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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S100B has been described as a marker of brain injury. However, not much is known regarding change in plasma S100B and its relation with mortality after spontaneous intracerebral hemorrhage (ICH). Thus, we sought to investigate change in plasma S100B level after ICH and to evaluate its relation with disease outcome. ⋯ A receiver operating characteristic curve identified plasma S100B cutoff level (192.5 pg/mL) that predicted 1-week mortality with the high sensitivity (93.8%) and specificity (70.4%) values (P < 0.001). The differences between areas under curves of plasma S100B levels and those of Glasgow Coma Scale scores and ICH volumes were not statistically significant (both P > 0.05). Increased S100B level is found after ICH and may contribute to the inflammatory process of ICH, in association with a poor clinical outcome.
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Glucocorticoid and epinephrine are important stress hormones secreted from the adrenal gland during critical illness. Adrenal glucocorticoid stimulates phenylethanolamine N-methyltransferase (PNMT) to convert norepinephrine to epinephrine in the adrenal medulla. Glucocorticoid is sometimes used in catecholamine-resistant septic shock in critically ill patients. ⋯ We conclude that without stress, when adrenocorticotropic hormone is low, high doses of exogenous dexamethasone stimulate PNMT and catecholamine synthesis, likely independently of adrenal corticosterone concentration. After stress, adrenocorticotropic hormone levels are elevated, and exogenous dexamethasone suppresses endogenous corticosterone and PNMT production. Nonetheless, catecholamines increase, possibly due to direct neural stimulation, which may override the hormonal regulation of epinephrine synthesis during stress.
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There are only few strategic and therapeutic options to improve the functional outcome of patients after cardiac arrest and resuscitation (CPR). The pathophysiology of reperfusion injury after global ischemia is not completely understood. We present here a murine model of cardiac arrest and resuscitation that allows an analysis of the pathophysiology of reperfusion injury, especially focusing on survival, tissue damage, and functional neurological parameters. ⋯ Histological examinations and blood analyses of CPR animals revealed significant leukocyte tissue infiltration and morphological damage of brain, lung, and kidneys. In summary, mice undergoing CPR after cardiac arrest present distinct neurological deficits, marked organ damage, and a 54% mortality rate. Our highly standardized and reproducible model of mice resuscitation provides a means for a better understanding of the post-CPR pathophysiology and thus opens new perspectives to develop relevant therapeutic approaches to minimize global I/R injury.
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Effective immunosuppressive therapy is essential to prevent transplant rejection but renders patients vulnerable to opportunistic infections. The present study investigates the effects of common immunosuppressive drugs on the course of septic peritonitis in an experimental mouse model. We show that treatment with a combination of tacrolimus, mycophenolate mofetil, and methylprednisolone resulted in highly elevated lethality of septic peritonitis. ⋯ These beneficial effects were linked to an elevated expression of activation markers and an increased production of reactive oxygen metabolites by peritoneal neutrophils and correlated with a reduced messenger RNA expression of the inhibitory cytokine IL-22. In contrast, systemic or peritoneal levels of IL-10, IL-12, TNF-alpha, keratinocyte chemoattractant, and monocyte chemoattractant protein 1, and splenic messenger RNA levels of IFN-gamma were not influenced by the immunosuppressive therapy. These results therefore suggest that combined immunosuppressive and antibiotic therapy may improve bacterial clearance and survival of septic peritonitis by a mechanism that involves enhanced activation and antimicrobial activity of neutrophils and reduced production of IL-22.