المؤلفون: G. Todd Milne, on behalf of the Ironwood team, Peter Sandner, Kathleen A. Lincoln, Paul C. Harrison, Hongxing Chen, Hong Wang, Holly Clifford, Hu Sheng Qian, Diane Wong, Chris Sarko, Ryan Fryer, Jeremy Richman, Glenn A. Reinhart, Carine M. Boustany, Steven S. Pullen, Henriette Andresen, Lise Román Moltzau, Alessandro Cataliotti, Finn Olav Levy, Robert Lukowski, Sandra Frankenreiter, Andreas Friebe, Timothy Calamaras, Robert Baumgartner, Angela McLaughlin, Mark Aronovitz, Wendy Baur, Guang-Rong Wang, Navin Kapur, Richard Karas, Robert Blanton, Stefan Hell, Scott A. Waldman, Jieru E. Lin, Francheska Colon-Gonzalez, Gilbert W. Kim, Erik S. Blomain, Dante Merlino, Adam Snook, Jeanette Erdmann, Jana Wobst, Thorsten Kessler, Heribert Schunkert, Ulrich Walter, Oliver Pagel, Elena Walter, Stepan Gambaryan, Albert Smolenski, Kerstin Jurk, Rene Zahedi, James R. Klinger, Raymond L. Benza, Paul A. Corris, David Langleben, Robert Naeije, Gérald Simonneau, Christian Meier, Pablo Colorado, Mi Kyung Chang, Dennis Busse, Marius M. Hoeper, Jaime L. Masferrer, Sarah Jacobson, Guang Liu, Renee Sarno, Sylvie Bernier, Ping Zhang, Roger Flores-Costa, Mark Currie, Katherine Hall, Dorit Möhrle, Katrin Reimann, Steffen Wolter, Markus Wolters, Evanthia Mergia, Nicole Eichert, Hyun-Soon Geisler, Peter Ruth, Robert Feil, Ulrike Zimmermann, Doris Koesling, Marlies Knipper, Lukas Rüttiger, Yasutake Tanaka, Atsuko Okamoto, Takashi Nojiri, Motofumi Kumazoe, Takeshi Tokudome, Koichi Miura, Jun Hino, Hiroshi Hosoda, Mikiya Miyazato, Kenji Kangawa, Vikas Kapil, Amrita Ahluwalia, Nazareno Paolocci, Philip Eaton, James C. Campbell, Philipp Henning, Eugen Franz, Banumathi Sankaran, Friedrich W. Herberg, Choel Kim, M. Wittwer, Q. Luo, V. Kaila, S. A. Dames, Andrew Tobin, Mahmood Alam, Olena Rudyk, Susanne Krasemann, Kristin Hartmann, Oleksandra Prysyazhna, Min Zhang, Lan Zhao, Astrid Weiss, Ralph Schermuly, Amie J. Moyes, Sandy M. Chu, Reshma S. Baliga, Adrian J. Hobbs, Stylianos Michalakis, Regine Mühlfriedel, Christian Schön, Dominik M. Fischer, Barbara Wilhelm, Ditta Zobor, Susanne Kohl, Tobias Peters, Eberhart Zrenner, Karl Ulrich Bartz-Schmidt, Marius Ueffing, Bernd Wissinger, Mathias Seeliger, Martin Biel, RD-CURE consortium, Mark J. Ranek, Kristen M. Kokkonen, Dong I. Lee, Ronald J. Holewinski, Vineet Agrawal, Cornelia Virus, Donté A. Stevens, Masayuki Sasaki, Huaqun Zhang, Mathew M. Mannion, Peter P. Rainer, Richard C. Page, Jonathan C. Schisler, Jennifer E. Van Eyk, Monte S. Willis, David A. Kass, Manuela Zaccolo, Michael Russwurm, Jan Giesen, Corina Russwurm, Ernst-Martin Füchtbauer, Nadja I. Bork, Viacheslav O. Nikolaev, Luis Agulló, Martin Floor, Jordi Villà-Freixa, Ornella Manfra, Gaia Calamera, Nicoletta C. Surdo, Silja Meier, Alexander Froese, Kjetil Wessel Andressen, Annemarie Aue, Fabian Schwiering, Dieter Groneberg, Gzona Bajraktari, Jürgen Burhenne, Walter E. Haefeli, Johanna Weiss, Katharina Beck, Barbara Voussen, Alexander Vincent, Sean P. Parsons, Jan D. Huizinga, Fabiola Zakia Mónica, Edward Seto, Ferid Murad, Ka Bian, Joseph R. Burgoyne, Daniel Richards, Marianne Bjørnerem, Andrea Hembre Ulsund, Jeong Joo Kim, Sonia Donzelli, Mara Goetz, Kjestine Schmidt, Konstantina Stathopoulou, Jenna Scotcher, Christian Dees, Hariharan Subramanian, Elke Butt, Alisa Kamynina, S. Bruce