well tolerated and appeared to be representative of the physiologic limitations of COPD.Keywords: chronic obstructive pulmonary disease, exercise testing, endurance, tiotropium

  6. A Comparative Pharmacokinetics Study of the Anti-Parkinsonian Drug Pramipexole

    Science.gov (United States)

    Putri, Ratih S. I.; Setiawati, Effi; Aziswan, Syifa A.; Ong, Fenny; Tjandrawinata, Raymond R.; Susanto, Liana W.

    2016-01-01

    The present study aimed to compare pharmacokinetic parameters of two pramipexole 0.25 mg formulations in order to show bioequivalence. The study was conducted in a randomized, open-label, two-period, two-sequence, and crossover design, involving 23 healthy volunteers. One of the 0.25 mg formulations of pramipexole evaluated in the study was manufactured by PT Dexa Medica, Palembang, Indonesia, the other, used as the reference, by Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany. All eligible subjects were required to fast before each drug administration period, which was separated by a one-week washout period. Pramipexole concentrations in plasma were assayed using a validated ultra performance liquid chromatography with mass spectrometry (UPLC-MS/MS) detector. The evaluated pharmacokinetic parameters included the area under the plasma concentration curve from time zero to the last observed measurable concentration (AUC0-t), the area under the plasma concentration curve extrapolated to infinite time (AUC0-∞), the maximum plasma concentration (Cmax), the time to reach Cmax (tmax), and the plasma concentration half-life (t1/2). To evaluate the bioequivalence of those two pramipexole formulations, 90% confidence intervals (CIs) for geometric mean ratios of both formulations were calculated for AUC and Cmax parameters, while tmax and t1/2 differences were analyzed on the non-transformed data using Wilcoxon matched-pairs and a Student’s paired t-test, respectively. The 90% CIs for the geometric mean ratios of the two pramipexole formulations were 95.89% (90.73%–101.34%), 95.53% (89.75%–101.68%), and 92.11% (84.35%–100.58%) for AUC0-t, AUC0-∞, and Cmax, respectively. There were no statistically significant differences for tmax and t1/2 between the two pramipexole formulations. It is concluded that two pramipexole formulations in this study were bioequivalent. PMID:27869754

  7. Adjusting for COPD severity in database research: developing and validating an algorithm

    Directory of Open Access Journals (Sweden)

    Goossens LMA

    2011-12-01

    Full Text Available Lucas MA Goossens1, Christine L Baker2, Brigitta U Monz3, Kelly H Zou2, Maureen PMH Rutten-van Mölken11Institute for Medical Technology Assessment, Erasmus University, Rotterdam, The Netherlands; 2Pfizer Inc, New York City, NY, USA; 3Boehringer Ingelheim International GmbH, Ingelheim am Rhein, GermanyPurpose: When comparing chronic obstructive lung disease (COPD interventions in database research, it is important to adjust for severity. Global Initiative for Chronic Obstructive Lung Disease (GOLD guidelines grade severity according to lung function. Most databases lack data on lung function. Previous database research has approximated COPD severity using demographics and healthcare utilization. This study aims to derive an algorithm for COPD severity using baseline data from a large respiratory trial (UPLIFT.Methods: Partial proportional odds logit models were developed for probabilities of being in GOLD stages II, III and IV. Concordance between predicted and observed stage was assessed using kappa-statistics. Models were estimated in a random selection of 2/3 of patients and validated in the remainder. The analysis was repeated in a subsample with a balanced distribution across severity stages. Univariate associations of COPD severity with the covariates were tested as well.Results: More severe COPD was associated with being male and younger, having quit smoking, lower BMI, osteoporosis, hospitalizations, using certain medications, and oxygen. After adjusting for these variables, co-morbidities, previous healthcare resource use (eg, emergency room, hospitalizations and inhaled corticosteroids, xanthines, or mucolytics were no longer independently associated with COPD severity, although they were in univariate tests. The concordance was poor (kappa = 0.151 and only slightly better in the balanced sample (kappa = 0.215.Conclusion: COPD severity cannot be reliably predicted from demographics and healthcare use. This limitation should be

  8. Differences in outcomes between GOLD groups in patients with COPD in the TIOSPIR® trial

    Directory of Open Access Journals (Sweden)

    Dusser D

    2016-01-01

    Full Text Available Daniel Dusser,1 Robert A Wise,2 Ronald Dahl,3 Antonio Anzueto,4,5 Kerstine Carter,6 Andy Fowler,7 Peter M Calverley8 1Service de Pneumologie, Hôpital Cochin, AP-HP, Université Paris Descartes, Sorbonne Paris Cité, Paris, France; 2Asthma and Allergy Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 3Allergy Centre, Odense University Hospital, Odense C, Denmark; 4Pulmonary/Critical Care, University of Texas, 5South Texas Veterans Health Care System, San Antonio, TX, USA; 6Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, CT, USA; 7Boehringer Ingelheim Pharma Ltd, Bracknell, UK; 8Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK  Background: The aim of this study was to evaluate whether Global Initiative for Chronic Obstructive Lung Disease (GOLD classification could predict mortality risk factors and whether baseline treatment intensity would relate to mortality within each group, using data from TIOSPIR®, the largest randomized clinical trial in COPD performed to date.Methods: A total of 17,135 patients from TIOSPIR® were pooled and grouped by GOLD grading (A–D according to baseline Medical Research Council breathlessness score, exacerbation history, and spirometry. All-cause mortality and adjudicated cardiovascular (CV and respiratory mortality were assessed.Results: Of the 16,326 patients classified, 1,248 died on treatment. Group B patients received proportionally more CV treatment at baseline. CV mortality risk, but not all-cause mortality risk, was significantly higher in Group B than Group C patients (CV mortality – hazard ratio [HR] =1.74, P=0.004; all-cause mortality – HR =1.18, P=0.11. Group D patients had a higher incidence of all-cause mortality than Group B patients (10.9% vs 6.6%. Similar trends were observed regardless of respiratory or CV medication at baseline. In contrast, respiratory deaths increased consistently from Groups A–D (0.3%, 0.8%, 1.6%, and 4.2% of

  9. Efficacy and safety of olodaterol once daily delivered via Respimat® in patients with GOLD 2–4 COPD: results from two replicate 48-week studies

    Directory of Open Access Journals (Sweden)

    Ferguson GT

    2014-06-01

    Full Text Available Gary T Ferguson,1 Gregory J Feldman,2 Peter Hofbauer,3 Alan Hamilton,4 Lisa Allen,5 Lawrence Korducki,5 Paul Sachs6 1Pulmonary Research Institute of Southeast Michigan, Livonia, MI, 2S Carolina Pharmaceutical Research, Spartanburg, SC, USA; 3Pneumologie, Weinheim, Germany; 4Boehringer Ingelheim, Burlington, ON, Canada; 5Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, 6Pulmonary Associates of Stamford, Stamford, CT, USA Background: Olodaterol is a long-acting β2-agonist with a 24-hour bronchodilator profile. Two replicate, randomized, double-blind, placebo-controlled, parallel-group, Phase III trials were performed as part of a comprehensive clinical program to investigate the long-term safety and efficacy of olodaterol in patients with moderate to very severe chronic obstructive pulmonary disease (COPD receiving usual-care background therapy. Methods: Patients received olodaterol 5 µg or 10 µg or placebo once daily for 48 weeks. Coprimary end points were forced expiratory volume in 1 second (FEV1 area under the curve from 0 to 3 hours (AUC0–3 response (change from baseline, and trough FEV1 response at 12 weeks. Secondary end points included additional lung function assessments, use of rescue medications, FEV1 AUC response from 0 to 12 hours, and Patient Global Rating over 48 weeks. Results: Overall, 624 and 642 patients were evaluated in studies 1222.11 and 1222.12, respectively. In both studies, olodaterol 5 µg and 10 µg significantly improved the FEV1 AUC0–3 response (P<0.0001 and trough FEV1 (study 1222.11, P<0.0001; study 1222.12, P<0.05, post hoc at week 12, with an incidence of adverse events comparable with that of placebo. Secondary end points supported the efficacy of olodaterol. Conclusion: These studies demonstrate the long-term efficacy and safety of once-daily olodaterol 5 µg and 10 µg in patients with moderate to very severe COPD continuing with usual-care maintenance therapy. Keywords: chronic obstructive

  10. Illness perceptions and coping determine quality of life in COPD patients

    Directory of Open Access Journals (Sweden)

    Tiemensma J

    2016-08-01

    Full Text Available Jitske Tiemensma,1 Erin Gaab,2 Maarten Voorhaar,3,4 Guus Asijee,3,5 Adrian A Kaptein6 1Psychological Sciences, 2Health Sciences Research Institute, University of California, Merced, CA, USA; 3Department of Family Medicine, Maastricht University, Care and Public Health Research Institute School for Public Health and Primary Care, Maastricht, the Netherlands; 4Boehringer Ingelheim, Alkmaar, the Netherlands; 5Boehringer Ingelheim, Amsterdam, the Netherlands; 6Department of Medical Psychology, Leiden University Medical Centre, Leiden, the Netherlands Background: A key goal of chronic obstructive pulmonary disease (COPD care is to improve patients’ quality of life (QoL. For outcomes such as QoL, illness perceptions and coping are important determinants.Aim: The primary aim was to assess the associations between illness perceptions, coping and QoL in COPD patients. A secondary aim was to compare illness perceptions and coping of patients with reference values derived from the literature.Patients and methods: A total of 100 patients were included in the study. Patients were asked to complete the Brief Illness Perception Questionnaire (B-IPQ, the Utrecht Proactive Coping Competence scale (UPCC, and a QoL item. Correlations and linear regression models were used to analyze the data. Student’s t-tests were used to compare patients with COPD with reference values derived from the literature.Results: Patients with better understanding of COPD utilized more proactive coping strategies (P=0.04. A more intense emotional response to COPD was related to less proactive coping (P=0.02. Patients who reported using more proactive coping techniques also reported to have a better QoL (P<0.01. Illness perceptions were also related to QoL: more positive illness perceptions were related to a better QoL (all P<0.05. Patients with COPD reported more negative illness perceptions than people with a common cold or patients with asthma (all P<0.01, but reported similar

  11. Lung function efficacy and symptomatic benefit of olodaterol once daily delivered via Respimat® versus placebo and formoterol twice daily in patients with GOLD 2–4 COPD: results from two replicate 48-week studies

    Directory of Open Access Journals (Sweden)

    Koch A

    2014-07-01

    Full Text Available Andrea Koch,1 Emilio Pizzichini,2 Alan Hamilton,3 Lorna Hart,3 Lawrence Korducki,4 Maria Cristina De Salvo,5 Pierluigi Paggiaro6 1Medical Clinic III for Pneumology, Allergology, Sleep and Respiratory Medicine, University Hospital Bochum-Bergmannsheil, Bochum, Germany; 2NUPAIVA (Asthma Research Center, Universidade Federal de Santa Catarina, Santa Catarina, Brazil; 3Boehringer Ingelheim, Burlington, Ontario, Canada; 4Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA; 5Centro Médico Dra. De Salvo, Fundación Respirar, Buenos Aires, Argentina; 6Cardio-Thoracic and Vascular Department, University of Pisa, Pisa, Italy Abstract: Two replicate, multicenter, randomized, double-blind, placebo-controlled, parallel-group, Phase III studies investigated the long-term efficacy and safety of once-daily olodaterol via Respimat® versus placebo and formoterol over 48 weeks in patients with moderate to very severe chronic obstructive pulmonary disease receiving usual-care background therapy. Patients received once-daily olodaterol 5 or 10 µg, twice-daily formoterol 12 µg, or placebo. Co-primary end points were forced expiratory volume in 1 second (FEV1 area under the curve from 0–3 hours response, FEV1 trough response, and Mahler transition dyspnea index total score after 24 weeks; secondary end points included St George's Respiratory Questionnaire. Overall, 904 (Study 1222.13 and 934 (Study 1222.14 patients received treatment. Olodaterol significantly improved FEV1 area under the curve from 0–3 hours versus placebo in both studies (with olodaterol 5 µg, 0.151 L and 0.129 L; with olodaterol 10 µg, 0.165 L and 0.154 L; for all comparisons P<0.0001 and FEV1 trough responses versus placebo (0.053–0.085 L; P<0.01, as did formoterol. Primary analysis revealed no significant difference in transition dyspnea index focal score for any active treatment versus placebo. Post hoc analysis using pattern mixture modeling (accounting for

  12. January 2015 Tucson pulmonary journal club: withdrawal of inhaled glucocorticoids in COPD

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    Wong C

    2015-02-01

    Full Text Available No abstract available. Article truncated at 150 words. Magnussen H, Disse B, Rodriguez-Roisin R, et al. Withdrawal of inhaled glucocorticoids and exacerbations of COPD. N Engl J Med. 2014;371(14:1285-94. GOLD guidelines recommend various combinations of inhaled corticosteroids (ICS, long-acting beta-agonists (LABA, and long-acting muscarinic agonists (LAMA to treat patients with chronic obstructive pulmonary disease (COPD who are at high risk of exacerbation. A substantial portion of patients are ultimately prescribed triple-therapy at some point. The WISDOM trial examined the risk of exacerbation among patients taking triple therapy who were subsequently weaned from their ICS treatment. The present WISDOM trial was a randomized, double-blind, non-inferiority trial sponsored by Boehringer Ingelheim Pharma. Over 4 years, approximately 2500 participants in 23 non-US countries with severe or very severe COPD were randomized. Participants were eligible if they were >40 years of age, were current or former smokers with ≥10 pack-year history, and had at least one exacerbation within the year prior to ...

  13. Bioequivalencia de una formulación nacional de Ambroxol BIOAVAILABILITY COMPARISON BETWEEN A CHILEAN GENERIC PREPARATION OF AMBROXOL AND THE ORIGINAL PRODUCT

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    IVÁN SAAVEDRA S.

    2003-01-01

    Full Text Available Objectives: To assess the relative bioavailability of two oral formulations of ambroxol commercialized in Chile, a generic syrup and the original product, MucosolvanR from Boehringer Ingelheim. Methods: A randomized, cross-over and double blind study was performed in twelve healthy volunteers who received a single oral dose of either Mucosolvan (90 mg or the generic formulation with at least a 14 day washout period between each single dose. Multiple blood samples were collected after each dose, the plasma ambroxol concentrations were determined by a validated High Performance Liquid Chromatography assay. Results: The 95% confidence intervals for all parameters were within the accepted range of 80-125% for bioequivalence, suggested by the US FDA. Non statistically significant differences were found in the mean parameters of bioequivalence: mean peak concentration (Cmax, area under the curve calculated from time zero to a determined time (AUC0-t, and area under the curve calculated from time zero to infinity (AUC0-oo, or in other parameters like: time to reach Cmax (t max, rate of absorption (Ka, rate of elimination (Ke, elimination half life (t1/2, and clearance (Cl. Conclusion: Pharmacokinetic results concluded that both formulations of ambroxol are bioequivalent and consequently the preparations can be considered interchangeable between them.

  14. A Clinical Comparison of Pycnogenol, Antistax, and Stocking in Chronic Venous Insufficiency.

    Science.gov (United States)

    Belcaro, Gianni

    2015-12-01

    This 8-week registry study was a comparative evaluation of Pycnogenol (French Maritime Pine Bark extract; Horphag Research, Geneva) and Antistax (grape leaf extract [GLE, Boehringer Ingelheim, Germany]) in controlling symptoms of chronic venous insufficiency (CVI). "Standard management" for CVI is compression; a group of comparable subjects was monitored to evaluate the effects of stockings. The registry included 183 patients (166 completing). Supplementation with Antistax (two tablets of 360 mg/d) or Pycnogenol (100 mg/d) was used. The groups were comparable for age, symptoms, venous incompetence, and microcirculation (with increased capillary filtration and skin flux) at inclusion. At 8 weeks, the rate of swelling (p Pycnogenol (p Pycnogenol (p Pycnogenol. An analog scale quantified symptoms. At 8 weeks, pain and edema were decreased with Pycnogenol and elastic compression (p Pycnogenol (p Pycnogenol was decreased by 40%. Induration was reduced only in the Pycnogenol group (p Pycnogenol were lower (96; 3.3 Euros) in comparison with the other groups (132;1.4 Euros for GLE and 149; 2.2 Euros for compression).

