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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Serum micro-RNAs (miRNAs) can be used for the diagnosis and prognosis of various diseases. Using genome-wide scans, we sought to identify serum miRNAs that could be used as prognostic predictors for sepsis patients. We used microarray screens to identify differentially expressed serum miRNAs by comparing samples from 12 surviving and 12 nonsurviving sepsis patients. ⋯ When the cutoff point was set at 0.288, these three combined variables provided 78.13% sensitivity and 91.84% specificity. Our results showed that serum miR-574-5p was correlated with the death of sepsis patients. The combined predictive capability of sepsis stage, Sepsis-Related Organ Failure Assessment scores, and serum miR-574-5p for the death of sepsis patients was better than any single indicator.
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Trauma patients are often transfused allogeneic red blood cells (RBCs) in an effort to augment tissue oxygen delivery. However, the effect of RBC transfusion on microvascular perfusion in this patient population is not well understood. To this end, we investigated the effect of RBC transfusion on sublingual microvascular perfusion in trauma patients. ⋯ Pretransfusion PPC may be selectively deranged in otherwise stable trauma patients. Patients with relatively altered baseline PPC tend to demonstrate improvement in perfusion following transfusion, whereas those with relatively normal perfusion at baseline tend to demonstrate either no change or, in fact, a decline in PPC. Bedside sublingual imaging may have the potential to detect subtle perfusion defects and ultimately inform clinical decision making with respect to transfusion.
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Neurohumoral disturbances characterize chronic heart failure (CHF) and are reflected, in part, as impairment of baroreflex sensitivity (BRS) and sympathetic function. However, the mechanisms that trigger these neurohumoral abnormalities in CHF are not clear. We hypothesized that the BRS is blunted early in CHF and that the humoral effects occur later and contribute to progressive loss of cardiovascular control in CHF. ⋯ The BRS was significantly reduced in all the CHF groups with no significant change in the basal RSNA (% of maximum) after 1 week of pacing; a small but insignificant rise in RSNA was seen at 2 weeks, and a significant rise in RSNA was observed at 3 weeks. Angiotensin II type 1 (AT-1) receptor protein (Western Blot) and mRNA (reverse transcriptase-polymerase chain reaction) expression in the rostral ventrolateral medulla exhibited a progressive increase with the duration of CHF, reaching significance after 3 weeks, the same time point in which RSNA was significantly elevated. These data are the first to examine early changes in central AT-1 receptors in CHF and suggest that the fall in BRS and hemodynamic changes occur early in the development of CHF followed by sympathoexcitation and overexpression of AT-1 receptors with the progression of CHF, causing further impairment of cardiovascular control.
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Inflammation and oxidative stress play important roles in the pathogenesis of neurodegenerative disorders such as stroke, traumatic injury, Parkinson disease, and Alzheimer disease. Paeonol, a natural compound extracted from Moutan cortex, is a potent anti-inflammatory and antioxidative agent. The aim of this study was to investigate the neuroprotective mechanisms of paeonol on lipopolysaccharide (LPS)-induced inflammation in rat primary microglia and 6-hydroxydopamine-induced oxidative damage in cortical neurons. ⋯ Posttreatment with paeonol also reduced inflammatory responses in LPS-activated microglia and increased cell viability in LPS-treated microglia culture medium-treated neurons. Furthermore, in 6-hydroxydopamine-treated cortical neurons, paeonol not only decreased reactive oxygen species production but also increased cell viability, superoxide dismutase activity, and the antiapoptotic protein B-cell lymphoma 2 expression. Taken together, the present results suggest that paeonol might be a potential neuroprotective agent via inhibiting microglia-mediated inflammation and oxidative stress-induced neuronal damage.
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Recently, we reported that Brown Norway (BN) rats were more resistant to lipopolysaccharide (LPS)-induced myocardial dysfunction than Dahl S (SS) rats. This differential sensitivity was exemplified by reduced production of proinflammatory cytokines and diminished nuclear factor-κB pathway activation. To further clarify the mechanisms of different susceptibility of these two strains to endotoxin, this study was designed to examine the alterations of cardiac and mitochondrial bioenergetics, proinflammatory cytokines, and signaling pathways after hearts were isolated and exposed to LPS ex vivo. ⋯ In addition, LPS significantly decreased complex I activity in SS hearts but not in BN hearts. Furthermore, LPS induced higher levels of tumor necrosis factor-α and increased phosphorylation of IκκB and p65 more in SS hearts than in BN hearts. Our results clearly demonstrate that less mitochondrial dysfunction combined with a reduced production of tumor necrosis factor-α and diminished activation of nuclear factor-κB are involved in the mechanisms by which isolated BN hearts were more resistant to LPS-induced myocardial dysfunction.