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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. 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.

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

    OpenAIRE

    Marx, Michael T.; Weirich, Oliver; Eisenbeis, Gerhard

    2010-01-01

    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 ...

  4. The inherent dangers of using computable general equilibrium models as a single integrated modelling framework for sustainability impact assessment. A critical note on Boehringer and Loeschel (2006)

    Energy Technology Data Exchange (ETDEWEB)

    Scrieciu, S. Serban [Cambridge Centre for Climate Change Mitigation Research, Department of Land Economy, The University of Cambridge, Cambridge, CB2 1QA (United Kingdom)

    2007-02-01

    The search for methods of assessment that best evaluate and integrate the trade-offs and interactions between the economic, environmental and social components of development has been receiving a new impetus due to the requirement that sustainability concerns be incorporated into the policy formulation process. A paper forthcoming in Ecological Economics (Boehringer, C., Loeschel, A., in press. Computable general equilibrium models for sustainability impact assessment: status quo and prospects, Ecological Economics.) claims that Computable General Equilibrium (CGE) models may potentially represent the much needed 'back-bone' tool to carry out reliable integrated quantitative Sustainability Impact Assessments (SIAs). While acknowledging the usefulness of CGE models for some dimensions of SIA, this commentary questions the legitimacy of employing this particular economic modelling tool as a single integrating modelling framework for a comprehensive evaluation of the multi-dimensional, dynamic and complex interactions between policy and sustainability. It discusses several inherent dangers associated with the advocated prospects for the CGE modelling approach to contribute to comprehensive and reliable sustainability impact assessments. The paper warns that this reductionist viewpoint may seriously infringe upon the basic values underpinning the SIA process, namely a transparent, heterogeneous, balanced, inter-disciplinary, consultative and participatory take to policy evaluation and building of the evidence-base. (author)

  5. The inherent dangers of using computable general equilibrium models as a single integrated modelling framework for sustainability impact assessment. A critical note on Boehringer and Loeschel (2006)

    International Nuclear Information System (INIS)

    The search for methods of assessment that best evaluate and integrate the trade-offs and interactions between the economic, environmental and social components of development has been receiving a new impetus due to the requirement that sustainability concerns be incorporated into the policy formulation process. A paper forthcoming in Ecological Economics (Boehringer, C., Loeschel, A., in press. Computable general equilibrium models for sustainability impact assessment: status quo and prospects, Ecological Economics.) claims that Computable General Equilibrium (CGE) models may potentially represent the much needed 'back-bone' tool to carry out reliable integrated quantitative Sustainability Impact Assessments (SIAs). While acknowledging the usefulness of CGE models for some dimensions of SIA, this commentary questions the legitimacy of employing this particular economic modelling tool as a single integrating modelling framework for a comprehensive evaluation of the multi-dimensional, dynamic and complex interactions between policy and sustainability. It discusses several inherent dangers associated with the advocated prospects for the CGE modelling approach to contribute to comprehensive and reliable sustainability impact assessments. The paper warns that this reductionist viewpoint may seriously infringe upon the basic values underpinning the SIA process, namely a transparent, heterogeneous, balanced, inter-disciplinary, consultative and participatory take to policy evaluation and building of the evidence-base. (author)

  6. 78 FR 21058 - New Animal Drugs; Change of Sponsor

    Science.gov (United States)

    2013-04-09

    ... applications (ANADAs) from Boehringer Ingelheim Vetmedica, Inc. to Strategic Veterinary Pharmaceuticals, Inc... Strategic Veterinary Pharmaceuticals, Inc., 100 NW. Airport Rd., St. Joseph, MO 64503: Table 1... entry for ``Strategic Veterinary Pharmaceuticals, Inc.''; and in the table in paragraph...

  7. The lung function profile of once-daily tiotropium and olodaterol via Respimat® is superior to that of twice-daily salmeterol and fluticasone propionate via Accuhaler® (ENERGITO® study)

    OpenAIRE

    Beeh KM; Derom E; Echave-Sustaeta J; Grönke L; Hamilton A; Zhai D; Bjermer L

    2016-01-01

    Kai-Michael Beeh,1 Eric Derom,2 José Echave-Sustaeta,3 Lars Grönke,4 Alan Hamilton,5 Dongmei Zhai,6 Leif Bjermer71Insaf GmbH Institut für Atemwegsforschung, Wiesbaden, Germany; 2Department of Internal Medicine, Ghent University Hospital, Ghent, Belgium; 3Servicio de Neumología, Hospital Universitario Quirón, Madrid, Spain; 4Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany; 5Boehringer Ingelheim, Burlington, ON, Canada; 6InVentiv Health Clinical,...

  8. Prevalence of hypertension and obesity in patients with type 2 diabetes mellitus in observational studies: a systematic literature review

    OpenAIRE

    Colosia AD; Palencia R; Khan S

    2013-01-01

    Ann D Colosia,1 Roberto Palencia,2 Shahnaz Khan1 1RTI Health Solutions, Research Triangle Park, NC, USA; 2Boehringer Ingelheim GmbH, Ingelheim, Germany Background: Hypertension and obesity are known to contribute, directly or indirectly, to the development of long-term complications of type 2 diabetes mellitus (T2DM). Knowing the prevalence of these comorbidities is important for determining the size of the population that may benefit from strategies that reduce blood pressure and weight whil...

  9. Prevalence of hypertension and obesity in patients with type 2 diabetes mellitus in observational studies: a systematic literature review

    OpenAIRE

    Colosia, Ann

    2013-01-01

    Ann D Colosia,1 Roberto Palencia,2 Shahnaz Khan1 1RTI Health Solutions, Research Triangle Park, NC, USA; 2Boehringer Ingelheim GmbH, Ingelheim, Germany Background: Hypertension and obesity are known to contribute, directly or indirectly, to the development of long-term complications of type 2 diabetes mellitus (T2DM). Knowing the prevalence of these comorbidities is important for determining the size of the population that may benefit from strategies that reduce blood pressure and weight whi...

  10. Improvement in self-reported exercise participation with the combination of tiotropium and rehabilitative exercise training in COPD patients

    OpenAIRE

    Kesten, Steven

    2008-01-01

    Steven Kesten1, Richard Casaburi2, David Kukafka3, Christopher B Cooper41Boehringer Ingelheim GmbH, Ingelheim, Germany; 2Harbor-UCLA Medical Center, Torrance, CA, USA; 3Northern Colorado Pulmonary Consultants PC, Fort Collins, CO, USA; 4UCLA School of Medicine, Los Angeles, CA, USABackground: Improvements in ventilatory mechanics with tiotropium increases exercise tolerance during pulmonary rehabilitation. We wondered whether tiotropium also increased physical activities outside of pulmonary ...

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

    OpenAIRE

    Rodríguez-Roisin,Roberto; Tetzlaff, Kay; Watz*, Henrik; Wouters, Emiel; Disse,Bernd; Finnigan, Helen; Magnussen, Helgo; Calverley, Peter MA

    2016-01-01

    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 Cli...

  12. Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1)

    DEFF Research Database (Denmark)

    Reck, Martin; Kaiser, Rolf; Mellemgaard, Anders;

    2014-01-01

    , stratified by ECOG performance status, previous bevacizumab treatment, histology, and presence of brain metastases, were allocated (by computer-generated sequence through an interactive third-party system, in 1:1 ratio), to receive docetaxel 75 mg/m(2) by intravenous infusion on day 1 plus either nintedanib...... adenocarcinoma. FUNDING: Boehringer Ingelheim....

  13. 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

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

    OpenAIRE

    Baker CL; Zou KH; Su J

    2014-01-01

    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 retro...

  15. ABSOLUTE BIOAVAILABILITY OF ORAL MELOXICAM IN HEALTHY DOGS

    OpenAIRE

    K. T. Mahmood and M. Ashraf*

    2010-01-01

    Meloxicam, a non-steroidal anti-Inflammatory drug has been registered in Pakistan as a safe substitute of diclofenacsodium which was banned for veterinary use, due to its relay toxicity associated with the catastrophic decline in vulturepopulation of the Indian subcontinent. In Pakistan, Injection is the only dosage form registered for veterinary purposeswhereas Boehringer Ingelheim are licensed to sell meloxicam liquid oral suspension in UK and USA for use in dogs.The aim of the present stud...

  16. Potential modification of the UKPDS risk engine and evaluation of macrovascular event rates in controlled clinical trials

    OpenAIRE

    Yang

    2013-01-01

    Fred Yang,1 June Ye,2 Kenneth Pomerantz,3 Murray Stewart1 1Alternative Development Program, GlaxoSmithKline, King of Prussia, PA, 2Discovery Biometrics, GlaxoSmithKline, Research Triangle Park, NC, 3Clinical Development and Medical Affairs, Boehringer-Ingelheim Pharmaceuticals, Inc, Ridgefield, CT, USA Background: The aim of this study was to evaluate a modified UKPDS risk engine in order to establish a risk prediction benchmark for the general diabetes population. Methods: Data sources were...

  17. Potential modification of the UKPDS risk engine and evaluation of macrovascular event rates in controlled clinical trials

    OpenAIRE

    Yang F; Ye J; Pomerantz K; Stewart M

    2013-01-01

    Fred Yang,1 June Ye,2 Kenneth Pomerantz,3 Murray Stewart1 1Alternative Development Program, GlaxoSmithKline, King of Prussia, PA, 2Discovery Biometrics, GlaxoSmithKline, Research Triangle Park, NC, 3Clinical Development and Medical Affairs, Boehringer-Ingelheim Pharmaceuticals, Inc, Ridgefield, CT, USA Background: The aim of this study was to evaluate a modified UKPDS risk engine in order to establish a risk prediction benchmark for the general diabetes population. Methods: Data sources were ...