  15. A new combination approach of CI jet and QESD to formulate pH-susceptible amorphous solid dispersions.

    Science.gov (United States)

    Kumar, Sumit; Linehan, Brian; Tseng, Yin-Chao

    2014-05-15

    A new combination approach of quasi-emulsion solvent diffusion (QESD) and confined impinging jet (CIJ) technologies was utilized to formulate pH-susceptible amorphous solid dispersions (ASDs) of a poorly soluble investigational compound (BI906) of Boehringer Ingelheim Pharmaceuticals. The objective of this study was to formulate small-size pH-susceptible ASDs of BI906 to enhance its dissolution and solubility. A design of experiment approach was utilized to study the influence of critical parameters: antisolvent-to-solvent ratio, stabilizer concentration, polymer-to-drug ratio and flow rate of solvent. The critical quality attributes of the pH-susceptible solid dispersions (SDs) were crystallinity, particle size, drug loading and dissolution. The particle size of SDs was dependent on the antisolvent-to-solvent ratio, polymer-to-drug ratio and solvent flow rate. An increase in the solvent flow rate and antisolvent-to-solvent ratio resulted in smaller particle size of SDs. It was observed that the drug crystallinity and drug release were dependent on the polymer-to-drug ratio. The formulations containing a polymer-to-drug ratio of 6:1 were amorphous and showed superior pH dependent in vitro drug release performance. This study demonstrates that this new combination approach is feasible to formulate small-size pH-susceptible ASDs and it can be applied to other poorly soluble drugs to enhance in vitro dissolution and solubility.

  16. Optimization of the Büchi B-90 spray drying process using central composite design for preparation of solid dispersions.

    Science.gov (United States)

    Gu, Bing; Linehan, Brian; Tseng, Yin-Chao

    2015-08-01

    A central composite design approach was applied to study the effect of polymer concentration, inlet temperature and air flow rate on the spray drying process of the Büchi B-90 nano spray dryer (B-90). Hypromellose acetate succinate-LF was used for the Design of Experiment (DoE) study. Statistically significant models to predict the yield, spray rate, and drying efficiency were generated from the study. The spray drying conditions were optimized according to the models to maximize the yield and efficiency of the process. The models were further validated using a poorly water-soluble investigational compound (BI064) from Boehringer Ingelheim Pharmaceuticals. The polymer/drug ratio ranged from 1/1 to 3/1w/w. The spray dried formulations were amorphous determined by differential scanning calorimetry and X-ray powder diffraction. The particle size of the spray dried formulations was 2-10 μm under polarized light microscopy. All the formulations were physically stable for at least 3h when suspended in an aqueous vehicle composed of 1% methyl cellulose. This study demonstrates that DoE is a useful tool to optimize the spray drying process, and the B-90 can be used to efficiently produce amorphous solid dispersions with a limited quantity of drug substance available during drug discovery stages.

  17. Development and Evaluation of a Rapid Antigen Detection and Serotyping Lateral Flow Antigen Detection System for Foot-and-Mouth Disease Virus.

    Directory of Open Access Journals (Sweden)

    Kazuki Morioka

    Full Text Available We developed a lateral flow strip using monoclonal antibodies (MAbs which allows for rapid antigen detection and serotyping of foot-and-mouth disease virus (FMDV. This FMDV serotyping strip was able to detect all 7 serotypes and distinguish serotypes O, A, C and Asia1. Its sensitivities ranged from 10(3 to 10(4 of a 50% tissue culture infectious dose of each FMDV stain; this is equal to those of the commercial product Svanodip (Boehringer Ingelheim Svanova, Uppsala, Sweden, which can detect all seven serotypes of FMDV, but does not distinguish them. Our evaluation of the FMDV serotyping strip using a total of 118 clinical samples (vesicular fluids, vesicular epithelial emulsions and oral and/or nasal swabs showed highly sensitive antigen detection and accuracy in serotyping in accordance with ELISA or RT-PCR. To the best of our knowledge, this is the first report on any FMDV serotyping strip that provides both rapid antigen detection and serotyping of FMDV at the same time on one strip without extra devices. This method will be useful in both FMD-free countries and FMD-infected countries, especially where laboratory diagnosis cannot be carried out.

  18. A better dissolution method for ranitidine tablets USP.

    Science.gov (United States)

    Cappola, M L

    2001-01-01

    Ranitidine tablets USP showed variable intra- and inter-lab dissolution results. In order to ascertain the reason for this behavior, ranitidine tablets USP produced by (BIPI) Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, and Zantac Tablets (brand of ranitidine USP), Glaxo Inc., Research Triangle, NC, were subjected to the compendia (USP) dissolution testing using paddle and basket apparatus. Two potencies of tablets 150 mg and 300 mg were tested. Comparison of BIPI tablets and matching Zantac tablets indicated that both brands of ranitidine tablets USP had similar dissolution behavior. When the basket apparatus was substituted for the paddle apparatus the overall rate and extent of tablet dissolution increased, while the individual tablet variability decreased. BIPI 150 mg tablets using the basket apparatus, but at reduced rotational speed of 30 rpm, showed increase in rate and extent of drug dissolved, with less individual tablet variability compared to the paddle apparatus at 50 rpm. The 300 mg tablet (30 rpm/basket apparatus) had an initial slower rate, but then rapidly equaled the paddle apparatus dissolution results, and had less individual tablet variability. Paddle apparatus tablet sinkers were used to prevent tablets from sticking to the bottom of the dissolution vessel. Overall dissolution for all tablets with sinkers showed a trend which was more rapid and complete than tablets without sinkers. Results showed that dissolution artifacts for ranitidine tablets could be reduced by the use of baskets or tablet sinkers.

  19. Direct-acting oral anticoagulants: pharmacology, indications, management, and future perspectives.

    Science.gov (United States)

    Gómez-Outes, Antonio; Suárez-Gea, Ma Luisa; Lecumberri, Ramón; Terleira-Fernández, Ana Isabel; Vargas-Castrillón, Emilio

    2015-11-01

    In recent years, several direct-acting oral anticoagulants (DOAC) have become available for use in Europe and other regions in indications related to prophylaxis and treatment of venous and arterial thromboembolism. They include the oral direct thrombin inhibitor dabigatran etexilate (Pradaxa, Boehringer Ingelheim) and the oral direct FXa inhibitors rivaroxaban (Xarelto, Bayer HealthCare), apixaban (Eliquis, Bristol-Myers Squibb), and edoxaban (Lixiana/Savaysa, Daiichi-Sankyo). The new compounds have a predictable dose response and few drug-drug interactions (unlike vitamin k antagonists), and they do not require parenteral administration (unlike heparins). However, they accumulate in patients with renal impairment, lack widely available monitoring tests for measuring its anticoagulant activity, and no specific antidotes for neutralization in case of overdose and/or severe bleeding are currently available. In this review, we describe the pharmacology of the DOAC, the efficacy, and safety data from pivotal studies that support their currently approved indications and discuss the postmarketing experience available. We also summarize practical recommendations to ensure an appropriate use of the DOAC according to existing data. Finally, we discuss relevant ongoing studies and future perspectives.

  20. Cognitive aspects of schizophrenia.

    Science.gov (United States)

    Harvey, Philip D

    2013-11-01

    Cognitive impairments are a central feature of schizophrenia and are present in most, if not all, cases. There are multiple domains of impairment seen and the level of severity of impairment is considerable. Impairments can be detected prior to the onset of clinical symptoms and the course of impairments involves some subtle early worsening followed by stability in most cases. Cognitive impairments are associated with functional disability, particularly in domains of vocational functioning and independence of residence. Both pharmacological and cognitive remediation interventions have been employed for the treatment of these impairments, with greater progress to date being made in cognitive remediation interventions. While much is known about cognitive impairments, treatment efforts are still in an early stage of development. WIREs Cogn Sci 2013, 4:599-608. doi: 10.1002/wcs.1253 CONFLICT OF INTEREST: Dr. Harvey has received consulting fees from Abbott Labs, Amgen, Boehringer Ingelheim, Genentech, Johnson and Johnson, Pharma Neuroboost, Roche Parma, Sunovion Pharma, and Takeda Pharma during the past year. For further resources related to this article, please visit the WIREs website.

  1. A cross-sectional study to assess inhalation device handling and patient satisfaction in COPD

    Directory of Open Access Journals (Sweden)

    Miravitlles M

    2016-02-01

    Full Text Available Marc Miravitlles,1 Jéssica Montero-Caballero,2 Frank Richard,2 Salud Santos,3 Juan Luis Garcia-Rivero,4 Francisco Ortega,5 Xavier Ribera61Pneumology Department, Hospital Universitari Vall d’Hebron, Ciber de Enfermedades Respiratorias (CIBERES, Barcelona, Spain; 2Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany; 3Pulmonology Department, Hospital Universitari de Bellvitge, IDIBELL, Universitat de Barcelona, Ciber de Enfermedades Respiratorias (CIBERES, Barcelona, Spain; 4Pneumology Department, Hospital de Laredo, Cantabria, Spain; 5Pneumology Department, Hospital Virgen del Rocío, Sevilla, Spain; 6Boehringer Ingelheim Pharma GmbH & Co KG, Barcelona, Spain Abstract: Delivery of inhaled medications via an inhaler device underpins the effectiveness of treatment for patients with chronic obstructive pulmonary disease (COPD. Correct inhaler technique among patients is also a predictor of achieving treatment compliance and adherence. Reporting of patient satisfaction with inhalers is therefore gaining increasing attention and is now recognized as an important patient-reported outcome in clinical trials involving patients with COPD or asthma. In this cross-sectional study, we use the validated Patient Satisfaction and Preference Questionnaire (PASAPQ to assess the handling and satisfaction for Respimat® Soft Mist™ Inhaler (SMI compared with the Breezhaler® dry powder inhaler (DPI among patients with COPD in Spain. Patients were already assigned to therapy with either SPIRIVA® (tiotropium Respimat® or with Hirobriz®/Onbrez®/Oslif® (indacaterol Breezhaler® for at least 3 but not more than 6 months before completing the PASAPQ at a single visit to the study site. The primary endpoint of the trial was the mean total PASAPQ score. Secondary endpoints were the performance score domain of the PASAPQ, the convenience score domain of the PASAPQ, and the overall satisfaction score of the PASAPQ. For the primary endpoint, the mean PASAPQ

  2. Efficacy and safety of eco-friendly inhalers: focus on combination ipratropium bromide and albuterol in chronic obstructive pulmonary disease

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    Panos RJ

    2013-04-01

    Full Text Available Ralph J Panos1,2 1Pulmonary, Critical Care, and Sleep Medicine Division, Cincinnati Veterans Affairs Medical Center, 2Pulmonary, Critical Care, and Sleep Medicine Division, University of Cincinnati College of Medicine, Cincinnati, OH, USA Background: Chronic obstructive pulmonary disease (COPD is a major cause of morbidity and mortality and its treatment is critical to improve quality of life, reduce symptoms, and diminish the frequency of COPD exacerbations. Due to the harmful environmental effects of pressurized metered-dose inhalers (pMDIs containing chlorofluorocarbons (CFCs, newer systems for delivering respiratory medications have been developed. Methods: A search of the literature in the PubMed database was undertaken using the keywords “COPD,” “albuterol,” “ipratropium bromide,” and “Respimat® Soft Mist Inhaler™”; pertinent references within the identified citations were included. The environmental effect of CFC-pMDIs, the invention of the Respimat® Soft Mist Inhaler™ (SMI (Boehringer Ingelheim, Ingelheim, Germany, and its use to deliver the combination of albuterol and ipratropium bromide for the treatment of COPD were reviewed. Results: The adverse environmental effects of CFC-pMDIs stimulated the invention of novel delivery systems including the Respimat SMI. This review presents its development, internal mechanism, and use to deliver the combination of albuterol and ipratropium bromide. Conclusion: CFC-pMDIs contributed to the depletion of the ozone layer and the surge in disorders caused by harmful ultraviolet B radiation. The banning of CFCs spurred the development of novel delivery systems for respiratory medications. The Respimat SMI is an innovative device that produces a vapor of inhalable droplets with reduced velocity and prolonged aerosol duration that enhance deposition within the lower airway and is associated with improved patient satisfaction. Clinical trials have demonstrated that the Respimat SMI

  3. Telmisartan Tablets in Different Dissolution Medium Leaching Behavior Comparison%替米沙坦片在不同溶出介质中的溶出行为比较

    Institute of Scientific and Technical Information of China (English)

    蒋玲; 毕学苑; 葛畅; 梅丽; 刘玮

    2013-01-01

    Objective Compare the in-vitro dissolution of telmisartan tablets from dif erent manufacturers. Methods The dissolution of telmisartan tablets from A、B、C and D manufacturers was determined by UV, and similarity for dissolution was evaluated by f2 factor. Results Compared with Micardis made by Boehringer Ingelheim, the similarity factors of telmisartan tablets made by manufacturers B, C and D in distil ed water were 83.0、86.4、84.3、65.8 and 37.7, respectively. In the hydrochloric acid solution(pH1.2), the similarity factors were 70.4、70.0、75.7、64.7 and 37.3, respectively. In the phosphate buf er(pH6.8), the similarity factors were 69.8、66.3、65.7、59.2 and 41.9, respectively. Conclusion The dissolution characteristics of manufacturers B and C were similar to Boehringer Ingelheim, and the dissolution characteristic of manufacturer D was dif erent significantly.%目的对替米沙坦片的体外溶出行为进行比较。方法采用UV法分别测定A、B、C、D厂替米沙坦片在水、盐酸溶液(pH1.2)、磷酸盐缓冲液(pH6.8)为溶出介质的累积溶出度,使用FDA推荐的相似因子法对溶出度曲线进行相似性比较。结果以原研厂家勃林格殷格翰公司的替米沙坦片(美卡素)为参比制剂,以水为溶出介质B(3批)、C、D厂的相似因子分别为83.0、86.4、84.3、65.8、37.7;以盐酸溶液(pH1.2)为溶出介质的 B(3批)、C、D厂的相似因子分别为70.4、70.0、75.7、64.7、37.3;以磷酸盐缓冲液(pH6.8)为溶出介质的B(3批)、C、D厂的相似因子分别为69.8、66.3、65.7、59.2、41.9。结论 B厂3批替米沙坦片在水、盐酸溶液(pH1.2)、磷酸盐缓冲液(pH6.8)3种溶出介质的溶出行为均与参比制剂非常相似;C厂有一定的相似性;D厂则存在较大差异。

  4. Effect of tiotropium on health-related quality of life as a primary efficacy endpoint in COPD

    Directory of Open Access Journals (Sweden)

    A-B Tonnel

    2008-06-01

    Full Text Available A-B Tonnel1, T Perez1, J-M Grosbois2, C Verkindre2, M-L Bravo3, M Brun3 on behalf of the TIPHON study groupa1Centre Hospitalier Régional Universitaire (CHRU de Lille, Lille Cedex, France; 2Centre Hospitalier de Béthune, Béthune, France; 3Boehringer Ingelheim France, Reims Cedex, France; aSee Appendix: participating investigatorsAbstract: Clinical manifestations of chronic obstructive pulmonary disease (COPD, including airflow limitation, dyspnea, and activity limitation, ultimately lead to impaired health-related quality of life (HRQoL. This 9-month, randomized, double-blind, multicenter study compared the effect of once-daily tiotropium 18 µg and placebo on HRQoL, spirometric parameters, and exacerbations in 554 patients with moderate-to-severe COPD. HRQoL was assessed using the St. George’s Respiratory Questionnaire (SGRQ and the new 8-item Visual Simplified Respiratory Questionnaire (VSRQ, which is currently being validated. The primary efficacy endpoint was the proportion of patients achieving a reduction of at least 4 units in the SGRQ total score at study end (Month 9. Mean ± SD baseline SGRQ total score was 47.4 ± 18.1. Significantly more tiotropium-treated patients achieved a reduction of at least 4 units in the SGRQ score vs placebo at study end (59.1% vs 48.2%, respectively; p = 0.029. Tiotropium significantly improved spirometric parameters (forced expiratory volume in 1 second [FEV1]: 0.11 ± 0.02 L vs 0.01 ± 0.02 L; between-group difference: 0.10 ± 0.03 L, p = 0.0001 and reduced exacerbations vs placebo. Maintenance treatment with tiotropium provided significant and clinically relevant improvements in HRQoL, as measured by the SGRQ.Keywords: chronic obstructive pulmonary disease, long-acting anticholinergic, health-related quality of life, tiotropium

  5. Validity, reliability, and responsiveness of a new short Visual Simplified Respiratory Questionnaire (VSRQ© for health-related quality of life assessment in chronic obstructive pulmonary disease

