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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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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Serum micro-RNAs (miRNAs) can be used for the diagnosis and prognosis of various diseases. Using genome-wide scans, we sought to identify serum miRNAs that could be used as prognostic predictors for sepsis patients. We used microarray screens to identify differentially expressed serum miRNAs by comparing samples from 12 surviving and 12 nonsurviving sepsis patients. ⋯ When the cutoff point was set at 0.288, these three combined variables provided 78.13% sensitivity and 91.84% specificity. Our results showed that serum miR-574-5p was correlated with the death of sepsis patients. The combined predictive capability of sepsis stage, Sepsis-Related Organ Failure Assessment scores, and serum miR-574-5p for the death of sepsis patients was better than any single indicator.
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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.
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Delta neutrophil index (DN) is the immature granulocyte fraction provided by a blood cell analyzer (ADVIA 2120; Siemens Healthcare Diagnostics, Deerfield, Ill), which is determined by subtracting the fraction of mature polymorphonuclear leukocytes from the sum of myeloperoxidase-reactive cells. The purpose of this study was to define the role of DN in differential diagnosis and prognosis prediction of patients with sepsis. Hospital records of 273 patients were retrospectively collected: 47 with systemic inflammatory response syndrome, 78 with sepsis, 51 with severe sepsis, and 97 control subjects. ⋯ The best cutoff value for DN for predicting sepsis was 2.7%. Delta neutrophil index was significantly higher in those who died than in the survivors (median [interquartile range], 11.5% [3.5%-25.0%] vs. 4.7% [2.2%-10.6%], P = 0.008) and was identified to be an independent predictor for 28-day mortality in patients with sepsis by Cox proportional hazards model. Delta neutrophil index may serve as a facile and useful marker for early diagnosis and prognostic assessment of patients with sepsis, as it is included in a routine complete blood count.