  18. Pharmacokinetics and safety of olodaterol administered with the Respimat Soft Mist inhaler in subjects with impaired hepatic or renal function

    Directory of Open Access Journals (Sweden)

    Kunz C

    2016-03-01

    Full Text Available Christina Kunz,1 Doreen Luedtke,1 Anna Unseld,2 Alan Hamilton,3 Atef Halabi,4 Martina Wein,5 Stephan Formella6 1Translational Medicine and Clinical Pharmacology, 2Global Biometrics and Clinical Applications, Boehringer Ingelheim Pharma GmbH and Co KG, Biberach, Germany; 3Boehringer Ingelheim, Burlington, ON, Canada; 4CRS Clinical Research Services Kiel GmbH, Kiel, 5Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharma GmbH and Co KG, Biberach, 6Medicine Coordination, Boehringer Ingelheim Pharma GmbH and Co KG, Ingelheim, Germany Purpose: In two trials, the influences of hepatic and renal impairment on the pharmacokinetics of olodaterol, a novel long-acting inhaled β2-agonist for treatment of COPD, were investigated.Subjects and methods: The first trial included eight subjects with mild hepatic function impairment (Child–Pugh A, eight subjects with moderate impairment (Child–Pugh B, and 16 matched healthy subjects with normal hepatic function. The second trial included eight subjects with severe renal impairment (creatinine clearance <30 mL·min-1 and 14 matched healthy subjects with normal renal function. Subjects received single doses of 20 or 30 µg olodaterol administered with the Respimat Soft Mist inhaler.Results: Olodaterol was well tolerated in all subjects. The geometric mean ratios and 90% confidence intervals of dose-normalized area under the plasma concentration-time curve from time zero to 4 hours (AUC0–4 for subjects with mild and moderate hepatic impairment compared to healthy subjects were 97% (75%–125% and 105% (79%–140%, respectively. Corresponding values for dose-normalized maximum concentration (Cmax were 112% (84%–151% (mild impairment and 99% (73%–135% (moderate impairment. The geometric mean ratio (90% confidence interval of AUC0–4 for subjects with severe renal impairment compared to healthy subjects was 135% (94%–195%, and for Cmax was 137% (84%–222%. There was no significant relationship

  19. Idiopathic pulmonary fibrosis: current treatment options and critical appraisal of nintedanib

    Directory of Open Access Journals (Sweden)

    Bonella F

    2015-12-01

    Full Text Available Francesco Bonella,1 Susanne Stowasser,2 Lutz Wollin3 1Interstitial and Rare Lung Disease Unit, Ruhrlandklinik, University Hospital, University of Duisburg-Essen, Essen, 2Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, 3Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany Abstract: Idiopathic pulmonary fibrosis (IPF is the most common type of idiopathic interstitial pneumonia and is characterized by a poor prognosis, with an estimated 5-year survival of approximately 20%. Progressive and irreversible lung functional impairment leads to chronic respiratory insufficiency with a severely impaired quality of life. In the last 2 decades, novel treatments for IPF have been developed as a consequence of an increasing understanding of disease pathogenesis and pathobiology. In IPF, injured dysfunctional alveolar epithelial cells promote fibroblast recruitment and proliferation, resulting in scarring of the lung tissue. Recently, pirfenidone and nintedanib have been approved for the treatment of IPF, having shown efficacy to slow functional decline and disease progression. This article focuses on the pharmacologic characteristics and clinical evidence supporting the use of nintedanib, a potent small-molecule tyrosine kinase inhibitor, as therapy for IPF. After introducing the mechanism of action and pharmacokinetics, an overview of the safety and efficacy results from the most recent clinical trials of nintedanib in IPF is presented. Keywords: tyrosine kinase, disease progression, treatment outcome, usual interstitial pneumonia, therapeutics

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

    OpenAIRE

    Kazuki Morioka; Katsuhiko Fukai; Kazuo Yoshida; Rie Kitano; Reiko Yamazoe; Manabu Yamada; Tatsuya Nishi; Toru Kanno

    2015-01-01

    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 det...

  1. 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

    OpenAIRE

    Vickers SP; Cheetham SC; Headl; Dell, KR; Dickinson K; Grempler R; Mayoux E; Mark M; Klein T.

    2014-01-01

    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 si...

  2. Prevention of mother-to-child HIV transmission in resource-limited settings: assessment of 99 Viramune Donation Programmes in 34 countries, 2000–2011

    OpenAIRE

    Ladner, Joël; Besson, Marie-Hélène; Rodrigues, Mariana; Sams, Kelley; Audureau, Etienne; Saba, Joseph

    2013-01-01

    Background Transmission of HIV from mother-to-child during pregnancy, labor, or breastfeeding is the primary cause of pediatric HIV infection in sub-Saharan Africa. A regimen of single-dose nevirapine administered to both HIV-positive pregnant women and their infants has been shown to lower the risk of mother-to-child transmission (MTCT) of HIV. In an effort to facilitate scale-up of PMTCT programs in low-income countries, Boehringer Ingelheim, the manufacturer of Viramune (branded nevirapine...

  3. 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

    OpenAIRE

    Guillemin, Isabelle

    2008-01-01

    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 o...

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

    DEFF Research Database (Denmark)

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

    Background: Diffusion-weighted magnetic resonance imaging (dw- MRI) utilizes differences in the motion of water molecules between tissues for image formation without administration of contrast materials. Inflammation in the bowel wall slows water transit resulting in lower apparent diffusions...... 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...

  5. OTC tamsulosin for benign prostatic hyperplasia.

    Science.gov (United States)

    2010-10-01

    Earlier this year, tamsulosin, an alpha blocker previously only available on prescription, became available for sale by pharmacists as a treatment for functional symptoms of benign prostatic hyperplasia (BPH) in men aged 45-75 years (Flomax Relief MR - Boehringer Ingelheim). A television advert for the over-the-counter (OTC) product claims that it is a "simple and effective" treatment that can relieve symptoms within 1 week, allowing the user to "take control of your annoying pee problems".¹ Here we review the evidence on tamsulosin and assess whether its availability as an OTC product confers worthwhile advantages. PMID:20926447

  6. 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

  7. Development of Respimat® Soft Mist™ Inhaler and its clinical utility in respiratory disorders

    Directory of Open Access Journals (Sweden)

    Dalby RN

    2011-09-01

    Full Text Available Richard N Dalby1, Joachim Eicher2, Bernd Zierenberg21Department of Pharmaceutical Sciences, University of Maryland, Baltimore, MD, USA; 2Boehringer Ingelheim, Ingelheim, GermanyAbstract: The Respimat® Soft Mist™ Inhaler (SMI (Boehringer Ingelheim International GmbH, Ingelheim, Germany was developed in response to the need for a pocket-sized device that can generate a single-breath, inhalable aerosol from a drug solution using a patient-independent, reproducible, and environmentally friendly energy supply. This paper describes the design and evolution of this innovative device from a laboratory concept model and the challenges that were overcome during its development and scaleup to mass production. A key technical breakthrough was the uniblock, a component combining filters and nozzles and made of silicon and glass, through which drug solution is forced using mechanical power. This allows two converging jets of solution to collide at a controlled angle, generating a fine aerosol of inhalable droplets. The mechanical energy comes from a spring which is tensioned by twisting the base of the device before use. Additional features of the Respimat® SMI include a dose indicator and a lockout mechanism to avoid the problems of tailing-off of dose size seen with pressurized metered dose inhalers. The Respimat® SMI aerosol cloud has a unique range of technical properties. The high fine particle fraction allied with the low velocity and long generation time of the aerosol translate into a higher fraction of the emitted dose being deposited in the lungs compared with aerosols from pressurized metered dose inhalers and dry powder inhalers. These advantages are realized in clinical trials in adults and children with obstructive lung diseases, which have shown that the efficacy and safety of a pressurized metered dose inhaler formulation of a combination bronchodilator can be matched by a Respimat® SMI formulation containing only one half or one quarter

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

    International Nuclear Information System (INIS)

    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

  9. 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.

  10. 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.

  11. 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

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

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    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

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

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    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

  14. 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

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    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

  15. Comparative review of the blood pressure-lowering and cardiovascular benefits of telmisartan and perindopril

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    Wang JG

    2014-04-01

    Full Text Available Ji-Guang Wang,1 Eduardo Pimenta,2 Frank Chwallek3 1Centre for Epidemiological Studies and Clinical Trials, Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Boehringer Ingelheim, Sydney, NSW, Australia; 3Boehringer Ingelheim Pharma, Biberach an der Riss, Germany Abstract: Hypertension is a major cardiovascular (CV risk factor, and blood pressure (BP-lowering treatment substantially reduces the risk. This review compares the available clinical evidence from the BP-lowering and CV-outcome studies of telmisartan and perindopril, which are among the most intensively studied members of their respective classes. The PubMed database was searched for telmisartan and perindopril publications meeting the following criteria: 1 head-to-head comparison trials for BP lowering; and 2 CV-outcome studies (ie, ones with a CV event, mortality, or hospitalization outcome in patients with CV risk factors but without heart failure. In comparative trials, telmisartan treatment resulted in significantly higher reduction in trough BP and mean ambulatory diastolic BP for the last 8 hours of the dosing interval compared with perindopril. In mainly placebo-controlled CV-outcome studies in patients with hypertension, CV benefits with perindopril were associated with large reductions in BP. There were no CV outcome studies with telmisartan in patients with hypertension. The beyond-BP-lowering CV-protective benefits of telmisartan were demonstrated in the active-controlled ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial trial, which included patients with controlled BP at baseline. In general, the trials discussed in this review reinforce the fact that perindopril and telmisartan are two long-acting antihypertensive drugs that reduce BP over 24 hours, and are the best-evidenced drugs in their class with proven CV protection. It is also clear

  16. 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). PMID:26648668

  17. ▼ Empagliflozin, diabetes and outcomes.

