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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Notch signaling, a critical pathway in cell fate determination, is well known to be involved in immune and inflammatory reactions, whereas its role in acute lung injury (ALI) remains unclear. Here, we report that notch signal activity is upregulated in lung tissue harvested from an ALI mouse model (induced by zymosan). We showed that notch signal activity in lung tissue was increased 6 h after zymosan injection and peaked at 24 h. ⋯ In conclusion, the role of notch signaling is functionally significant in the development of ALI. Inhibition of notch signaling by pretreatment or posttreatment with DAPT likely exerts its effects in part by mediating the expression of proinflammatory and anti-inflammatory cytokines and influencing tissue neutrophil recruitment. These results also imply that notch inhibitors may help attenuate local inflammatory lung damage.
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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.
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Pulse pressure variation (PPV) has been proposed as a promising resuscitation goal, but its ability to predict fluid responsiveness has been questioned in various conditions. The purpose of this study was to assess the performance of PPV in predicting fluid responsiveness in experimental hemorrhagic shock with endotoxemia, while comparing it with goals determined by a conventional set of guidelines. ⋯ Acute resuscitation guided by PPV was comparable with the strategy guided by CVP, mean arterial pressure, and SvO2. Central venous pressure and PPV were individually limited but independently predictive of fluid responsiveness.