Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Acute kidney injury (AKI) frequently occurs in hospitalized patients, particularly in the elderly. However, studies on outcome-modifying factors in geriatric patients with AKI are absent, especially the influence of body mass index (BMI). ⋯ The U-shaped association of BMI with hospital mortality in geriatric AKI patients contains a widened base and a shifted nadir comparing with chronic dialysis and other AKI patients. This finding is interesting and warrants our attention.
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Small molecule nonpeptidyl molecules are potentially attractive drug candidates as adjunct therapies in the treatment of sepsis-induced metabolic complications. As such, the current study investigates the use of aurintricarboxylic acid (ATA), which stimulates insulinlike growth factor 1 receptor and AKT signaling, for its ability to ameliorate the protein metabolic effects of endotoxin (lipopolysaccharide [LPS]) + interferon γ (IFN-γ) in C2C12 myotubes and sepsis in skeletal muscle. Aurintricarboxylic acid dose- and time-dependently increases mTOR (mammalian or mechanistic target of rapamycin)-dependent protein synthesis. ⋯ The ability of ATA to antagonize LPS/IFN-γ-induced changes in protein metabolism was associated with its ability to prevent the increases in interleukin 6 and nitric oxide synthase 2 and decreases in insulinlike growth factor 1. In vivo studies indicate ATA acutely increases skeletal muscle, but not cardiac, protein synthesis and attenuates the loss of lean body mass over 5 days. These data suggest ATA and other small molecule agonists of endogenous anabolic hormones may prove beneficial in treating sepsis by decreasing the inflammatory response and improving muscle protein balance.