    Science.gov (United States)

    2016-07-01

    The prevalence of type 2 diabetes is rising, and in 2015 more than 5% of adults in the UK were affected by this condition.(1,2) Management of type 2 diabetes includes encouraging lifestyle changes (increased exercise, modification of diet and smoking cessation) alongside the provision of medication to minimise long-term complications and manage blood sugar control while avoiding unwanted effects of drug treatment.(3) Of particular importance, people with type 2 diabetes are at increased risk of cardiovascular disease, and therefore the aims of treatment also include modification of associated risk factors.(2-5)▼ Empagliflozin (Jardiance-Boehringer Ingelheim) is the third sodium-glucose co-transporter-2 (SGLT2) inhibitor licensed for use in the UK. It was launched in August 2014, and acts in a similar way to the other SGLT2 inhibitors, ▼ dapagliflozin and ▼ canagliflozin, by inhibiting renal glucose resorption and promoting glycosuria.(6) It is indicated for the treatment of type 2 diabetes in adults to improve glycaemic control, as monotherapy when metformin cannot be used, and in combination with other glucose-lowering drugs including insulin. Here we review the evidence for empagliflozin and discuss the results of a recent study that assessed cardiovascular outcomes. PMID:27417322

  18. The Pharmaceutical Aerosol Deposition Device on Cell Cultures (PADDOCC) in vitro system: design and experimental protocol.

    Science.gov (United States)

    Hein, Stephanie; Bur, Michael; Kolb, Tobias; Muellinger, Bernhard; Schaefer, Ulrich F; Lehr, Claus-Michael

    2010-08-01

    The development of aerosol medicines typically involves numerous tests on animals, due to the lack of adequate in vitro models. A new in vitro method for testing pharmaceutical aerosol formulations on cell cultures was developed, consisting of an aerosolisation unit fitting a commercial dry powder inhaler (HandiHaler(c), Boehringer Ingelheim, Germany), an air-flow control unit (Akita(c), Activaero, Germany) and a custom-made sedimentation chamber. This chamber holds three Snapwell(c) inserts with monolayers of pulmonary epithelial cells. The whole set-up, referred to as the Pharmaceutical Aerosol Deposition Device On Cell Cultures (PADDOCC) system, aims to mimic the complete process of aerosol drug delivery, encompassing aerosol generation, aerosol deposition onto pulmonary epithelial cells and subsequent drug transport across this biological barrier, to facilitate the investigation of new aerosol formulations in the early stages of development. We describe here, the development of the design and the protocol for this device. By testing aerosol formulations of budesonide and salbutamol sulphate, respectively, reproducible deposition of aerosol particles on, and the integrity of, the pulmonary cell monolayer could be demonstrated. PMID:20822321

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

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    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.

  20. 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.

  1. The role of structural information in the discovery of direct thrombin and factor Xa inhibitors.

    Science.gov (United States)

    Nar, Herbert

    2012-05-01

    The quest for novel medications to treat thromboembolic disorders such as venous thrombosis, pulmonary embolism and stroke received a boost when the 3D structures of two major players in the blood coagulation cascade were determined in 1989 and 1993. Structure-guided design of inhibitors of thrombin (factor IIa, fIIa) and factor Xa (fXa) eventually led to the discovery of potent, selective, efficacious, orally active and safe compounds that proved successful in clinical studies. In 2008, the direct thrombin inhibitor dabigatran etexilate developed by Boehringer Ingelheim became the first novel antithrombotic molecular entity to enter the market in 50 years. Additional compounds targeting factor Xa were subsequently granted marketing authorization or are in late-stage clinical studies. In this review, I use selected case studies to describe the discovery of novel fIIa and fXa inhibitors, with a particular emphasis on the pre-eminent role that structural information played in this process. PMID:22503439

  2. The lung function profile of once-daily tiotropium and olodaterol via Respimat® is superior to that of twice-daily salmeterol and fluticasone propionate via Accuhaler® (ENERGITO® study

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    Beeh KM

    2016-02-01

    Full Text Available Kai-Michael Beeh,1 Eric Derom,2 José Echave-Sustaeta,3 Lars Grönke,4 Alan Hamilton,5 Dongmei Zhai,6 Leif Bjermer71Insaf GmbH Institut für Atemwegsforschung, Wiesbaden, Germany; 2Department of Internal Medicine, Ghent University Hospital, Ghent, Belgium; 3Servicio de Neumología, Hospital Universitario Quirón, Madrid, Spain; 4Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany; 5Boehringer Ingelheim, Burlington, ON, Canada; 6InVentiv Health Clinical, Wilmington, DE, USA; 7Department of Respiratory Medicine and Allergology, Lund University, Lund, SwedenBackground: Tiotropium + olodaterol has demonstrated improvements beyond lung function benefits in a large Phase III clinical program as a once-daily maintenance treatment for COPD and may be a potential option for the initiation of maintenance treatment in COPD. Despite guideline recommendations that combined long-acting β2-agonists and inhaled corticosteroids should only be used in individuals at high risk of exacerbation, there is substantial use in individuals at lower risk. This raises the question of the comparative effectiveness of this combination as maintenance treatment in this group compared to other combination regimens.Objective: The study aimed to assess the effect on lung function of once-daily tiotropium + olodaterol versus twice-daily salmeterol + fluticasone propionate in all participants with Global initiative for chronic Obstructive Lung Disease 2 or 3 (moderate to severe COPD.Methods: This was a randomized, double-blind, double-dummy, four-treatment, complete crossover study in which participants received once-daily tiotropium + olodaterol (5/5 µg and 2.5/5 µg via Respimat® and twice-daily salmeterol + fluticasone propionate (50/500 µg and 50/250 µg via Accuhaler® for 6 weeks. The primary end point was change in forced expiratory volume in 1 second (FEV1 area under the curve from 0 hour to 12 hours (AUC0–12 relative to the baseline after 6

  3. Proposing a standardized method for evaluating patient report of the intensity of dyspnea during exercise testing in COPD

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    Hareendran A

    2012-05-01

    Full Text Available Asha Hareendran,1 Nancy K Leidy,2 Brigitta U Monz,3 Randall Winnette,1 Karin Becker,3 Donald A Mahler41United BioSource Corporation, London, UK; 2United BioSource Corporation, Bethesda, MD, USA; 3Boehringer Ingelheim, Ingelheim, Germany; 4Dartmouth Medical School, Hanover, NH, USABackground: Measuring dyspnea intensity associated with exercise provides insights into dyspnea-limited exercise capacity, and has been used to evaluate treatment outcomes for chronic obstructive pulmonary disease (COPD. Three patient-reported outcome scales commonly cited for rating dyspnea during exercise are the modified Borg scale (MBS, numerical rating scale for dyspnea (NRS-D, and visual analogue scale for dyspnea (VAS-D. Various versions of each scale were found. Our objective was to evaluate the content validity of scales commonly used in COPD studies, to explore their ability to capture patients' experiences of dyspnea during exercise, and to evaluate a standardized version of the MBS.Methods: A two-stage procedure was used, with each stage involving one-on-one interviews with COPD patients who had recently completed a clinic-based exercise event on a treadmill or cycle ergometer. An open-ended elicitation interview technique was used to understand patients' experiences of exercise-induced dyspnea, followed by patients completing the three scales. The cognitive interviewing component of the study involved specific questions to evaluate the patients' perspectives of the content and format of the scales. Results from Stage 1 were used to develop a standardized version of the MBS, which was then subjected to further content validity assessment during Stage 2.Results: Thirteen patients participated in the two-stage process (n = 6; n = 7. Mean forced expiratory volume in 1 second (FEV1 percent predicted was 40%, mean age 57 years, and 54% were male. Participants used a variety of terms to describe the intensity and variability of exercise-induced dyspnea. Subjects

  4. Prevalence of hypertension and obesity in patients with type 2 diabetes mellitus in observational studies: a systematic literature review

