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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This study investigated the effects of heme oxygenase 1 (HO-1) on thrombomodulin (TM) and endothelial protein C receptor (EPCR) expression in sepsis-induced kidney injury. The role of HO-1 was evaluated in a cecal ligation and puncture (CLP)-induced model. Wistar rats were randomly assigned into four groups: sham, CLP, CLP + hemin (an HO-1 inducer), CLP + ZnPP (zinc protoporphyrin IX, an HO-1 inhibitor), and CLP + bilirubin. ⋯ The administration of hemin lowered the plasma levels of cystatin C, creatinine, blood urea nitrogen, tumor necrosis factor α, interleukin 1β, TM, and EPCR; elevated plasma level of activated protein C; prolonged prothrombin time and activated partial thromboplastin time; attenuated microthrombus formation; and upregulated the expression of TM and EPCR and mRNA levels of TM and EPCR in the kidney in the CLP + hemin group. In contrast, ZnPP had the opposite effects. The results indicated that the enhanced induction of HO-1 increased the expression of TM and EPCR in the kidney and exerted an anticoagulant effect, thereby attenuating kidney injury in septic rats.
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Ischemia/reperfusion (I/R) of the liver contributes to the pathobiology of liver injury in transplantation, liver surgery, and hemorrhagic shock. Ischemia/reperfusion induces an inflammatory response that is driven, in part, by Toll-like receptor 4 (TLR) signaling. CD14 is known to participate in the function of TLR4. We hypothesized that CD14 would be involved in the pathobiology of warm hepatic I/R. ⋯ CD14 is actively involved in hepatic I/R injury. Its deficiency or blockade ischemia attenuates liver injury and inflammatory response. CD14 mediates liver damage and inflammatory responses in the setting of warm hepatic I/R in mice.
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Burn is one of the most common and devastating forms of trauma. Major burn injury disturbs the immune system, resulting in marked alterations in bone marrow hematopoiesis and a progressive suppression of the immune response, which are thought to contribute to increased susceptibility to secondary infections and the development of sepsis. Immunosuppression in patients with severe burn and sepsis leads to high morbidity and mortality in these patients. mononuclear phagocytes system (MPS) is a critical component of the innate immune response and plays key roles in burn immunity. ⋯ Severe burn and sepsis profoundly inhibit the functions of dendritic cells, monocytes, and macrophages. Adoptive transfer of MPS or stem cells to patients with severe burn and sepsis that aim to restore MPS function is promising. A better understanding of the roles played by MPS in the pathophysiology of severe burn and sepsis will guarantee a more rational and effective immunotherapy of patients with severe burn and sepsis.
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Multicenter Study
Prospective comparison of three risk score models at three different surgical intensive care units.
Although risk score models are of great value, their use is restricted because of the additional effort involved. The aim of this study was to compare three different score systems. Each of these requires a different degree of effort by the medical staff. One of the score systems is solely based on routine laboratory parameters. Data were collected on three different ICUs units, with each showing a large variety in patients' health conditions. ⋯ The results of this first multicenter study comparing three risk score systems indicate that it is possible to establish a general risk score for surgical intensive care patients on admission date. Such a risk score is solely based on quality-controlled, low-cost routine laboratory parameters.
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Invariant natural killer T cells (iNKT) cells are emerging as key mediators of innate immune cellular and inflammatory responses to sepsis and peritonitis. Invariant natural killer T cells mediate survival following murine septic shock. Macrophages are pivotal to survival following sepsis. ⋯ This dysfunction was reversed when peritoneal macrophages from iNKT(-/-) mice were cocultured with wild-type iNKT cells. Together, our results indicate that sepsis induces liver iNKT-cell exodus into the peritoneal cavity mediated by programmed death receptor 1, and these peritoneal iNKT cells appear critical to regulation of peritoneal macrophage phagocytic function. Invariant natural killer T cells offer therapeutic targets for modulating immune responses and detrimental effects of sepsis.