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Breakdown of endothelial barrier function is a hallmark event across a variety of pathologies such as inflammation, cancer, and diabetes. It has also been appreciated that steroid hormones impart direct biological activity on endothelial cells at many levels. The purpose of this investigation was to explore the effect of the androgen-like steroid, danazol, on endothelial cell barrier function in vitro. Primary human endothelial cells exposed to 0.01-50 μM danazol were evaluated for changes in permeability. We found that danazol altered endothelial permeability in a biphasic manner in which nanomolar concentrations enhance barrier function while micromolar concentrations are detrimental. Monitoring of trans-endothelial electrical resistance demonstrated that these barrier enhancing effects were rapid (within 5 min) and lasted for over 24h. Analysis of intracellular f-actin organization showed that barrier enhancement also correlated with the formation of a submembranous cortical actin ring. Conversely, at higher danazol concentrations, contractile cell phenotypes were observed, represented by stress fiber formation. Competitive binding studies performed using steroid hormone receptor antagonists proved that this activity is the result of androgen and estrogen receptor ligation. These findings suggest that low dose danazol may provide a therapeutic window for diseases involving vascular leakage., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The amount of oxidative stress in severely traumatized patients is usually based on various individual parameters such as total antioxidants and lipid peroxidation. Serial measurements of plasma oxidation-reduction potential (ORP) in severely traumatized patients as a simple mean of assessing overall oxidative stress is described. Serial whole blood samples were obtained from multi-trauma patients (N=39) and healthy individuals (N=10). Plasma ORP in multi-trauma patients increased during the first few days of hospitalization and approached normal ORP levels upon discharge. On the ORP maxima day (5.8 days+/-0.5 SEM), a statistically significant decrease (p<0.05) was observed for negative acute phase reactants such as plasma paraoxonase-arylesterase (PON-AE) activity and total plasma protein in comparison with admission plasma levels. Monitoring ORP could be a useful tool for assessing the degree of oxidative stress, inflammation, severity of injury, and potential efficacy of treatment.