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    Colosia AD

    2013-09-01

    Full Text Available Ann D Colosia,1 Roberto Palencia,2 Shahnaz Khan1 1RTI Health Solutions, Research Triangle Park, NC, USA; 2Boehringer Ingelheim GmbH, Ingelheim, Germany Background: Hypertension and obesity are known to contribute, directly or indirectly, to the development of long-term complications of type 2 diabetes mellitus (T2DM. Knowing the prevalence of these comorbidities is important for determining the size of the population that may benefit from strategies that reduce blood pressure and weight while controlling blood glucose. Methods: In this systematic literature review, electronic searches of PubMed, Embase, and the Cochrane Library were conducted to identify observational studies of hypertension and/or obesity prevalence in patients with T2DM throughout the world. The searches were limited to studies reported in English from January 1, 2001 to February 16, 2012. Results: From a total of 2,688 studies, 92 observational studies provided prevalence rates for hypertension and/or obesity specifically in adults with T2DM. Fifteen studies of specific subtypes of hypertension or subpopulations with T2DM were subsequently excluded, leaving 78 studies (in 77 articles for inclusion in this article. Of these, 61 studies reported hypertension prevalence, 44 reported obesity prevalence, and 12 reported the prevalence of hypertension with obesity. Most studies had a low risk of bias regarding diagnosis of T2DM (70/78, hypertension (59/69, or obesity (45/47. The continental regions with the most observational studies of hypertension or obesity prevalence were Europe (n = 30 and Asia (n = 26. Hypertension rates typically were high in all regions; most studies presented rates above 50%, and many presented rates above 75%. Obesity rates exceeded 30% in 38 of 44 studies and 50% in 14 of 44 studies, especially those assessing central obesity (based on waist circumference. Among obese adults, hypertension rates were at or above 70% in Asia and above 80% in Europe; rates

  5. 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

  6. Improvement in self-reported exercise participation with the combination of tiotropium and rehabilitative exercise training in COPD patients

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    Steven Kesten

    2008-03-01

    Full Text Available Steven Kesten1, Richard Casaburi2, David Kukafka3, Christopher B Cooper41Boehringer Ingelheim GmbH, Ingelheim, Germany; 2Harbor-UCLA Medical Center, Torrance, CA, USA; 3Northern Colorado Pulmonary Consultants PC, Fort Collins, CO, USA; 4UCLA School of Medicine, Los Angeles, CA, USABackground: Improvements in ventilatory mechanics with tiotropium increases exercise tolerance during pulmonary rehabilitation. We wondered whether tiotropium also increased physical activities outside of pulmonary rehabilitation.Methods: COPD patients participating in 8 weeks of pulmonary rehabilitation were studied in a randomized, double-blind, placebo-controlled trial of tiotropium 18 µg daily (tiotropium = 47, placebo = 44. Study drug was administered for 5 weeks prior to, 8 weeks during, and 12 weeks following pulmonary rehabilitation. Patients completed a questionnaire documenting participation in pre-defined activities outside of pulmonary rehabilitation during the 2 weeks prior to each visit. Patients who submitted an activity questionnaire at week 4 and on at least one subsequent visit were included in the analysis. For each patient, the number of sessions was multiplied with the duration of each activity and then summed to give overall activity duration.Results: Patients (n = 46 had mean age of 67 years, mean baseline FEV1 of 0.84 L (33% predicted. Mean (SE increase in duration of activities (minutes during 2 weeks prior to each visit from week 4 (prior to PR to week 13 (end of PR was 145 (84 minutes with tiotropium and 66 (96 minutes with placebo. The increase from week 4 to week 25 (end of follow-up was 262 (96 and 60 (93 minutes for the respective groups. Increases in activity duration from week 4 to weeks 17, 21, and 25 were statistically significant with tiotropium. No statistical differences over time were observed within the placebo-treated group and differences between groups were not significant.Conclusions: Tiotropium appears to amplify the

  7. Guideline-based survey of outpatient COPD management by pulmonary specialists in Germany

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    Buhl R

    2012-02-01

    Full Text Available Thomas Glaab1,2, Claus Vogelmeier3, Andreas Hellmann4, Roland Buhl11Department of Respiratory Diseases III, Medical Center of the Johannes Gutenberg-University, Mainz, 2Medical Affairs Germany, Respiratory Medicine, Boehringer Ingelheim Pharma GmbH and Co, KG, Ingelheim, 3Department of Respiratory Diseases, University Hospitals of Giessen and Marburg, Marburg, 4Federal Association of Pneumologists, Augsburg, GermanyBackground: Little is known about the role of guidelines for the practical management of chronic obstructive pulmonary disease (COPD by office-based pulmonary specialists. The aim of this study was to assess their outpatient management in relation to current guideline recommendations for COPD.Methods: A nationwide prospective cross-sectional COPD questionnaire survey in the form of a multiple-choice questionnaire was sent to 1000 office-based respiratory specialists in Germany. The product-neutral questions focused on routine COPD management and were based on current national and international COPD guideline recommendations being consistent in severity classification and treatment recommendations.Results: A total of 590 pulmonary specialists (59% participated in the survey. Body plethysmography was considered the standard for diagnosis (65.9%, followed by spirometry (32%. Most respondents were able to cite the correct spirometric criteria for classifying moderate (87% to very severe COPD (77%. A quarter of the respondents equated the World Health Organization (WHO definition of chronic bronchitis with COPD. Notably, most participants preferred the updated national COPD guidelines (51.4% to the Global Initiative for Chronic Obstructive Lung Disease (GOLD guidelines (40.2%. Improvement of functional exercise capacity and quality of life were considered the two most relevant treatment goals; whereas impact on mortality was secondary. Treatment of COPD largely complied with the guidelines. However, a significant percentage of the

  8. 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

  9. 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

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    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

  10. Differential pharmacology and clinical utility of emerging combination treatments in the management of COPD – role of umeclidinium/vilanterol

    Directory of Open Access Journals (Sweden)

    Malerba M

    2014-06-01

    Full Text Available Mario Malerba,1 Jaymin Bhagwanji Morjaria,2 Alessandro Radaeli3 1Department of Internal Medicine, University of Brescia, Brescia, Italy; 2Department of Academic Respiratory Medicine, Hull York Medical School, University of Hull, Castle Hill Hospital, Cottingham, United Kingdom; 3Department of Emergency, Spedali Civili di Brescia, Brescia, Italy Abstract: Chronic obstructive pulmonary disease (COPD is a preventable and treatable disease characterized by airflow limitation that is not fully reversible. Bronchodilator therapy is the cornerstone in COPD treatment. Bronchodilation in COPD is mainly achieved via administration of long- and ultralong-acting β2-agonists and with long-acting muscarinic antagonists. New combinations of bronchodilators with dual-acting muscarinic antagonist and β2-agonist properties have been licensed, and others are currently being developed with the aim of achieving once-daily dosing, and therefore may improve the likelihood of treatment compliance. These combination bronchodilators include glycopyrronium bromide/indacaterol maleate, umeclidinium (UMEC bromide/vilanterol trifenatate (VI, aclidinium bromide/formoterol and tiotropium bromide/olodaterol (Boehringer Ingelheim, Germany. This review will focus mainly on studies and clinical trials involving the novel fixed-dose combination of UMEC/VI at doses of 125/25 µg and 62.5/25 µg in patients with COPD. Data from large clinical trials involving more than 4,500 COPD patients indicate that UMEC/VI is an effective once-daily treatment in COPD with improved pulmonary function. Future studies assessing the impact of this combination on exacerbations, delay in disease progression, and health status in patients with COPD are warranted. Keywords: COPD treatment, umeclidinium, vilanterol, bronchodilators combination, long acting beta2-agonists, long acting muscarinic receptor antagonists

  11. A simple semipaced 3-minute chair rise test for routine exercise tolerance testing in COPD

    Directory of Open Access Journals (Sweden)

    Aguilaniu B

    2014-09-01

    Full Text Available Bernard Aguilaniu,1,2 Hubert Roth,3 Jesus Gonzalez-Bermejo,4 Marie Jondot,5 Jocelyne Maitre,5 François Denis,6 Thomas Similowski4,7 1Medicine Faculty, Université Joseph Fourier, Grenoble, France; 2McGill University, Montreal, Canada; 3Centre de Recherche en Nutrition Humaine Rhône-Alpes, CHU Grenoble, France; 4Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Respiratory and Intensive Care Medicine, Paris, France; 5Clinique Universitaire de Pneumologie, CHU Grenoble, France, Grenoble, France; 6Boehringer Ingelheim, 7Université Paris, Paris, France Abstract: The functional work capacity of chronic obstructive pulmonary disease (COPD patients is usually assessed with walk tests such as the 6-minute walk test (6MWT or the shuttle test. Because these exercise modalities require a controlled environment which limits their use by pulmonologists and severely restricts their use among general practitioners, different modalities of a short (1 minute or less sit-to-stand test were recently proposed. In this study, we evaluated a new modality of a semipaced 3-minute chair rise test (3CRT in 40 patients with COPD, and compared the reproducibility of physiological responses and symptoms during the 3CRT and their interchangeability with the 6MWT. The results demonstrate that physiological variables, heart rate, pulse oxygen saturation, work done, and symptoms (Borg dyspnea and fatigue scores, during the 3CRT were highly reproducible, and that the physiological responses and symptoms obtained during the 3CRT and the 6MWT were interchangeable for most patients. Moreover, these preliminary data suggest that patients able to perform more than 50 rises during 3 minutes had no significant disability. The simplicity and ease of execution of the 3CRT will facilitate the assessment of exercise symptoms and disability in COPD patients during routine consultations with pulmonologists and general practitioners, and will thus contribute

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

    Directory of Open Access Journals (Sweden)

    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. 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

  14. The antiplasmodial and spleen protective role of crude Indigofera oblongifolia leaf extract traditionally used in the treatment of malaria in Saudi Arabia

