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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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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The mechanisms contributing to hypoxia in lung contusion (LC) remain unclear and not temporally associated with the peak onset of acute inflammation. We investigated the role of oxidative stress in alteration of pulmonary arterial (PA) reactivity following LC. In addition, the role of antioxidants in reversing this process was examined. ⋯ SOD1 and 2 mRNA were upregulated, and soluble guanylyl cyclase mRNA was downregulated 24 h after LC. Immunohistochemistry and mass spectrometry revealed that levels of 3-nitrotyrosine were increased markedly at 4 h following LC consistent with superoxide generation and formation of peroxynitrite. Collectively, these data suggest that consumption of NO due to excess superoxide resulting in peroxynitrite formation leads to diminished vascular reactivity following LC.