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    T Perez

    2008-12-01

    Full Text Available T Perez1, B Arnould2, J-M Grosbois3, V Bosch2, I Guillemin2, M-L Bravo4, M Brun4, A-B Tonnel1 on behalf of TIPHON Study Group1Centre Hospitalier Régional Universitaire (CHRU, Lille, France; 2Mapi Values, Lyon, France; 3Service de Pneumologie, Centre Hospitalier de Béthune, Béthune, France; 4Boehringer Ingelheim France, Reims Cédex, FranceAbstract: The Visual Simplified Respiratory Questionnaire (VSRQ was designed to assess health-related quality of life (HRQoL in patients with chronic obstructive pulmonary disease (COPD. It contains eight items: dyspnea, anxiety, depressed mood, sleep, energy, daily activities, social activities and sexual life. Psychometric properties were assessed during a clinical trial that evaluated the impact of tiotropium on HRQoL of COPD patients. These included the determination of structure, internal consistency reliability, concurrent validity with the St George’s Respiratory Questionnaire (SGRQ, test – retest reliability, clinical validity and responsiveness to change over two weeks. Minimal important difference (MID was calculated; cumulative response curves (CRC were based on the dyspnea item. Psychometric analyses showed that VSRQ structure was unidimensional. The questionnaire demonstrated good internal consistency reliability (Cronbach’s alpha = 0.84, good concurrent validity with SGRQ (Spearman = −0.70 and clinical validity, good test-retest reproducibility (ICC = 0.77, and satisfactory responsiveness (standardized response mean = 0.57; Guyatt’s statistic = 0.63. MID was 3.4; CRC median value of the ‘minimally improved’ patients was 3.5. In conclusion, VSRQ brevity and satisfactory psychometric properties make it a good candidate for large studies to assess HRQoL in COPD patients. Further validation is needed to extend its use in clinical practice.Keywords: chronic obstructive pulmonary disease, VSRQ, SGRQ, health-related quality of life, minimal important difference

  6. Combination of the sodium-glucose cotransporter-2 inhibitor empagliflozin with orlistat or sibutramine further improves the body-weight reduction and glucose homeostasis of obese rats fed a cafeteria diet

    Directory of Open Access Journals (Sweden)

    Vickers SP

    2014-07-01

    Full Text Available Steven P Vickers,1 Sharon C Cheetham,1 Katie R Headland,1 Keith Dickinson,1 Rolf Grempler,2 Eric Mayoux,2 Michael Mark,2 Thomas Klein2 1RenaSci, BioCity Nottingham, Nottingham, UK; 2Boehringer Ingelheim Pharma, Biberach an der Riss, Germany Abstract: The present study assessed the potential of the sodium glucose-linked transporter (SGLT-2 inhibitor empagliflozin to decrease body weight when administered alone or in combination with the clinically effective weight-loss agents orlistat and sibutramine in obese rats fed a cafeteria diet. Female Wistar rats were exposed to a cafeteria diet to induce obesity. Empagliflozin was dosed once daily (10, 30, and 60 mg/kg for 28 days. Combination studies were subsequently performed using a submaximal empagliflozin dose (10 mg/kg with either sibutramine or orlistat. Body weight, food, and water intake were recorded daily. The effect of drug treatment on glucose tolerance, relevant plasma parameters, and carcass composition was determined. Empagliflozin dose-dependently reduced body weight, plasma leptin, and body fat though increased urinary glucose excretion. The combination of empagliflozin and orlistat significantly reduced body weight compared to animals treated with either drug alone, and significantly improved glucose tolerance, plasma insulin, and leptin compared to vehicle-treated controls. The effect of sibutramine to improve glycemic control in an oral glucose-tolerance test was also significantly increased, with empagliflozin and combination treatment leading to a reduction in carcass fat greater than that observed with either drug alone. These data demonstrate that empagliflozin reduces body weight in cafeteria-fed obese rats. In combination studies, empagliflozin further improved the body-weight or body-fat loss of animals in comparison to orlistat or sibutramine alone. Such studies may indicate improved strategies for the treatment of obese patients with prediabetes or type 2 diabetes. Keywords

  7. Ultrasound enhanced prehospital thrombolysis using microbubbles infusion in patients with acute ST elevation myocardial infarction: Rationale and design of the Sonolysis study

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    van Dijk Arie PJ

    2008-12-01

    Full Text Available Abstract Background - Experimental studies have shown that ultrasound contrast agents enhance the effectiveness of thrombolytic agents in the presence of ultrasound in vitro and in vivo. Recently, we have launched a clinical pilot study, called "Sonolysis", to study this effect in patients with ST-elevation myocardial infarction based on proximal lesions of the infarct-related artery. Methods/design - In our multicenter, randomized, placebo controlled clinical trial we will include patients between 18 and 80 years of age with their first ST-elevation myocardial infarction based on a proximal lesion of the infarct-related artery. After receiving a single bolus alteplase 50 mg IV (Actilyse® Boehringer Ingelheim GmbH, a loading dose of aspirin 500 mg, and heparin 5000 IU in the ambulance according to the prehospital thrombolysis protocol, patients, following oral informed consent, are randomized to undergo 15 minutes of pulsatile ultrasound with intravenous administration of ultrasound contrast agent or placebo without ultrasound. Afterwards coronary angiography and, if indicated, percutaneous coronary intervention will take place. A total of 60 patients will be enrolled in approximately 1 year. The primary endpoints are based on the coronary angiogram and consist of TIMI flow, corrected TIMI frame count, and myocardial blush grade. Follow-up includes 12-lead ECG, 2D-echocardiography, cardiac MRI, and enzyme markers to obtain our secondary endpoints, including the infarct size, wall motion abnormalities, and the global left ventricular function. Discussion - The Sonolysis study is the first multicenter, randomized, placebo controlled clinical trial investigating the therapeutic application of ultrasound and microbubbles in acute ST-elevation myocardial infarction patients. A positive finding may stimulate further research and technical innovations to implement the treatment in the ambulance and maybe obtain even more patency at an earlier stage

  8. Lack of paradoxical bronchoconstriction after administration of tiotropium via Respimat® Soft Mist™ Inhaler in COPD

    Directory of Open Access Journals (Sweden)

    Hodder R

    2011-04-01

    Full Text Available Rick Hodder1, Demetri Pavia2, Angela Lee2, Eric Bateman31Divisions of Pulmonary and Critical Care, University of Ottawa, Ottawa, ON, Canada; 2Boehringer Ingelheim Limited, Bracknell, England, UK; 3Division of Pulmonology, Department of Medicine, University of Cape Town, Cape Town, South AfricaAbstract: Bronchoconstriction has been reported in asthma and chronic obstructive pulmonary disease (COPD patients after administration of some aqueous inhalation solutions. We investigated the incidence of this event during long-term clinical trials of tiotropium delivered via Respimat® Soft Mist™ Inhaler (SMI. We retrospectively analyzed pooled data from two identical Phase III clinical trials, in which 1990 patients with COPD received 48 weeks' treatment with once-daily tiotropium (5 or 10 µg or placebo inhaled via Respimat® SMI. We recorded the incidence of bronchospasm and of a range of respiratory events that could suggest bronchoconstriction during the first 30 minutes after inhalation of study treatment on each of the eight test days. No patients reported bronchospasm. Six patients (0.3% reported a combination of at least two events suggestive of bronchoconstriction, and 21 (1.1% reported either rescue medication use or a respiratory adverse event. Asymptomatic falls in forced expiratory volume in one second (FEV1 of ≥15% were recorded on all test days, with no change in incidence over time, and affected 8.2% of those in the tiotropium groups and 14.5% of those on placebo. In COPD patients receiving long-term treatment with tiotropium 5 or 10 µg via Respimat® SMI, no bronchospasm was recorded, and the number of events possibly indicative of paradoxical bronchoconstriction was very low.Keywords: inhalation device, bronchoconstriction, COPD, tiotropium

  9. Specific antidotes in development for reversal of novel anticoagulants: a review.

    Science.gov (United States)

    Gomez-Outes, Antonio; Suarez-Gea, M L; Lecumberri, Ramon; Terleira-Fernandez, Ana I; Vargas-Castrillon, Emilio

    2014-01-01

    In the last decade, several direct oral anticoagulants (DOAC; dabigatran, rivaroxaban, apixaban, edoxaban) have been marketed for prophylaxis and/or treatment of thromboembolism without having specific antidotes available for their reversal. Current management of bleeding associated to DOAC includes the removal of all antithrombotic medications and supportive care. Non-specific procoagulant agents (prothrombin complex concentrates and activated factor VIIa) have been used in case of serious bleeding. Currently, some specific antidotes for the DOAC are under development. Idarucizumab (BI 655075; Boehringer Ingelheim) is a fragment of an antibody (Fab), which is a specific antidote to the oral direct thrombin inhibitor dabigatran. Andexanet alfa (r-Antidote, PRT064445; Portola Pharmaceuticals) is a truncated form of enzymatically inactive factor Xa, which binds and reverses the anticoagulant action of the factor Xa inhibitors (e.g.: rivaroxaban, apixaban and edoxaban). Aripazine (PER-977, ciraparantag; Perosphere Inc.) is a synthetic small molecule (~500 Da) that reverses oral dabigatran, apixaban, rivaroxaban, as well as subcutaneous fondaparinux and LMWH in vivo. These antidotes could provide an alternative for management of life-threatening bleeding events occurring with the above-mentioned anticoagulants. In addition, the specific antidote anivamersen (RB007; Regado Biosciences Inc.) is an RNA aptamer in clinical development to reverse the anticoagulant effect of the parenteral factor IXa inhibitor pegnivacogin, which is also in development. This anticoagulant-antidote pair may provide an alternative in situations in which a fast onset and offset of anticoagulation is needed, like in patients undergoing cardiac surgery with extracorporeal circulation, as an alternative to the heparin/protamine pair. This patent review includes a description of the pharmacological characteristics of the novel specific antidotes, the available results from completed non

  10. Hot topic: investigating the risk of violative meat residues in bob veal calves fed colostrum from cows treated at dry-off with cephapirin benzathine.

    Science.gov (United States)

    Hausler, K; Godden, S M; Schneider, M J; Lightfield, A R; Bulthaus, M; Haines, D

    2013-04-01

    The objective was to conduct a study to investigate if violative meat residues are detected in very young bob veal calves that are fed first-milking colostrum harvested from cows that were dry treated, on-label, with cephapirin benzathine. First-milking colostrum was collected from cows that were given intramammary treatment at dry off, on-label, with cephapirin benzathine (ToMORROW, Boehringer Ingelheim Vetmedica Inc., St. Joseph, MO). Newborn bull calves meeting study inclusion criteria were removed from their dams shortly after birth and before suckling, and assigned to 1 of 2 trials. For the first trial, 6 treated calves were fed 3.8L of fresh maternal colostrum and 1 control calf was fed 1.5 doses of a plasma-derived colostrum replacer (Secure Calf Colostrum Replacer, VitaPlus Inc., Madison, WI) within 1h after birth. For the second trial, 5 treated calves were fed 3.8L of fresh maternal colostrum and 1 control calf was fed 1.5 doses of Secure Calf Colostrum Replacer within 1h after birth. All calves were humanely euthanized at 24h (trial 1) or 48h (trial 2) of age, and tissues were harvested for antimicrobial residue testing. Samples of maternal colostrum and colostrum replacer were also submitted for antimicrobial residue testing. Kidneys collected from all study calves tested negative for cephapirin benzathine residues when using both the KIS assay (Charm Sciences, Lawrence, MA) and liquid chromatography-tandem mass spectrometry analysis. The potential transfer of cephapirin from cows treated on-label at dry off to calves via colostrum may not be a significant source of cephapirin residues in veal tissues.

  11. The burden of chronic obstructive pulmonary disease associated with maintenance monotherapy in the UK

    Directory of Open Access Journals (Sweden)

    Edwards SC

    2016-11-01

    Full Text Available Susan C Edwards,1 Sian E Fairbrother,2 Anna Scowcroft,3 Gavin Chiu,4 Andrew Ternouth,3 Brian J Lipworth5 1Department of Market Access Pricing & Outcomes Research, 2Department of Medical Affairs - Respiratory, 3Department of Market Access, 4Department of Prescription Medicine - Respiratory, Boehringer Ingelheim, Bracknell, UK; 5Asthma and Allergy Research Group, Division of Cardiovascular and Diabetes Medicine, Scottish Centre for Respiratory Research, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK Background: This study characterized a cohort of chronic obstructive pulmonary disease (COPD patients on maintenance bronchodilator monotherapy for ≥6 months to establish their disease burden, measured by health care utilization.Methods: Data were extracted from the UK Clinical Practice Research Datalink and linked to Hospital Episode Statistics. The monotherapy period spanned the first prescription of a long-acting β2-adrenergic agonist or a long-acting muscarinic antagonist until the end of the study (December 31, 2013 or until step up to dual/triple therapy, for example, addition of another long-acting bronchodilator, an inhaled corticosteroid, or both. A minimum of four consecutive prescriptions and 6 months on continuous monotherapy were required. Patients <50 years old at first COPD diagnosis or with another significant respiratory disease before starting monotherapy were excluded. Disease burden was evaluated by measuring patients’ rate of face-to-face interactions with a health care professional (HCP, COPD-related exacerbations, hospitalizations, and referrals.Results: A cohort of 8,811 COPD patients (95% Global initiative for chronic Obstructive Lung Disease stage A/B on maintenance monotherapy was identified between 2002 and 2013; 45% of these patients were still on monotherapy by the end of the study. Median time from first COPD diagnosis to first monotherapy prescription was 56 days, while the median time on

  12. Increase in skeletal muscle protein content by the ß-2 selective adrenergic agonist clenbuterol exacerbates hypoalbuminemia in rats fed a low-protein diet

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    A.L. Sawaya

    1998-06-01

    Full Text Available This investigation examined how the nutritional status of rats fed a low-protein diet was affected when the animals were treated with the ß-2 selective agonist clenbuterol (CL. Males (4 weeks old from an inbred, specific-pathogen-free strain of hooded rats maintained at the Dunn Nutritional Laboratory were used in the experiments (N = 6 rats per group. CL treatment (Ventipulmin, Boehringer-Ingelheim Ltd., 3.2 mg/kg diet for 2 weeks caused an exacerbation of the symptoms associated with protein deficiency in rats. Plasma albumin concentrations, already low in rats fed a low-protein diet (group A, were further reduced in CL rats (A = 25.05 ± 0.31 vs CL = 23.64 ± 0.30 g/l, P<0.05. Total liver protein decreased below the level seen in either pair-fed animals (group P or animals with free access to the low-protein diet (A = 736.56 ± 26 vs CL = 535.41 ± 54 mg, P<0.05, whereas gastrocnemius muscle protein was higher than the values normally described for control (C animals (C = 210.88 ± 3.2 vs CL = 227.14 ± 1.7 mg/g, P<0.05. Clenbuterol-treated rats also showed a reduction in growth when compared to P rats (P = 3.2 ± 1.1 vs CL = -10.2 ± 1.9 g, P<0.05. This was associated with a marked decrease in fat stores (P = 5.35 ± 0.81 vs CL = 2.02 ± 0.16 g, P<0.05. Brown adipose tissue (BAT cytochrome oxidase activity, although slightly lower than in P rats (P = 469.96 ± 16.20 vs CL = 414.48 ± 11.32 U/BAT x kg body weight, P<0.05, was still much higher than in control rats (C = 159.55 ± 11.54 vs CL = 414.48 ± 11.32 U/BAT x kg body weight, P<0.05. The present findings support the hypothesis that an increased muscle protein content due to clenbuterol stimulation worsened amino acid availability to the liver and further reduced albumin synthesis causing exacerbation of hypoalbuminemia in rats fed a low-protein diet.

