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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Lipopolysaccharide (LPS), a component of the outer membrane of Gram-negative bacteria, plays a key role in cardiac dysfunction in sepsis. Low circulating levels of insulin-like growth factor 1 (IGF-1) are found in sepsis, although the influence of IGF-1 on septic cardiac defect is unknown. This study was designed to examine the impact of IGF-1 on LPS-induced cardiac contractile and intracellular Ca2+ dysfunction, activation of stress signal and endoplasmic reticulum (ER) stress. ⋯ Interestingly, these LPS-induced changes in mechanical and intracellular Ca2+ properties, ROS, protein carbonyl, apoptosis, stress signal activation, and ER stress markers were effectively ablated by IGF-1. In vitro LPS exposure (1 microg mL(-1)) produced cardiomyocyte mechanical dysfunction reminiscent of the in vivo setting, which was alleviated by exogenous IGF-1 (50 nM). These data collectively suggested a beneficial of IGF-1 in the management of cardiac dysfunction under sepsis.
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Acute lung injury following intestinal I/R depends on neutrophil-endothelial cell interactions and on cytokines drained from the gut through the lymph. Among the mediators generated during I/R, increased serum levels of IL-6 and NO are also found and might be involved in acute lung injury. Once intestinal ischemia itself may be a factor of tissue injury, in this study, we investigated the presence of IL-6 in lymph after intestinal ischemia and its effects on human umbilical vein endothelial cells (HUVECs) detachment. ⋯ Intestinal ischemia and absence of constitutive NOS activity leading to additional intestinal stress both cause release of IL-6 and increase of lung microvascular permeability. Because anti-IL-6 prevented the endothelial cell injury caused by lymph at the ischemia period, the lymph-borne IL-6 might be involved with endothelial cell activation. At the reperfusion period, this cytokine does not seem to be modulated by NO.
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The aim of the present study was to evaluate the role of endogenous and exogenous peroxisome proliferator-activated receptor alpha (PPAR-alpha), a nuclear receptor, on the regulation of inflammation in macrophages. To address this question, we have stimulated peritoneal macrophages from PPAR-alpha wild-type mice and PPAR-alpha knockout mice (PPAR-alpha) with 10 microg/mL LPS and 100 U/mL IFN-gamma. We report here that the absence of a functional PPAR-alpha gene in PPAR-alpha knockout mice resulted in a significant augmentation of various inflammatory parameters in peritoneal macrophages. ⋯ To elucidate whether the protective effects of clofibrate is related to activation of the PPAR-alpha receptor, we also investigated the effect of clofibrate treatment on PPAR-alpha-deficient mice. The absence of the PPAR-alpha receptor significantly abolished the protective effect of the PPAR-alpha agonist against LPS/IFN-gamma-induced macrophage inflammation. In conclusion, our study demonstrates that the endogenous and exogenous PPAR-alpha ligands reduce the degree of macrophage inflammation caused by LPS/IFN-gamma stimulation.
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Procalcitonin (PCT) is a marker of severe bacterial infections and organ failure due to sepsis. The purpose of the present study was to identify the appropriate cutoff level of PCT based on the findings of a blood culture and polymerase chain reaction (PCR). The PCT levels were measured in 116 patients in an intensive care unit who were suspected of having bacteremia, to examine its relationship with a blood culture or PCR. ⋯ The appropriate cutoff values of PCT for bacteremia were 0.38 microg/L for the high negative predictive value and 0.83 microg/L for the high positive predictive value. Procalcitonin was slightly related to mortality, and the combination of a blood culture and PCR was thus found to increase the sensitivity for mortality. These findings suggest that PCT is useful for the diagnosis of bacteremia and that the diagnostic value of PCT in combination a with blood culture and PCR for bacterial infection or mortality further increases.
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Respiratory rate (RR) is a basic vital sign, measured and monitored throughout a wide spectrum of health care settings, although RR is historically difficult to measure in a reliable fashion. We explore an automated method that computes RR only during intervals of clean, regular, and consistent respiration and investigate its diagnostic use in a retrospective analysis of prehospital trauma casualties. At least 5 s of basic vital signs, including heart rate, RR, and systolic, diastolic, and mean arterial blood pressures, were continuously collected from 326 spontaneously breathing trauma casualties during helicopter transport to a level I trauma center. "Reliable" RR data were identified retrospectively using automated algorithms. ⋯ For identifying casualties subsequently diagnosed with a major hemorrhagic injury and requiring blood transfusion, standard RR yields an AUC of 0.60 (0.49-0.70), whereas reliable RR yields 0.77 (0.67-0.85), P < 0.001. Reliable RR, as determined by an automated algorithm, is a useful parameter for the diagnosis of respiratory pathology and major hemorrhage in a trauma population. It may be a useful input to a wide variety of clinical scores and automated decision-support algorithms.