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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Observational Study
The Value of Extracellular Cold-Inducible RNA-Binding Protein (eCIRP) in Predicting the Severity and Prognosis of Patients After Cardiac Arrest: A Preliminary Observational Study.
Extracellular cold-inducible RNA-binding protein (eCIRP) acting as a novel damage-associated molecular pattern molecule promotes systemic inflammatory responses, including neuroinflammation in cerebral ischemia. We aimed to observe the changes of serum eCIRP and evaluate whether the increased serum eCIRP was associated with the severity and prognosis in patients with restoration of spontaneous circulation (ROSC). ⋯ Systemic inflammatory response with increased serum eCIRP occurred in patients after ROSC. Increased eCIRP level was positively correlated with the aggravation of systemic inflammatory response and the severity after ROSC. Serum eCIRP serves as a potential predictor for 28-day mortality and poor neurological prognosis after ROSC.
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A potential cause of the variable response to injury and sepsis is the variability of a patient's human glucocorticoid receptor (hGR) profile. To identify hGR variants, blood samples were collected on admission and biweekly thereafter from hospitalized patients who sustained at least a 20% total body surface area burn injury. A hyperactive G1376T single-nucleotide polymorphism (SNP) isoform was identified. ⋯ With the combination of both RU486 and hydrocortisone, G459V activity was repressed, but greater than that of RU486 alone. Finally, when hGRα was cotransfected with G459V to simulate isoform interaction, the activity was closer to that of the hGRα profile than the G459V isoform. The unique activity of the G459V isoform shows that some variants of hGR have the potential to alter a person's response to stress and steroid treatment and may be a factor as to why mitigating the clinical response to sepsis and other stressors has been so elusive.
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Bone marrow-derived mononuclear cells (BMMNCs) secrete anti-inflammatory mediators that protect against acute inflammation. Current evidence suggests that BMMNC transplantation can reduce acute tissue injury caused by systemic inflammation and lung dysfunction. This study evaluated the role of BMMNCs in reducing systemic inflammatory responses to vascular endothelial injury in sepsis. ⋯ Ultrastructural analysis revealed that the glycocalyx structure was maintained and the continuity of the vascular endothelial glycocalyx layer was preserved in the BMMNC group, compared with the case for the Control group at 6 and 12 h. Therefore, BMMNC transplantation may provide reduced systemic inflammation and endothelial glycocalyx damage, dramatically improving the survival of rats. These findings provide insights into formulating potential therapeutic strategies against sepsis.
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Secondary brain injury following hemorrhagic shock (HS) is a frequent complication in patients, even in the absence of direct brain trauma, leading to behavioral changes and more specifically anxiety and depression. Despite preclinical studies showing inflammation and apoptosis in the brain after HS, none have addressed the impact of circulating mediators. Our group demonstrated an increased uric acid (UA) circulation in rats following HS. ⋯ Finally, the forced swim, elevated plus maze, and social interaction tests detected anxiety-like behavior after HS, which was blunted in rats treated with the uricase. In conclusion, we have identified UA as a new circulatory inflammatory mediator, responsible for brain alterations and anxious behavior after HS in a murine model. The ability to target UA holds the potential of an adjunctive therapeutic solution to reduce brain dysfunction related to hemorrhagic shock in human.
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Splanchnic vasodilation by inodilators is an argument for their use in critical cardiac dysfunction. To isolate peripheral vasoactivity from inotropy, such drugs were investigated, and contrasted to vasopressors, in a fixed low cardiac output (CO) model resembling acute cardiac dysfunction effects on the gastrointestinal tract. We hypothesized that inodilators would vasodilate and preserve the aerobic metabolism in the splanchnic circulation in low CO. ⋯ Splanchnic vasodilation by levosimendan and milrinone may be negligible in low CO, thus rejecting the hypothesis. High-dose vasopressors may have side effects in the splanchnic circulation.