  13. Initiation of triple therapy maintenance treatment among patients with COPD in the US

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    Simeone JC

    2016-12-01

    Full Text Available Jason C Simeone,1 Rakesh Luthra,2 Shuchita Kaila,2 Xiaoyun Pan,1 Tarun D Bhagnani,1 Jieruo Liu,1 Teresa K Wilcox1 1Real-World Evidence, Evidera, Waltham, MA, 2HEOR Value Demonstration Team, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA Background: The Global Initiative for Chronic Obstructive Lung Disease (GOLD recommends triple therapy (long-acting muscarinic receptor antagonists, long-acting beta-2 agonists, and inhaled corticosteroids for patients with only the most severe COPD. Data on the proportion of COPD patients on triple therapy and their characteristics are sparse and dated. Objective 1 of this study was to estimate the proportion of all, and all treated, COPD patients receiving triple therapy. Objective 2 was to characterize those on triple therapy and assess the concordance of triple therapy use with GOLD guidelines. Patients and methods: This retrospective study used claims from the IMS PharMetrics Plus database from 2009 to 2013. Cohort 1 was selected to assess Objective 1 only; descriptive analyses were conducted in Cohort 2 to answer Objective 2. A validated claims-based algorithm and severity and frequency of exacerbations were used as proxies for COPD severity. Results: Of all 199,678 patients with COPD in Cohort 1, 7.5% received triple therapy after diagnosis, and 25.5% of all treated patients received triple therapy. In Cohort 2, 30,493 COPD patients (mean age =64.7 years who initiated triple therapy were identified. Using the claims-based algorithm, 34.5% of Cohort 2 patients were classified as having mild disease (GOLD 1, 40.8% moderate (GOLD 2, 22.5% severe (GOLD 3, and 2.3% very severe (GOLD 4. Using exacerbation severity and frequency, 60.6% of patients were classified as GOLD 1/2 and 39.4% as GOLD 3/4. Conclusion: In this large US claims database study, one-quarter of all treated COPD patients received triple therapy. Although triple therapy is recommended for the most severe COPD patients

  14. Long-acting bronchodilator use after hospitalization for COPD: an observational study of health insurance claims data

    Directory of Open Access Journals (Sweden)

    Baker CL

    2014-05-01

    Full Text Available Christine L Baker,1 Kelly H Zou,1 Jun Su21Pfizer Inc., New York, NY, USA; 2Boehringer-Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USABackground: Treatment of stable chronic obstructive pulmonary disease (COPD with long-acting bronchodilator (LABD medications is recommended by the 2014 Global initiative for chronic Obstructive Lung Disease (GOLD guidelines. The primary objective of this study was to examine LABD prescription fills after a COPD-related hospitalization.Methods: This retrospective observational study used claims from Truven Health MarketScan® Commercial and Medicare Supplemental databases. Patients (age ≥40, commercial; age ≥65, Medicare supplemental had a first hospitalization with a primary COPD diagnosis between April 1, 2009 and June 30, 2011 (index hospitalization and were continuously enrolled for 1 year before and 9 months after hospitalization. Patients were categorized according to pre-index and/or post-index pharmacy claims.Results: A total of 27,738 patients had an index hospitalization and met inclusion/exclusion criteria. Of those, 19,783 patients had COPD as a primary or secondary diagnosis during the year before index hospitalization and were included in the analysis. Approximately one quarter of the patients (26.32% did not fill a prescription for an LABD or short-acting bronchodilator both 90 days before and 90 days after hospitalization. During the 90-day pre-index period, 40.57% of patients filled an LABD (with or without a short-acting bronchodilator prescription. Over half of the patients (56.88% filled an LABD prescription at some point during the 180-day post-index period, but, of those, a significantly greater proportion of patients filled an LABD prescription in the 1- to 90-day post-index period than in the 91- to 180-day post-index period (51.27% versus 43.66%; P<0.0001.Conclusion: A significant proportion of COPD patients in this study did not fill an LABD prescription before hospitalization for

  15. 口服抗凝药解毒剂的研究进展%Research progress on antidotes for oral anticoagulants

    Institute of Scientific and Technical Information of China (English)

    孙双勇; 郝春华; 张蕊; 石冰卓; 赵专友; 王维亭

    2016-01-01

    In recent years, new oral anticoagulants (NOACs) had made great development, and they gradually replaced the traditional anticoagulants to become the first-line drug of choice for clinic. Compared with conventional anticoagulants, their bleeding side effects were close to or less, but they still had a certain risk of bleeding. Traditional anticoagulant antidotes had poor detoxifying effect of NOACs, which led to a great deal of inconvenience and risk for the use of these drugs. Specific antidotes for NOACs were under development, and preliminary tests had achieved good results. Most representative drugs of these antidotes included andexanet alfa of Portola Pharmaceuticals, idarucizumab of Boehringer Ingelheim, and aripazine of Perosphere. This article reviewed research progress and problems of these three NOACs antidotes.%近年来新型口服抗凝药(NOACs)取得很大的发展,逐渐取代传统抗凝药而成为临床一线的首选药物。尽管与传统抗凝药物相比,NOACs 的出血副作用相当或更小,但依然存在着一定的出血风险。传统抗凝药物的解毒剂对 NOACs 的解毒效果不佳,为该类药物的使用带来很大的风险和不便。针对NOACs的特殊解毒剂正在开发当中,前期试验已取得不错的结果。这些解毒剂最具有代表性的药物包括Portola制药公司的andexanet alfa、勃林格殷格翰公司的idarucizumab以及Perosphere公司的aripazine,主要针对这3种NOACs解毒剂的研究进展以及存在的问题进行综述。

  16. Three-minute constant rate step test for detecting exertional dyspnea relief after bronchodilation in COPD

    Directory of Open Access Journals (Sweden)

    Borel B

    2016-11-01

    Full Text Available Benoit Borel,1,2 Courtney A Wilkinson-Maitland,3 Alan Hamilton,4 Jean Bourbeau,5 Hélène Perrault,6 Dennis Jensen,3,5,7 François Maltais2 1Laboratoire HAVAE, Université de Limoges, Limoges, France; 2Centre de Recherche, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, 3Clinical Exercise and Respiratory Physiology Laboratory, Department of Kinesiology and Physical Education, McGill University, Montréal, QC, 4Boehringer Ingelheim (Canada Limited, Burlington, ON, 5Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, McGill University Health Center, Montreal, QC, 6Faculty of Health Sciences, University of Ottawa, Ottawa, ON, 7Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada Background: The aim of this study was to evaluate the responsiveness of the 3-minute constant rate step test (3-MST to detect the relief of exertional dyspnea (respiratory discomfort after acute bronchodilation in COPD patients. Patients and methods: A total of 40 patients with moderate-to-severe COPD (mean forced expiratory volume in 1 second: 45.7 (±14.7, % predicted performed four 3-MSTs at randomly assigned stepping rates of 14, 16, 20 and 24 steps/min after inhalation of nebulized ipratropium bromide (500 µg/salbutamol (2.5 mg and saline placebo, which were randomized to order. Patients rated their intensity of perceived dyspnea at the end of each 3-MST using Borg 0–10 category ratio scale. Results: A total of 37 (92.5%, 36 (90%, 34 (85% and 27 (67.5% patients completed all 3 minutes of exercise at 14, 16, 20 and 24 steps/min under both treatment conditions, respectively. Compared with placebo, ipratropium bromide/salbutamol significantly decreased dyspnea at the end of the third minute of exercise at 14 steps/min (by 0.6±1.0 Borg 0–10 scale units, P<0.01 and 16 steps/min (by 0.7±1.3 Borg 0–10 scale

  17. COPD patient satisfaction with ipratropium bromide/albuterol delivered via Respimat: a randomized, controlled study

    Directory of Open Access Journals (Sweden)

    Ferguson GT

    2013-03-01

    Full Text Available Gary T Ferguson,1 Mo Ghafouri,2 Luyan Dai,2 Leonard J Dunn31Pulmonary Research Institute of Southeast Michigan, Livonia, MI, USA; 2Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT, USA; 3Clinical Research of West Florida, Inc, Clearwater, FL, USABackground: Ipratropium bromide/albuterol Respimat inhaler (CVT-R was developed as an environmentally friendly alternative to ipratropium bromide/albuterol metered-dose inhaler (CVT-MDI, which uses a chlorofluorocarbon propellant.Objective: The objective of this study was to evaluate patient satisfaction, device usage, and long-term safety of CVT-R compared to CVT-MDI, and to the simultaneous administration of ipratropium bromide hydrofluoroalkane (HFA; I and albuterol HFA (A metered-dose inhalers as dual monotherapies (I + A.Design: This is a 48-week, open-label, randomized, active-controlled, parallel-group study (n = 470 comparing CVT-R to CVT-MDI and to I + A.Participants: Patients were at least 40 years of age, diagnosed with chronic obstructive pulmonary disease (COPD, and current or exsmokers.Interventions: Patients were randomized to receive: (1 CVT-R, one inhalation four times daily (QID; or (2 CVT-MDI, two inhalations QID; or (3 I + A two inhalations of each inhaler QID.Main measures: Patient Satisfaction and Preference Questionnaire (PASAPQ performance score (primary endpoint and adverse events.Key results: PASAPQ performance score was significantly higher (CVT-R versus CVT-MDI, 9.6; and CVT-R versus I + A, 6.2; both P < 0.001 when using CVT-R compared to CVT-MDI or I + A at all visits starting from week 3, while CVT-MDI and I + A treatment groups were similar. Time to first COPD exacerbation was slightly longer in the CVT-R group compared to the other treatment groups, although it did not reach statistical significance (CVT-R versus CVT-MDI, P = 0.57; CVT-R versus I + A, P = 0.22. Rates of withdrawal and patient refusal to continue treatment were lower in CVT-R compared with CVT

  18. Interleukin-32, not reduced by salmeterol/fluticasone propionate in smokers with chronic obstructive pulmonary disease

    Institute of Scientific and Technical Information of China (English)

    Du Yipeng; Wang Wei; Yang Wei; He Bei

    2014-01-01

    Background The interleukin (IL)-32/tumor necrosis factor (TNF) α pathway is supposed to play a key role in the amplification of the immune response in chronic obstructive pulmonary disease (COPD) inflammation.Inhaled corticosteroids (ICS) in combination with long-acting β2-agonists (LABA) have shown airway anti-inflammatory effects in recent studies,but the mechanism is still uncertain.Methods Patients were treated in a randomized,open-labeled,parallel group clinical trial with either a combination of salmeterol xinafoate/fluticasone propionate (SF; Seretide,GlaxoSmithKline) Diskus (50/500 μg twice daily) or ipratropium bromide/salbutamol (IS; Combivent,Boehringer Ingelheim) MDI (42 μg/240 μg quartic daily) for 12 weeks.At the start and the end of treatment,induced sputum was collected and the concentration of IL-32 and TNF-α,the number of neutrophils and eosinophils were measured.Results Following 12 weeks of treatment,a statistically significant fall from baseline in the concentration of TNF-α in sputum (P=0.004) was seen after treatment with SF but not with IS.However,neither treatment had significant effects on the concentration of IL-32 in sputum.There was a decrease from baseline in the number of sputum neutrophils with SF that approached statistical significance (P=0.028) but not with IS,while the number of sputum eosinophils did not change significantly from baseline in either treatment group.There was a statistically significant decline from baseline in the quality of life as assessed by the St George's respiratory questionnaire in both the SF (P=0.004) and IS (P=0.030) treatment groups,but no evidence of improvement in lung function was observed in either group.Conclusion The sputum TNF-α and neutrophils,but not IL-32 and macrophages,could be reduced by ICS/LABA treatment,suggesting that IL-32 could be involved in the corticosteroid resistance of COPD inflammation.

  19. Disability related to COPD tool (DIRECT: towards an assessment of COPD-related disability in routine practice

    Directory of Open Access Journals (Sweden)

    Aguilaniu B

    2011-07-01

    Full Text Available B Aguilaniu1, J Gonzalez-Bermejo2, A Regnault3, C Dias Barbosa3, B Arnould3, M Mueser4, G Granet5, M Bonnefoy6, T Similowski2,71HYLAB, Physiologie Clinique, Grenoble, France; 2Assistance Publique – Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Service de Pneumologie et Réanimation, Paris, France; 3Mapi Values, Lyon, France; 4Formerly Boehringer Ingelheim, Paris, France; 5General Practitioner, Sainte-Foy-lès-Lyon, Paris, France; 6Centre Hospitalier Lyon Sud, Lyon, France; 7Université Paris 6 Pierre et Marie Curie, ER10, Paris, FranceBackground: Chronic Obstructive Pulmonary Disease (COPD is a worldwide public health concern. It is also a major source of disability that is often overlooked, depriving patients of effective treatments. This study describes the development and validation of a questionnaire specifically assessing COPD-related disability.Methods: The DIsability RElated to COPD Tool (DIRECT was developed according to reference methods, including literature review, patient and clinician interviews and test in a pilot study. A 12-item questionnaire was included for finalization and validation in an observational cross-sectional study conducted by 60 French pulmonologists, who recruited 275 COPD patients of stage II, III and IV according to the GOLD classification. Rasch modeling was conducted and psychometric properties were assessed (internal consistency reliability; concurrent and clinical validity.Results: The DIRECT score was built from the 10 items retained in the Rasch model. Their internal consistency reliability was excellent (Cronbach's alpha = 0.95. The score was highly correlated with the Saint George's Respiratory Questionnaire Activity score (r = 0.83 and the London Handicap Scale (r = –0.70, a generic disability measure. It was highly statistically significantly associated to four clinical parameters (P < 0.001: GOLD classification, BODE index, FEV1 and 6-minute walk distance.Conclusion: DIRECT is a

  20. The burden of chronic obstructive pulmonary disease among employed adults

    Directory of Open Access Journals (Sweden)

    DiBonaventura MD

    2012-03-01

    Full Text Available Marco daCosta DiBonaventura1, Ryne Paulose-Ram2, Jun Su3, Margaret McDonald2, Kelly H Zou2, Jan-Samuel Wagner1, Hemal Shah31Health Sciences Practice, Kantar Health, New York, NY, USA; 2Pfizer, Inc, New York, NY, USA; 3Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT, USAObjective: To examine quality of life, work productivity, and health care resource use among employed adults ages 40–64 years with chronic obstructive pulmonary disease (COPD in the United States.Methods: Data from the 2009 National Health and Wellness Survey were used. All employed adults ages 40–64 years with or without a self-reported diagnosis of COPD were included in the study. Impact on quality of life (using the mental and physical component summary scores and health utilities from the Short Form-12v2, work productivity and activity impairment (using the Work Productivity and Activity Impairment questionnaire, and resource use were analyzed using regression modeling.Results: There were 1112 employed adults with COPD versus 18,912 employed adults without COPD. After adjusting for demographics and patient characteristics, adults with COPD reported significantly lower mean levels of mental component summary (46.8 vs 48.5, physical component summary (45.6 vs 49.2, and health utilities (0.71 vs 0.75 than adults without COPD. Workers with COPD reported significantly greater presenteeism (18.9% vs 14.3%, overall work impairment (20.5% vs 16.3%, and impairment in daily activities (23.5% vs 17.9% than adults without COPD. Employed adults with COPD also reported more mean emergency room visits (0.21 vs 0.12 and more mean hospitalizations (0.10 vs 0.06 in the previous 6 months than employed adults without COPD. All of the above differences were significant at two-sided P < 0.05.Conclusion: After adjusting for various confounders, employed adults with COPD reported significantly lower quality of life and work productivity, and increased health care resource utilization

  1. Canagliflozin, dapagliflozin and empagliflozin monotherapy for treating type 2 diabetes: systematic review and economic evaluation.

    Science.gov (United States)

    Johnston, Rhona; Uthman, Olalekan; Cummins, Ewen; Clar, Christine; Royle, Pamela; Colquitt, Jill; Tan, Bee Kang; Clegg, Andrew; Shantikumar, Saran; Court, Rachel; O'Hare, J Paul; McGrane, David; Holt, Tim; Waugh, Norman

    2017-01-01

    haemoglobin or body mass index. Data on elderly patients were lacking. CONCLUSIONS Dapagliflozin, canagliflozin and empagliflozin are effective in improving glycaemic control, with added benefits of some reductions in BP and weight. Adverse effects are urinary and genital tract infections in a small proportion of users. In monotherapy, the three drugs do not appear cost-effective compared with gliclazide or pioglitazone, but may be competitive against sitagliptin (Januvia, Boehringer Ingelheim, Bracknell, UK). FUNDING The National Institute for Health Research Health Technology Assessment programme. PMID:28105986

  2. SU-E-J-266: Cone Beam Computed Tomography (CBCT) Inter-Scan and Inter-Observer Tumor Volume Variability Assessment in Patients Treated with Stereotactic Body Radiation Therapy (SBRT) for Early Stage Non-Small Cell Lung Cancer (NSCLC)

    Energy Technology Data Exchange (ETDEWEB)

    Hou, Y; Aileen, C; Kozono, D; Killoran, J; Wagar, M; Lee, S; Hacker, F; Aerts, H; Lewis, J; Mak, R [Brigham and Women’s Hospital, Boston, MA (United States)

    2015-06-15

    award; Disclosure/Conflict of interest: Raymond H. Mak: Stock ownership: Celgene, Inc. Consulting: Boehringer-Ingelheim, Inc.

