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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Lipopolysaccharide (LPS) is the main agonist of gram-negative bacteria and initiates inflammation. We recently reported that plasmas from sepsis patients revealed increased levels of following group of biomarkers; VCAM-1, ICAM1, CRP, resistin, and proteasome LMP subunits. Our objective here was to compare effects of resveratrol (shown to be a nonspecific proteasome inhibitor by us) and a known LMP7 inhibitor (ONX-0914, specific inhibitor) on proteasome's activities, as well as on inflammatory markers mentioned above in human blood monocytes. ⋯ Collectively, our data suggest that resveratrol is a less potent inhibitor of all three; CT-like (predominantly LMP7), T-like and PA protease activities and is less toxic to human monocytes than ONX-0914 (a selector inhibitor of only LMP7) as observed by an autophagy detection kit. Also, resveratrol reduces LPS-induced inflammatory cytokine expression by decreasing the translocation of NF-κB due to an increase in inhibitor pIκBα. Therefore, resveratrol can be used to curb inflammation in diseased states like sepsis and other disorders.
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The aim of this study was to evaluate the clinical utility of the lactate/albumin (L/A) ratio as a predictive factor of 28-day mortality in critically ill sepsis patients. ⋯ The prognostic performance of the L/A ratio was superior to that of a single lactate measurement for predicting 28-day mortality of critically ill sepsis patients. L/A ratio can be a useful prognostic factor regardless of initial lactate level and the presence of hepatic or renal dysfunction.
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Traumatic brain injury (TBI) results in systemic changes in coagulation and inflammation that contribute to post-traumatic morbidity and mortality. The potential interaction of platelets and pro-inflammatory cytokines in the modulation of coagulation, microthrombosis, and venous thromboembolic events after moderate TBI has not been determined. Using a murine model, we hypothesized that the degree of platelet-induced coagulation varies depending on the platelet aggregation agonist platelet-induced coagulation changes in a time-dependent manner following TBI, and changes in platelet-induced coagulation are mirrored by changes in the levels of circulating pro-inflammatory cytokines. ⋯ Platelet function and coagulability returned to baseline levels 24 h following head injury. Our data demonstrate that after TBI, acute platelet dysfunction occurs followed by rebound platelet hyperaggregation. Alterations in post-TBI platelet aggregation are reflected in whole blood thromboelastometry and are temporally associated with the systemic pro-inflammatory response.
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Mechanical ventilation (MV) may induce or aggravate lung injury through the production of cytokines, inflammatory infiltration of neutrophils, and changes in the permeability of the alveolar-capillary barrier. The use of positive end-expiratory pressure (PEEP) helps improve gas exchanges avoiding alveolar collapse at the end of expiration. The present study aimed to analyze inflammatory response and redox imbalance in lungs of rats submitted to MV with and without PEEP. ⋯ MV with PEEP caused redox imbalance and inflammation in lungs of healthy rats.
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Nucleotide-binding oligomerization domain 2 (NOD2) is the innate receptor of muramyl dipeptide (MDP). Our previous study revealed that MDP could enhance thermal injury-induced inflammatory cytokine production and organ function injury in rats. The present study was to determine the effect of MDP on autophagy and NOD2/receptor-interacting serine/threonine protein kinases (RICK) signaling pathway of lung injury after thermal injury. ⋯ MDP enhances thermal injury-induced autophagy and proinflammatory cytokine response of lung injury, which could be achieved via activating the NOD2/RICK signaling pathway in rats.