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    Dkhil MA

    2015-11-01

    Full Text Available Mohamed A Dkhil,1,2 Mahmoud Y Lubbad,1,3 Esam M Al-Shaebi,1 Denis Delic,4 Saleh Al-Quraishy1 1Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia; 2Department of Zoology and Entomology, Faculty of Science, Helwan University, Helwan, Egypt; 3General Directorate of Environmental and Occupational Health, Public Health Agency, Ministry of Health, Riyadh, Saudi Arabia; 4Boehringer-Ingelheim Pharma, Biberach, Germany Abstract: Malaria is one of the most serious natural hazards faced by human society. Although plant leaves of Indigofera oblongifolia have been used for the treatment of malaria in Saudi Arabian society, there is no laboratory-based evidence for the effectiveness and safety of the plant. This study therefore was designed to investigate the antimalarial and spleen protective activity of I. oblongifolia leaf extract (IOLE in mice. Three doses (100, 200 and 300 mg/kg of IOLE were used to treat mice infected with Plasmodium chabaudi-parasitized erythrocytes. The suppressive effect produced by the 100 mg/kg dose on parasitemia was highly significant compared to the infected nontreated group. This dose was also able to repair the change in the thickness of the mice spleen and significantly lower the number of apoptotic cells in the spleen. Moreover, I. oblongifolia also altered gene expression in the infected spleen. On day 7 postinfection, the mRNA expression of six genes – with immune response functions – was upregulated by more than twofold, while that of 24 other genes was downregulated. Among the differentially up- and downregulated genes under the effect of IOLE, we quantified the expression of Ccl8, Saa3, Cd209a, and Cd209b mRNAs. The expression data, determined by microarrays, were largely consistent with the expression analyses we performed with several arbitrarily selected genes using quantitative polymerase chain reaction (PCR. Based on our results, I. oblongifolia exhibits antimalarial activity

  15. Effect of oral calcium bolus supplementation on early-lactation health and milk yield in commercial dairy herds.

    Science.gov (United States)

    Oetzel, G R; Miller, B E

    2012-12-01

    The objective of this study was to evaluate the effect of supplementation with oral Ca boluses after calving on early-lactation health and milk yield. Cows in their second lactation or greater (n=927) from 2 large dairies in Wisconsin were enrolled during the summer of 2010. Both herds were fed supplemental anions during the prefresh period and less than 1% of fresh cows were treated for clinical milk fever. Cows were scored before calving for lameness and body condition, and then randomly assigned to either a control group or an oral Ca bolus-supplemented group. Control cows received no oral Ca boluses around calving. Cows in the oral Ca bolus group received 2 oral Ca boluses (Bovikalc, Boehringer Ingelheim, St. Joseph, MO), one bolus 0 to 2h after calving and the second 8 to 35 h after calving. The oral Ca bolus administration schedule allowed fresh cows to be restrained in headlocks only once daily. Whole-blood samples were collected immediately before the second oral Ca bolus was given and were analyzed for ionized Ca (Ca(2+)) concentration. Early-lactation health events were recorded and summed for each cow. Only 6 cases (0.6% of calvings) of clinical milk fever occurred during the trial, and only 14% of cows tested were hypocalcemic (Ca(2+) less than 1.0 mmol/L) at 8 to 35 h after calving. Mean Ca(2+) concentrations were not different between the control and oral Ca bolus-supplemented groups. Blood samples from the cows given oral Ca boluses were collected an average of 20.6 h after administration of the first bolus. Subpopulations of cows with significant responses to oral Ca bolus supplementation were identified based on significant interactions between oral Ca bolus supplementation and covariates in mixed multiple regression models. Lame cows supplemented with oral Ca boluses averaged 0.34 fewer health events in the first 30 d in milk compared with lame cows that were not supplemented with oral Ca boluses. Cows with a higher previous lactation mature

  16. 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

  17. 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.

  18. Potential modification of the UKPDS risk engine and evaluation of macrovascular event rates in controlled clinical trials

    Directory of Open Access Journals (Sweden)

    Yang F

    2013-07-01

    Full Text Available Fred Yang,1 June Ye,2 Kenneth Pomerantz,3 Murray Stewart1 1Alternative Development Program, GlaxoSmithKline, King of Prussia, PA, 2Discovery Biometrics, GlaxoSmithKline, Research Triangle Park, NC, 3Clinical Development and Medical Affairs, Boehringer-Ingelheim Pharmaceuticals, Inc, Ridgefield, CT, USA Background: The aim of this study was to evaluate a modified UKPDS risk engine in order to establish a risk prediction benchmark for the general diabetes population. Methods: Data sources were summary demographic and risk factor data from the major type 2 diabetes mellitus outcomes studies, including ACCORD, ADVANCE, VADT, RECORD, PROactive, ADOPT, and BARI 2D. Patients in these studies spanned a wide spectrum of disease, from drug-naïve to insulin-dependent. Cardiovascular events/major adverse coronary events (CVE/MACE were primary or safety end points. Overall observed rates for cardiovascular events/MACE were summarized, and the observed annualized event rates were calculated using linear approximation. Simulation studies were then conducted using original (cardiovascular history excluded and modified (cardiovascular history included United Kingdom Prospective Diabetes Study (UKPDS models; the predicted event rates were then compared with the observed event rates for all studies. The consistency of the predicted rates derived from each model was then evaluated using descriptive statistics and linear regression. Results: The original UKPDS model tended to overestimate event rates across studies. The ratio of predicted events versus observed MACE ranged from 0.9 to 2.0, with mean of 1.5 ± 0.4 and a coefficient of variation of 26% (R2 = 0.80. However, cardiovascular risk predictions were more precise using a modified UKPDS model; the ratio of predicted versus observed MACE events ranged from 1.8 to 2.4, with a mean of 2.1 ± 0.25 and a coefficient of variation of 13% (R2 = 0.94. Conclusion: A modified UKPDS model which includes adjustments for

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

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    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.

  20. Addition of anticholinergic solution prolongs bronchodilator effect of beta 2 agonists in patients with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Levin, D C; Little, K S; Laughlin, K R; Galbraith, J M; Gustman, P M; Murphy, D; Kram, J A; Hardie, G; Reuter, C; Ostransky, D; McFarland, K; Petty, T L; Silvers, W; Rennard, S I; Mueller, M; Repsher, L H; Zuwallack, R L; Vale, R

    1996-01-29

    A randomized, double-blind placebo-controlled clinical trial was designed to assess the safety, efficacy, and duration of the bronchodilation resulting from the addition of 500 micrograms of ipratropium bromide (Atrovent; Boehringer Ingelheim, CT) inhalation solution to standard small volume nebulizer treatments with 2.5 mg albuterol inhalation solution. A total of 195 patients (63% men, average age 64 years) with > 10 pack-year smoking histories and stable, moderate-to- severe chronic obstructive pulmonary disease (COPD; forced expiratory volume in 1 second [FEV1] 1.02 liter, 38.8% predicted) from eight university-affiliated chest clinics in seven U.S. cities were enrolled into the study. Asthma, rhinitis, and eosinophilia were exclusions, as was daily use of > 10 mg of prednisone (or 20 mg on alternate days). There was a 2-week stabilization period during which the patients were instructed in the use of the small volume nebulizers, which they used three times daily with albuterol alone. They were asked to keep daily logs of peak flow rates, pulmonary symptoms, and additional medication usage. On their test day 1 the subjects came to the pulmonary function laboratory having been off theophylline for 24 hours and beta 2-agonists for 12 hours and performed a baseline spirometry. They then received their morning small volume nebulizer treatment of albuterol to which was added either 500 micrograms if ipratropium bromide or a saline placebo. Spirometry was repeated at 15, 30, and 60 minutes, and then hourly for 8 hours. Subjects then took home a 2-week supply of albuterol and test drug for thrice daily use in their small volume nebulizer. They were evaluated for pulmonary symptoms and adverse effects every 14 days. The 8-hour spirometry was repeated on test day 43 and finally on test day 85. Primary data evaluated were the peak increase in FEV1 and the area between the FEV1 baseline value and the 8-hour FEV1 curve. Similar calculations were made for forced vital

  1. Blood calcium dynamics after prophylactic treatment of subclinical hypocalcemia with oral or intravenous calcium.

    Science.gov (United States)

    Blanc, C D; Van der List, M; Aly, S S; Rossow, H A; Silva-del-Río, N

    2014-11-01

    Total serum Ca dynamics and urine pH levels were evaluated after prophylactic treatment of subclinical hypocalcemia after parturition in 33 multiparous Jersey × Holstein crossbreed cows. Cows were blocked according to their calcemic status at the time of treatment [normocalcemic (8.0-9.9 mg/dL; n = 15) or hypocalcemic (5.0-7.9 mg/dL; n = 18)] and randomly assigned to 1 of 3 treatments: control [no Ca supplementation (n = 11)]; intravenous Ca [Ca-IV (n = 11), 500 mL of 23% calcium gluconate (10.7 g of Ca and 17.5 g of boric acid as a solubilizing agent; Durvet, Blue Springs, MO)]; or oral Ca [Ca-Oral (n = 11), 1 oral bolus (Bovikalc bolus, Boehringer Ingelheim, St. Joseph, MO) containing CaCl2 and CaSO4 (43 g of Ca) 2 times 12h apart]. Total serum Ca levels were evaluated at 0, 1, 2, 4, 8, 12, 16, 20, 24, 36, and 48 h, and urine pH was evaluated at 0, 1, 12, 24, 36, and 4 8h after treatment initiation. Total serum Ca levels were higher for Ca-IV than for control and Ca-Oral cows at 1, 2, and 4h after treatment initiation, but lower than Ca-Oral cows at 20, 24, and 36 h and lower than control cows at 36 and 48 h. At 1h after treatment initiation, when serum Ca levels for Ca-IV cows peaked (11.4 mg/dL), a greater proportion of Ca-IV (n = 8) cows had total serum Ca levels >10mg/dL than control (n = 0) and Ca-Oral (n = 1) cows. At 24h after treatment initiation, when Ca-IV cows reached the total serum Ca nadir (6.4 mg/dL), a greater proportion of Ca-IV (n = 10) cows had serum Ca levels cows. Treatment, time, and treatment × time interaction were significant for urine pH. Mean urine pH was lower for Ca-Oral cows (6.69) than for control (7.52) and Ca-IV (7.19) cows. Urine pH levels at 1h after treatment were lower for Ca-IV cows compared with both control and Ca-Oral cows, a finding likely associated with the iatrogenic administration of boric acid added as a solubilizing agent of the intravenous Ca solution used. At 12, 24, and 36 h, urine pH levels were lower for Ca

