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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The cholinergic nervous system can inhibit the release of proinflammatory cytokines such as TNF-alpha from LPS-stimulated macrophages. Acetylcholine, the principal neurotransmitter of the vagus nerve, is the key mediator of this so-called cholinergic anti-inflammatory pathway, specifically interacting with alpha7 cholinergic receptors expressed by macrophages and other cell types to inhibit TNF-alpha production. The aim of the current study was to determine the capacity of the selective alpha7 cholinergic receptor agonist 3-(2,4-dimethoxybenzylidene) anabaseine (GTS-21), administered locally into the airways, to inhibit LPS-induced inflammatory responses in the mouse lung in vivo. ⋯ Intranasal inoculation with GTS-21 also dose-dependently inhibited TNF-alpha release into the lung compartment after intrapulmonary delivery of LPS in mice in vivo, whereas IL-6 concentrations were not affected. However, GTS-21 did not influence the influx of neutrophils into bronchoalveolar lavage fluid elicited by LPS and increased the concentrations of the neutrophil-attracting chemokines cytokine-induced neutrophil chemoattractant and macrophage inflammatory protein 2. These data indicate that local administration of GTS-21 inhibits TNF-alpha release in the lung during LPS-induced inflammation.
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Endogenous arginine vasopressin (AVP) levels in multiple trauma patients are unknown. Arginine vasopressin is considered to play an important role in severe hemorrhage. In this prospective study, 87 multiple trauma patients (Injury Severity Score >15) and 50 healthy volunteers were enrolled. ⋯ Copeptin concentrations were correlated with AVP (r2 = 0.718, P < 0.001). In conclusion, AVP was significantly increased in multiple trauma patients and seems to be an integral part of the neuroendocrine response to severe injury. In ICU patients, AVP decreased to moderately elevated levels within 24 h after ED admission.
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We investigated the possible differences in epidemiology, clinical course, management, and outcome between early and late occurrence of shock using data from the Sepsis Occurrence in Acutely Ill Patients Study, a large European multicenter study, which prospectively collected data from all adult intensive care unit (ICU) patients admitted to a participating center within a 2-week period in 2002. Shock was defined as hemodynamic compromise necessitating the administration of vasopressor agents. Early and late shock were defined as onset of shock within the first 2 days in the ICU or later, respectively. ⋯ Intensive care unit and hospital mortality rates were greater in patients who developed shock late, rather than early (52.4% vs. 36.8% and 55.3% vs. 43%, respectively, P < 0.02). In a multivariable analysis, late shock was associated with an independent risk of higher ICU mortality in shock patients (odds ratio, 2.6; 95% confidence interval, 1.6-4.3, P < 0.001). These observations have important implications in establishing individual prognosis as well as in the design and interpretation of clinical trials.
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Although multiple organ failure (MOF) remains the leading cause of death after trauma, the pathogenic cellular and molecular mechanisms underlying MOF are poorly understood. In addition to proinflammatory and anti-inflammatory mediator cascades, the temporal onset of MOF has generated recent interest because the organ systems involved into MOF seem to deteriorate in a time-dependent fashion after trauma. We therefore investigated the temporal course of MOF in traumatized human patients and evaluated and compared the distribution patterns of cytokine expression, including interleukin (IL) 6, IL-8, IL-10, and the soluble tumor necrosis factor-[alpha] receptors sTNF-R p55 and sTNF-R p75 in early-onset versus late-onset MOF. ⋯ In addition, the initial values (days 0-1) of sTNF-R p55 and sTNF-R p75 expression levels had a good predictive capacity for the development of LMOF (p55, 0.75; p75, 0.72); values greater than 0.65 were accepted to have a predictive capacity. These results demonstrate that mortality differs significantly between the development of EMOF and LMOF after traumatic injury. Our results also suggest that serum cytokine measurements may be important early biochemical markers for predicting the development of delayed MOF.
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The present study was designed to investigate the proteomic alteration of hepatic mitochondria during sepsis and to explore the possible effects induced by heat shock treatment. Sepsis was induced by cecal ligation and puncture in Sprague-Dawley rats. Liver mitochondrial proteins were isolated and evaluated by 2-dimensional electrophoresis with broad pH-ranged (pH 3 - 10) immobile DryStrip and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. ⋯ Phosphoprotein staining showed that the degree of phosphorylation is higher in MP1 and MP2 than that in MP3. The enzyme activity assay showed that ALDH2 activity was downregulated in nonheated septic rats of 18 h after cecal ligation and puncture operation, and preserved in heated septic rats. The results of this study suggest that posttranslation modification, highly possible the phosphorylation, in ALDH2 may play a functional role in the pathogenesis of sepsis and provide a novel protective mechanism of heat shock treatment.