King, Cor de Witt, Lars I. Leichert, Friederike Cuello, Hyazinth Dobrowinski, Moritz Lehners, Michael Paolillo Hannes Schmidt, Susanne Feil, Lai Wen, Martin Thunemann, Marcus Olbrich, Harald Langer, Meinrad Gawaz, Cor de Wit, Daniela Bertinetti, Hossein-Ardeschir Ghofrani, Friedrich Grimminger, Ekkehard Grünig, Yigao Huang, Pavel Jansa, Zhi Cheng Jing, David Kilpatrick, Stephan Rosenkranz, Flavia Menezes, Arno Fritsch, Sylvia Nikkho, Reiner Frey, Marc Humbert, Manuela Harloff, Joerg Reinders, Jens Schlossmann, Joon Jung, Jessica A. Wales, Cheng-Yu Chen, Linda Breci, Andrzej Weichsel, Sylvie G. Bernier, Robert Solinga, James E. Sheppeck, Paul A. Renhowe, William R. Montfort, Liying Qin, Ying-Ju Sung, Darren Casteel, Alexander Kollau, Andrea Neubauer, Astrid Schrammel, Bernd Mayer, Mika Takai, Chieri Takeuchi, Mai Kadomatsu, Shun Hiroi, Kanako Takamatsu, Hirofumi Tachibana, Marissa Opelt, Emrah Eroglu, Markus Waldeck-Weiermair, Roland Malli, Wolfgang F. Graier, John T. Fassett, Selene J. Sollie, Maria Hernandez-Valladares, Frode Berven, Kjetil W. Andressen, Miki Arai, Yutaka Suzuki, Meinoshin Okumura, Shinpei Kawaoka, Stefanie Peters, Hannes Schmidt, B. Selin Kenet, Sarah Helena Nies, Katharina Frank, Fritz G. Rathjen, Olga N. Petrova, Isabelle Lamarre, Michel Négrerie, Jerid W. Robinson, Jeremy R. Egbert, Julia Davydova, Laurinda A. Jaffe, Lincoln R. Potter, Nicholas Blixt, Leia C. Shuhaibar, Gordon L. Warren, Kim C. Mansky, Simone Romoli, Tobias Bauch, Karoline Dröbner, Frank Eitner, Mihály Ruppert, Tamás Radovits, Sevil Korkmaz-Icöz, Shiliang Li, Péter Hegedűs, Sivakanan Loganathan, Balázs Tamás Németh, Attila Oláh, Csaba Mátyás, Kálmán Benke, Béla Merkely, Matthias Karck, Gábor Szabó, Ulrike Scheib, Matthias Broser, Shatanik Mukherjee, Katja Stehfest, Christine E. Gee, Heinz G. Körschen, Thomas G. Oertner, Peter Hegemann, Deborah M. Dickey, Alexandre Dumoulin, Ralf Kühn, Laurinda Jaffe, Sophie Schobesberger, Peter Wright, Claire Poulet, Catherine Mansfield, Sian E. Harding, Julia Gorelik, Gerald Wölkart, Antonius C. F. Gorren, Gerburg K. Schwaerzer, Darren E. Casteel, Nancy D. Dalton, Yusu Gu, Shunhui Zhuang, Dianna M. Milewicz, Kirk L. Peterson, Renate Pilz, Aikaterini I. Argyriou, Garyfalia Makrynitsa, Ioannis I. Alexandropoulos, Andriana Stamopoulou, Marina Bantzi, Athanassios Giannis, Stavros Topouzis, Andreas Papapetropoulos, Georgios A. Spyroulias, Dennis J. Stuehr, Arnab Ghosh, Yue Dai, Saurav Misra, Boris Tchernychev, Inmaculada Silos-Santiago, Gerhard Hannig, Vu Thao-Vi Dao, Martin Deile, Pavel I. Nedvetsky, Andreas Güldner, César Ibarra-Alvarado, Axel Gödecke, Harald H. H. W. Schmidt, Angelos Vachaviolos, Andrea Gerling, Stefan Z. Lutz, Hans-Ulrich Häring, Marcel A. Krüger, Bernd J. Pichler, Michael J. Shipston, Sara Vandenwijngaert, Clara D. Ledsky, Obiajulu Agha, Dongjian Hu, Ibrahim J. Domian, Emmanuel S. Buys, Christopher Newton-Cheh, Donald B. Bloch, Nadine Mauro, Jonas Keppler, Wilson A. Ferreira, Hanan Chweih, Pamela L. Brito, Camila B. Almeida, Carla F. F. Penteado, Sara S. O. Saad, Fernando F. Costa, Paul S. Frenette, Damian Brockschnieder, Johannes-Peter Stasch, Nicola Conran, Daniel P. Zimmer, Jenny Tobin, Courtney Shea, Kimberly Long, Kim Tang, Peter Germano, James Wakefield, Ali Banijamali, G-Yoon Jamie Im, Albert T. Profy, Mark G. Currie