  3. Design, rationale, and baseline demographics of SEARCH I: a prospective cluster-randomized study

    Directory of Open Access Journals (Sweden)

    Albers F

    2012-07-01

    Full Text Available Frank Albers,1 Asif Shaikh,2 Ahmar Iqbal,31Medical Affairs Respiratory, 2Clinical Development and Medical Affairs, Field Based Medicine-Respiratory, Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT, USA; 3Respiratory Medical Affairs, Pfizer Inc, New York, NY, USAAbstract: Questionnaires are available to identify patients at risk for several chronic diseases, including COPD, but are infrequently utilized in primary care. COPD is often underdiagnosed, while at the same time the US Preventive Services Task Force recommends against spirometric screening for COPD in asymptomatic adults. Use of a symptom-based questionnaire and subsequent handheld spirometric device depending on the answers to the questionnaire is a promising approach to identify patients at risk for COPD. Screening, Evaluating and Assessing Rate CHanges of diagnosing respiratory conditions in primary care 1 (SEARCH I was a prospective cluster-randomized study in 168 US primary care practices evaluating the effect of the COPD-Population Screener (COPD-PS™ questionnaire. The effect of this questionnaire alone or sequentially with the handheld copd-6TM device was evaluated on new diagnoses of COPD and on respiratory diagnostic practice patterns (including referrals for pulmonary function testing, referrals to pulmonologists, new diagnoses of COPD, and new respiratory medication prescriptions. Participating practices entered a total of 9704 consecutive consenting subjects aged ≥ 40 years attending primary care clinics. Study arm results were compared for new COPD diagnosis rates between usual care and (1 COPD-PS plus copd-6 and (2 COPD-PS alone. A cluster-randomization design allowed comparison of the intervention effects at the practice level instead of individuals being the subjects of the intervention. Regional principal investigators controlled the flow of study information to sub-investigators at participating practices to reduce observation bias (Hawthorne effect. The

  4. New approaches to the modulation of inflammatory processes in airway disease models: ATS 2001, May 18-23, San Francisco

    Directory of Open Access Journals (Sweden)

    Hele David J

    2001-07-01

    Full Text Available Abstract The 97th American Thoracic Society meeting proved to be an excellent meeting, providing a wealth of new information on inflammatory diseases of the airways. Once again there appeared to be an increased emphasis on chronic obstructive pulmonary disease (COPD with most of the major drug companies concentrating a large part of their efforts in this field. An assessment of the new British Thoracic Society guidelines, which are designed to promote better management of COPD, was also presented at the meeting. Potential new treatments for inflammatory diseases of the airways including COPD were described, ranging from phase III trial data with GlaxoSmithKline's PDE4 inhibitor, Cilomilast (Ariflo® to the development of AstraZeneca's novel dual dopamine D2-receptor/β2-adrenoreceptor agonist, Viozan™. Of particular interest was Byk Gulden's Ciclesonide, a new corticosteroid with equivalent efficacy to the market leaders but with an improved safety profile. The same company also presented data on their PDE4 inhibitor, Roflumilast, which is now in phase II/III. Bayer presented data on their PDE4 inhibitor, BAY 19-8004, in a smoking animal model and claimed greater anti-inflammatory efficacy than with a steroid. Asta Medica (now known as Elbion also described a new potent PDE4 inhibitor, AWD 12-281, with anti-inflammatory activity. In the bronchodilator field, an analysis of data from a one-year trial with Boehringer Ingelheim's Tiotropium revealed a possible improvement in lung function in COPD patients; this needs to be confirmed in a specifically designed study. Inhibitors of p38 (c-Jun NH2-terminal kinase and syk kinase were also discussed as anti-inflammatory agents with potential in the treatment of COPD and asthma. GlaxoSmithKline's p38 kinase inhibitor, SB 239063, appeared to be the most advanced of these with clinical data expected in two to three years. Lyn kinase was also discussed as a novel target for inflammatory airway diseases.

  5. Randomized noninferiority clinical trial evaluating 3 commercial dry cow mastitis preparations: I. Quarter-level outcomes.

    Science.gov (United States)

    Arruda, A G; Godden, S; Rapnicki, P; Gorden, P; Timms, L; Aly, S S; Lehenbauer, T W; Champagne, J

    2013-07-01

    The study objective was to compare the efficacy of 3 commercial dry cow mastitis formulations regarding quarter-level prevalence of intramammary infections (IMI) postcalving, cure of preexisting infections over the dry period, prevention of new infections during the dry period, and risk for a clinical mastitis case between calving and 100d in milk (DIM). A total of 1,091 cows (4,364 quarters) from 6 commercial dairy herds in 4 different states (California, Iowa, Minnesota, and Wisconsin) were enrolled and randomized to 1 of the 3 treatments at dry-off: Quartermaster (QT; 1,000,000 IU of procaine penicillin G and 1 g of dihydrostreptomycin; Pfizer Animal Health, New York, NY), Spectramast DC (SP; 500 mg of ceftiofur hydrochloride; Pfizer Animal Health), or ToMorrow Dry Cow (TM; 300mg of cephapirin benzathine; Boehringer Ingelheim Vetmedica Inc., St. Joseph, MO). Quarter milk samples were collected for routine bacteriological culture before dry cow therapy treatment at dry-off, 0 to 6 DIM, and 7 to 13 DIM and an on-farm record-keeping system was used to retrieve data on clinical mastitis cases. Noninferiority analysis was used to evaluate the effect of treatment on the primary outcome, risk for a bacteriological cure during the dry period. Multivariable logistic regression techniques were used to describe the effect of treatment on risk for presence of IMI postcalving and risk of a new IMI during the dry period. Cox proportional hazards regression was used to describe the effect of treatment on the risk and time for quarters to experience an episode of clinical mastitis between calving and 100 DIM. The overall crude quarter-level prevalence of infection at dry-off was 19.2%. The most common pathogen isolated from milk samples at dry-off was coagulase-negative Staphylococcus, followed by Aerococcus spp. and other Streptococcus spp. Noninferiority analysis showed no effect of treatment on risk for a cure between dry-off and calving [least squares means (LSM): QT=93

  6. Patent Pooling for Promoting Access to Antiretroviral Drugs (ARVs) - A Strategic Option for India.

    Science.gov (United States)

    Satyanarayana, Kanikaram; Srivastava, Sadhana

    2010-01-19

    The current HIV/AIDS scenario in India is quite grim with an estimated 2.4 million people living with HIV/AIDS (PLHA) in 2008, just behind South Africa and Nigeria. The anti-retroviral drugs (ARVs) remain the main stay of global HIV/AIDS treatment. Over 30 ARVs (single and FDCs) available under six categories viz., NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), Protease inhibitors, the new Fusion inhibitors, Entry inhibitors-CCR5 co-receptor antagonists and HIV integrase strand transfer inhibitors. The major originator companies for these ARVs are: Abbott, Boehringer Ingelheim (BI), Bristol-Myers Squibb (BMS), Gilead, GlaxoSmithKline (GSK), Merck, Pfizer, Roche, and Tibotec. Beginning with zidovidine in 1987, all the drugs are available in the developed countries. In India, about 30 ARVs are available as generics manufactured by Aurobindo, Hyderabad, Andhra Pradesh; Cipla Limited, Goa; Emcure Pharmaceuticals, Pune, Maharashtra; Hetero Drugs, Hyderabad, Andhra Pradesh; Macleods Pharmaceuticals, Daman; Matrix Laboratories, Nashik, Maharashtra; Ranbaxy, Sirmour, Himachal Pradesh; and Strides Arcolab, Bangalore, Karnataka. The National AIDS Control Organization (NACO) set up in 1992 by the Govt. of India provides free ARVs to HIV positive patients in India since 2004. The drugs available in India include both single drugs and FDCs covering both first line and second line ARVs. Even while there are claims of stabilization of the disease load, there is still huge gap of those who require ARVs as only about 150,000 PLHA receive the ARVs from the Govt. and other sources. Access to ARVs therefore is still a cause of serious concern ever since India became fully Trade Related Aspects of Intellectual Property Rights (TRIPS)-complaint in 2005. Therefore, the Indian pharmaceutical companies cannot make generics for those for drugs introduced post-2005 due to product patent regime. Other concerns include heat stable

  7. Dabigatran for the prevention of stroke and systemic embolism in atrial fibrillation: A NICE single technology appraisal.

    Science.gov (United States)

    Faria, Rita; Spackman, Eldon; Burch, Jane; Corbacho, Belen; Todd, Derick; Pepper, Chris; Woolacott, Nerys; Palmer, Stephen

    2013-07-01

    The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of dabigatran etexilate (Boehringer Ingelheim Ltd, UK) to submit evidence for the clinical and cost-effectiveness of this drug for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF) as part of the NICE single technology appraisal process. The Centre for Reviews and Dissemination and the Centre for Health Economics at the University of York were commissioned to act as the evidence review group (ERG). This article presents a summary of the manufacturer's submission, the ERG report and the subsequent development of NICE guidance for the use of dabigatran within the UK National Health Service. Dabigatran was granted marketing authorisation by the European Medicines Agency for a sequential dosing regimen (DBG sequential), in which patients under 80 years are treated with dabigatran 150 mg twice daily (DBG150) and patients 80 years and over are given dabigatran 110 mg twice daily (DBG110). NICE decisions are bound by the marketing authorisation; therefore, the decision problem faced by the committee was whether the DBG sequential regimen was effective and cost-effective compared with warfarin or aspirin for patients with non-valvular AF and one or more risk factors. The RE-LY trial, a large multi-centre non-inferiority randomised clinical trial, was the primary source of clinical evidence. DBG150 was shown to be non-inferior, and subsequently superior to warfarin, for the primary outcome of all stroke/systemic embolism. DBG110 was found to be non-inferior to warfarin. Results were presented for a post hoc subgroup analysis for patients under and over 80 years of age, where DBG110 showed a statistically significant reduction of haemorrhagic stroke and intracranial haemorrhage in comparison to warfarin in patients over 80 years of age. This post hoc subgroup analysis by age was the basis for the licensed DBG sequential regimen

  8. Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D)

    DEFF Research Database (Denmark)

    Smith, Colette J; Ryom, Lene; Weber, Rainer;

    2014-01-01

    BACKGROUND: With the advent of effective antiretroviral treatment, the life expectancy for people with HIV is now approaching that seen in the general population. Consequently, the relative importance of other traditionally non-AIDS-related morbidities has increased. We investigated trends over t...... Ingelheim, Bristol-Myers Squibb, Gilead Sciences, ViiV Healthcare, Merck, Pfizer, F Hoffmann-La Roche, and Janssen Pharmaceuticals....

  9. Rendix的大规模临床试验开始

    Institute of Scientific and Technical Information of China (English)

    李燕燕(摘)

    2006-01-01

    Boehringer Ingelheim公司已经开始了据称是针对血栓栓塞病迄今最大规模的临床试验项目,即对其新的口服直接凝血酶抑制剂dabigatran etexilate(商品名Rendix)(Ⅰ)的试验。

  10. [The determination of the urea content in cow's milk with the help of the dry chemical system Reflotron].

    Science.gov (United States)

    Staudacher, G

    1989-01-01

    The dry chemistry laboratory unit "Reflotron" (Boehringer Mannheim) is tested for its efficacy in the determination of urea in dairy milk with the test Urea. It gives reliable results. The system is easy to handle. The storage of milk is of no influence on the level of urea.

  11. 新药临床开发、上市和应用 心脑血管系统药物:02016 FDA批准Micardis HCT

    Institute of Scientific and Technical Information of China (English)

    沈建英

    2001-01-01

    美国食品和药物管理局已批准Boehringer Ingelheim公司的Micardis HCT(Ⅰ)为高血压的二线治疗药。(Ⅰ)为含血管紧张素Ⅱ拮抗剂(telmisartan,替米沙坦)和利尿剂(HCTZ)的合剂。

  12. afatinib可改善肺癌患者的无进展生存期

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    独立的德国药物制造商BoehringerIngelheim公司在意大利米兰召开的第35届欧洲肿瘤学会会议上宣布了两项临床试验的结果,这两项试验是关于他们所研究的抗癌化合物afatinib(BIBW2992)(I)的。

  13. Boehringer公司公布RE-LY研究结果

    Institute of Scientific and Technical Information of China (English)

    朱园园

    2009-01-01

    Boehringer Ingelheim公司公布了其抗凝药Pradaxa(dabigatran etexilate)(Ⅰ)新的正性试验结果,试验数据显示与竞争对手华法林(warfarin)(Ⅱ)相比,该药物可以降低卒中的发生风险,并且不增加出血风险。

  14. 西班牙给药物剂型创新产品以补偿

    Institute of Scientific and Technical Information of China (English)

    陆颖(摘)

    2009-01-01

    西班牙将补偿Novartis公司用于治疗阿尔茨海默病的Exelon(rivastigamine)透皮贴剂(Ⅰ)和Boehringer Ingelheim公司用于初级预防静脉血栓事件的Pradaxa(dabigatran)(Ⅱ)。西班牙卫生部因为这两个药物的给药方式而给予高度评价。

  15. Micardis比其他ARB降压效果更好

    Institute of Scientific and Technical Information of China (English)

    李雅娟(摘)

    2007-01-01

    德国Boehringer Ingelheim公司称,在欧洲高血压学会年会上公布的新数据显示,Micardis(telmisartan,替米沙坦)与其他主流的血管紧张素受体阻断剂比较,能提供更优越、有效的降压效果。

  16. 05011 欧洲3~4月份批准和上市的新药/新适应症

    Institute of Scientific and Technical Information of China (English)

    刘敏

    2001-01-01

    批准新药 Boehringer Ingeheim公司的溶栓药Metalyse(tenecteplase)在欧盟获准.单次冲击剂量给药用于心机梗塞治疗。该公司准备不久在奥地利、丹麦、芬兰、德国、瑞典和荷兰推出。

  17. Effects of ecological flooding on the temporal and spatial dynamics of carabid beetles (Coleoptera, Carabidae) and springtails (Collembola) in a polder habitat.

    Science.gov (United States)

    Lessel, Tanja; Marx, Michael Thomas; Eisenbeis, Gerhard

    2011-01-01

    Within the scope of the Integrated Rhine Program an ecological flood gate and channel was inserted into the polder "Ingelheim" to enhance animal and plant diversity. In 2008, carabid beetles and springtails were collected, using pitfall traps, to measure the effects of ecological flooding and a strong precipitation event at a flood-disturbed and a dry location in this area. At both localities, xerophilic and mesophilic carabid beetle species were dominant throughout the study period. The total number of individuals of hygrophilic species was comparatively constant, while species number increased, partly due to the changed moisture conditions caused by ecological flooding and strong precipitation. Carabid beetle diversity and evenness decreased marginally when ecological flooding was absent. Springtails represent a less mobile arthropod order, and as such the impact of ecological flooding was stronger. An increase in both numbers of species and individuals of hygrophilic and hygrotolerant species occurred in the flood-disturbed location after ecological flooding. After the sites at both locations had dried, the number of individuals belonging to these species declined rapidly. In contrast to carabid species, the strong precipitation event showed no influence on hygrophilic springtail species. Thus, collembolan diversity and evenness decreased markedly in the absence of flooding. We showed that ecological flooding has an influence on the spatial and temporal dynamics of different arthropod groups that inhabit the polder "Ingelheim". These findings demonstrate the importance of using different arthropod groups as bioindicators in determining the ecological value of a particular polder design.

  18. 口服药物dabigetran与伊诺肝素同样有效

    Institute of Scientific and Technical Information of China (English)

    罗娟(摘)

    2007-01-01

    德国Boehringer Ingelheim药物公司称,RE-MODEL试验的结果显示,他们研发的新型口服抗凝血剂dabigatran etexilate(Ⅰ)有助于完成由NICE起草的预防静脉血栓栓塞(VTE)治疗指南。NICE是英国政府的顾问部门,负责评估英国和威尔士药物以及临床治疗的效果。

  19. Bayer/J&J和BI公司的房颤药物“可能产生轰动效应”

    Institute of Scientific and Technical Information of China (English)

    王吉云(; 摘)

    2007-01-01

    据美国的调查与顾问公司Decision Resources称,在未来的二十年有两种新药“可能产生轰动性效应”,主要是由于目前缺乏预防房颤患者脑卒中的更安全和更方便的药物。一个药物是rivaroxaban,由德国Bayer制药公司和美国J&J公司生产。另一个药物是德国Boehringer Ingelheim制药公司的dabigatran etexilate。

  20. 用于纯水生产的浮子流量计——浮子流量计可精确完成纯水的计量

    Institute of Scientific and Technical Information of China (English)

    Ulrich; Trager; Kay; Rickert

    2007-01-01

    浮子流量计不仅检测精度高,而且工作安全可靠,这也是Werner公司的纯水生产设备一直使用Krohne公司生产的浮于流量计的主要原因。在Werner公司为Boehringer Ingelheim公司最新生产的纯水设备中,您可以看到该流量计是如何精确完成计量任务的。

  1. DNA Methylation Alterations in Breast Cancer

    Science.gov (United States)

    2002-07-01

    EDTA buffer (1-1TE), mary tumor prostate tissues, five matched pairs of normal 5 ViL of 10 x T4 DNA ligase buffer, 1.25 giL each of and primary tumor... DNA ligase were added, and the DNA was incubated breast tissues, was used in the study. The breast and overnight at 16’C. The ligated DNA was...nanograms of Notl primer tion endonuclease Notl and T4 DNA ligase were pur- and 30 ng of Msel primer were used for PCR with chased from Boehringer Mannheim

  2. Quantitative measurement of HbA1c by an immunoturbidimetric assay compared to a standard HPLC method.

    Science.gov (United States)

    Hamwi, A; Schweiger, C R; Veitl, M; Schmid, R

    1995-07-01

    Determination of hemoglobin A1c (HbA1c) is one of the most important monitoring procedures for long-term control of diabetes mellitus. Several analytical methods have been developed for the measurement of glycohemoglobin (GHb). Those most frequently used are ion-exchange chromatography for HbA1c and affinity chromatography for total GHb. In this study, a new turbidimetric immunoassay for HbA1c (Boehringer Mannheim, Germany) was evaluated that was performed on a Hitachi 911 clinical chemistry analyzer (Boehringer Mannheim). Good linearity in the range of 5% to 15% HbA1c, within-run and between-run coefficients of variation ranging from 2.4% to 5.9% were obtained. Results of 179 diabetic and nondiabetic patients showed good correlation to those of a routine HPLC method (r = 0.96). In addition, HbA2, HbS, and HbF in samples from nondiabetic patients were not detected by the immunoturbimetric assay and the "labile" HbA1c fraction (Schiff base) did not interfere with the new test.

