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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Substance P (SP) is a neuropeptide that contributes to a proinflammatory state by binding to the neurokinin 1 receptor (NK-1R). Limiting this interaction has been shown to attenuate the acute inflammation. Our hypothesis was that NK-1R activation would contribute to the morbidity and mortality of sepsis in a model using mice genetically deficient in the NK-1R. ⋯ These data confirm the hypothesis that eliminating the SP/NK-1R interaction in a highly lethal murine model of sepsis leads to decreased morbidity and mortality through multiple mechanisms.
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Excessive inflammation reactions with a cytokine storm in the lungs have historically been thought as the primary cause of fatal acute respiratory distress syndrome (ARDS). However, interruption of inflammatory cytokine activation failed to attenuate ARDS, suggesting that other therapies are required to treat this illness and improve survival. Etoposide (ET), a cytotoxic agent, and prednisolone (PSL), a corticosteroid with strong anti-inflammatory activity, have been used to treat other disease involving similar cytokine-activated macrophages and hemophagocytic activity. ⋯ Furthermore, whereas ET alone improved lung edema, it did not increase the survival rate, indicating the necessity of PSL in the treatment of ARDS. Surprisingly, combination therapy did not reduce the production of cytokines and chemokines in the lungs, demonstrating that inflammatory cells, rather than hypercytokinemia, are the direct target of these compounds and primary cause of ARDS-related death. Thus, combination therapy with ET and PSL that targets inflammatory cells has the potential to attenuate fatal ARDS.
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Aortic occlusion during cardiopulmonary resuscitation (CPR) increases systemic arterial pressures. Correct thoracic placement during the resuscitative endovascular balloon occlusion of the aorta (REBOA) may be important for achieving effective CPR. ⋯ Thoracic aortic occlusion in zone Ic during CPR may be more effective in increasing systemic arterial pressures than occlusion in zone Ib. REBOA during CPR was found to be associated with a more favorable acid-base status of circulating blood. If REBOA is used as an adjunct in CPR, it may be of importance to carefully determine the aortic occlusion level.The study was performed following approval of the Regional Animal Ethics Committee in Linköping, Sweden (application ID 418).
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Extracellular vesicles (EVs) in the plasma mediate important intercellular communications in the pathogenesis of cancer and inflammatory diseases. EVs express integrins that regulate target specificities and programmed cell death ligand 1 and 2 (PD-L1 and 2) that suppress lymphocyte activation. However, the roles of these molecules on EVs in systemic inflammatory response syndrome (SIRS) and sepsis remain little understood. ⋯ Furthermore, EV expression of β2 integrin in sepsis patients correlated with hypotension and reduced kidney function. In addition, soluble PD-L1 levels correlated with sepsis severity, impaired kidney function, and impaired central nervous system function. These results suggest the potential involvements of the EV β2 integrin, as well as EV PD-L2 and soluble PD-L1, in the septic pathogenesis that occurs with the systemic immune activation leading to multiple organ dysfunctions.