المصدر: BMC Pharmacology and Toxicology, Vol 18, Iss S1, Pp 1-35 (2017)

مصطلحات موضوعية: Therapeutics. Pharmacology, RM1-950, Toxicology. Poisons, RA1190-1270

وصف الملف: electronic resource

العلاقة: http://link.springer.com/article/10.1186/s40360-017-0170-5Test; https://doaj.org/toc/2050-6511Test

الوصول الحر: https://doaj.org/article/30c72e01121341e5b4f739303af28413Test

المؤلفون: Glenn A. Reinhart, Paul C. Harrison, Kathleen Lincoln, Hongxing Chen, Peng Sun, Jon Hill, Hu Sheng Qian, Mark C. McHugh, Holly Clifford, Khing Jow Ng, Hong Wang, Danielle Fowler, Kristina Gueneva-Boucheva, Jehrod B. Brenneman, Todd Bosanac, Diane Wong, Ryan M. Fryer, Chris Sarko, Carine M. Boustany-Kari, Steven S. Pullen

المصدر: The Journal of pharmacology and experimental therapeutics.

مصطلحات موضوعية: Pharmacology, Molecular Medicine

الوصف: Activation of soluble guanylate cyclase (sGC) to restore cyclic guanosine monophosphate (cGMP) and improve functionality of nitric oxide (NO) pathways impaired by oxidative stress is a potential treatment for diabetic and chronic kidney disease. We report the pharmacology of BI 685509, a novel, orally active small molecule sGC activator with disease modifying potential. BI 685509 and human sGC α1/β1 heterodimer containing a reduced heme group, produced concentration-dependent increases in cGMP that were elevated modestly by NO whereas heme-free sGC and BI 685509 greatly enhanced cGMP with no effect of NO. BI 685509 increased cGMP in human and rat platelet-rich plasma treated with the heme-oxidant ODQ; respective EC