  3. Particle counting assay for anti-toxoplasma IgG antibodies. Comparison with four automated commercial enzyme-linked immunoassays.

    Science.gov (United States)

    Galanti, L M; Dell'Omo, J; Wanet, B; Guarin, J L; Jamart, J; Garrino, M G; Masson, P L; Cambiaso, C L

    1997-09-24

    An assay for anti-toxoplasma IgG antibodies based on agglutination of latex particles was set up and compared with commercial immunoassays. The reaction was measured by instrumental counting of particles remaining unagglutinated. The running time was 45 min. This test (PaC) was compared using 243 serum samples with four automated commercial immunoassays: the Enzymum test Toxo IgG (ES300, Boehringer), the Vidas Toxo IgG (Biomérieux), the IMX Toxo IgG (Abbott), the Magia Toxoplasma gondii IgG (Merck). The mean values (+/- SD) obtained by IMX (25 IU +/- 68) and ES300 (45 IU +/- 142) were significantly lower than the values obtained by Vidas (73 IU +/- 237, p Magia (80 IU +/- 300, p < 10(-4) and p = 0.0005) and by PaC (70 IU +/- 260, p < 10(-4) and p = 0.0126). The correlations between PaC and Toxo IgG Boehringer, Biomérieux, Abbott, Merck were r = 0.97, r = 0.98, r = 0.94, r = 0.98, respectively. The correlation coefficients between the enzyme-immunoassays ranged from 0.96 to 0.99. All positive samples by PaC were found to be positive by enzyme-immunoassays except for eight sera which were doubtful positives by the Enzymum test ToxoIgG from Boehringer. No negative sample by PaC was found positive by any of the enzyme-immunoassays. In PaC, when two latex preparations coated with different antigen were compared, the correlation was rather weak (r = 0.93) suggesting that the selection of the antigen can be critical. In conclusion, the four automated commercial immunoassays now available gave similar results. However, the discrepancies observed in this study underlined the importance of clinical and biological follow-up of the patients and the necessity to confirm the result. The introduction of a new technique such as PaC, which is now available for a large variety of assays in Clinical Chemistry and Microbiology, is justified by its intrinsic advantage of homogeneity. Therefore, automation is easy as well as the control of possible interference.

  4. 2010年美国FDA批准新药%The new drugs approved by FDA of the United States in 2010

    Institute of Scientific and Technical Information of China (English)

    马培奇

    2011-01-01

    @@ 2010年,美国FDA共批准了14个新分子实体和7个新生物制剂(表1),同时还批准了3个重要疫苗(表2).其中,Novartis公司的芬戈莫特(fingolimod/Gilenya)、Amgen公司的德诺苏单抗(denosumab/Prolia)、Boehringer Ingelheim公司的达比加曲酯(dabigatran etexilate/Pradaxa)、Pfizer公司的13价肺炎球菌结合疫苗(pneumococcal 13-valent conjugate vaccine/Prevnar 13)和Dendreon公司的治疗性前列腺癌疫苗sipuleucelT(Provenge)都极可能在日后成长成为"巨型炸弹"级的畅销药物(疫苗).

  5. 达比加群酯甲磺酸盐%dabigatran etexilate mesylate

    Institute of Scientific and Technical Information of China (English)

    张孟迪

    2011-01-01

    @@ 德国Boehringer Ingelheim公司开发的凝血酶抑制剂达比加群酯胶囊(dabigatran etexilate mesylate.商品名为Pradaxa)于2008年4月首先在德国和英国上市,2010年10月19日又获得FDA批准.用于预防人工关节置换术后并发深静脉血栓形成和肺动脉栓塞[1].达比加群酯是继华法林之后50年来首个上市的全新口服直接抗凝血药物.

  6. 盐酸度洛西汀获准用于新的适应证

    Institute of Scientific and Technical Information of China (English)

    马培奇

    2005-01-01

    据报道,由Eli Lilly和Boehringer Ingelheim公司共同开发的5-羟色胺和去甲肾上腺素的重吸收抑制剂盐酸度洛西汀(duloxetine hydrochloride,商品名Cymbalta)在先期获准用于治疗成人抑郁症之后,又于2004年春季和秋季分别被欧盟和美国FDA批准用于妇女中度至重度应激性尿失禁和成人糖尿病继发的外周神经痛的治疗。

  7. [Adverse hemodynamic changes during laparoscopic cholecystectomy and their possible suppression with clonidine premedication. Comparison with intravenous and intramuscular premedication].

    Science.gov (United States)

    Málek, J; Knor, J; Kurzová, A; Lopourová, M

    1999-06-01

    Laparoscopic cholecystectomies have adverse haemodynamic effects which limit their use in risk patients with heart disease. This applies in particular to significant hypertension. The etiology is analysed in detail in a review of the literature. The authors confirmed in their work involving 21 patients the incidence of these effects and tried to suppress them by premedication with clonidine (CATAPRESAN, Boehringer). 21 patients were given 0.15 mg clonidine in an infusion 15 minutes before operation and 21 patients 0.15 mg clonidine by the i.m. route 60-90 min. before operation. Standard anaesthesia was administered. A highly significant drop in the incidence of hypertension was recorded during operation for systolic pressure (p premedication). Premedication with intravenous clonidine can be recommended as a routine procedure before laparoscopic cholecystectomies.

  8. Comparison of serum copper determination by colorimetric and atomic absorption spectrometric methods in seven different laboratories. The S.F.B.C. (Société Française de Biologie Clinique) Trace Element Group.

    Science.gov (United States)

    Arnaud, J; Chappuis, P; Zawislak, R; Houot, O; Jaudon, M C; Bienvenu, F; Bureau, F

    1993-02-01

    An interlaboratory collaborative trial was conducted on the determination of serum copper using two different methods, based on colorimetry (test combination Copper, Boehringer Mannheim, Mannheim, Germany) and flame atomic absorption spectrometry (FAAS). The general performance of the colorimetric method was below that of FAAS, except for sensitivity and linear range, as assessed by detection limit (0.44 versus 1.32 mumol/L) and upper limit of linearity (150 versus 50 mumol/L). The range of the between-run CVs and the recovery of standard additions were, respectively, 2.3-11.9% and 92-127% for the colorimetric method and 1.1-6.0% and 93-101% for the FAAS method. Interferences were minimal with both methods. The two techniques correlated satisfactorily (the correlation coefficients ranged from 0.945-0.970 among laboratories) but the colorimetric assay exhibited slightly higher results than the FAAS method. Each method was transferable among laboratories.

  9. Graphical Synthetic Routes of Telmisartan%替米沙坦合成路线图解

    Institute of Scientific and Technical Information of China (English)

    徐桂清; 李伟; 郝二军

    2009-01-01

    @@ 替米沙坦(telmisartan,1),化学名为4'-[[1,4'-二甲基-2'-丙基(2,6'-双-1H-苯并咪唑)-1'-基]-甲基][1,1'-联苯基]-2-羧酸,由德国BoehringerIngelheim药厂开发,1999年首次在美国上市,商品名为Micardis[1,2],2001年在我国进口上市.本品是一种非肽类血管紧张素Ⅱ受体转换酶拮抗剂,可选择性阻断血管紧张素Ⅱ与AT1受体结合,从而阻断血管紧张素Ⅱ的血管收缩和醛固酮分泌作用.

  10. A GROWTH INHIBITOR SECRETED FROM CULTURED RABBIT SMOOTHMUSCLE CELLS IS DISTINCT FROM TGF-β

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To ascertain whether the growth inhibitor in conditioned medium from cultured rabbit arte rial cells is distinct from TGF-β. Methods Rabbit aortic smooth muscle ceils were grown from explained segments of the aorta. Conditioned medium from cultured rabbit aortic smooth muscle ceils and anti-TGF-β were employed in this study. Smooth muscle cell proliferation was measured by XTT detection (Boehringer Mannheim). Results Acidified conditioned medium from smooth muscle ceils had significantly stronger effects of growth inhibition than controls, and anti-TGF-β did not affect the growth inhibitory effect of conditioned medium from cultured rabbit arterial smooth muscle cells. Conclusion The growth inhibiting substance in conditioned medium from cultured rabbit aortic smooth muscle cells is distinct from TGF-β.

  11. Comparison of two dry chemistry analyzers and a wet chemistry analyzer using canine serum.

    Science.gov (United States)

    Lanevschi, Anne; Kramer, John W.

    1996-01-01

    Canine serum was used to compare seven chemistry analytes on two tabletop clinical dry chemistry analyzers, Boehringer's Reflotron and Kodak's Ektachem. Results were compared to those obtained on a wet chemistry reference analyzer, Roche Diagnostic's Cobas Mira. Analytes measured were urea nitrogen (BUN), creatinine, glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), cholesterol and bilirubin. Nine to 12 canine sera with values in the low, normal, and high range were evaluated. The correlations were acceptable for all comparisons with correlation coefficients greater than 0.98 for all analytes. Regression analysis resulted in significant differences for both tabletop analyzers when compared to the reference analyzer for cholesterol and bilirubin, and for glucose and AST on the Kodak Ektachem. Differences appeared to result from proportional systematic error occurring at high analyte concentrations.

  12. Vol. 4 in the series: Site profiles of persistent chlorinated hydrocarbons - cause-oriented monitoring in aquatic media; Pestizide aus der Reihe der persistenten chlorierten Kohlenwasserstoffe in Gewaessern der Rhein-Region - Ergebnisse nachhaltiger Steuerungen von Wirtschaft und Politik. Bd. 4 der Reihe: Standortprofile persistenter chlorierter Kohlenwasserstoffe - ursachenorientiertes Monitoring in aquatischen Medien

    Energy Technology Data Exchange (ETDEWEB)

    Heinisch, E.; Kettrup, A.; Bergheim, W.; Wenzel, S.

    2003-07-01

    Evaluating the analytical data of DDT and its metabolites, the isomers of HCH as well as (sometimes) of aldrin and dieldrin in surface water, suspended matter, eels, breams and roaches from the rivers Rhine, Neckar, Kocher, Enz, Main (upto km 360), Weschnitz, Modau, Schwarzbach, Hengstbach, Grundbach, Nidda, Rodau, Kinzig, Werra, Diemel, Lahn, Nahe, Mosel, Sauer, Saar, Ahr, Kyll, Sieg and Laacher See distance profiles (partly from Konstanz till Markermeer) and time series (partly from 1984-2001) were elaborated. The primary data come from about 15 mainly regional investigation departments, the IKSR and the Environmental Specimen Bank. The chemical enterprises in Rheinfelden, Grenzach, Ludwigshafen, Lampertheim, Gernsheim, Darmstadt, Hoechst, Kelsterbach, Offenbach, Ingelheim, Loelsdorf, Leverkusen, Elberfeld, Krefeld-Uerdingen and Huels could partly be made transparent by the course of the sDDT and sHCH values and the profiles of the constituents and isomers, resp., in the distance profiles (especially from the river Rhine) mainly from 1990/92. The corresponding graph for the year 2000 shows that there is no longer a human and ecotoxicological relevance of the compounds to be expected. (orig.)

  13. Substrate selectivity of various lipases in the esterification of cis- and trans-9-octadecenoic acid.

    Science.gov (United States)

    Borgdorf, R; Warwel, S

    1999-04-01

    The substrate selectivity of numerous commercially available lipases from microorganisms, plants and animal tissue towards 9-octadecenoic acids with respect to the cis/trans configuration of the C=C double bond was examined by the esterification of cis- and trans-9-octadecanoic acid (oleic and elaidic acid respectively) with n-butanol in n-hexane. A great number of lipases studied, e.g. those from Pseudomonas sp., porcine pancreas or Carica papaya, were unable to discriminate between the isomeric 9-octadecenoic acids. However, lipases from Candida cylindracea and Mucor miehei catalysed the esterification of oleic acid 3-4 times faster than the corresponding reaction of elaidic acid and therefore have a high preference for the cis isomer. Of all biocatalysts examined, only recombinant lipases from Candida antarctica favoured elaidic acid as substrate. While the preference of Candida antarctica lipase B for the trans isomer was quite low, Candida antarctica lipase A had an extraordinary substrate selectivity and its immobilized enzyme preparation [Chirazyme L-5 (3) from Boehringer] esterified elaidic acid about 15 times faster than oleic acid.

  14. Graphical Synthetic Routes of Dabigatran Etexilate%达比加群酯合成路线图解

    Institute of Scientific and Technical Information of China (English)

    方干; 郑永勇; 张晓培; 李建其

    2011-01-01

    达比加群酯(dabigatran etexilate,1),化学名为3-[[[2-[[[4-[[[(己氧基)羰基]氨基]亚氨甲基]苯基]氨基]甲基]-1-甲基-1H-苯并咪唑-5-基]羰基](吡啶-2-基)氨基]丙酸乙酯,由德国Boehringer Ingelheim公司研发,2008年3月经欧盟委员会批准在德国和英国上市,商品名Pradaxa,临床用于预防全髋或全膝置换术后患者的静脉血栓栓塞[1].本品是一种新型的直接凝血酶抑制剂,为达比加群的前体药物[2].1具有可口服、强效、无需特殊用药监测及药物相互作用少等优点[3-5].

  15. Applications of Cr-Based Metal Nitride Hard Coatings Using Multi-Magnetron Sputtering Sources and Elemental Metal Targets

    Institute of Scientific and Technical Information of China (English)

    ShicaiYang; EricWiemann; D.C.Teer

    2004-01-01

    Cr-based nitride hard coatings were produced by multi-magnetron sputtering sources using elemental metal materials. Cr, Ti, Mo, V, A1, and Y target materials were used for the metal sources whilst nitrogen was introduced at the same time to produce multilayer nitride hard coatings. The deposition process was optimised according to the properties of hardness, adherence and wear measured using microhardness, scratch, Rockwell indentation and pin-on-disc tests. The coatings were deposited onto hard metal carbide as well as high speed steel cutting tools such as inserts and drills. The coated inserts were tested on a wide range of difficult to machine materials using a Boehringer VDF180-C CNC lathe. The machining was performed under interrupted cutting conditions and the results were compared with those obtained using an advanced commercially available TiA1N coating. The coated carbide drills were tested under dry conditions to cut hard alloy steel and the coated tool steel drills were tested under lubricant conditions to cut carbon steel with comparing the similar tests on commercial TiN coatings. These test results were compared with those from drills coated with a commercial TiN.

  16. COX-2选择性抑制剂在关节炎治疗上受到限制

    Institute of Scientific and Technical Information of China (English)

    孙峰

    2004-01-01

    National Institute for Excellence(NICE)根据英国卫生部(Nationai Health Service in Englandand Wales)的意见向消费者建议:COX-2选择性抑制剂不应该作为治疗类风湿性关节炎(PA)和骨关节炎(OA)的常规处方药。法玛西亚/辉瑞公司的Celebrex(celecoxib)、默克公司的Vioxx(rofecoxib)、美国家用产品公司的Lodine SR(etodolac)、Boehringer lngelheim公司的Mobic(meloxicam)只能被用来替代非甾体抗炎药(NSAID)治疗那些正患有严重胃肠道疾病(GI)的、可能是高危(HR)的RA或者OA患者。NICE还把高危病人定义为那些年龄在65周岁或者65周岁以上的、已经在服用其它能够引起GI症状药物的病人以及那些一直存在GI症状的病人。

  17. Biological function of modified nucleotides T54 and ψ55 of yeast tRNAAla

    Institute of Scientific and Technical Information of China (English)

    蒋华琦; 金由辛; 王德宝

    1997-01-01

    The 3’ half molecule of yeast tRNAAla (nucleotides 36-75) was hybridized with a DNA fragment (5’GGAATCGAACC 3’) and the hybrid was then digested with E. coli RNase H (from Boehringer). The enzyme can specifically cleave the 3’ half molecule at the 3’ side of nucleotide ψ55, thus a fragment C36-ψ55 was prepared. The 3’-terminal T or Tψ of this fragment was removed by one or two cycles of periodate oxidation and $-elimination. The products were fragments C36-T54 and C36-G53. Three yeast tRNAAla fragments C56-A76, U55-A76 (with ψ55 replaced by U), U54-A76 (with T54ψ55 replaced by UU) were synthesized and ligated with three prepared fragments (C36-ψ55 C36-T54 and C36-G53) respectively by T4 RNA ligase. The products were further ligated with the 5’ half molecule (nu-cleotides 1-35). Using this method, one reconstituted yeast tRNAAla (tRNAr) and two yeast tRNAAla analogs: (i) tRNAa with U55 instead of ψ55; (ii) tRNAb with U54U55 instead of T54ψ55 were synthesized. The charging and incorporation activi

  18. Fozivudine: BM 211290, fozivudine tidoxil, FZT, HDP 990002, W 09726867.

    Science.gov (United States)

    2004-01-01

    Fozivudine [BM 211290, fozivudine tidoxil, FZT, HDP 990002, W 09726867] is a thioether lipid conjugate of zidovudine (AZT) in clinical development with Heidelberg Pharma Holdings for the potential treatment of HIV infection. Heidelberg Pharma's proprietary Linker-Cleavag-Enzyme Technology (LCE_Technology) is used to conjugate specific carriers to parent compounds, significantly improving their pharmacological, toxicological and/or clinical profile. LCE_Technology was originated at Boehringer Mannheim, which was acquired by, and integrated into, Roche. In 1999, when Heidelberg Pharma was founded, following a management buy-out from Roche Diagnostics GmbH, the new company acquired full ownership of the intellectual property and documentation related to various proprietary compounds, the LCE_Technology and its applications. According to Heidelberg Pharma's pipeline, published in August 2003, the product candidate, HDP 99.0002 (the company-specific code for fozivudine) will be in phase III development until early 2006, at which time the company hopes to file an NDA. A phase II study of fozivudine in 72 antiretroviral-naive patients with HIV infection was completed in the US and France by Roche.

