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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Toll-like receptor 2 (TLR2) signaling plays a critical role in orchestrating the innate immune response and the development of sepsis and subsequent organ dysfunction after trauma. The objectives of this prospective study were to identify haplotype tag single-nucleotide polymorphisms (htSNPs) within the entire TLR2 gene and to investigate their clinical relevance in patients with major trauma. A total of 410 patients with major trauma were prospectively recruited. ⋯ In addition, the patients with the haplotype ATT had lower sepsis morbidity rate than those without the haplotype ATT. Therefore, three SNPs might act as htSNPs for the entire TLR2 gene in the Chinese population. The rs3804099 and the haplotype ATT might be used as relevant risk estimates for the development of sepsis and MOD in patients with major trauma.
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Sepsis results from an overwhelming response to infection and is a major contributor to death in intensive care units worldwide. In recent years, we and others have shown that neutrophil functionality is impaired in sepsis. This correlates with sepsis severity and contributes to aggravation of sepsis by precluding bacterial clearance. ⋯ We also demonstrate that inhibition of sGC activity increased survival in a murine model of sepsis, which was paralleled by restored neutrophil migratory function and increased bacterial clearance. Finally, the beneficial effect of sGC inhibition could also be demonstrated in mice treated after the onset of sepsis. Our results suggest that the beneficial effects of sGC inhibition in sepsis could be at least in part attributed to a recovery of neutrophil functionality.
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Recently, we developed liposome-encapsulated hemoglobin (LEH), a novel cellular hemoglobin-based oxygen carrier. We hypothesized that the LEH effectively suppresses scavenging of nitrogen oxides by sequestering hemoglobin, thereby being useful for resuscitation from hemorrhagic shock, especially in prehospital settings where blood transfusion is not available. However, putting a catheter into the peripheral vessels is sometimes difficult in prehospital resuscitation, because these vessels collapse in patients with hemorrhagic shock. ⋯ Thereafter, the mice were rescued with intraosseous transfusion of LEH or RBCs. Unlike intravenous transfusion, intraosseous transfusion with LEH (but not such transfusion with RBCs) significantly increased mouse survival without scavenging of NO2 or NO3, presumably because LEH vesicles were much smaller than RBCs, thereby effectively flowing into the circulation from the femur. Thus, intraosseous transfusion with LEH may be a candidate strategy for efficient prehospital resuscitation from hemorrhagic shock.
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Streptococcus pyogenes of the M1 serotype is frequently associated with severe streptococcal infections. M1 protein challenge can cause widespread microthrombosis, suggesting a role of platelets in streptococcal sepsis. Herein, we hypothesized that platelets may play a role in M1 protein-induced lung inflammation and injury. ⋯ On the other hand, neutrophil depletion abolished M1 protein-induced edema formation and tissue damage in the lung. Our data suggest that neutrophils but not platelets are involved in the pathophysiology of M1 protein-provoked pulmonary damage. Thus, neutrophils may constitute a key target in infections caused by S. pyogenes of the M1 serotype.
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Human inter-α inhibitor proteins are endogenous human plasma proteins that function as serine protease inhibitors. Inter-α inhibitor proteins can block the systemic release of proteases in sepsis and block furin-mediated assembly of protective antigen, an essential stop in the intracellular delivery of the anthrax exotoxins, lethal toxin and edema toxin. ⋯ These human plasma proteins possess combined actions against anthrax as general inhibitors of excess serine proteases in sepsis and specific inhibitors of anthrax toxin assembly. Inter-α inhibitor proteins could represent a novel adjuvant therapy for the treatment of established anthrax infection.