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::62247eda3ea47ef82756bd1ee47aafe3Test
https://pubmed.ncbi.nlm.nih.gov/36507845Test

المؤلفون: Neil Moss, Lee Fader, Jeremy R Richman, Stanley Kugler, Matthew A. Cerny, Jennifer Burke, Raquel Arenas, Derek Cogan, Federico Colombo, Maolin Yu, Kosea Frederick, John Lord, Zhidong Chen, Jean-Huges Parmentier, Balestra Michael, Nicholas F. Brown, Steven M. Weldon, Xin Guo, Daniel R. Goldberg, Michael Zhang, Holly Clifford, Jennifer Schmenk, Kenneth M. Meyers, Daniel Richard Marshall, Keith R Hornberger

المصدر: Bioorganic & Medicinal Chemistry Letters. 28:979-984

مصطلحات موضوعية: 0301 basic medicine, Aldosterone synthase, Clinical Biochemistry, Pharmaceutical Science, Biochemistry, Structure-Activity Relationship, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, In vivo, Drug Discovery, medicine, Cytochrome P-450 CYP11B2, Humans, Enzyme Inhibitors, Molecular Biology, chemistry.chemical_classification, Aldosterone, Dose-Response Relationship, Drug, Molecular Structure, ATP synthase, biology, Organic Chemistry, Isoxazoles, Metabolism, In vitro, 030104 developmental biology, Enzyme, medicine.anatomical_structure, chemistry, 030220 oncology & carcinogenesis, Hepatocyte, biology.protein, Molecular Medicine

الوصف: 6,7-Dihydro-5H-2,1-benzisoxazol-4-one analogs are potent inhibitors of aldosterone synthase (CYP11B2) with selectivity over the highly homologous enzyme cortisol synthase (CYP11B1). These compounds are unique among inhibitors of CYP11B2 in their lack of a strong-heme binding group such as a pyridine or imidazole. Poor metabolic stability in hepatocyte incubations was found to proceed via a reduction of the isoxazole ring. While the enzyme responsible for the reductive metabolism remains unknown, the rate of metabolism could be attenuated by the addition of polar functionality. The in vitro CYP11B2 potency and selectivity were confirmed in vivo in a cynomolgus monkey model by the inhibition of ACTH stimulated aldosterone production without impacting plasma cortisol concentrations.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::44b0efa78c0594d187a77fbd86938a66Test
https://doi.org/10.1016/j.bmcl.2017.12.015Test

المؤلفون: Kristina Gueneva-Boucheva, Chris Sarko, Hong Wang, Holly Clifford, Ryan M. Fryer, Hu Sheng Qian, Todd Bosanac, Kathleen A Lincoln, Jeremy Richman, Carine M. Boustany-Kari, Diane Wong, Hongxing Chen, Xiaomei Zhang, Paul C. Harrison, Steven S. Pullen

المصدر: Journal of Pharmacology and Experimental Therapeutics. 356:712-719

مصطلحات موضوعية: Male, 0301 basic medicine, medicine.medical_specialty, Mean arterial pressure, Enalaprilat, Enzyme Activators, Receptors, Cytoplasmic and Nuclear, 030204 cardiovascular system & hematology, Nephropathy, Diabetic nephropathy, Excretion, 03 medical and health sciences, Soluble Guanylyl Cyclase, 0302 clinical medicine, Internal medicine, Diabetes mellitus, medicine, Animals, Diabetic Nephropathies, Pharmacology, Chemistry, Glomerulosclerosis, medicine.disease, Rats, Rats, Zucker, 030104 developmental biology, Endocrinology, Diabetes Mellitus, Type 2, Guanylate Cyclase, Disease Progression, Molecular Medicine, Soluble guanylyl cyclase, medicine.drug