  2. Increase energy efficiency in the cold production; Steigerung der Energieeffizienz in der Kaelteerzeugung

    Energy Technology Data Exchange (ETDEWEB)

    Paatzsch, Rene [Institut fuer Luft- und Kaeltetechnik gGmbH, Dresden (Germany). Hauptbereich Kaelte- und Waermepumpentechnik; Berg, Hans-Peter [Boehringer Ingelheim Pharma GmbH und Co. KG, Ingelheim (Germany)

    2011-12-15

    According to a study by ILK Dresden the cold production in the field of pharmaceutical manufacturing at Boehringer has been adjusted. By installing a turbo chiller and the sliding control of the cooling water temperature depending on the wet bulb temperature the COP of the cold production was improved of 3.1 to 4.5 currently. (orig.)

  3. Examination of four different instruments for measuring the blood lactate concentration

    OpenAIRE

    Medbø, Jon Ingulf; Mamen, Asgeir; Olsen, Ole Holt; Evertsen, Frank

    2000-01-01

    ABSTRACT There is incomplete information on the performance of different instruments used to measure the blood lactate concentration. We have therefore examined instruments from Yellow Springs Instruments (YSI 23L and YSI 1500), and three cheaper and simpler instruments: Dr. Lange’s LP8+, Lactate Pro from Arkray, KDK, and Accusport from Boehringer Mannheim. First a number of blood samples were analysed by standard enzymatic photofluorometry (our control method) and in additi...

  4. Erratum

    OpenAIRE

    Nappi, Rossella

    2010-01-01

    Rossella E Nappi, Ellis Martini, Erica Terreno, et al. Management of hypoactive sexual desire disorder in women: current and emerging therapies. International Journal of Women’s Health. 2010;2:167–175.The authors would like to disclose the following conflicts of interest: During the past 2 years Rossella E Nappi has had financial relationships with Bayer-Schering Pharma, Boehringer Ingelhein, Merck-Theramex, Novo Nordisk, Procter and Gamble Pharmaceuticals, and Schering-Pl...

  5. 11115 2014年COPD市场的销售额将达到120亿美元

    Institute of Scientific and Technical Information of China (English)

    施桂兰(摘)

    2006-01-01

    根据保健研究公司Decision Resources(DR)的发现,昂贵的维持治疗的消耗量在逐年上涨,包括GlaxoSmithKline、Astra-Zeneca、Boehringer Ingelheim和Pfizer公司的药物。将帮助拉动慢性阻塞性肺病(COPD)治疗市场每年大约9%的稳定市场增长率。

  6. Measurement of cytokeratin 19 fragments as a marker of lung cancer by CYFRA 21-1 enzyme immunoassay.

    OpenAIRE

    Takada, M; Masuda, N.; Matsuura, E.; Kusunoki, Y; Matui, K.; Nakagawa, K.; Yana, T.; Tuyuguchi, I.; Oohata, I.; Fukuoka, M

    1995-01-01

    Soluble cytokeratin fragment 19 levels were measured with an enzyme immunoassay method developed by Boehringer Mannheim (Enzymun-Test CYFRA 21-1) in the serum of 185 patients with lung cancer [149 with non-small-cell lung cancer (NSCLC) and 36 with small-cell lung cancer (SCLC)] and 97 patients with benign lung diseases in order to determine its clinical usefulness in the diagnosis of lung cancer and follow-up of treatment. We used the cut-off value of 3.5 ng ml-1, established by the Japan CY...

  7. 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).

  8. A Maximum Power Point Tracking Control Method of a Photovoltaic Power Generator with Consideration of Dynamic Characteristics of Solar Cells

    Science.gov (United States)

    Watanabe, Takashi; Yoshida, Toshiya; Ohniwa, Katsumi

    This paper discusses a new control strategy for photovoltaic power generation systems with consideration of dynamic characteristics of the photovoltaic cells. The controller estimates internal currents of an equivalent circuit for the cells. This estimated, or the virtual current and the actual voltage of the cells are fed to a conventional Maximum-Power-Point-Tracking (MPPT) controller. Consequently, this MPPT controller still tracks the optimum point even though it is so designed that the seeking speed of the operating point is extremely high. This system may suit for applications, which are installed in rapidly changeable insolation and temperature-conditions e.g. automobiles, trains, and airplanes. The proposed method is verified by experiment with a combination of this estimating function and the modified Boehringer's MPPT algorithm.

  9. Multi-centre evaluation of the speed-oligo Mycobacteria assay for differentiation of Mycobacterium spp. in clinical isolates

    Directory of Open Access Journals (Sweden)

    Hofmann-Thiel Sabine

    2011-12-01

    Full Text Available Abstract Background A new DNA line probe assay (Speed-oligo Mycobacteria, Vircell has been launched for rapid differentiation of Mycobacterium spp. from cultures. Compared to other line-probe assays, Speed-oligo Mycobacteria covers a relatively limited spectrum of species but uses a simpler and faster dip-stick technique. The present multi-centre, multi-country study aimed at evaluating the utility and usability of Speed-oligo Mycobacteria in routine mycobacteriology diagnostics. Results from Speed-oligo Myobacteria were compared to those from Genotype CM (HAIN lifescience, Nehren, Germany, another line-probe assay. Methods Speed-oligo Mycobacteria assay was performed in three main steps: 1 DNA extraction from cultured material 2 PCR amplification of the target gene and an internal control and 3 hybridization of the PCR products to specific probes by means of a dip-stick. Results Two hundred forty-two clinical isolates were recovered from consecutive positive mycobacterial cultures at two German (IML Gauting, Bioscientia Ingelheim, one Czech (KLINLAB Prague, and at a Sudanese (Khartoum laboratory. All Mycobacterium species covered by the assay were reliably recognized. The rate of false positive results was 1.2% and concerned only the species M. marinum and M. peregrinum. The identification rate, i.e. the proportion of isolates which was correctly differentiated to the level of species or complex by the assay, differed significantly among laboratories being 94.9%, 90.7%, and 75.0% at the study sites IML Gauting, KLINLAB Prague and Bioscientia Ingelheim, respectively. This difference was caused by different spectra of NTM species encountered by the laboratory centres in daily routine diagnostics. Conclusions Speed-oligo Mycobacteria assay was proved a rapid and easy-to-perform alternative to conventional line-probe assays. The assay showed excellent sensitivity with regard to identification of genus Mycobacterium and species/complexes covered by

  10. 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.)

  11. Using heart rate to predict energy expenditure in large domestic dogs.

    Science.gov (United States)

    Gerth, N; Ruoß, C; Dobenecker, B; Reese, S; Starck, J M

    2016-06-01

    The aim of this study was to establish heart rate as a measure of energy expenditure in large active kennel dogs (28 ± 3 kg bw). Therefore, the heart rate (HR)-oxygen consumption (V˙O2) relationship was analysed in Foxhound-Boxer-Ingelheim-Labrador cross-breds (FBI dogs) at rest and graded levels of exercise on a treadmill up to 60-65% of maximal aerobic capacity. To test for effects of training, HR and V˙O2 were measured in female dogs, before and after a training period, and after an adjacent training pause to test for reversibility of potential effects. Least squares regression was applied to describe the relationship between HR and V˙O2. The applied training had no statistically significant effect on the HR-V˙O2 regression. A general regression line from all data collected was prepared to establish a general predictive equation for energy expenditure from HR in FBI dogs. The regression equation established in this study enables fast estimation of energy requirement for running activity. The equation is valid for large dogs weighing around 30 kg that run at ground level up to 15 km/h with a heart rate maximum of 190 bpm irrespective of the training level. PMID:26344575

  12. Dynamic formulation of a top-down and bottom-up merging energy policy model

    International Nuclear Information System (INIS)

    The impact of energy policy measures is not restricted to the energy system and should therefore be analysed within an economy-wide framework, while keeping the essential details of the energy sector. The aim of this paper is to present new developments in the field of the consistent evaluation of indicators for the sustainability assessment of energy policy measures. Starting from the static concept of Boehringer (Energy Econ. 20 (1998) 233), this paper shows how the complementarity format can be used in computable general equilibrium (CGE) modelling for a dynamic formulation of bottom-up and top-down approach merging models. While a hybrid approach increases the credibility of CGE models in energy policy analysis by replacing the energy sector generic functional forms with a bottom-up activity analysis based on specific technologies, the endogenous formulation of investment decisions makes an explicit description of evolving specific capital stocks and technology mixes possible. Both features are essential when assessing effects of policy measures that may be affected by structural change--which is typically the case in the long-term assessment of energy policy measures

