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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Septic shock is the most common cause of death in intensive care units. During the last two decades, new strategies have focused on the diagnosis and on the immunological changes in critically ill patients. There have been conflicting reports whether monocyte human leukocyte antigen (HLA) DR expression poses a useful parameter to characterize clinical outcome of these patients. ⋯ As expected, HLA-DR expression was significantly higher in the group of survivors (n = 279) than in the group of nonsurvivors (n = 134; mABs/cell: 23,038 [SD, 11,150] vs. 18,070 [SD, 8,906]; P < 0.001). When minimal HLA-DR values per patient were compared, no cutoff values could be identified between the groups of survivors and nonsurvivors (mABs/cell: 19,611 [SD, 11,129] vs. 14,944 [SD, 8,013]; P < 0.001). In conclusion, in this sizable cohort we could again show that HLA-DR expression is decreased in critically ill patients but it is not suitable as a prognostic or predictive parameter for clinical outcome.
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Tissue-specific circulating micro-RNAs (miRNAs) are released into the blood after organ injury. In an ischemic porcine cardiogenic shock model, we investigated the release pattern of cardiac-specific miR-208b and liver-specific miR-122 and assessed the effect of therapeutic hypothermia on their respective plasma levels. Pigs were anesthetized, and cardiogenic shock was induced by inflation of a percutaneous coronary intervention balloon in the proximal left anterior descending artery for 40 min followed by reperfusion. ⋯ Therapeutic hypothermia significantly diminished the increase in miR-122 compared with the normothermic group (P < 0.005). In our model, hypothermia was initiated after coronary reperfusion and did not affect either myocardial damage as previously assessed by magnetic resonance imaging or the plasma level of miR-208b. Our results indicate that liver-specific miR-122 is released into the circulation in the setting of cardiogenic shock and that therapeutic hypothermia significantly reduces the levels of miR-122.
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Lipocalin-2 (LCN-2) is a 25-kDa secretory protein currently used as a biomarker for renal injury and inflammation. Its source and cause of the increased serum levels are unclear. The current study compares LCN-2 gene expression with known major acute-phase proteins in the liver in a rat and mouse model of turpentine oil-induced sterile abscess. ⋯ Lipocalin-2 is the major acute-phase protein in rat as compared with α₂-macroglobulin and hemoxygenase 1 and comparable with serum amyloid A in mouse whose gene expression is mainly controlled by interleukin 6. The liver is the main source of serum LCN-2 in the case of APR. ABBREVIATIONS-LCN-2-lipocalin-2-α₂M-α₂-macroglobulin-HO-1-hemoxygenase 1-IL-6-interleukin 6-SAA-serum amyloid A-TO-turpentine oil-APR-acute-phase reaction.
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Clinical Trial
Modifications in erythrocyte membrane protein content are not responsible for the alterations in rheology seen in sepsis.
Red blood cell (RBC) rheology is altered in sepsis and may contribute to the microcirculatory alterations in these patients, but the mechanisms of these changes are not well defined. An increase in the RBC protein band 3/α-spectrin ratio has been observed in a mouse model of septic shock, suggesting a possible alteration in the RBC membrane integral/peripheral protein ratio. This protein modification could contribute to the alterations in RBC rheology observed in sepsis. ⋯ The majority of RBC membrane protein ratios, including band 3/spectrin, were more elevated in critically ill patients (nonseptic and septic) than in volunteers, but RBC membrane skeletal protein content was similar in septic and nonseptic patients. There were no significant differences in cryohemolysis results among groups. Alterations in RBC rheology in sepsis are therefore mainly due to alterations in membrane compounds other than skeletal proteins, like carbohydrates, such as sialic acid and/or lipids.