الوصف: Therapies that restore renal cGMP levels are hypothesized to slow the progression of diabetic nephropathy. We investigated the effect of BI 703704, a soluble guanylate cyclase (sGC) activator, on disease progression in obese ZSF1 rats. BI 703704 was administered at doses of 0.3, 1, 3, and 10 mg/kg/d to male ZSF1 rats for 15 weeks, during which mean arterial pressure (MAP), heart rate (HR), and urinary protein excretion (UPE) were determined. Histologic assessment of glomerular and interstitial lesions was also performed. Renal cGMP levels were quantified as an indicator of target modulation. BI 703704 resulted in sGC activation, as evidenced by dose-dependent increases in renal cGMP levels. After 15 weeks of treatment, sGC activation resulted in dose-dependent decreases in UPE (from 463 ± 58 mg/d in vehicle controls to 328 ± 55, 348 ± 23, 283 ± 45, and 108 ± 23 mg/d in BI 703704-treated rats at 0.3, 1, 3, and 10 mg/kg, respectively). These effects were accompanied by a significant reduction in the incidence of glomerulosclerosis and interstitial lesions. Decreases in MAP and increases in HR were only observed at the high dose of BI 703704. These results are the first demonstration of renal protection with sGC activation in a nephropathy model induced by type 2 diabetes. Importantly, beneficial effects were observed at doses that did not significantly alter MAP and HR.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::95609501cd699f0fc38a0d6c48276bb0Test
https://doi.org/10.1124/jpet.115.230706Test

