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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Severe sepsis is characterized by rapid development of multiple organ failure associated with high mortality. Bacterial toxin release triggers a sequence of events that activates intracellular pathways to produce inflammatory mediators and nitric oxide. There have been numerous attempts to interrupt this devastating cascade by removing toxins, removing or inhibiting mediators, and by blocking receptors of mediators. ⋯ Attempts to remove toxins to treat sepsis may appear futile if we cannot access this space or when the level of induced clearance is too low compared with natural clearance. The impact of these considerations is highly dependent on the exact toxin biology in vivo. Extrapolated to other toxins, we indicate a set of general requirements to be met to facilitate successful toxin removal by a pheresis technique.
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Trauma patients are often transfused allogeneic red blood cells (RBCs) in an effort to augment tissue oxygen delivery. However, the effect of RBC transfusion on microvascular perfusion in this patient population is not well understood. To this end, we investigated the effect of RBC transfusion on sublingual microvascular perfusion in trauma patients. ⋯ Pretransfusion PPC may be selectively deranged in otherwise stable trauma patients. Patients with relatively altered baseline PPC tend to demonstrate improvement in perfusion following transfusion, whereas those with relatively normal perfusion at baseline tend to demonstrate either no change or, in fact, a decline in PPC. Bedside sublingual imaging may have the potential to detect subtle perfusion defects and ultimately inform clinical decision making with respect to transfusion.
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We hypothesized that severely injured obese patients would display increased concentrations of proinflammatory cytokines when compared with patients of normal body mass index (BMI) and that this would be associated with multiple organ failure (MOF). This was a retrospective review of prospectively collected data in the "Inflammation and the Host Response to Injury" trauma-related database. Data were collected prospectively from US level I trauma centers. ⋯ Despite prior reports suggesting a proinflammatory cytokine profile in obese individuals, obese patients sustaining severe injury show a depressed early cytokine response when compared with patients of normal BMI. This may confer increased susceptibility to nosocomial infection and later MOF. Further study of immune dysfunction in the postinjury obese patient should assess the possibility of early immune suppression.
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Recently, we reported that Brown Norway (BN) rats were more resistant to lipopolysaccharide (LPS)-induced myocardial dysfunction than Dahl S (SS) rats. This differential sensitivity was exemplified by reduced production of proinflammatory cytokines and diminished nuclear factor-κB pathway activation. To further clarify the mechanisms of different susceptibility of these two strains to endotoxin, this study was designed to examine the alterations of cardiac and mitochondrial bioenergetics, proinflammatory cytokines, and signaling pathways after hearts were isolated and exposed to LPS ex vivo. ⋯ In addition, LPS significantly decreased complex I activity in SS hearts but not in BN hearts. Furthermore, LPS induced higher levels of tumor necrosis factor-α and increased phosphorylation of IκκB and p65 more in SS hearts than in BN hearts. Our results clearly demonstrate that less mitochondrial dysfunction combined with a reduced production of tumor necrosis factor-α and diminished activation of nuclear factor-κB are involved in the mechanisms by which isolated BN hearts were more resistant to LPS-induced myocardial dysfunction.
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Inflammation and oxidative stress play important roles in the pathogenesis of neurodegenerative disorders such as stroke, traumatic injury, Parkinson disease, and Alzheimer disease. Paeonol, a natural compound extracted from Moutan cortex, is a potent anti-inflammatory and antioxidative agent. The aim of this study was to investigate the neuroprotective mechanisms of paeonol on lipopolysaccharide (LPS)-induced inflammation in rat primary microglia and 6-hydroxydopamine-induced oxidative damage in cortical neurons. ⋯ Posttreatment with paeonol also reduced inflammatory responses in LPS-activated microglia and increased cell viability in LPS-treated microglia culture medium-treated neurons. Furthermore, in 6-hydroxydopamine-treated cortical neurons, paeonol not only decreased reactive oxygen species production but also increased cell viability, superoxide dismutase activity, and the antiapoptotic protein B-cell lymphoma 2 expression. Taken together, the present results suggest that paeonol might be a potential neuroprotective agent via inhibiting microglia-mediated inflammation and oxidative stress-induced neuronal damage.