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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If the inflammatory response becomes excessive or uncontrolled by some stimuli, inappropriate inflammatory responses occur. Monocytes are extremely important cells for regulating the cytokine network and tumor necrosis factor alpha (TNFalpha) and interleukin- (IL) 10, which are mainly synthesized by monocytes, are representative cytokines that play a central role in the cytokine network. Protease inhibitors such as gabexate mesilate (GM) and ulinastatin (UTI) have been shown to have various beneficial effects by inhibiting the activation of leukocytes, but the mechanism for this has yet to be fully elucidated. ⋯ GM also suppressed the NFkappaB activity of LPS-stimulated monocytes. UTI decreased the TNFalpha production of LPS-stimulated monocytes, but did not inhibit the TNFalpha mRNA expression. The present study shows that the inhibitory effect of GM on the TNFalpha production of activated human monocytes is mediated by the suppression of NFkappaB activation, while the mechanism of UTI inhibiting TNFalpha production of human monocytes may be due to the inhibition of either the translation or secretion of TNFalpha.
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This study was designed to investigate the role of NO and effect of iNOS inhibitor on the lung neutrophil deposition and damage after burn. In Experiment 1, specific pathogen-free (SPF) Sprague-Dawley rats underwent 35% total body surface area (TBSA) burn. On the 4th, 8th, 16th, and 24th h after burn, blood was collected for peroxynitrite-mediated dihydrorhodamine 123 (DHR 123) oxidation assay, and lung tissues were harvested for myeloperoxidase (MPO) test and histologic study. ⋯ In conclusion, thermal injury induces blood DHR 123 oxidation, lung neutrophil deposition, lung iNOS expression, and lung damage. Peroxynitrite might play an important role in thermal injury-induced lung neutrophil deposition and damage. Specific inhibition of lung iNOS expression and blood DHR 123 oxidation with SMT on thermal injury not only attenuated the lung neutrophil deposition, but also reduced lung damage.
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This prospective, multi-center, observational study of 2069 multiple trauma patients evaluated the prognostic significance of the posttrauma base deficit (BD) on hospital and intensive care unit (ICU) admission to hemodynamic changes, volume and transfusion requirements, lactate and coagulation, as well as mortality. Furthermore, the importance of the BD development throughout a patient's course of critical illness from the time of injury to ICU admission is analyzed as a prognostic factor for fatal outcome. The data were obtained by the trauma registry of the 'Deutsche Gesellschaft für Unfallchirurgie.' The patients were subdivided into five categories of increasing BD values on hospital and ICU admission: Category I, BD < or = -2; Category II, -2 < BD < or = 2; Category III, 2 < BD < or = 6; Category IV, 6 < BD < or = 10; and Category V, BD > 10. ⋯ Mortality increased significantly (P < 0.0001) with a worsening of BD from hospital to ICU admission (from a mortality of 13% in patients with a hospital and an ICU admission BD of <6 to 45% in patients with a hospital and an ICU admission BD of >6). These data show that the base deficit is an early available important indicator to identify trauma patients with hemodynamic instability, high transfusion requirements, metabolic and coagulatory decompensation, as well as a high probability of death. The base deficit development may help to guide an early and aggressive therapy for the trauma/hemorrhage induced tissue hypoxia.
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The purpose of this study was to investigate the feasibility of using near infrared (NIR) spectroscopy of the liver to simultaneously assess oxygen content in combination with tissue pH, an indicator of anaerobic metabolism. Six anesthetized swine were subjected to 45 min of hemorrhagic shock followed by resuscitation with blood and crystalloid. Calibration models between NIR spectra and reference measurements of tissue pH, hepatic venous oxygen saturation (S(V)O2), and blood hemoglobin concentration (Hb) were developed using partial least-squares regression. ⋯ Estimated accuracy, the root mean squared deviation between spectral, and reference measurements was 0.03 pH units, 0.3 g/dL, and 6%. NIR determination of hepatic oxygen content and tissue pH during shock and resuscitation demonstrated that there can be a variance between hepatic venous oxygenation and regional tissue acidosis. NIR spectroscopy provides a technique to explore the implications of post-shock depression of tissue pH and evaluate new methods of resuscitation.
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Reactive oxygen species generated by xanthine oxidase during reperfusion of ischemic liver might in part be responsible for ischemic organ injury. In normothermic ischemia/reperfusion rat model, we investigated whether allopurinol pretreatment improved ischemia-induced mitochondrial dysfunction. Rats were subjected to 60 min of hepatic ischemia and to 1 h and 5 h of reperfusion thereafter. ⋯ However, treatment with allopurinol resulted in significantly higher ATP levels. Allopurinol treatment preserved the concentration of AMP in ischemic liver but inhibited the accumulation of xanthine in reperfused liver. Our findings suggest allopurinol protects against mitochondrial injury, which prevents a mitochondrial oxidant stress and lipid peroxidation and preserves the hepatic energy metabolism.