المؤلفون: Fritz G. Rathjen, Timothy D. Calamaras, Hong Wang, Motofumi Kumazoe, Sarah Helena Nies, Jerid W. Robinson, Andreas Friebe, Balázs Tamás Németh, Michel Negrerie, Kjetil W. Andressen, Clara D. Ledsky, Sivakanan Loganathan, Kerstin Jurk, Barbara Voussen, Julia Gorelik, Mi Kyung Chang, Johannes-Peter Stasch, Friederike Cuello, Nicholas C. Blixt, S. A. Dames, Nazareno Paolocci, Gzona Bajraktari, Katherine C. Hall, Markus Waldeck-Weiermair, Marcel A. Krüger, Antonius C.F. Gorren, Donté A. Stevens, Daniel Bloch, Deborah M. Dickey, Maria Hernandez-Valladares, Lan Zhao, Alex Vincent, Jenna Scotcher, Andrzej Weichsel, Tamás Radovits, Jeremy Richman, Sophie Schobesberger, Stavros Topouzis, Regine Mühlfriedel, Dennis Busse, Reiner Frey, Sean P. Parsons, René P. Zahedi, Evanthia Mergia, Mathias W. Seeliger, Angela McLaughlin, Sylvia Nikkho, Fernando Ferreira Costa, Pavel Jansa, Ornella Manfra, Wilson A. Ferreira, Inmaculada Silos-Santiago, B. Selin Kenet, Marc Humbert, Garyfalia Makrynitsa, Katja Stehfest, Lise Román Moltzau, Shiliang Li, Chris Sarko, Lincoln R. Potter, Yusu Gu, Scott A. Waldman, Nicole Eichert, David Kilpatrick, Roland Malli, Jun Hino, Robert Solinga, Banumathi Sankaran, William R. Montfort, Alexander Kollau, Julia Davydova, Andriana Stamopoulou, Olena Rudyk, Johanna Weiss, Kenji Kangawa, Arno Fritsch, Meinrad Gawaz, Peter Sandner, Robert M. Blanton, Friedrich Grimminger, Laurinda Jaffe, Atsuko Okamoto, Elke Butt, Stefanie Peters, Christine E. Gee, Ronald J. Holewinski, Zhi Cheng Jing, Andrea Gerling, Mika Takai, Alexander Froese, Hiroshi Hosoda, Mara Goetz, Yasutake Tanaka, Ioannis I. Alexandropoulos, Amie J Moyes, Hyazinth Dobrowinski, Michael J. Shipston, Ulrike Scheib, Stefan W. Hell, Oleksandra Prysyazhna, Lukas Rüttiger, Dieter Groneberg, Vu Thao-Vi Dao, Ulrich Walter, Hariharan Subramanian, Roger Flores-Costa, Richard C. Page, Joerg Reinders, Huaqun Zhang, Dianna M. Milewicz, Martin Thunemann, Albert T. Profy, Chieri Takeuchi, Andrew B. Tobin, Darren E. Casteel, Sarah Jacobson, Philip Eaton, Cor de Witt, Nadine Mauro, Mark Aronovitz, Sevil Korkmaz-Icöz, Barbara Wilhelm, Angelos Vachaviolos, Kim Tang, Axel Gödecke, Christian Meier, Carine M. Boustany, Daniel P. Zimmer, Bernd J. Pichler, Adrian J. Hobbs, Marianne Bjørnerem, Wolfgang F. Graier, Selene J. Sollie, Jenny Tobin, Jürgen Burhenne, Meinoshin Okumura, Nancy D. Dalton, Matthias Karck, Ernst-Martin Füchtbauer, Karoline Dröbner, Kristen M. Kokkonen, Flavia Menezes, Heribert Schunkert, Kirk L. Peterson, Ying-Ju Sung, Georgios A. Spyroulias, Olga N. Petrova, Frank Eitner, Mark G. Currie, Choel Kim, Ulrike Zimmermann, Steven S. Pullen, Shunhui Zhuang, Camila B. Almeida, Sylvie Bernier, M. Wittwer, Steffen Wolter, Stylianos Michalakis, Ralf Kühn, Sara S. O. Saad, Catherine Mansfield, Joon Jung, Jennifer E. Van Eyk, Navin K. Kapur, Renate B. Pilz, David Langleben, Diane Wong, Sylvie G. Bernier, Leia C. Shuhaibar, Heinz G. Körschen, César Ibarra-Alvarado, Courtney Shea, Ryan M. Fryer, Corina Russwurm, Gilbert W. Kim, Gerald Wölkart, Marius M. Hoeper, Astrid Weiss, Harald F. Langer, Ibrahim J. Domian, Lars I. Leichert, Bernd Wissinger, Paul Allan Renhowe, Richard H. Karas, Masayuki Sasaki, Finn Olav Levy, Cor de Wit, Sonia Donzelli, Michael Russwurm, Eberhart Zrenner, Reshma S. Baliga, Holly