Bench-to-bedside review: High-mobility group box 1 and critical illness

High-mobility group box 1 (HMGB1) is a DNA-binding protein that also exhibits proinflammatory cytokine-like activity. HMGB1 is passively released by necrotic cells and also is actively secreted by immunostimulated macrophages, dendritic cells, and enterocytes. Although circulating HMGB1 levels are increased relative to healthy controls in patients with infections and severe sepsis, plasma or serum HMGB1 concentrations do not discriminate reliably between infected and uninfected critically ill patients. Nevertheless, administration of drugs that block HMGB1 secretion or of anti-HMGB1 neutralizing antibodies has been shown to ameliorate organ dysfunction and/or improve survival in numerous animal models of critical illness. Because HMGB1 tends to be released relatively late in the inflammatory response (at least in animal models of endotoxemia or sepsis), this protein is an attractive target for the development of new therapeutic agents for the treatment of patients with various forms of critical illness

Aerodynamic data on a large semispan tilting wing with 0.5-diameter chord, double-slotted flap, and both left-hand and right-hand rotation of a single propeller

Longitudinal aerodynamic data on large-scale semispan V/STOL tilt-wing configuration having single propeller with left and right hand rotatio

Bench-to-bedside review: Amelioration of acute renal impairment using ethyl pyruvate

Inflammation and oxidative stress cause renal impairment. Renal failure exacerbates the effect of oxidative stress on many organ systems. Antioxidants can prevent or treat renal failure in various experimental models and clinical situations. Pyruvate is an endogenous antioxidant with beneficial effects in animal models of oxidative stress. Because sodium pyruvate rapidly degrades in solution, a simple derivative of pyruvic acid, namely ethyl pyruvate, has been investigated as a therapeutic agent in preclinical studies. Ethyl pyruvate reduces organ system damage in ischaemia/reperfusion injury and haemorrhagic and endotoxic shock, at least in part through its antioxidant action. In addition, ethyl pyruvate appears to have direct beneficial effects on cytokine expression and proinflammatory gene regulation. The effect is long lasting and, importantly, even when it is administered after the onset of inflammation it can ameliorate organ damage and improve survival. Ethyl pyruvate is a widely used as a food additive and was shown to be safe in phase I clinical trials. We suggest ethyl pyruvate warrants further evaluation in the management of acute renal impairment