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10.1667/RR14403.2 http://scihub22266oqcxt.onion/10.1667/RR14403.2 C5278768!5278768 !27841740     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=27841740 &cmd=llinks): Failed to open stream: HTTP request failed! 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IPW-5371 Proves Effective as a Radiation Countermeasure by Mitigating Radiation-Induced Late Effects |pdf=|usr=}}{{27841740 }} gab.com Text IPW-5371 Proves Effective as a Radiation Countermeasure by Mitigating Radiation-Induced Late Effects JO: Radiat Res http://www.kidney.de/pget.php?&tw=1&pmid=27841740 #FOAvip There is an ongoing and significant need for radiation countermeasures to reduce morbidities and mortalities associated with exposure of the heart and lungs from a radiological or nuclear incidents. Radiation-induced late effects occur months to years after exposure, stemming from significant tissue damage and remodeling, resulting in fibrosis and loss of function. TGF-? is reported to play a role in both pulmonary and cardiac fibrosis. We investigated the ability of a small molecule TGF-? receptor 1 inhibitor, IPW-5371, to mitigate the effects of thoracic irradiation in C57L/J mice, a murine model that most closely resembles that observed in humans in the induction of fibrosis and dose response. To simulate a radiological event, radiation was administered in two doses: 5 Gy total-body irradiation (eliciting a whole-body response) and immediately after that, a thoracic "top-up" of 6.5 Gy irradiation, for a total dose of 11.5 Gy to the thorax. IPW-5371 was administered once daily, orally, starting 24 h postirradiation for 6 or 20 weeks at a dose of 10 mg/kg or 30 mg/kg. Animals were monitored for a period of 180 days for survival, and cardiopulmonary injury was assessed by echocardiography, breathing rate and arterial oxygen saturation. Exposure of the thorax (11.5 Gy) induced both pulmonary and cardiac injury, resulting in a reduced life span with median survival of 135 days. IPW-5371 treatment for 6 weeks, at both 10 mg/kg and 30 mg/kg, delayed disease onset and mortality, with median survival of 165 days. Twenty weeks of IPW-5371 treatment at 30 mg/kg preserved arterial O(2) saturation and cardiac contractile reserve and resulted in significant decreases in breathing frequency and cardiac and pulmonary fibrosis. This led to dramatic improvement in survival compared to the irradiated, vehicle-treated group (P < 0.001), and was statistically insignificant from the nonirradiated group. We observed that IPW-5371 treatment resulted in decreased pSmad3 tissue levels, confirming the effect of IPW-5371 on TGF-? signaling. These results demonstrate that IPW-5371 represents a potentially promising radiation countermeasure for the treatment of radiation-induced late effects. Twit Text FOAVip IPW-5371 Proves Effective as a Radiation Countermeasure by Mitigating Radiation-Induced Late Effects ????Radiat Res http://www.kidney.de/pget.php?&tw=1&pmid=27841740 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27841740 #FOAvip English Wikipedia <ref>{{Cite pmid|27841740 }}</ref> IPW-5371 Proves Effective as a Radiation Countermeasure by Mitigating Radiation-Induced Late Effects #MMPMID27841740 Rabender C ; Mezzaroma E ; Mauro AG ; Mullangi R ; Abbate A ; Anscher M ; Hart B ; Mikkelsen R Radiat Res 2016[Nov]; 186 (5 ): 478-488 PMID27841740 show ga There is an ongoing and significant need for radiation countermeasures to reduce morbidities and mortalities associated with exposure of the heart and lungs from a radiological or nuclear incidents. Radiation-induced late effects occur months to years after exposure, stemming from significant tissue damage and remodeling, resulting in fibrosis and loss of function. TGF-? is reported to play a role in both pulmonary and cardiac fibrosis. We investigated the ability of a small molecule TGF-? receptor 1 inhibitor, IPW-5371, to mitigate the effects of thoracic irradiation in C57L/J mice, a murine model that most closely resembles that observed in humans in the induction of fibrosis and dose response. To simulate a radiological event, radiation was administered in two doses: 5 Gy total-body irradiation (eliciting a whole-body response) and immediately after that, a thoracic "top-up" of 6.5 Gy irradiation, for a total dose of 11.5 Gy to the thorax. IPW-5371 was administered once daily, orally, starting 24 h postirradiation for 6 or 20 weeks at a dose of 10 mg/kg or 30 mg/kg. Animals were monitored for a period of 180 days for survival, and cardiopulmonary injury was assessed by echocardiography, breathing rate and arterial oxygen saturation. Exposure of the thorax (11.5 Gy) induced both pulmonary and cardiac injury, resulting in a reduced life span with median survival of 135 days. IPW-5371 treatment for 6 weeks, at both 10 mg/kg and 30 mg/kg, delayed disease onset and mortality, with median survival of 165 days. Twenty weeks of IPW-5371 treatment at 30 mg/kg preserved arterial O(2) saturation and cardiac contractile reserve and resulted in significant decreases in breathing frequency and cardiac and pulmonary fibrosis. This led to dramatic improvement in survival compared to the irradiated, vehicle-treated group (P < 0.001), and was statistically insignificant from the nonirradiated group. We observed that IPW-5371 treatment resulted in decreased pSmad3 tissue levels, confirming the effect of IPW-5371 on TGF-? signaling. These results demonstrate that IPW-5371 represents a potentially promising radiation countermeasure for the treatment of radiation-induced late effects. |Animals [MESH] |Cardiomyopathies/drug therapy/etiology/metabolism/pathology [MESH] |Collagen/metabolism [MESH] |Female [MESH] |Half-Life [MESH] |Lung/drug effects/metabolism/radiation effects [MESH] |Male [MESH] |Mice [MESH] |Myocardium/metabolism [MESH] |Protein Serine-Threonine Kinases/antagonists & inhibitors [MESH] |Radiation Injuries, Experimental/drug therapy/etiology/metabolism/pathology [MESH] |Radiation-Protective Agents/pharmacokinetics/*pharmacology/therapeutic use [MESH] |Receptor, Transforming Growth Factor-beta Type I [MESH] |Receptors, Transforming Growth Factor beta/*antagonists & inhibitors [MESH] |Respiration/drug effects/radiation effects [MESH] |Signal Transduction/drug effects/radiation effects [MESH] |Survival Analysis [MESH]IPW-5371 Proves Effective as a Radiation Countermeasure by Mitigating (epmc).pdf DeepDyve Pubget Overpricing