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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Endothelial progenitor cells (EPCs) and polymorphonucleated leukocytes (PMNLs) migrate to and accumulate at the site of tissue injury where they express complementary sets of surface receptors (CD11b/CD18, CD54), suggesting a possible cellular interaction. Trauma-activated PMNLs release inflammatory mediators and reactive oxygen species (ROS) produced by the NADPH oxidase, which may negatively impact EPCs. To characterize the interactions between PMNLs and EPCs, we identified common surface receptors and measured the role played by NADPH oxidase and neutrophil elastase. ⋯ Our results demonstrate that EPCs and PMNLs do interact via complementary receptors and that this interaction results in PMNL-derived ROS-induced EPC damage. The effect of neutrophil-derived elastase was found to be negligible. These findings suggest that EPC damage by activated PMNLs may contribute to impaired wound healing observed after severe trauma.
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Gastric aspiration is the major cause of acute lung injury (ALI) and acute respiratory distress syndrome. Aspiration-induced ALI is believed to be, at least in part, facilitated by neutrophil-derived mediators and toxic molecules. We conducted a prospective cohort study based on the hypothesis that sivelestat, a specific neutrophil elastase inhibitor, is effective for treating ALI following gastric aspiration. ⋯ In univariate analyses, the proportions of patients with LIS lower than 1.0 on day 7 and a P/F greater than 300 on day 7 were significantly higher in the sivelestat group than in the control group (60.9% vs. 26.3%, P = 0.03; 87.0% vs. 36.8%, P = 0.001). In the logistic regression model, the use of sivelestat was an independent predictor for LIS lower than 1.0 on day 7 (relative risk, 7.4; 95% confidence interval [CI], 1.51-36.48) and for a P/F ratio higher than 300 on day 7 (relative risk, 18.5; 95% CI, 2.72-126.46). In the Cox proportional hazards model, the use of sivelestat was associated with a lower cumulative proportion of patients who received mechanical ventilation during the initial 14 days (hazard ratio, 2.6; 95% CI, 1.17-5.55).
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Thrombomodulin (TM) is expressed on the surface of monocytes and is a key regulator of actual immune capacity. Propofol is an anesthetic agent that exerts anti-inflammatory effects. The objective of this study was to determine whether propofol could modulate TM in TNF-α-stimulated monocytes. ⋯ In conclusion, the inhibition of TM expression in TNF-α-treated monocytes was mediated by the activation of NADPH oxidase and the expression of TTP. Propofol may inhibit the downregulation of TM by mediating NADPH oxidase and TTP inactivation and through the activation of HuR in vitro and in vivo. Utilizing TTP and HuR to control TM expression may be a promising approach for controlling systemic inflammation, and propofol may possess potential implications for the clinical immunity of monocytes after anesthesia or surgery.
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Hemorrhagic shock and splanchnic arterial occlusion (SAO) followed by reperfusion are associated with high mortality. However, rapid cardiovascular failure and death may also occur before reperfusion in hemorrhagic shock and SAO. We show in a rat SAO model that, upon gut ischemia, mean arterial blood pressure transiently elevates and then drops fatally in one of two time courses: (i) gradually over ∼1 to 3 h or (ii) rapidly (often by >80 mmHg) over a period of 1 to 6 min. ⋯ Total subdiaphragmatic vagotomy or glycopyrrolate treatment significantly reduced the incidence to 0% (P < 0.008), although slow fatal pressure drops still occurred. ANGD did not prevent FFPDs, but delayed onset of slow fatal pressure drops (P < 0.013). These results suggest that gut ischemia can cause sudden death via an autonomic nervous system mechanism and that SAO with Glucose and xylazine may serve as a useful model for the study of neurogenic shock or autonomic dysregulation associated with sudden death.