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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Increased therapeutic intensity has translated into better survival at a price of infectious and toxic life-threatening complications, chiefly affecting the lungs. Yet, no study specifically evaluated outcomes in cancer patients admitted to the intensive care unit (ICU) for septic shock of pulmonary origin. This is a multicenter cohort study of cancer patients admitted to the ICU for septic shock and pneumonia between 1998 and 2008. ⋯ Survival in cancer patients with septic shock from pulmonary origin is substantial, even when organ dysfunctions are not rapidly reversible. Delayed ICU management is an independent predictor of death. Studies assessing survival benefits from early ICU management are warranted.
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The objective of this study was to analyze the association between candidate gene polymorphisms and susceptibility to acute respiratory distress syndrome (ARDS) in patients with severe sepsis. ⋯ The presence of the allele D of the ACE gene is associated with ARDS in patients with severe sepsis.
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Exocytosis of neutrophil granules contributes to acute lung injury (ALI) induced by infection or inflammation, suggesting that inhibition of neutrophil exocytosis in vivo could be a viable therapeutic strategy. This study was conducted to determine the effect of a cell-permeable fusion protein that inhibits neutrophil exocytosis (TAT-SNAP-23) on ALI using an immune complex deposition model in rats. The effect of inhibition of neutrophil exocytosis by intravenous administration of TAT-SNAP-23 on ALI was assessed by albumin leakage, neutrophil infiltration, lung histology, and proteomic analysis of bronchoalveolar lavage fluid (BALF). ⋯ Proteomic analysis of BALF revealed that components of the complement and coagulation pathways were significantly reduced in BALF from TAT-SNAP-23-treated animals. Our results indicate that administration of a TAT-fusion protein that inhibits neutrophil exocytosis reduces in vivo ALI. Targeting neutrophil exocytosis is a potential therapeutic strategy to ameliorate ALI.
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Streptococcal toxic shock syndrome is most frequently associated with Streptococcus pyogenes of the M1 serotype. Simvastatin protects against M1 protein-induced acute lung damage, although downstream mechanisms remain elusive. Herein, we hypothesized that geranylgeranylation might regulate proinflammatory effects in M1 protein-induced lung injury. ⋯ Notably, GGTI-2133 abolished M1 protein-induced gene expression of CXC chemokines in alveolar macrophages. These novel findings indicate that geranylgeranyl transferase is an important regulator of neutrophil recruitment and CXC chemokine production in the lung. Thus, targeting geranylgeranyl transferase might be a potent way to ameliorate streptococcal M1 protein-triggered acute lung injury.
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Sepsis is primarily a disease of the aged, with 65% of sepsis cases reported in patients older than 65 years and 80% of deaths due to sepsis occurring in this age group. Klotho knockout mice (Klotho mice) are a mouse model of accelerated aging and shortened life span. The purpose of the study was to elucidate the immunological changes occurring in Klotho mice during sepsis. ⋯ Both flow cytometric and immunohistological analyses showed a dramatic increase in caspase 3-positive cells in the thymus and spleen of Klotho-CLP mice (P < 0.01). Serum concentrations of interleukin 6, tumor necrosis factor α, and interleukin 10 were higher in Klotho-CLP mice than in WT-CLP mice. Hypercytokinemia with impaired bacterial clearance and increased apoptosis of lymphocytes may be related to poor survival in Klotho-septic mice.