  19. Peroxidase-coupled method for kinetic colorimetry of total creatine kinase activity in serum.

    Science.gov (United States)

    Wimmer, M C; Artiss, J D; Zak, B

    1985-10-01

    We describe a peroxidase-coupled method involving a colorimetric indicator reaction for determining the total activity of creatine kinase (EC 2.7.3.2) in serum. The kinetically favorable reverse reaction is exploited to generate adenosine 5'-triphosphate, which is used in the glycerol kinase-catalyzed phosphorylation of glycerol. The glycerol 3-phosphate so generated is oxidized in the presence of alpha-glycerophosphate oxidase to produce hydrogen peroxide, which is reduced in the presence of peroxidase with the simultaneous oxidation and coupling of 4-aminoantipyrene and 2-hydroxy-3,5-dichlorobenzenesulfonate to produce an intensely colored red chromogen. Results of the proposed method (y) correlate well with those of the Boehringer-Mannheim "CK-NAC UV" method as applied to the Hitachi 705 chemistry analyzer (y = 1.025 chi - 18.1, r = 0.9985, n = 100, range = 19-4531 U/L). The sensitivity of the method, based on molar absorptivities, is nearly fourfold that of procedures involving the reduction of NADP+.

  20. Chromosomal DNA probes for the identification of asaccharolytic anaerobic pigmented bacterial rods from the oral cavity of cats.

    Science.gov (United States)

    Love, D N; Bailey, G D; Bastin, D

    1992-06-01

    A dot-blot hybridisation assay using isolated high molecular weight DNA as whole chromosomal probes of the cat pigmented asaccharolytic Bacteroides/Porphyromonas species was used against both purified high molecular weight DNA and DNA released on membranes from whole cells for the identification of B. salivosus and for its differentiation from the other anaerobic species isolated from normal and diseased mouths of cats and horses. 32P-labelled probes were compared with digoxigenin (DIG)-labelled probes (Boehringer-Mannheim). The whole chromosomal probes were specific--differentiating B. salivosus from a variety of species (including members of the genera Bacteroides, Fusobacterium, Eubacterium, and Prevotella) found in normal and abnormal mouths of cats and horses. Likewise, asaccharolytic black pigmented Group 2 strains were distinguishable from all strains tested. However, cat strains of P. gingivalis which show 68-76% DNA-DNA homology with human strain P. gingivalis ATCC 33277T, were not distinguishable from each other using either 32P-labelled or DIG-labelled probes. The minimum amount of pure Bacteroides DNA which could be detected by the 32P-labelled probe was 100-300 pg, while the amount of pure DNA detected by the DIG system was 1-3 mg after room temperature colour development for 1 h and 100-300 pg after 6 h colour development.

  1. Applications of Cr-Based Metal Nitride Hard Coatings Using Multi-Magnetron Sputtering Sources and Elemental Metal Targets

    Institute of Scientific and Technical Information of China (English)

    Shicai Yang; Eric Wiemann; D.G. Teer

    2004-01-01

    Cr-based nitride hard coatings were produced by multi-magnetron sputtering sources using elemental metal materials. Cr, Ti, Mo, V, Al, and Y target materials were used for the metal sources whilst nitrogen was introduced at the same time to produce multilayer nitride hard coatings. The deposition process was optimised according to the properties of hardness, adherence and wear measured using microhardness, scratch, Rockwell indentation and pin-on-disc tests. The coatings were deposited onto hard metal carbide as well as high speed steel cutting tools such as inserts and drills. The coated inserts were tested on a wide range of difficult to machine materials using a Boehringer VDF180-C CNC lathe. The machining was performed under interrupted cutting conditions and the results were compared with those obtained using an advanced commercially available TiA1N coating. The coated carbide drills were tested under dry conditions to cut hard alloy steel and the coated tool steel drills were tested under lubricant conditions to cut carbon steel with comparing the similar tests on commercial TiN coatings. These test results were compared with those from drills coated with a commercial TiN.

  2. Incretinas, incretinomiméticos, inhibidores de DPP IV: (2ª parte Incretins, Incretinmimetics, Inhibitors (2nd part

    Directory of Open Access Journals (Sweden)

    Claudia Bayón

    2010-09-01

    Full Text Available En los últimos años se reconoce un nuevo mecanismo involucrado en la fisiopatología de la Diabetes Mellitus tipo 2: el déficit de producción y/o acción de las incretinas. Las incretinas son enterohormonas que estimulan la secreción de insulina en respuesta a la ingesta de nutrientes. Glucagon like peptide-1 (GLP1 y Polipéptido insulinotrópico glucosa dependiente (GIP son las principales incretinas descubiertas hasta hoy. Ambas presentan también efecto trófico sobre las células beta de los islotes pancreáticos. GLP-1 presenta otras acciones como son la inhibición de la secreción de glucagón, enlentecimiento del vaciamiento gástrico e inhibición del apetito. Ambas incretinas son rápidamente clivadas por la enzima dipeptidil peptidasa 4 (DPP-4. Nuevas drogas como los incretinomiméticos, análogos y los inhibidores de DPP-4 se presentan como una terapéutica prometedora para los pacientes con diabetes tipo 2. Conflicto de intereses: Dr. León Litwak - Miembro del Board Latinoamericano de Eli Lilly y Sanofi Aventis - Miembro del Board Nacional de los laboratorios Novo Nordisk, Novartis, GlaxoSmithKline, Sanofi Aventis, Boheringer Ingelheim, Bristol Myers, Astra Zeneca - Investigador principal de protocolos pertenecientes a Eli Lilly, Novo Nordisk, Novartis, GlaxoSmithKline, Takeda, PPDF, Pfizer, Merck Sharp and Dôhme, Amger, Roche, Minimed, Quintiles - Conferencista de los laboratorios mencionados.Two main pathophysiological mechanisms are currently involved in Type 2 Diabetes (T2DM, insulin resistance and impairment of beta cell function. However, in recent years a new mechanism was reported: a significant decrease in incretins production and/or action. Incretins are gastrointestinal hormones whose main action is stimulating insulin secretion in response to nutrients. The best known incretins are glucagon like peptide-1 (GLP-1 and Gastric insulinotropic peptide (GIP. GLP-1 and GIP not only increase insulin secretion, but also

  3. Effects of balneotherapy on the reactants of acute inflammation phase in Ankylosing spondylitis

    Directory of Open Access Journals (Sweden)

    Stamenković Bojana

    2009-01-01

    Full Text Available Introduction. Ankylosing spondylitis (AS is a chronic inflammatory disease that affects sacroiliac joints, spinal column and peripheral joints. Beside medication therapy, physical and balneotherapy play an important role in its complex treatment. Objective. The aim of the research was to establish serum concentrations of C-reactive protein (CRP, α 1-acid glycoprotein (α 1-AGP, ceruloplasmine (CP and erythrocyte sedimentation rate (SE before and after the balneotherapy in ankylosing spondylitis. Methods. The research included 50 AS patients according to the revised New York criteria, of mean age 43 years, who were treated for 14 days on the average at the Clinic for Rheumatology of the Institute 'Niška Banja'. All the patients received medications and balneotherapy (radioactive oligomineral baths, peloid, massage, kinesitherapy; the serum concentrations of CRP, α1-AGP, CP and SE were measured before and after balneotherapy. Serum proteins were determined using original Nor Partigen plates Boehringer. Erythrocyte sedimentation rate was measured by Westergreen method. Balneotherapy was applied individually, intensively or mildly, depending on the AS stage and activity phase. Results. After dosed balneotherapy, a significant decrease in the concentrations of CP (p<0.05, α1-AGP (p<0.01 and CRP (p<0.05 was registered in the serums of AS patients. ESR was not significantly reduced. Conclusion. The research proved that α 1-acid glycoprotein, ceruloplasmine and C-reactive protein represent more sensitive inflammation markers as compared to erythrocyte sedimentation rate. The identification of acute phase reactants is important in the evaluation of dosed balneotherapy efficiency in the treatment of ankylosing spondylitis.

  4. 美洛昔康的合成%Synthesis of Meloxicam

    Institute of Scientific and Technical Information of China (English)

    黄爱军; 张立颖

    2000-01-01

    @@ 美洛昔康(meloxicam,1),化学名4-羟基-2-甲基-N-(5-甲基-2-噻唑基)-2H-1,2-苯并噻嗪-3-甲酰胺1,1-二氧化物,是德国Boehringer Ingelheim公司开发的一种烯醇酸非甾体抗炎药[1].1996年首次在南非上市.它能选择性地抑制环氧合酶-2(COX-2),具有显著而持久的抗炎作用和一定的镇痛、解热作用.其作用强于目前常用的NSAID如吡咯昔康、双氯芬酸钠、吲哚美辛、萘普生,而剂量却低得多,且对胃肠道的损伤很小.因此,1是一个疗效好、副作用少、药动学优良、服用方便的新型NSAID,主要用于治疗骨关节炎和风湿性关节炎[2].国内已有进口,但未见生产.文献[3]报道1是由4-羟基-2-甲基-2H-1,2-苯并噻嗪-3-羧酸乙酯1,1-二氧化物(2)和2-氨基-5-

  5. Kidney Function Indices in Mice after Long Intake of Agaricus brasiliensis Mycelia (=Agaricus blazei, Agaricus subrufescens Produced by Solid State Cultivation

    Directory of Open Access Journals (Sweden)

    Dalla S. O. Roberto

    2009-01-01

    Full Text Available Problem statement: Agaricus brasiliensis (=Agaricus blazei, Agaricus subrufescens or Sun mushroom has widespread use for potential health benefits such anti-tumor and immunomodulatory effects. Studies detected that others edible mushrooms affected renal metabolism and despite the widespread use of A. brasiliensis there are no studies that address biological effects on the renal function indices after their oral administration. Therefore, this study had as objective to verify the effects on kidney function indices after long intake of A. brasiliensis mycelium. Approach: Wheat grains was cultured during 18 days with Agaricus brasiliensis mycelium by solid state culture and used for chown formulation. Groups of female Swiss mice (20 per group were fed during 14 weeks with 100 and 50% of the formulated feed denominated A100 and A50, respectively. Control group received formulated chown with wheat grains without mycelium. The water intake and excreted urine volume; the physic chemistry analysis of the urine and the serum levels of glucose, proteins, urea, creatinin and uric acid was determined (Meditron Junior-Boehringer, reagent strips Combur 10; microscopy and ADVIA 1650 Bayer. Results: A100 and A50 groups ingested 19.1 and 15.8% more water compared to C group, respectively. The urine and serum analysis showed that the verified parameters remained invariables for all groups, including glucose levels, which resulted in a 10% reduction of A100 group, without statistical difference (p>0.05 Vs C. Conclusion/Recommendations: The prolonged intake of supplemented feed with A. brasiliensis mycelium didn’t result in indicative alterations in the kidney function indices. The preventive use of the mushroom did not show any deleterious effects on kidney; however complementary studies are necessary to guarantee complete safety; possible correlation between increase of urinary excretion and hypotensive effect

  6. Capillary blood glucose screening for gestational diabetes: a preliminary investigation.

    Science.gov (United States)

    Landon, M B; Cembrowski, G S; Gabbe, S G

    1986-10-01

    Home glucose monitoring with the use of reflectance meters is an important adjunct in the care of pregnant women with insulin-dependent diabetes. The accuracy of reflectance meters for the assay of capillary glucose specimens has been well documented. The present preliminary study was undertaken to determine the utility of outpatient screening for gestational diabetes mellitus with the use of a reflectance meter (Accu-Chek, Boehringer Mannheim Co.). One hundred twenty-five patients in our high-risk practice had a standard 50 gm glucose load at 26 to 28 weeks' gestation. Capillary glucose values were measured on site with the Accu-Chek. Venous plasma glucose levels were measured by the central laboratory chemistry analyzer. While the laboratory (x) and meter (y) glucose determinations between the two sets of values were highly correlated (R = 0.89, p less than 0.001), there was a significant difference in their average values (x = 111.74, y = 136.35, p less than 0.0001). With the use of a receiver operator characteristic curve, a meter value of 160 mg/dl was determined as the optimal threshold for performing a 3-hour glucose tolerance test. The sensitivity and specificity with the use of a meter value of 160 mg/dl were 93% and 96%, respectively, for detecting an abnormal screening test in venous plasma (greater than or equal to 135 mg/dl). A total of 32 glucose tolerance tests were performed, with four patients included who had venous values less than 135 mg/dl. All eight patients with gestational diabetes mellitus were correctly identified. These data suggest that a glucose reflectance meter can be used for accurate outpatient screening of gestational diabetes mellitus. The potential advantages of capillary blood glucose screening include both cost and efficiency. Patients with abnormal screening values can be promptly identified and scheduled for a follow-up 3-hour glucose tolerance test.

  7. Effect of the hemoglobin-based oxygen carrier HBOC-201 on laboratory instrumentation: cobas integra, chiron blood gas analyzer 840, Sysmex SE-9000 and BCT.

    Science.gov (United States)

    Wolthuis, A; Peek, D; Scholten, R; Moreira, P; Gawryl, M; Clark, T; Westerhuis, L

    1999-01-01

    As part of a clinical trial, we evaluated the effects of the hemoglobin-based oxygen-carrier (HBOC) HBOC-201 (an ultrapurified, stroma-free bovine hemoglobin product, Biopure, Cambridge, MA, USA) on our routine clinical chemistry analyzer (Cobas Integra, F. Hoffmann-La Roche Ltd, Basel, Switzerland ), blood gas analyzer (Chiron 840, Chiron Diagnostics Corporation, East Walpole, MA, USA), routine hemocytometry analyzer (Sysmex SE-9000, TOA Medical Electronics Co Ltd., Kobe, Japan), hemostasis analyzer (BCT, Dade-Behring, Marburg, Germany) and bloodbanking system (Dia-Med-ID Micro Typing System, DiaMed AG, Cressier, Switzerland). The maximum tested concentration of HBOC-201 was 65 g/l. Of the 27 routine clinical chemistry tests challenged with HBOC-201, bilirubin-direct, creatine kinase MB-fraction (CK-MB), creatine kinase (CK), gamma-glutamyltransferase (GGT), magnesium and uric acid were influenced by even low concentrations of HBOC-201. These tests were excluded from use on the plasma of patients treated with HBOC-201. Since the non-availability of the cardiac marker CK-MB may lead to problems in acute situations, we introduced the qualitative Trop T-test (Boehringer Mannheim), which was not influenced. The applicability of another nine tests was limited by the concentration of the HBOC-201 in the patients' plasma. No interference of HBOC-201 in routine hemocytometry, hemostasis-analysis and red-blood cell agglutination detection (blood-bank tests) was observed. Although immediate patient-care was not compromised, routine use of hemoglobin-based oxygen carriers will have a strong impact on logistical management. The development of robust laboratory tests free from the interference of the pigmented oxygen carriers should therefore precede its introduction into routine transfusion medicine.

  8. Evaluation and interference study of hemoglobin A1c measured by turbidimetric inhibition immunoassay.

    Science.gov (United States)

    Chang, J; Hoke, C; Ettinger, B; Penerian, G

    1998-03-01

    The technical performance of the turbidimetric immunoinhibition (TI) assay for hemoglobin (Hb) A1c (Tina-quant Hb A1c, Boehringer Mannheim, Indianapolis, Ind) was evaluated by using the BM/Hitachi 911 analyzer. Intra-assay imprecision was less than 2.7%, and interassay imprecision was less than 2.8% as measured by coefficient of variation. In 93 subjects with diabetes who did not have hemoglobin variants, results of the TI assay for Hb A1c correlated strongly with those obtained by using a high-performance liquid chromatography analyzer (Diamat, BioRad Laboratories, Hercules, Calif). Among 241 subjects who had or did not have hemoglobin variants, the TI assay for Hb A1c correlated strongly with results of affinity chromatography for total glycated hemoglobin (Glyc-Affin GHb, IsoLab, Akron, Ohio). We also studied the effect of various percentages of hemoglobin S, C, E, and F on the accuracy of the TI Hb A1c assay. Only high hemoglobin F percentages caused interference. More than 14 times as many samples can be analyzed per hour by using the TI Hb A1c assay than can be analyzed by using the HPLC assay. For high-volume reference laboratories, using the fully automated TI Hb A1c assay to monitor glycemic control in patients with diabetes may be preferable to using the conventional ion-exchange high-performance liquid chromatography Hb A1c assay because the TI assay measures Hb A1c more accurately in patients with diabetes who have hemoglobin variants, and it requires less time.

