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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Interleukin 1 receptor-like 1 (ST2) has been implicated as a negative regulator of Toll-like receptor signaling. We here sought to elucidate the role of ST2 in cytokine release and systemic infection caused by two common human sepsis pathogens, Streptococcus pneumoniae (gram-positive) and Klebsiella pneumoniae (gram-negative). ⋯ ST2 augments rather than inhibits cytokine release by blood leukocytes and splenocytes exposed to S. pneumoniae or K. pneumoniae, but plays a limited role in host defense during sepsis caused by these pathogens.
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Acute respiratory distress syndrome (ARDS) is a serious complication of sepsis and sepsis-associated ARDS is associated with significant morbidity and mortality. To date, no study has directly examined the epidemiology of ARDS in severe sepsis from the earliest presentation to the health care system, the Emergency Department (ED). ⋯ In patients presenting to the ED with severe sepsis, the rate of sepsis-associated ARDS development varied across the continuum of care. ARDS developed rapidly and was associated with significant mortality. Elevated serum lactate levels in the ED and a recently validated clinical prediction score were independently associated with the development of ARDS in severe sepsis.
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Sepsis is an acute inflammatory condition that can result in multiple organ failure and acute lung injury (ALI). Growth arrest-specific protein 6 (Gas6) is a broad regulator of the innate immune response involved with the NF-κB signaling pathway. We hypothesized that Gas6 could have a protective role in attenuating the severity of ALI and sepsis. ⋯ Moreover, rmGas6 reduced the in-vitro migration of differentiated human promyelocytic HL60 cells by 64%. Finally, the 10-day survival rate of mice subjected to CLP was increased from 31% in the vehicle group to 67% in the rmGas6 group (P<0.05). Thus, Gas6 has potential to be developed as a novel therapeutic agent to treat patients with sepsis and acute lung injury.
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Panax quinquefolium saponin (PQS) alleviates hypoxia-reoxygenation injury of cardiomyocytes in vitro by inhibiting excessive endoplasmic reticulum stress (ERS)-related apoptosis. We hypothesized that inhibition of excessive ERS-related apoptosis contributes to cardioprotection in ventricular remodeling after acute myocardial infarction (AMI). Sprague-Dawley rats subjected to AMI were randomly treated with water, PQS (50 mg/kg per day, 100 mg/kg per day, or 200 mg/kg per day), or taurine (300 mg/kg per day), an ERS inhibitor, for 4 weeks. ⋯ Panax quinquefolium saponin treatment (200 mg/kg per day) mimicked the results achieved from the taurine-treated rats. Expression of CHOP positively correlated with the apoptosis index of cardiomyocytes in the noninfarcted myocardium (r = 0.797, P < 0.01). Taken together, PQS treatment significantly improves AMI-induced LV remodeling, and this may be attributed to inhibiting CHOP-mediated ERS-related apoptosis.