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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Severely burned patients typically experience a systemic response expressed as increased metabolism, inflammation, alteration of cardiac and immune function, and associated hyperglycemia. Hyperglycemia has been associated with an increased risk of morbidity and mortality in critically ill patients. ⋯ The literature on the management of hyperglycemia in severely burned patients is sparse, with most of the available studies involving only small numbers of burned patients. The purpose of this article is to describe the pathophysiology of hyperglycemia after severe burns and to review the available literature on the outcome of intensive insulin treatment and other anti-hyperglycemic modalities in burned patients in an evidence-based medical approach.
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Neutrophil elastase plays an important role in the development of acute respiratory distress syndrome (ARDS) and disseminated intravascular coagulation (DIC) in sepsis. Sivelestat is a selective neutrophil elastase inhibitor. It is possible that sivelestat improves the outcome of septic patients associated with ARDS and DIC. ⋯ A stepwise multiple logistic-regression analysis showed the sivelestat administration to be an independent predictor of survival of the septic patients associated with both ARDS and DIC. The length of ICU stay of the sivelestat group was significantly shorter than that of the control group. In addition, sivelestat administration was found to be an independent predictor of survival of those patients.
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In the present study, we investigated the signaling pathways involved in the inhibition of cyclooxygenase 2 (COX-2) and iNOS by moscatilin under LPS challenge in murine macrophage-derived cell line RAW264.7. The results showed that moscatilin (10-100 microM) had a significant inhibition in a concentration-dependent manner on proinflammatory enzymes (COX-2 and iNOS) expression and macrophage activation under LPS (100 ng/mL) treatment. Hypoxia-inducible factor 1 (HIF-1)alpha was reported to initiate inflammation under cytokine stimulation or hypoxic conditions. ⋯ Moreover, the results showed that moscatilin suppressed nuclear translocation of nuclear factor (NF)-kappaB subunits, p65 and p50, and NF-kappaB activity by inhibiting phosphorylation of inhibitor of kappaBalpha. Taken together, we demonstrated that moscatilin inhibited both COX-2 and iNOS expressions after LPS treatment in RAW264.7. Furthermore, the inhibition of moscatilin seemed to be dependent on the repression of HIF-1alpha accumulation and NF-kappaB activation.
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Recent studies from our laboratory demonstrated the involvement of endothelial cell reactive oxygen species (ROS) formation and activation of apoptotic signaling in vascular hyperpermeability after hemorrhagic shock (HS). The objective of this study was to determine if (-)-deprenyl, an antioxidant with antiapoptotic properties, would attenuate HS-induced vascular hyperpermeability. In rats, HS was induced by withdrawing blood to reduce the MAP to 40 mmHg for 60 min followed by resuscitation for 60 min. ⋯ Hemorrhagic shock induced vascular hyperpermeability, mitochondrial ROS formation, DeltaPsim decrease, cytochrome c release, and caspase-3 activation (P G 0.05). (-)-Deprenyl (0.15 mg/kg) attenuated all these effects (P < 0.05). Similarly in rat lung microvascular endothelial cells, (-)-deprenyl attenuated BAK peptide-induced monolayer hyperpermeability (P < 0.05), ROS formation, DeltaPsim decrease, cytochrome c release (P<0.05), and caspase-3 activation (P < 0.05). The protective effects of (-)-deprenyl on vascular barrier functions may be due to its protective effects on DeltaPsim, thereby preventing mitochondrial release of cytochrome c and caspase-3--mediated disruption of endothelial adherens junctions.
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Signaling pathways and mediators in LPS-induced lung inflammation in diabetic rats: role of insulin.
Diabetic patients are more susceptible to infections, and their inflammatory response is impaired. This is restored by insulin treatment. In the present study, we investigated the effect of insulin on LPS-induced signaling pathways and mediators in the lung of diabetic rats. ⋯ Treatment of diabetic rats with insulin completely or partially restored all these parameters. In conclusion, data presented show that insulin regulates mitogen-activated protein kinase, phosphatidylinositol 3'-kinase, protein kinase C pathways, expression of the inducible enzymes, cyclooxygenase 2 and iNOS, and levels of IL-6 and CINC-2 in LPS-induced lung inflammation in diabetic rats. These results suggest that the protective effect of insulin in sepsis could be due to modulation of cellular signal transduction factors.