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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Patients with chronic kidney disease (CKD) requiring dialysis have a higher risk of sepsis and a 100-fold higher mortality. The severity of cardiac dysfunction predicts mortality among septic patients. Here we investigated the roles of pre-existing CKD on the cardiac outcome in mice with sepsis, and whether inhibition of IκB kinase (IKK) reduces the cardiac dysfunction in these animals. ⋯ Pre-existing CKD aggravates the cardiac dysfunction caused by LPS or CLP in mice; this may (at least in part) be due to increased cardiac activation of NF-κB and iNOS expression.(Figure is included in full-text article.).
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For the treatment of severe inflammation, sepsis and septic shock by membrane-adsorption based extracorporeal blood purification technologies, cytokines are basic targets that have to be removed effectively in order to improve the patient's health status. Although there are different adsorbents commercially available, the success of their clinical use is limited. In order to suppress systemic effects in these disease patterns, effective removal of cytokines below a critical threshold is necessary. ⋯ These results confirm the assumption, that cytokine removal from the blood should approach physiological levels in order to prevent endothelial cell activation.
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Systemic inflammatory response syndrome (SIRS) is a highly complex cascade of pro- and anti-inflammatory mechanisms, which results in a generalized activation of the immune system. Reactive oxygen species (ROS) and mitochondria, as one of the major sources of them play a key role in this process. Considering the deleterious effects of ROS, antioxidant molecules targeting mitochondria can have therapeutic potential. We aimed to test the effects of mitochondria targeted antioxidant (mtAOX) treatment in an animal model of SIRS of varying severity. ⋯ Depending on the severity of experimental SIRS, the effect of mtAOX was either beneficial or detrimental. Since mitochondrial ROS are important molecules of intracellular signaling pathways, we hypothesize that mtROS can activate deleterious and beneficial signaling upon "milder" and "severe" SIRS, respectively. Elucidation of the exact mechanisms is still underway.
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In addition to standard management of hemorrhagic shock (HS) hyperoxia (mechanical ventilation at FiO2=1.0) and hypothermia can be used to increase O2 supply and to reduce O2 demand. However, hypothermia and hyperoxia can aggravate oxidative stress and metabolic acidosis. Since the latter is linked to deranged glucose metabolism, we investigated their effects on glucose metabolism during hemorrhage and resuscitation. ⋯ Supported by the Federal German Department of Defence (AZ E/U2AD/CF523/DF556).
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Dysfunction of the intestinal barrier plays an important role in the pathological process of heatstroke. Omega-3 (or n-3) polyunsaturated fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), help protect the intestinal mucosal barrier. This study assessed if pretreating rats with EPA or DHA could alleviate heat stress-induced damage to the intestinal barrier caused by experimental heatstroke. ⋯ Our results indicate that EPA pretreatment is more effective than DHA pretreatment in attenuating heat-induced intestinal dysfunction and preventing TJ damage. Enhanced expression of TJ proteins that support the epithelial barrier integrity may be important for maintaining a functional intestinal barrier during heatstroke.