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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Midkine, a multifunctional cytokine, in patients with severe sepsis and septic shock: a pilot study.
The objective of the study was to evaluate whether severe sepsis and septic shock are related to alterations in midkine concentrations, to identify disease-related factors associated with these alterations, and to initially appraise whether midkine might serve as a biomarker in sepsis. Prospective observational cross-sectional study with 5-day follow-up. Circulating midkine was measured (enzyme-linked immunosorbent assay) in 38 septic (13 with severe sepsis, 25 with septic shock), 82 active inflammatory bowel disease (IBD) (26 with systemic inflammatory response syndrome [SIRS]) patients, and 87 healthy subjects. ⋯ In conclusion, sepsis and septic shock are associated with midkine elevation, substantially more pronounced than in inflammation, even systemic, revealing a new potential mediator of deregulation of neutrophil migration. Sepsis-related global hypoxia seems to contribute to midkine elevation. Our results substantiate further research on possible midkine application as a sepsis biomarker: in differentiating SIRS from sepsis and identifying gram-positive sepsis and septic patients at risk of CVI and shock.
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Sepsis develops as a result of the host response to infection, and its mortality rate in ICU remains high. Severe inflammation usually causes overproductions of proinflammatory cytokines, i.e., TNF-α and reactive oxygen species, which lead to mitochondrial damage and energetic depletion. Autophagy is a survival mechanism for eukaryote to recycle intracellular nutrients and maintain energy homeostasis. ⋯ The tissue localization of autophagy was identified by immunohistochemistry and transmission electron microscopy. Our results showed that (a) increase in LC3-II level in liver tissue occurs at 3 h, peaks at 6 h, and then surprisingly declines quickly until 18 h after CLP (CLP18h); (b) significant hepatic dysfunction was observed at CLP18h; (c) ratio of LC3 aggregation is significantly higher in hepatocytes than in Kupffer cells, and (d) loss of Atg7, an essential gene for autophagosome formation, exaggerates the TNF-α-induced cell death, depletion of ATP, and decrease of albumin production in hepatocytes. These results indicate that autophagy occurs transiently in hepatocytes at early stage, and the decline in autophagy at late stage may contribute to the functional failure in liver during polymicrobial sepsis.
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Resveratrol protects against organ injury caused by trauma-hemorrhage, although the mechanism remains unknown. We have previously shown that it exerts protective effects in the liver via estrogen receptors and their signaling. Thus, we set out to determine whether resveratrol-mediated estrogen receptor-dependent p38 mitogen-activated protein kinase (MAPK)/heme oxygenase 1 activation protects the intestine after trauma-hemorrhage. ⋯ Administration of ICI 182,780, SB-203850, or chromium-mesoporphyrin with resveratrol abolished the resveratrol-mediated improvement of the above parameters. Resveratrol administration also attenuated trauma-hemorrhage-induced cardiac dysfunction and edema of the lung. These results suggest that estrogen receptor-dependent upregulation of the p38 MAPK/heme oxygenase 1 pathway plays a critical role in mediating the salutary effects of resveratrol on shock-induced intestinal injury.
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To investigate the effect of Shen-Fu injection (SFI) for the management of postresuscitation myocardial dysfunction in a porcine model of cardiac arrest. Ventricular fibrillation was induced electrically in anesthetized domestic swine. After 4 min of untreated ventricular fibrillation, cardiopulmonary resuscitation was initiated. ⋯ The SFI treatment also produced lower serum cardiac troponin I, lactate levels, and left ventricle malondialdehyde content after ROSC, whereas left ventricle superoxide dismutase, Na-K-ATPase, and Ca-ATPase activity were significantly increased in the SFI group when compared with saline group. The cardioprotective effect of SFI was further confirmed by myocardial ultrastructure examination. Shen-Fu injection can attenuate postresuscitation myocardial dysfunction through beneficial effects on energy metabolism and remarkable antioxidant capacity.