The Journal of surgical research
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The renin-angiotensin system (RAS) affects inflammatory responses during sepsis. Nonproteolytic activation of prorenin by the (pro)renin receptor has recently been shown to stimulate the tissue RAS. In the present study, the effect of (pro)renin receptor blocker (PRRB) pretreatment on sepsis in a rat cecal ligation and puncture (CLP) model was investigated. ⋯ PRRB significantly improved the survival rate of rats with clinically relevant sepsis, possibly by attenuating a sepsis-induced systemic inflammatory response. We propose that overactivation of the RAS by activation of prorenin in foam cells may be a significant contributor to sepsis.
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Most studies have categorized all antiplatelet drugs into one category. The aim of our study was to evaluate the utility of repeat head computed tomography (RHCT) and outcomes in patients on low-dose aspirin (acetylsalicylic acid; ASA) therapy. ⋯ Low-dose aspirin therapy is not associated with progression of initial insult on RHCT or clinical deterioration. Prehospital low-dose aspirin therapy as a sole criterion should not warrant a routine repeat head CT in traumatic brain injury.
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High-mobility group box 1 (HMGB1) is a critical mediator in the pathogenesis of many inflammatory diseases. Penehyclidine hydrochloride (PHC) has been proven to reduce sepsis-related mortality and sepsis-induced pathological complications. These effects are because of the reduced expression and release of many inflammatory mediators, although it is not clear whether PHC affects the expression and release of HMGB1. In this study, we explored the effect of PHC on the release of HMGB1 in lipopolysaccharide (LPS)-activated RAW264.7 cells and cecal ligation and puncture (CLP)-induced septic mice. ⋯ Our study demonstrates that PHC inhibits the translocation of HMGB1 from the nucleus to the cytoplasm and the expression of HMGB1 messenger RNA in a dose-dependent manner. The mechanism responsible for these effects involves the NF-κB signaling pathway. Moreover, PHC can significantly protect important organs, such as the liver, kidney, and heart in mice with sepsis.
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Comparative Study
Superiority of acetate compared with lactate in a rodent model of severe hemorrhagic shock.
Recently, we have shown that the use of lactated Ringer's (LR) solution is inferior to pure Ringer's solution (RS) in treatment of severe hemorrhagic shock in rats. The present study was performed to evaluate whether this is a specific effect of lactate or also applies to another metabolizable anion, namely acetate. ⋯ In severe hemorrhagic shock, resuscitation with both RS and NS is superior to administration of LR solution but initial outcome is even further improved if AR solution is used. Mere amelioration of the acid-base status by AR solution may explain its superior role compared with RS and NS but cannot be responsible for its superiority compared with LR solution. Here, direct injury by lactate has to be discussed.
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ischemic preconditioning (IPC) protects against liver ischemia-reperfusion (IR) injury. The mechanism involves nitric oxide metabolism but the importance of endothelial nitric oxide synthase (eNOS) has not been established. Heme oxygenase-1 (HO-1) protects against liver IR but it is unclear if this depends on nitric oxide synthase. ⋯ This study developed and used an eNOS-/- model to demonstrate that eNOS mediates protection against liver IR injury by IPC. The eNOS expression and activity and HO-1 expression are increased independently in liver IPC and IR, with HO-1 expression increased in the later stages of IPC and IR.