Clifford, Jonathan C. Schisler, Cheng-Yu Chen, Nicola Conran, Jens Schlossmann, Vikas Kapil, Pablo Colorado, Boris Tchernychev, Isabelle Lamarre, Katrin Reimann, Francheska Colon-Gonzalez, Ralph T. Schermuly, Hans-Ulrich Häring, Vineet Agrawal, Peter Germano, Bernd Mayer, Katharina Beck, Moritz Lehners, Sara Vandenwijngaert, Fabíola Z. Mónica, Pavel I. Nedvetsky, Kimberly Kafadar Long, Silja Meier, Paul A. Corris, Takeshi Tokudome, Shatanik Mukherjee, Joseph R. Burgoyne, Martin Deile, Jan Giesen, Ferid Murad, G. Todd Milne, Shinpei Kawaoka, Koichi Miura, Jessica A. Wales, David A. Kass, Doris Koesling, Hongxing Chen, Frode S. Berven, Jeong Joo Kim, Friedrich W. Herberg, Kristin Hartmann, Martin Biel, Raymond L. Benza, Monte S. Willis, Daniela Bertinetti, Jaime L. Masferrer, Stefan Z. Lutz, Guang-Rong Wang, Peter Ruth, Viacheslav O. Nikolaev, Tobias Peters, Karl Ulrich Bartz-Schmidt, Arnab Ghosh, Lai Wen, Mai Kadomatsu, Sandy M. Chu, Yutaka Suzuki, Marcus Olbrich, Yigao Huang, Tobias Bauch, Thorsten Kessler, Amrita Ahluwalia, Robert Feil, Daniel Richards, Hu Sheng Qian, M Currie, Christopher Newton-Cheh, V. Kaila, Liying Qin, Peter Hegemann, Peter Wright, G-Yoon Jamie Im, Hirofumi Tachibana, Kjestine Schmidt, Pamela L. Brito, Alisa Kamynina, James C. Campbell, Adam E. Snook, Fabian Schwiering, Martin Floor, Jordi Villà-Freixa, Jana Wobst, Alexandre Dumoulin, Ali R. Banijamali, Csaba Mátyás, Harald H.H.W. Schmidt, Susanne Kohl, Mark J. Ranek, Manuela Zaccolo, Robert Lukowski, Robert Naeije, Peter P. Rainer, Stephan Rosenkranz, Emmanuel S. Buys, Simone Romoli, Andreas Papapetropoulos, Kim C. Mansky, James Wakefield, Kálmán Benke, Takashi Nojiri, Aikaterini I. Argyriou, Dongjian Hu, Glenn A. Reinhart, Cornelia Virus, Marius Ueffing, Marlies Knipper, Gerhard Hannig, Kanako Takamatsu, Athanassios Giannis, Miki Arai, Stepan Gambaryan, James E. Sheppeck, Mathew M. Mannion, S. Bruce King, Henriette Andresen, Min Zhang, Jan D. Huizinga, Jeanette Erdmann, Matthias Broser, Astrid Schrammel, Dante J. Merlino, Hossein Ardeschir Ghofrani, Gaia Calamera, Obiajulu Agha, Kathleen A Lincoln, Gerburg K. Schwaerzer, Gordon L. Warren, Andrea Neubauer, Claire Poulet, Nicoletta C. Surdo, Attila Oláh, Damian Brockschnieder, Emrah Eroglu, Carla Fernanda Franco Penteado, Walter E. Haefeli, Mihály Ruppert, Ekkehard Grünig, Konstantina Stathopoulou, Elena Walter, Gérald Simonneau, Béla Merkely, Andreas Güldner, J Keppler, Katharina Frank, Renee Sarno, Sandra Frankenreiter, Sian E. Harding, Dorit Möhrle, Paul C. Harrison, Péter Hegedűs, Hyun-Soon Geisler, James R. Klinger, Markus Wolters, Philipp Henning, Jieru E. Lin, Erik S. Blomain, Alessandro Cataliotti, Ditta Zobor, Mikiya Miyazato, Marissa Opelt, Christian Schön, John Fassett, Yue Dai, Q. Luo, Thomas G. Oertner, Linda Breci, Robert A Baumgartner, Shun Hiroi, Ping Zhang, Albert Smolenski, Paul S. Frenette, Mahmood M. Alam, Jeremy R. Egbert, Dennis J. Stuehr, Eugen Franz, Hanan Chweih, Dong I. Lee, Nadja I. Bork, Guang Liu, Hannes Schmidt, Ka Bian, Annemarie Aue, Christian Dees, Edward Seto, Manuela Harloff, Michael Paolillo Hannes Schmidt, Susanne Feil, Susanne Krasemann, Andrea Hembre Ulsund, Marina Bantzi, Laurinda A. Jaffe, Luis Agulló, Dominik M. Fischer, Wendy Baur, Kjetil Wessel Andressen, Saurav Misra, Gábor Szabó, Oliver Pagel