  13. Dynamic formulation of a top-down and bottom-up merging energy policy model

    Energy Technology Data Exchange (ETDEWEB)

    Frei, C.W. [Swiss Federal Inst. of Technology, Lausanne (Switzerland). Centre for Energy Policy and Economics; Haldi, P.A.; Sarlos, G. [Swiss Federal Inst. of Technology, Lausanne (Switzerland). Lab. of Energy Systems

    2003-08-01

    The impact of energy policy measures is not restricted to the energy system and should therefore be analysed within an economy-wide framework, while keeping the essential details of the energy sector. The aim of this paper is to present new developments in the field of the consistent evaluation of indicators for the sustainability assessment of energy policy measures. Starting from the static concept of Boehringer (Energy Econ. 20 (1998) 233), this paper shows how the complementarity format can be used in computable general equilibrium (CGE) modelling for a dynamic formulation of bottom-up and top-down approach merging models. While a hybrid approach increases the credibility of CGE models in energy policy analysis by replacing the energy sector generic functional forms with a bottom-up activity analysis based on specific technologies, the endogenous formulation of investment decisions makes an explicit description of evolving specific capital stocks and technology mixes possible. Both features are essential when assessing effects of policy measures that may be affected by structural change - which is typically the case in the long-term assessment of energy policy measures.(author)

  14. Effect of Low Dose Gamma Radiation on Some Biochemical Indicators in the Blood Plasma of Chickens

    International Nuclear Information System (INIS)

    Full text: An attempt was made to determine the effect of irradiation of eggs by low dose ionising radiation before incubation on concentration of total protein, glucose and cholesterol in the blood plasma of chickens hatched from irradiated eggs. The eggs of heavy breeding chickens were irradiated by dose of 0.15 Gy gamma radiation (60Co) before incubation. Along with the chickens which were hatched from irradiated eggs, there was the control group of chickens hatched from nonirradiated eggs. All other conditions were the same for the both groups. After hatching, blood samples were taken from the wing vein on days 1, 3, 5, 7, 10, 20, 30 and 42. The concentration of all three parameters was determined spectrophotometrically using Boehringer Mannheim GmbH optimized kits. The concentration of total protein was significantly decreased in the blood plasma of chickens hatched from irradiated eggs on days 3, 7 and 30 and increased only on day 5. The concentration of glucose in the blood plasma was increased in the same chickens on days 1 and 30. The concentration of the cholesterol was decreased in the same chickens on day 7, and increased on day 10. Obtained results indicate that low-dose of gamma radiation has effects on some metabolic processes in the chickens hatched from eggs irradiated before incubation. (author)

  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. 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.

  17. Graphite-teflon composite bienzyme electrodes for the determination of cholesterol in reversed micelles. Application to food samples.

    Science.gov (United States)

    Peña, N; Ruiz, G; Reviejo, A J; Pingarrón, J M

    2001-03-15

    A bienzyme amperometric composite biosensor for the determination of free and total cholesterol in food samples is reported. Cholesterol oxidase and horseradish peroxidase, together with potassium ferrocyanide as a mediator, are incorporated into a graphite-70% Teflon matrix. The compatibility of this biosensor design with predominantly nonaqueous media allows the use of reversed micelles as working medium. The reversed micelles are formed with ethyl acetate as continuous phase (in which cholesterol is soluble), a 4% final concentration of 0.05 mol L(-1) phosphate buffer solution, pH 7.4, as dispersed phase, and 0.1 mol L(-1) AOT as emulsifying agent. Studies on the repeatability of the amperometric response obtained at +0.10 V, with and without regeneration of the electrode surface by polishing, on the useful lifetime of one single biosensor and on the reproducibility in the fabrication of different pellets illustrate the robustness of the biosensor design. Determination of free and total cholesterol in food samples such as butter, lard, and egg yoke was carried out, and the obtained results were advantageously compared with those provided by using a commercial Boehringer test kit. PMID:11305650

  18. 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

  19. [Investigations on the usefulness of the dry chemistry blood anaylsis system SPOTCHEM SP-4410in laboratory diagnosis of cattle].

    Science.gov (United States)

    Lorenz, I; Aigner, M; Klee, W

    2001-01-01

    The usefulness of the dry-chemistry blood analyzer, SPOTCHEM SP-4410, for analysis of bovine blood chemistry was studied in a veterinary clinic. The control serum Precipath-U, Boehringer-Mannheim, was used to measure precision within each run and between days. The coefficients of variation (CV) ranged between 1.54% and 4.86%, with the exception of albumin and creatine phosphokinase showing a CV of 6.3% and 10.03% for between-day precision. For methodological comparison bovine serum samples were assayed with both the SPOTCHEM SP-4410 and the automated blood analyzer HITACHI 705, which served as a wet-chemistry reference system. The following analytes were measured: glucose, urea, creatinine, total protein, albumin, total bilirubin and the enzymes AST, CPK and gamma-GT. For hemoglobin, which was measured in heparinized whole blood, the CO oximeter 855, CIBA-CORNING, was used as a reference system. The comparative analysis showed very good correlation in eight of ten parameters and their correlation coefficients (r) ranged between 0.962 and 0.998. Only the correlation coefficients of the analysis of total bilirubin (r = 0.903) and albumin (r = 0.771) were less satisfactory. The recovery test was carried out with the two parameters glucose and blood urea. The recovery of glucose was 93.7% and of urea 98.8%. The SPOTCHEM SP-4410 is easy to use and proved to be reliable and accurate, and therefore it seems to be useful for analysis of bovine blood samples. PMID:11225499

  20. The immunocytochemistry of cytokeratin in fish tissues.

    Science.gov (United States)

    Bunton, T E

    1993-09-01

    An increasing interest in fish species as sentinels of environmental pollution and in carcinogenesis research has led to the identification of diagnostically challenging neoplasms of uncertain cellular origin and the need for additional diagnostic methods. To determine the potential of using commercially available antibodies to intermediate filament proteins on paraffin-embedded fish tissues for immunocytochemistry in tumor diagnosis, the application of three antikeratin antibodies to normal adult tissues from two fish species was assessed. Multiple tissues from 12-14-in. striped bass (Morone saxatilis) and 6-month-old medaka (Oryzias latipes) of both sexes were fixed in Bouin's or formalin fixatives. Formalin-fixed neoplasms from several mammalian species, including cat, dog, hedgehog (Atelerix albiventris, Erinaceus europaeus), rhesus macaque (Macaca mulatta), and sloth bear (Melursus ursinus), were also used as positive controls. Using a strepavidin horseradish peroxidase method on paraffin-embedded tissues, the broad spectrum antibodies AE1/AE3 (Boehringer Mannheim, Indianapolis, IN) and MAK-6 (Triton Biosciences, Alameda, CA), which recognize most of the 19 human cytokeratins, and CAM 5.2 (Becton Dickinson, Mountain View, CA), which recognizes cytokeratins present in human liver, were used as primary antibodies. Epithelia from skin, gills, cornea, bile ducts, renal tubules, gastrointestinal tract, and thymus were strongly positive with AE1/AE3 and MAK-6 in striped bass, but nonepithelial tissues such as bone and muscle were negative. Skin, gills, cornea, and portions of the gastrointestinal tract were strongly positive in medaka with the same antibodies, whereas bile duct, renal, and intestinal epithelia were less so. Tissue digestion improved the intensity of staining, and fixation with Bouin's fixative improved results somewhat compared with formalin fixation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7505508

  1. Thyroid function in newborn infants from goitrous and non goitrous mothers.

    Science.gov (United States)

    Sunartini; Nakamura, H

    1991-12-01

    Endemic goiter is one of the health effects of iodine deficiency. Enlargement of the thyroid is often seen during pregnancy especially in the endemic iodine deficiency disorders (IDD) areas. Thyroid hormones have a vital role in the fetal development and maturation of the brain. The lack of these hormones may result in neurological damage. We measured thyroid hormones and TSH in cord blood and TSH in newborn's blood from dry blood spots on filter paper in 5-14 th days, from 58 non goitrous and 61 goitrous mothers. T4, T3 and TSH concentrations in cord blood were measured by enzymeimmunoassay (EIA) using enzymum test Boehringer and TSH from dry blood spots on filter paper were measured by radioimmunoassay (RIA). Goiter size was graded as follows: O, I, II and III. There were significant differences in cord serum T3 concentrations between non goitrous and goitrous mothers with grade I, II and III. TSH concentration in newborn's blood from goitrous mothers of grade III were significantly higher than those from non goitrous mothers and from goitrous mothers of grade I. T4 concentration in cord blood from non goitrous mothers in IDD area was significantly lower than those from non IDD area and those from goitrous mothers in the IDD area. There were significant differences also between TSH concentration in newborn's blood spots from goitrous mothers in IDD area and those from goitrous mothers in non IDD area and from non goitrous mothers in IDD area. Two cases of congenital hypothyroidism were found in infants from goitrous mothers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1817205

  2. Concentration of total proteins in blood plasma of chickens hatched from irradiated eggs with low dose gamma radiation

    International Nuclear Information System (INIS)