  9. The dynamics of blood biochemical parameters in cosmonauts during long-term space flights

    Science.gov (United States)

    Markin, Andrei; Strogonova, Lubov; Balashov, Oleg; Polyakov, Valery; Tigner, Timoty

    Most of the previously obtained data on cosmonauts' metabolic state concerned certain stages of the postflight period. In this connection, all conclusions, as to metabolism peculiarities during the space flight, were to a large extent probabilistic. The purpose of this work was study of metabolism characteristics in cosmonauts directly during long-term space flights. In the capillary blood samples taken from a finger, by "Reflotron IV" biochemical analyzer, "Boehringer Mannheim" GmbH, Germany, adapted to weightlessness environments, the activity of GOT, GPT, CK, gamma-GT, total and pancreatic amylase, as well as concentration of hemoglobin, glucose, total bilirubin, uric acid, urea, creatinine, total, HDL- and LDL cholesterol, triglycerides had been determined. HDL/LDL-cholesterol ratio also was computed. The crewmembers of 6 main missions to the "Mir" orbital station, a total of 17 cosmonauts, were examined. Biochemical tests were carryed out 30-60 days before lounch, and in the flights different stages between the 25-th and the 423-rd days of flights. In cosmonauts during space flight had been found tendency to increase, in compare with basal level, GOT, GPT, total amylase activity, glucose and total cholesterol concentration, and tendency to decrease of CK activity, hemoglobin, HDL-cholesterol concentration, and HDL/LDL — cholesterol ratio. Some definite trends in variations of other determined biochemical parameters had not been found. The same trends of mentioned biochemical parameters alterations observed in majority of tested cosmonauts, allows to suppose existence of connection between noted metabolic alterations with influence of space flight conditions upon cosmonaut's body. Variations of other studied blood biochemical parameters depends on, probably, pure individual causes.

  10. Effects of p53 overexpression on neoplastic cell pro-liferation and apoptosis in thymic carcinoma

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To investigate p53 overexpression and its correlation with neoplastic cell proliferation and apoptosis in 20 thymic carcinomas. Methods: 20 surgical samples of thymic carcinoma were collected randomly during the past 15 years in the Guangzhou area. Immunohistochemical staining was performed using LSAB method with anti-p53 monoclonal antibody (DO-7) and proliferating cell nuclear antigen (clone PC 10) as primary antibodies. The p53 index was indicated by the number of p53 positive cells among 100 carcinoma cells. More than 25 percentage of p53 positive cells found in tissue sections was recognized as p53 overexpression. Carcinoma cell proliferation activity was assayed by PCNA index (PI), and apoptosis degree was evaluated by TUNEL (TdT-mediated dUTP-X nick end labeling) index (TI) using Boehringer Mannheim In Situ Death Detection Kit. Results: P53 positive cells could be found in vast majority of thymic carcinomas (19/20) and the overexpression rate reached 35% (7/20). The median PI (40%) of 7 cases with p53 overexpression was higher than that (31%) of 13 cases without p53 overexpression, but there was no statistical significance that existed between these two data (P>0.05). The median TI (0.5/HPF) of 7 p53 overexpression cases was much lower than that (4.5/HPF) of 13 non-overexpression cases, and there was a significant difference statistically (P<0.05). Conclusion: p53 expression was a frequent finding in thymic carcinoma cells, and the p53 overexpression which might represent p53 inactivation or gene mutation was often involved in thymic carcino-genesis. The median PCNA index of p53 overexpression group was higher than that of non-overexpression group though there existed no statistical difference. This indicates that the inhibiting function of p53 on cell proliferation seemed lost in p53 overexpressed thymic carcinomas. It is worthy to be specially mentioned that the inducing function of p53 on cell apoptosis was markedly lost in p53 overexpressed thymic

  11. Estudo da correlação entre a velocidade de reação motora e o lactato sanguíneo, em diferentes tempos de luta no judô Estudio de la correlación entre la velocidad de reacción motora y el lactato sanguíneo en distintos tiempos de lucha en el judo Study of the correlation between the velocity of motor reaction and blood lactate in different times of combat in judo

    Directory of Open Access Journals (Sweden)

    Elessandro Váguino de Lima

    2004-10-01

    Full Text Available A velocidade de reação motora humana ou tempo de reação (TR é uma capacidade física importante para judocas, sendo observada na reação aos ataques ou pegadas do adversário, a fim de realizar um contragolpe ou uma esquiva. Durante uma luta de alta intensidade, há um aumento considerável na concentração de lactato sanguíneo (LS, relacionado à fadiga muscular, podendo interferir na capacidade de reação do atleta. Fisiologicamente, a fadiga pode ocorrer em diferentes níveis, desde a percepção do sinal externo, até a contração muscular. O objetivo deste trabalho foi de verificar a influência das concentração do LS, após estímulo de luta (Randori de 1min e 30s, 3min e 5min, no TR em atletas de judô de alto nível. Foram analisados 11 indivíduos masculinos, competidores, saudáveis, com idade média de 23,4 anos ± 2 anos. Para o registro do TR simples foi utilizado o sistema Cybex Reactor. Para os registros do LS foi utilizado um lactímetro Accusport®, com fitas Boehringer Mannheim®. A análise da variância (Kruskal-Wallis mostrou diferença significativa entre o LS antes e após a luta (p 0,05. Conclui-se que a concentração de LS não influencia a capacidade dos atletas de reagir rapidamente ao estímulo visual, mas faz com que haja uma diminuição na eficiência na tarefa de TR, provavelmente devido a diminuição na capacidade de concentração dos atletas de judô após condição fatigante de luta.La velocidad de reacción motora humana o el tiempo de reacción (TR es una capacidad física importante para luchadores de judo que se observa en la reacción a los ataques o golpes del adversario con contragolpeos o esquivos. Durante una lucha de alta intensidad, hay un aumento considerable en la concentración de lactato sanguíneo (LS que se relaciona a la fatiga muscular, pudiendo interferir con la capacidad de reacción del atleta. En términos fisiológicos, la fatiga puede ocurrir en niveles diferentes, desde

  12. Tianeptine pretreatment for the neurotoxity of methamphetamine%噻萘普汀预处理对甲基苯丙胺神经毒性的影响

    Institute of Scientific and Technical Information of China (English)

    王雪; 黄明生; 李静; 孙学礼; 康林; 李素霞; 周家秀

    2005-01-01

    BACKGROUND: Methamphetamine (MA) has neurotoxic effects to central nervous system. However, as the 5-hydroxytryplamine reuptake enhancer, it is uncertain that if there are protective effects of tianeptine to the damages of 5-hydroxytryp-taminergic neurons caused by MA.OBJECTIVE: To investigate the neurotoxicity of MA and the neuroprotective effects of tianeptine as well as the acting mechanism.DESIGN: Randomized case control study based on animals.SETTING: Animal research room and pathology research room of a university.MATERIALS: The experiment was completed in the Experimental Animal Centre of Sichuan University and Molecular Pathology Laboratory of West China Hospital during June to August 2003. Totally 25 male Wistar rats were injected MA through abdominal cavity to build model. Methamphetamine was provided by National Institute for the Control of Pharmaceutical and Biological Products(NICPBP) while tianeptine was given by French Servier Company (Batch No. OE3086). The TUNEL testing kit was purchased from Boehringer Mannheim Company.INTERVENTIONS: There were one control group and four experimental groups(A, B, C, D). A group was used intraperitoneal injection of MA while B, C, D, groups were administered tianeptine 7 days, 4 days before and the same day of MA administration. Normal saline with same volume was injected into rats of control group. HE stain and silver stain were conducted after experiment to observe the morphologic changes of neurons. And TUNEL method was used to detect apoptotic cells.MAIN OUTCOME MEASURES: The HE stain and silver stain of brain tissue sections and counts of TUNEL positive neurons.RESULTS: MA could damage the axon and dendrite of neurons and the absorbance of silver positive cell was(50.74 ± 1.86) . It could also induce cell apoptosis while the apoptotic cell count every high power field was 29.26 ±4. 14. There were less apoptotic cells in the group with 7 days usage of tianeptine with the cell count of( 18.90 ± 1.60) per high

  13. CLINICAL SIGNIFICANCE OF URINARY ALBUMIN AND URINARY β-2 MICROGLOBULIN IN ORGANOPHOSPHATE POISONING%有机磷中毒患者尿白蛋白和尿β-2微球蛋白的临床意义

    Institute of Scientific and Technical Information of China (English)

    刘拴虎; 王志祥; 王春霞; 刘雅丽

    2011-01-01

    [目的]探讨检测有机磷中毒患者尿白蛋白和尿β-2微球蛋白的临床意义.[方法]选择某院2008年1月~2010年11月收治的35例有机磷中毒患者作为研究对象,另选正常健康体检者30例作为对照组,β2-MG检测使用美国雅培公司提供的AXSYM化学发光仪,采用微粒子酶免(MEIA)法进行检测.尿白蛋白检测采用黄金标记目测免疫测定法,使用德国宝灵曼公司生产的尿微白蛋白试条(Micral-TestⅡ)进行测定.[结果]中毒后1 d检测两组患者的尿白蛋白和尿β2微球蛋白的含量发现,尿β微球蛋白、尿白蛋白含量均较正常对照组升高明显(P﹤0.05,P﹤0.01),且随着中毒程度的加重,尿β微球蛋白、尿白蛋白含量增高更明显(P﹤0.05).有机磷中毒患者血清CK、CK-MB、LDH及cTnI均明显高于正常对照组(P﹤0.05).[结论]联合检测有机磷中毒患者的尿白蛋白和尿β2微球蛋白,及同时检测心肌酶谱与肌钙蛋白,有助于早期发现肾损害及中毒程度,提高抢救成功率和判断预后.%[Objective]To investigate the detection of urinary albumin in patients with organophosphate poisoning and urinary β-2 microglobulin in clinical significance.[Methods]35 cases with organophosphate poisoning in our hospital in January 2008-November 2010 were treated as a research subjects, chose another 30 cases of normal healthy volunteers as control group, β2-MG was detected using Abbott's AXSYM chemical companies chemiluminescence, using microparticle enzyme immunoassay (MEIA) method for testing.Urinary albumin detected by gold labeled visual immunoassay, using the German company Boehringer Mannheim urine microalbumin test strip (Micral-Test Ⅱ ) to determine.[Results]1d after poisoning, urinary albumin and urinary β2-microglobulin levels were detected in patients, which found that urinary β-microglobulin, urine albumin levels increased significantly comparing with normal control group (P < 0.05, P < 0.01), and

  14. A 90 minute soccer match decreases triglyceride and low density lipoprotein but not high-density lipoprotein and cholesterol levels

    Directory of Open Access Journals (Sweden)

    Nader - Rahnama

    2009-11-01

    Full Text Available

    • BACKGROUND: The association between the lipid profiles level and the incidence and severity of coronary heart disease (CHD is very pronounced in epidemiological studies, and an inverse relation between physical fitness and the incidence of coronary heart disease has been observed in many studies. The aim of this study was to investigate the impact of a soccer match on lipid parameters of professional soccer players.
    • METHODS: Twenty two professional soccer players participated in the study. Blood (10ml for determination of lipid profiles was obtained at rest and immediately after a 90 minute soccer match. Lipid parameters were measured using Boehringer Mannheim kits and Clinilab and BioMerieux analyser.
    • RESULTS: The results of this study showed that the triglyceride was significantly higher before the match than afterwards (159.09 ± 58.2 vs. 88.63 ± 34.1 mg/dl, p < 0.001, whereas the low-density lipoprotein (LDL was lower before the match than after it (98.04 ± 28.9 vs. 112.31 ± 30.5 mg/dl. Moreover, there were no significant differences in cholesterol concentration (171.4 ± 30.28 mg/dl vs. 173.18 ± 32.75 mg/dl and high-density lipoprotein (HDL concentration (34.04 ± 5.58 mg/dl vs. 34.4 ± 4.6 mg/dl between before and after the match.
    • CONCLUSIONS: Although the soccer competitive match has no favourable acute effect on lipid

    • ROSAT Discovers Unique, Distant Cluster of Galaxies

      Science.gov (United States)

      1995-06-01

      measured (by obtaining spectra of the arcs and measuring their redshift). The masses of galaxy clusters are important for the determination, for instance of the mean density and distribution of matter in the universe. This is because these clusters are the most massive, clearly defined objects known and as such trace these parameters in the universe on very large scales. Another possibility to derive the cluster mass is offered by X-ray observations, because the distribution of the hot, X-ray emitting gas traces the gravitational field of the cluster. Recently, in some clusters there has been a discrepancy between the mass determined in this way and that found from gravitational lensing effects. The team of astronomers now hopes that follow-up X-ray observations of RXJ1347.5-1145 will help to solve this puzzle. Moreover, the combination of extremely high X-ray brightness and the possibility to perform a rather accurate mass determination by the gravitational lensing effect makes this particular cluster a truly unique object. In view of the exceptional X-ray brightness, a very high mass is expected. The exact determination will be possible, as soon as spectra have been obtained of the two arcs. Contrary to what is the case in other clusters, this will not be so difficult, due to their unusual brightness and their ideal geometrical configuration. [1] This is a joint Press Release of ESO and the Max-Planck-Society. It is accompanied by a B/W photo. [2] The investigation described in this Press Release is the subject of a Letter to the Editor which will soon appear in the European journal Astronomy & Astrophysics, with the following authors: Sabine Schindler (Max-Planck-Institut fuer Extraterrestrische Physik and Max-Planck-Institut fuer Astrophysik, Garching, Germany), Hans Boehringer, Doris M. Neumann and Ulrich G. Briel (Max-Planck-Institut fuer Extraterrestrische Physik, Garching, Germany), Luigi Guzzo (Osservatorio Astronomico di Brera, Merate, Italy), Guido Chincarini

    • 抗地高辛Fab片段治疗时监测未结合地高辛——一种未来的治疗药物监测新模式

      Institute of Scientific and Technical Information of China (English)

      Valdes,R; Jr,; 郭玮; 等

      2001-01-01

      @@地高辛是能被解除毒性的少数治疗药物之一。用抗地高辛Fab片段成功地治疗因服用地高辛过量而造成的毒性作用已超过20年。用木瓜蛋白酶裂解绵羊地高辛特异抗体IgG,产生两个地高辛特异的Fab片段(每个50 000 000)和一个50 000 000的Fc片段。平衡透析后测定上述处理过的Fab片段,测得其结合地高辛的内源性亲和常数为1010 L/mol。在一定实验条件(一定的K+浓度和膜分离的类型)下,地高辛与其受体(钠泵)结合的亲和常数为106~108 L/mol。Fab片段与地高辛的亲和力比钠泵更高,这是使用Fab片段来减少地高辛毒性作用的理论基础。使用Fab片段后,细胞外未与受体结合的地高辛浓度有所下降,这时由于胞内外的平衡作用,与受体结合的地高辛最终与受体解离并释放至细胞外。尽管毛地黄毒甙与Fab片段结合的亲和力比地高辛低10倍,毛地黄毒甙中毒时使用Fab片段也足以发挥临床功效。 临床上运用Fab片段的剂量必须与体内总的地高辛量大致上等摩尔,而了解地高辛量可通过检测血清地高辛浓度或进一步了解病人用药情况。Glaxo Wellcome公司的Digibind是美国及世界各地的抗地高辛Fab片段最常用的药品商标。Boehringer-Mannheim公司也生产解毒用的抗地高辛Fab片段。抗地高辛Fab片段也已作为因过量服用其他地高辛属如夹竹桃甙、含蟾蜍二烯羟酸内酯的催欲药、毛地黄毒甙和洋地黄提取物等药物时的解毒药。抗地高辛Fab片段还成功地用于治疗由血中地高辛样免疫反应因子增高引起的高血压。在90%的洋地黄中毒的病人中,用Digibind治疗达到最佳疗效时间的中位数为19 min。由洋地黄中毒引起的高血钾也可通过应用Fab片段而使血钾下降。 Fab片段在体内的分布为0.4 L/kg,半衰期为16~20 h,体内清除率为0.324 ml*min-1*kg-1。肾脏和肾外组织(