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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Hemorrhagic shock is the leading cause of preventable deaths in civilian and military trauma. Use of fresh frozen plasma (FFP) in patients requiring massive transfusion is associated with improved outcomes. FFP contains significant amounts of adiponectin, which is known to have vascular protective function. ⋯ Immunodepletion of adiponectin from FFP abolished FFP's effects on blocking endothelial hyperpermeability in vitro, and on improving lung vascular barrier function in HS mice. Replenishment with adiponectin rescued FFP's effects. These findings suggest that adiponectin is an important component in FFP resuscitation contributing to the beneficial effects on vascular barrier function after HS.
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To investigate the roles of epithelial-dendritic cell transformation (EDT) characterized by the expression of dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) in the occurrence of tissue inflammation induced by hemorrhagic hypotension (HH), the protective effect of vitamin C (VitC), and the potential mechanisms. ⋯ HH induces EDT in rat intestine epithelial cells. VitC maintains GSK-3β activity, attenuates the suppression of E-cadherin caused by hypoxia, and ultimately decreases DC-SIGN expression.
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We evaluated central venous oxygen saturation (Scvo2) and lactate levels as a combination measure to predict mortality in patients with severe sepsis or septic shock. ⋯ Oxygenation category, as represented by initial Scvo2 and lactate levels, was significantly associated with 28-day mortality in patients with severe sepsis or septic shock. Associations between Scvo2 ≥70% and 28-day survival were observed only in patients without severe lactic acidosis.
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Sepsis following hemorrhagic shock is a common clinical condition, in which innate immune system suffers from severe suppression. B and T lymphocyte attenuator (BTLA) is an immune-regulatory coinhibitory receptor expressed not only on adaptive, but also on innate immune cells. Our previous data showed that BTLA gene deficient mice were protected from septic mortality when compared with wild-type control C57BL/6 mice. ⋯ Here, we report that BTLA expression is elevated on innate immune cells after Hem/CLP. However, anti-BTLA antibody treatment increased cytokine (TNF-α, IL-12, IL-10)/chemokine (KC, MIP-2, MCP-1) levels and inflammatory cells (neutrophils, macrophages, dendritic cells) recruitment in the peritoneal cavity, which in turn aggravated organ injury and elevated these animals' mortality in Hem/CLP. When compared with the protective effects of our previous study using BTLA gene deficient mice in a model of lethal septic challenge, we further confirmed BTLA's contribution to enhanced innate cell recruitment, elevated IL-10 levels, and reduced survival, and that engagement of antibody with BTLA potentiates/exacerbates the pathophysiology in Hem/sepsis.
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The lipopolysaccharide (LPS) molecule is composed of a hydrophobic lipid region (Lipid A), an oligosaccharide core, and an O-Antigen chain. Lipid A has been described as the molecular region responsible for inducing activation of immune cells. We hypothesize that the O-Antigen plays a critical role in the activation and responsiveness of mononuclear cell immune function. ⋯ Structural variants of LPS activate monocytes differentially. The complete O-Antigen is important for maximal activation of MAPK, cytokine synthesis, and cytokine secretion. LPS with attenuated O-Antigen and Lipid A activate only certain components of these pathways. LPS with a complete O-Antigen stimulates cytokine secretion that is partially independent of CD14, but shortening or removal of the O-Antigen inhibits this secretion.