    It is known that low-dose ionising radiation may have stimulating effects on chickens. Low doses may also cause changes in the concentration of blood plasma total proteins, glucose and cholesterol in chickens. This study investigates the effects of low dose gamma-radiation on the concentration of total proteins in the blood plasma of chickens hatched from eggs irradiated with a dose of 0.15 Gy on incubation days 7 and 19. Results were compared with the control group (chickens hatched from non-irradiated eggs). After hatching, all other conditions were the same for both groups. Blood samples were drawn from the heart, and later from the wing vein on days 1, 3, 5, 7,10, 20, 30 and 42. The concentration of total proteins was determined spectrophotometrically using Boehringer Mannheim GmbH optimised kits. The concentration of total proteins in blood plasma in chickens hatched from eggs irradiated with 0.15 Gy on incubation day 7 showed a statistically significant decrease on the sampling day 3 (P less than 0.05) and 7 (P less than 0.01). The concentration of total proteins in blood plasma in chickens hatched from eggs irradiated with 0.15 Gy on incubation day 19 showed a statistically significant increase only on sampling day 1 (P less than 0.05). These results suggest that exposure of eggs to 0.15 Gy of gamma-radiation on the 7th and 19th day of incubation could produce different effects on the protein metabolism in chickens.(author)

  3. Laboratory and bedside evaluation of portable glucose meters.

    Science.gov (United States)

    Nichols, J H; Howard, C; Loman, K; Miller, C; Nyberg, D; Chan, D W

    1995-02-01

    A two-phase, laboratory and bedside, evaluation of blood glucose meters was conducted in this study. Four meters, the AccuData Easy (Boehringer-Mannheim, Indianapolis, IN), HemoCue Glucose (HemoCue, Mission Viejo, CA), LifeScan One Touch II (LifeScan, Milpitas, CA), and Miles Encore QA (Miles, Elkhart, IN) systems, were compared to the Nova Stat Profile 5 (Nova, Waltham, MA) as the laboratory reference. Precision, linearity, correlation to the laboratory method, interference from hematocrit, data management, and operator preference were examined. None of the meters were found to satisfy all of the study's evaluation criteria. Therefore, institutions must weigh which criteria are most important to their individual settings. Although the HemoCue Glucose was found to be technically superior, this meter had no data management capabilities. The Encore QA had greater variance and low bias, whereas the AccuData Easy had bias affected by hematocrit and glucose concentration, and the One Touch II had a negative hematocrit bias and limited linear range when compared to the Nova. Only meters meeting both minimal analytical performance and computerization requirements, the One Touch II and AccuData Easy, were selected for further evaluation. At the bedside, the One Touch II demonstrated performance consistent with the lab evaluation, whereas the AccuData Easy showed greater imprecision in the low glucose range and a correlation that varied with sample type: capillary, venous, or arterial blood. This evaluation indicates that the clinician must interpret near-patient glucose results with respect to meter limitations. FDA approval and marketing statistics, alone, are insufficient to judge the performance of the meters in routine institutional use. Independent method validation, under actual operating conditions, is a better means of predicting future performance of the meters. PMID:7856571

  4. The Service Laboratory - A GTZ-BgVV project: Health protection through adapted veterinary diagnostic techniques

    International Nuclear Information System (INIS)

    The customary diagnostic methods of today have been developed in industrialized countries. High costs for personnel resulted in a trend towards automation and prefabricated test kits. Consequently, these techniques are not sufficiently adapted to local conditions in developing countries, where, as a rule, skilled and ancillary staff is available whereas foreign currency reserves for purchasing laboratory equipment and material from abroad are rather limited. Furthermore, the training of personnel from developing countries has usually been oriented towards thenon-transferable standards and methods of industrialized countries. This leads to a long term dependence of the diagnostic services on external funding. A diagnostic technology adapted to the specific local conditions of developing countries is needed to overcome this situation. The project activities concentrate on serological diagnostic work. Here, basic knowledge of the common diagnostic techniques and their set-up for specific diseases, methods for the production of related reagents (antigens, antibodies, conjugates, complement, etc.) and cleaning procedures for the reuse of 'one way' plastic material is spread by training programmes, specific publications and information leaflets. For two of the more complex test procedures, the most frequently quoted prescribed test for international trade, CFT, and the increasingly important ELISA (OIE, Manual of Standards for Diagnostic Techniques, Paris, 1992), we have calculated the cost reduction potential of adaptation through self-production of reagents and reuse of plastic materials. Material costs per microtitre test plate for the diagnosis of brucellosis can be reduced from US $3.79 to 0.82 for CFT and from US $3.88 to 1.13 for ELISA. In comparison, commercial ELISA kits cost about US $80 to 90 per plate (e.g. Bommeli, IDEXX, Boehringer)

  5. Dynamics of ceruloplasmin amd of some blood parameters in piglets suffering from acute radiation disease

    International Nuclear Information System (INIS)

    Changes in oxidase activity of ceruloplasmin (CP) were followed up after treatment with gamma rays of 60Co with a dose of 4 Ey (dose power 0.68 Ey/min) in the blood serum of male piglets of an average life weight of 18+-3 kg. CP level from 217 E/l raised to 376 E/l on the 16th hour after radiation and on the 16th day decreased to 296 e/l. Moreover, serum copper increased from 25 μmol/l to 42.3 μmol/l on the 16th hour following irradiation but on the 14th day its level dropped to 32.5 μmol/l. Erythrocyte and leucocyte count decreased from 5.83x1012/l and 19.94x1012/l to 2.47x1012/l and 2.0x109/l, respectively. Besides, serum albumin decreased, but α-and β-globulins increased. Examination of ailing piglets showed a paraclinical pattern of an inflammatory process by acute radiation disease. CP as an antioxidant participates in reactions with toxic radiacals on radiation. By the rising of its level on radiation it again was characterized as an acute-phase protein. Serum CP was determined according to the method of Ravin using as substrate P-phenylendiamine dihydrochloride; serum copper - by the test of Boehringer Mannheim; serum proteins were studied electrophoretically on agarose gels using veronal buffer, pH 8.6

  6. 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

  7. Radioimmunoassay of serum digoxin levels in digitalis intoxication

    International Nuclear Information System (INIS)

    For 101 hospitalized patients where clinical symptoms of a glucosidine intoxication as a consequence of oral digoxin treatment were noted, serum digoxin levels were determined using a RIA kit of the Boehringer company (I-125 tracer, solid phase tube separation technique) on a fasted stomach prior to oral drug administration. An ECG was performed simultaneously and in addition kidney function parameters and electrolyte levels were determined. An anamnesis and clinical examination of the patients were also conducted. Interferences in the RIA method and gastro-intestinal illness resulting in changes in resorption behaviour were excluded. The group of patients showed collectively an average serum digoxin level of 2.9 +- 0.9 ng/ml with a range from 1.8 to 6.8 ng/ml, which was statistically significantly higher than the average value for 101 patients receiving long-term oral medication but without symptoms of glycosidine intoxication. According to the manufacture's specifications for the RIA kit, values > 2.0 ng/ml are considered as toxic, with values between 1.6 and 2.0 ng/mg falling into a ''grey zone''. A correlation was found between toxic serum values with changes in ECG pattern and subjective clinical symptoms of intoxication. A limitation of kidney function was responsible for the high serum glycoside levels in 62% of the patients. It was shown that the differing response of patients towards digitalis medication, above all in the case of long-term therapy, warrants an RIA determination of serum glycoside values in order to adjust the digoxin dose to individual requirements. (orig./MG)

  8. 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

  9. 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

    • Title of paper: the induction of P-53 independent programmed cell death (apoptosis) with ionizing radiation and 5-fluorouracil (5-FU) in the HT-29 human colon carcinoma cell line

      International Nuclear Information System (INIS)

      Purpose/Objective: The role of programmed cell death (apoptosis) as a cellular response to cancer therapy such as radiation or chemotherapy is the subject of much study, and manipulation of the apoptotic response in tumor cells may be valuable in the treatment of a variety of cancers. Both p53 dependent and independent apoptotic pathways have been identified; p53 is mutated in at least 50 % of human cancers and a majority of radiation resistant tumors contain p53 mutations. This study is designed to examine the induction of programmed cell death in a human colon carcinoma cell line that possesses two mutated p53 alleles. Ionizing radiation alone, or in combination with the chemotherapeutic drug 5-fluorouracil (5-FU), were used to elicit the apoptotic response. This study will focus on whether these treatments can induce a significant apoptotic response in cells that have mutated p53 alleles. Materials and Methods: HT-29 cells were assessed for clonogenic survival after being plated at a variety of densities, and treated with single graded doses of radiation (0, 1, 2, 4, 6, 8, 10 Gy) either alone or immediately prior to a 24 hour exposure to 5-FU (2 ug/ml). The extent of radiation and 5-FU-induced apoptosis was determined in the HT-29 cell line after single doses of 0, 2, 5, and 10 Gy either alone or immediately prior to a 24 hour incubation in 5-FU (2 ug/ml). Three separate assays were used to evaluate the apoptotic response. Cells undergoing apoptosis undergo gross morphological changes including a condensation of chromatin, membrane blebbing, and an eventual release of membrane bound cytoplasmic fragments. Hematoxylin and eosin staining were used to visualize some of these morphological changes. Another characteristic of the apoptotic response is the activation of an endonuclease that cleaves DNA into specific fragments. Accordingly, an ELISA cell death assay (Boehringer Mannheim, Indianapolis IN) was used to quantitate cytoplasmic histone-associated DNA