المصدر: BMC Pharmacology and Toxicology. 18

مصطلحات موضوعية: 0301 basic medicine, Pharmacology, 03 medical and health sciences, 030104 developmental biology, business.industry, Pharmacology toxicology, MEDLINE, Medicine, Pharmacology (medical), business

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::05aec48c975e5d82e92dcd44250525f9Test
https://doi.org/10.1186/s40360-017-0170-5Test

المؤلفون: Carine M Boustany-Kari, Paul C Harrison, Xongxing Chen, Hu Kathleen Lincoln, Sheng Qian, Holly Clifford, Hong Wang, Xiaomei Zhang, Kristina Gueneva-Boucheva, Todd Bosanac, Diane Wong, Ryan M Fryer, Jeremy G Richman, Chris Sarko, Steven S Pullen

المساهمون: The Pennsylvania State University CiteSeerX Archives

المصدر: http://jpet.aspetjournals.org/content/jpet/early/2016/01/04/jpet.115.230706.full.pdfTest.

وصف الملف: application/pdf

العلاقة: http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.1082.1305Test; http://jpet.aspetjournals.org/content/jpet/early/2016/01/04/jpet.115.230706.full.pdfTest

الإتاحة: http://jpet.aspetjournals.org/content/jpet/early/2016/01/04/jpet.115.230706.full.pdfTest

المؤلفون: Holly Clifford, Glenn Pearson, Peter Franklin, Roz Walker, Graeme Zosky

المصدر: University of Tasmania
University of Western Australia

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=dedup_wf_001::2c5475bbda52a563ba39d782b7f59f30Test
http://healthbulletin.org.auTest/

المؤلفون: Diane Wong, Kathleen A Lincoln, Paul C. Harrison, Hong Wang, Holly Clifford, Jeremy Richman, Carine M. Boustany, Hongxing Chen, HuSheng Qian, Chris Sarko, Jehrod Burnett Brenneman, Glenn A. Reinhart, Steven S. Pullen, Ryan M. Fryer

المصدر: BMC Pharmacology & Toxicology

مصطلحات موضوعية: Pharmacology, medicine.medical_specialty, Creatinine, Mean arterial pressure, Activator (genetics), business.industry, Glomerulosclerosis, medicine.disease, Nitric oxide, Diabetic nephropathy, chemistry.chemical_compound, Endocrinology, chemistry, Internal medicine, Meeting Abstract, Heart rate, medicine, Pharmacology (medical), Enalapril, business, medicine.drug

الوصف: The pathogenesis of diabetic nephropathy is associated with abnormalities of renal nitric oxide generation and signaling. We evaluated the effect of BI 684067, a soluble guanylate cyclase (sGC) activator, in combination with the current standard of care (SoC), on the progression of diabetic nephropathy. Male ZSF1 rats were administered enalapril (3 mg/kg in drinking water) for 10 days, after which they were randomized to either continue to receive enalapril alone or the combination of enalapril and one of three doses of BI 684067 (20, 40 and 80 mg/kg) in chow for 10 weeks. Weekly urinary protein to creatinine ratio (UPCR) as well as daily mean arterial pressure (MAP) and heart rate (HR) were measured. At study end, kidneys were assessed for glomerular lesions and α-SMA expression, a marker of myofibroblast activation. The combination of BI 684067 and enalapril resulted in significant dose-dependent decreases of the following when compared to enalapril alone: UPCR (BI 684067 at 20, 40, and 80 mg/kg : 27, 39, 48% reductions respectively), incidence of glomerulosclerosis (BI 684067 at 20, 40, and 80 mg/kg: 29, 32, 44% reductions, respectively) and α-SMA expression (BI 684067at 20, 40, and 80 mg/kg : 26, 40, 42% reductions, respectively). The MAP was significantly reduced by BI 684067 in combination with enalapril (- 3 mm Hg vs enalapril alone at the doses of 40 and 80 mg/kg), however there was no significant effect on HR. These results support the efficacy of an sGC activator in preventing the progression of diabetic nephropathy when combined with the SoC.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::104bc246a477aaea5aa694330486f287Test