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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Endotoxin, an outer membrane component of gram-negative bacteria, plays an important role in the pathogenesis of septic shock. Endotoxin adsorption therapy by polymyxin B-immobilized fiber column hemoperfusion (PMX) has been used for the treatment of septic shock patients in Japan since 1994. The covalent binding of polymyxin B onto the surface of the polystyrene-based carrier fiber in PMX inactivates the endotoxin in the blood without exerting toxicity. ⋯ These beneficial effects may be attributable to the direct adsorption of endotoxin, monocytes, activated neutrophils, and anandamide, as well as indirect decrease in inflammatory cytokines and other mediators. Polymyxin B-immobilized fiber column hemoperfusion treatment has additional effects on reducing endothelial damage, proapoptotic activity, and immunosuppression. Further studies will be needed to confirm the efficacy and mechanism of PMX treatment in septic shock.
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Controlled Clinical Trial
The influence of experimental alcohol load and alcohol intoxication on S100B concentrations.
Because nearly 50% of patients with mild head trauma are alcohol intoxicated, it often remains unclear if the neurological deficits are due to alcohol intoxication or to intracerebral damage. To avoid unnecessary head computed tomography investigations in patients with mild head trauma, S100B is currently used as an exclusion marker for cellular brain damage. However, whether S100B levels are influenced by alcohol itself remains to be unclear. ⋯ In contrast, compared with the control group (n = 60 sober and healthy), the ethyl alcohol-intoxicated patients (n = 61; mean ethyl alcohol, 251 [SD, 87] mg/dL) had higher S100B concentrations (0.193 [SD, 0.45] vs. 0.063 [SD, 0.059] μg/L; P < 0.001), and 39% of them had levels greater than the pathologic cutoff at greater than 0.104 μg/L. However, no significant correlation was found between ethyl alcohol concentrations and S100B within the respective group. Our clinical data suggest that blood alcohol concentrations far in excess of 100 mg/dL are associated with increased S100B levels in alcohol-intoxicated patients.
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The contribution of the adaptive and innate immune systems to the pathogenesis and outcome of sepsis remains a fundamental yet controversial question. Here, we use mice lacking the recombination activating gene 1 (Rag-1) to study the role of T and B cells in sepsis after cecal ligation and puncture (CLP). Spleens of Rag-1 mice were atrophic and completely devoid of CD3 T cells and CD19 B cells. ⋯ Levels for most mediators were unaffected by the absence of T and B lymphocytes. Only the concentrations of IL-6 and IL-17 were found to be significantly lower in Rag-1 mice compared with wild-type mice. In conclusion, the absence of T and B cells in the CLP model used does not appear to affect the acute outcome of severe sepsis.
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Mortality from pneumonia is mediated, in part, through extrapulmonary causes. Epidermal growth factor (EGF) has broad cytoprotective effects, including potent restorative properties in the injured intestine. The purpose of this study was to determine the efficacy of EGF treatment following Pseudomonas aeruginosa pneumonia. ⋯ To determine whether the intestine was sufficient to account for extrapulmonary effects induced by EGF, a separate set of experiments was done using transgenic mice with enterocyte-specific overexpression of EGF (IFABP-EGF [intestinal fatty acid-binding protein linked to mouse EGF] mice), which were compared with wild-type mice subjected to pneumonia. IFABP-EGF mice had improved survival compared with wild-type mice following pneumonia (50% vs. 28%, respectively, P < 0.05) and were protected from pneumonia-induced intestinal injury. Thus, EGF may be a potential adjunctive therapy for pneumonia, mediated in part by its effects on the intestine.
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We investigated the effect of the angiotensin-converting enzyme (ACE) inhibitor captopril in a clinically relevant ovine model of smoke and burn injury, with special reference to oxidative stress and activation of poly(ADP-ribose) polymerase, in the lung and in circulating leukocytes. Female, adult sheep (28-40 kg) were divided into three groups. After tracheostomy and under deep anesthesia, both vehicle-control-treated (n = 5) and captopril-treated (20 mg/kg per day, i.v., starting 0.5 h before the injury) (n = 5) groups were subjected to 2 × 20%, third-degree burn injury and were insufflated with 48 breaths of cotton smoke. ⋯ Our results suggest that the ACE inhibitor captopril exerts beneficial effects on the pulmonary function in burn/smoke injury. The effects of the ACE inhibitor may be related to the prevention of reactive oxygen species-induced poly(ADP-ribose)polymerase overactivation. Angiotensin-converting enzyme inhibition may also exert additional beneficial effects by inhibiting the expression of the profibrotic mediator transforming growth factor β.