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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Previous studies have indicated that gut-derived endotoxin played a pivotal role for aggravating systemic inflammatory response to multi-organ dysfunction under heatstroke. Dexmedetomidine (DEX) could protect against inflammation and multi-organ injury in various scenarios. The aim of this study was to explore the protective effect of DEX on heatstroke and the mechanism involved. ⋯ Finally, to evaluate the anti-apoptosis effect of DEX, the pro-apoptotic protein Bax and anti-apoptotic protein Bcl-2 were analyzed by western blot, and terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL) staining was conducted. The results showed that DEX decreased TUNEL-positive cells induced by heatstroke in a Bax/Bcl-2-related manner. Taken together, our results indicate that DEX could protect against inflammation and multi-organ injury induced by heatstroke via sustaining the intestinal integrity.
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Burn patients suffer muscle mass loss associated with hyperinflammation and hypercatabolism. The mitochondria are affected by this metabolic alteration. Mitochondrial fission activates a caspase cascade that ultimately leads to cell death. We postulate that burn-induced muscle loss is associated with increased mitochondrial fission and subsequent functional impairment. Further, we investigated whether the cytokine IL-6 plays a major role in mitochondrial fission-associated cell death after burn. ⋯ Burn serum caused muscle cell death associated with increased mitochondrial fission and functional impairment. This alteration was alleviated with IL-6 antibody treatment, suggesting the cytokine plays a role in mitochondrial changes in muscle after systemic injury.
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Increased activation of CD95/Fas by Fas ligand in viral hepatitis and autoimmunity is involved in pathogenesis of fulminant hepatitis and liver failure. We designed a bile-acid phospholipid conjugate ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE with LPE containing oleate at the sn-1) as a hepatoprotectant that was shown to protect against fulminant hepatitis induced by endotoxin. We herein further assessed the ability of UDCA-LPE to prevent death receptor CD95/Fas-induced fulminant hepatitis. ⋯ Moreover, UDCA-LPE attenuated inflammatory response by lowering the levels of Jo-2-induced proinflammatory cytokines TNF-α, IL-6, and IL-1β in liver and serum. UDCA-LPE was also able to decrease the levels of stimulated Th1/Th17 cytokines in Jo-2-primed isolated splenocytes. Taken together, UDCA-LPE exhibited potent anti-inflammatory effects against CD95/Fas-induced fulminant hepatitis.
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Sepsis-associated encephalopathy is a major complication during sepsis, and an effective treatment remains unknown. Although minocycline (MINO) has neuroprotective effects and is an attractive candidate for treating sepsis-associated encephalopathy, the effect of MINO on synaptic plasticity during sepsis is still unclear. In the present study, we investigated the effects of MINO on long-term potentiation (LTP) in the hippocampus in a cecal ligation and puncture (CLP) mouse model. ⋯ High doses of MINO prevented the LTP impairment during sepsis in the CLP + MINO group. Interleukin (IL)-1ra administration ameliorated LTP impairment only in the CLP + vehicle group (P < 0.05); it had no additional effects on LTP in the CLP + MINO group. In conclusion, we have provided the first evidence that MINO prevents impaired LTP related to sepsis-induced encephalopathy in the mouse hippocampus, and that mechanisms associated with IL-1 receptor activity may be involved.
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Review
Is Coagulopathy an Appropriate Therapeutic Target During Critical Illness Such as Trauma or Sepsis?
Coagulopathy is a common and vexing clinical problem in critically ill patients. Recently, major advances focused on the treatment of coagulopathy in trauma and sepsis have emerged. ⋯ To analyze the state of the science regarding coagulopathy in critical illness, a symposium addressing the problem was organized at the 39th annual meeting of the Shock Society in the summer of 2016. This manuscript synthesizes the viewpoints of the four expert panelists at the debate and presents an overview of the potential positive and negative consequences of targeting coagulopathy in trauma and sepsis.