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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Several lines of evidence suggest a biological role for peroxisome proliferator-activated receptor (PPAR) beta/delta in the pathogenesis of a number of diseases. The aim of this study was to investigate the effects of a high-affinity PPAR-beta/delta agonist, GW0742, in a mouse model of carrageenan (CAR)-induced pleurisy. ⋯ Administration of GW0742 (0.3 mg/kg, i.p. bolus) 30 min before and 30 min after a challenge with CAR caused a reduction in all the parameters of inflammation measured. Thus, based on these findings, we propose that a PPAR-beta/delta agonist such as GW0742 may be useful in the treatment of various inflammatory diseases.
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Microcirculatory dysfunction plays a pivotal role in the clinical development and manifestation of severe sepsis and as a marker for mortality. During this process, endothelial damage is characterized by structural and functional alterations that contribute to a great extent to tissue edema. Recent findings revealed the vagus nerve as an important transmitter of the cholinergic anti-inflammatory pathway. ⋯ On the other hand, venular wall shear rate showed no differences. In summary, by inducing the cholinergic anti-inflammatory pathway, physostigmine reduced the capillary leakage and the leukocyte-endothelial interaction. The treatment with physostigmine in endotoxemia may be of interest for clinical use, and further studies should be performed.
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This study describes increased sarcolemmal permeability and myofilamentar damage that occur together with lipid peroxidation and protein nitration in the myocardium in severe sepsis induced by cecal ligation and puncture. Male C57BL/6 mice were submitted to moderate and severe septic injury and sham operation. Using light and laser confocal microscopy, diffuse foci of myocytolysis associated with focal disruption of the actin/myosin contractile apparatus could be seen in hearts with severe septic injury. ⋯ On electron microscopy, these changes were seen to correspond to spread blocks of a few myocytes with fragmentation and dissolution of myofibrils, intracellular edema, and, occasionally, rupture of the sarcolemma. In addition, oxidative damage to lipids, using anti-4-hydroxynonenal, an indicator of oxidative stress and disruption of plasma membrane lipids, and to proteins, using antinitrotyrosine, a stable biomarker of peroxynitrite-mediated protein nitration, was demonstrated. These findings make plausible the hypothesis that increased sarcolemmal permeability might be a primary event in myocardial injury in severe sepsis possibly due to oxidative damage to lipids and proteins that could precede phenotypic changes that characterize a septic cardiomyopathy.
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The Acute Kidney Injury Network (AKIN) group has recently proposed modifications to the risk of renal failure, injury to kidney, failure of kidney function, loss of kidney function, and end-stage renal failure (RIFLE) classification system. The few studies that have compared the two classifications have revealed no substantial differences. This study aimed to compare the AKIN and RIFLE classifications for predicting outcome in critically ill patients. ⋯ Hosmer and Lemeshow goodness-of-fit test results demonstrated good fit in both systems. The AKIN and RIFLE scoring systems displayed good areas under the receiver operating characteristic curves (0.720 + or - 0.030, P = 0.001; 0.738 + or - 0.030, P = 0.001, respectively). Compared with RIFLE criteria, this study indicated that AKIN classification does not improve the sensitivity and ability of outcome prediction in critically ill patients.