Biomedical Engineering and Bioengineering Commons^™

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, …

Effect Of Cannabinoid Treatment On Immune Cell Functions During Acute Lung Injury, Amira Kamil Mohammed

Theses and Dissertations

Staphylococcal enterotoxin B (SEB) is a highly potent CDC select agent that can trigger acute lung injury (ALI) via robust T cell proliferation and differentiation, and massive cytokine and chemokine release. Δ9-Tetrahydrocannabinol (THC) is a psychoactive ingredient found in Cannabis sativa. In the current study, we investigated the effects of treatment with THC on SEB-induced acute lung injury. To this end, acute lung injury was induced by a dual dose of SEB in C3H/HeJ mice, which were then treated with vehicle or THC. THC-treatment led to survival of all the SEB-administered mice when compared to vehicle-treated. This corroborated with THC-induced …

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 …

99mtc-Hexamethylpropyleneamine Oxime Imaging For Early Detection Of Acute Lung Injury In Rats Exposed To Hyperoxia Or Lipopolysaccharide Treatment, Said H. Audi, Anne V. Clough, Steven T. Haworth, Meetha Medhora, Mahsa Ranji, John C. Densmore, Elizabeth R. Jacobs

Biomedical Engineering Faculty Research and Publications

^99mTc-Hexamethylpropyleneamine oxime (HMPAO) is a clinical single-photon emission computed tomography biomarker of tissue oxidoreductive state. Our objective was to investigate whether HMPAO lung uptake can serve as a preclinical marker of lung injury in two well-established rat models of human acute lung injury (ALI).

Rats were exposed to >95% O₂ (hyperoxia) or treated with intratracheal lipopolysaccharide (LPS), with first endpoints obtained 24 h later. HMPAO was administered intravenously before and after treatment with the glutathione-depleting agent diethyl maleate (DEM), scintigraphy images were acquired, and HMPAO lung uptake was quantified from the images. We also measured breathing rates, heart …

In Vivo Detection Of Hyperoxia-Induced Pulmonary Endothelial Cell Death Using 99mTc-Duramycin, Said H. Audi, Elizabeth R. Jacobs, Ming Zhao, David L. Roerig, Steven T. Haworth, Anne V. Clough

Biomedical Engineering Faculty Research and Publications

Introduction

^99mTc-duramycin, DU, is a SPECT biomarker of tissue injury identifying cell death. The objective of this study is to investigate the potential of DU imaging to quantify capillary endothelial cell death in rat lung injury resulting from hyperoxia exposure as a model of acute lung injury.

Methods

Rats were exposed to room air (normoxic) or > 98% O₂ for 48 or 60 hours. DU was injected i.v. in anesthetized rats, scintigraphy images were acquired at steady-state, and lung DU uptake was quantified from the images. Post-mortem, the lungs were removed for histological studies. Sequential lung sections were immunostained …

Differential Lung Uptake Of 99mtc-Hexamethylpropyleneamine Oxime And 99mtc-Duramycin In The Chronic Hyperoxia Rat Model, Anne V. Clough, Said H. Audi, Steven Thomas Haworth, David L. Roerig

Biomedical Engineering Faculty Research and Publications

Noninvasive radionuclide imaging has the potential to identify and assess mechanisms involved in particular stages of lung injury that occur with acute respiratory distress syndrome, for example. Lung uptake of ^99mTc-hexamethylpropyleneamine oxime (HMPAO) is reported to be partially dependent on the redox status of the lung tissue whereas ^99mTc-duramycin, a new marker of cell injury, senses cell death via apoptosis or necrosis. Thus, we investigated changes in lung uptake of these agents in rats exposed to hyperoxia for prolonged periods, a common model of acute lung injury. Methods: Male Sprague–Dawley rats were preexposed to either normoxia (21% O …