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An Acute Respiratory Distress Syndrome Drug Development Collaboration Stimulated By The Virginia Drug Discovery Consortium, John S. Lazo, Ruben M.L. Colunga-Biancatelli, Pavel A. Solopov, John D. Catravas
An Acute Respiratory Distress Syndrome Drug Development Collaboration Stimulated By The Virginia Drug Discovery Consortium, John S. Lazo, Ruben M.L. Colunga-Biancatelli, Pavel A. Solopov, John D. Catravas
Bioelectrics Publications
The genesis of most older medicinal agents has generally been empirical. During the past one and a half centuries, at least in the Western countries, discovering and developing drugs has been primarily the domain of pharmaceutical companies largely built upon concepts emerging from organic chemistry. Public sector funding for the discovery of new therapeutics has more recently stimulated local, national, and international groups to band together and focus on new human disease targets and novel treatment approaches. This Perspective describes one contemporary example of a newly formed collaboration that was simulated by a regional drug discovery consortium. University of Virginia, …
The Hsp90 Inhibitor, Auy-922, Protects And Repairs Human Lung Microvascular Endothelial Cells From Hydrochloric Acid-Induced Endothelial Barrier Dysfunction, Ruben M.L. Colunga Biancatelli, Pavel Solopov, Betsy Gregory, John D. Catravas
The Hsp90 Inhibitor, Auy-922, Protects And Repairs Human Lung Microvascular Endothelial Cells From Hydrochloric Acid-Induced Endothelial Barrier Dysfunction, Ruben M.L. Colunga Biancatelli, Pavel Solopov, Betsy Gregory, John D. Catravas
Bioelectrics Publications
Exposure to hydrochloric acid (HCl) leads acutely to asthma-like symptoms, acute respiratory distress syndrome (ARDS), including compromised alveolo-capillary barrier, and respiratory failure. To better understand the direct effects of HCl on pulmonary endothelial function, we studied the characteristics of HCl-induced endothelial barrier dysfunction in primary cultures of human lung microvascular endothelial cells (HLMVEC), defined the involved molecular pathways, and tested the potentially beneficial effects of Heat Shock Protein 90 (HSP90) inhibitors. HCl impaired barrier function in a time- and concentration-dependent manner and was associated with activation of Protein Kinase B (AKT), Ras homolog family member A (RhoA) and myosin light …
The Hsp90 Inhibitor, Auy-922, Ameliorates The Development Of Nitrogen Mustard-Induced Pulmonary Fibrosis And Lung Dysfunction In Mice, Pavel Solopov, Ruben M.L. Colunga Biancatelli, Margarita Marinova, Christiana Dimitropoulou, John D. Catravas
The Hsp90 Inhibitor, Auy-922, Ameliorates The Development Of Nitrogen Mustard-Induced Pulmonary Fibrosis And Lung Dysfunction In Mice, Pavel Solopov, Ruben M.L. Colunga Biancatelli, Margarita Marinova, Christiana Dimitropoulou, John D. Catravas
Bioelectrics Publications
Increased levels of heat shock protein 90 (HSP90) have been recently implicated in the pathogenesis of pulmonary fibrosis and the use of HSP90 inhibitors constitutes a potential therapeutic approach. Similarly, acute exposure to nitrogen mustard (NM) is related to the development of chronic lung injury driven by TNF-α, TGF-β, ERK and HSP90. Thus, we developed a murine model of NM-induced pulmonary fibrosis by instilling C57BI/6J mice with 0.625 mg/kg mechlorethamine hydrochloride. After 24 h, mice began receiving AUY-922, a second generation HSP90 inhibitor, at 1 mg/kg 2 times per week or 2 mg/kg 3 times per week, for either 10 …