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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The adipocyte-specific protein adiponectin reveals anti-inflammatory, antioxidant, antiatherosclerotic and vasoprotective effects. This study aims to investigate adiponectin expression in cultured human adipocytes within an inflammatory model and in patients with severe sepsis and evaluates treatment effects of drotrecogin α (activated) (DAA). In an in vitro inflammatory model of adipocyte cell culture, the effect of DAA on adiponectin mRNA expression was evaluated. ⋯ On day 5 after 96-h infusion of DAA (24 μg/kg per hour), adiponectin levels significantly increased in DAA patients and equalized toward DAA patients (P > 0.1). Adiponectin might be involved in the pathogenesis of the systemic inflammatory response during sepsis. Administration of DAA upregulates adiponectin expression under circumstances of systemic inflammation.
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Large surface area burn injuries lead to activation of the innate immune system, which can be blocked by parasympathetic inputs mediated by the vagus nerve. We hypothesized that vagal nerve stimulation (VNS) would alter the inflammatory response of peritoneal macrophages after severe burn injury. Male BALB/c mice underwent right cervical VNS before 30% total body surface area steam burn and were compared with animals subjected to burn alone. ⋯ We identified a protective role for VNS in blocking peritoneal macrophage activation. Analysis of the phosphorylation state of nuclear factor κB pathway mediator, p65 Rel A, revealed a VNS-mediated reduction in p65 phosphorylation levels after exposure to LPS compared with burn alone. In combination, these studies suggest VNS mediates the inflammatory response in peritoneal macrophages by affecting the set point of LPS responsiveness.
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The hemoglobin vesicle (Hb-vesicle) is a cellular-type artificial oxygen carrier showing a resuscitative effect comparable to that of blood transfusion in several animal models. However, the efficacy of Hb-vesicles for resuscitation when the hemorrhage cannot be controlled remains unclear. Therefore, we used Hb-vesicles in a rat hemorrhagic shock model caused by continuous bleeding. ⋯ Meanwhile, the hematocrit levels of the HbV, Alb, and HES groups showed sharp decreases (HbV: 6.8% ± 1.7%, Alb: 6.8% ± 0.8%, HES: 5.5% ± 0.7% at 100% total circulated blood volume; final hematocrit of the HbV group: 1.5% ± 0.5%). These results suggest that shocked animals can survive longer when the Hb-vesicle supply is maintained and that HbV showed a similar effect to wRBC in maintaining the circulating volume and oxygen metabolism. Continuous infusion of Hb-vesicles may extend the survival of trauma victims with uncontrolled hemorrhage until they have reached a trauma center.
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Since the definition of systemic inflammatory response syndrome/sepsis was originally proposed, a large amount of new information has been generated showing a much more complex scenario of inflammatory and counterinflammatory responses during sepsis. Moreover, some fundamental mechanisms of sensing and destroying invading microorganisms have been uncovered, which include the discovery of TLR4 as the lipopolysaccharide (LPS) gene, implications of innate immune cells as drivers of the adaptive response to infection, and the modulation of multiple accessory molecules that stimulate or inhibit monocyte/macrophage and lymphocyte interactions. ⋯ In this review, we discuss aspects of bacterial recognition and induced cellular activation during sepsis. Because of the relevance of endotoxin (LPS) research in the field, we focus on LPS and host interactions as a clue to understand microorganisms sensing and cell signaling, then we discuss how this response is modulated in septic patients.
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Sepsis is still a leading cause of death on intensive care units. Despite intensive research, only few new therapies have been developed and used in the clinical setting. The fibrin fragment Bβ15-42 was already shown to preserve endothelial barrier function by binding to VE-cadherin and thus stabilize the interendothelial junctions. ⋯ Analysis alanine aminotransferase and aspartate aminotransferase further indicated reduced liver damage following polymicrobial sepsis. In vitro experiments using endothelial cells and macrophages further revealed that Bβ15-42 had no direct effect on Toll-like receptor-mediated inflammation. Therefore, we assume that attenuated inflammation is rather due to sustained vascular integrity and thus suppresses vascular leakage and subsequently leukocyte infiltration during sepsis.