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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Cirrhotic patients admitted to intensive care units (ICUs) have high mortality rates. This study evaluated specific predictors and scoring systems for hospital and 6-month mortality in critically ill cirrhotic patients. This investigation is a prospective clinical study performed in a 10-bed specialized hepatogastroenterology ICU in a tertiary care university hospital in Taiwan. ⋯ Cumulative survival rates at the 6-month follow-up after hospital discharge differed significantly (P < 0.05) for AKIN stage 0 vs. stages 1, 2, and 3, and for AKIN stage 1 vs. stage 3. The AKIN, SOFA, and Model for End-stage Liver Disease (MELD) scores showed well discriminative power in predicting hospital mortality in this group of patients. The AKIN scoring system proved to be a reproducible evaluation tool with excellent prognostic abilities for these patients.
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Hypertonic saline (HS) has been investigated as an immune modulator following hemorrhagic shock and sepsis. The polymorphonuclear neutrophil (PMN) response to HS is regulated by the release of ATP, which is converted to adenosine and activates adenosine receptors. Binding to A3 adenosine receptors promotes PMN activation, and inhibition of A3 receptors improves the efficacy of HS resuscitation. ⋯ Stimulation with fMLP or HS increased A3 expression in normal volunteers, but only in patients with ISS of less than 25 or without hypovolemic shock. A3 receptor expression on the surface of PMNs is upregulated by injury, and increased expression levels are associated with greater injury severity and hypovolemic shock. Hypertonic saline increases A3 expression of PMNs from healthy volunteers and less severely injured patients.
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Cytokine production is critical in sepsis. 2-Methoxyestradiol (2ME2), an endogenous metabolite of estradiol, inhibits hypoxia-inducible factor 1α (HIF-1α) and is an antiangiogenic and antitumor agent. We investigated the effect of 2ME2 on cytokine production and survival in septic mice. Using i.p. ⋯ In vivo and in vitro effects of 2ME2 on LPS-induced macrophage inflammation were determined. The effect of 2ME2 on HIF-1α expression, nuclear factor κB (NF-κB), and inducible NO synthase (iNOS) in LPS-treated RAW264.7 cells, a murine macrophage cell line, was determined using Western blotting. 2-Methoxyestradiol treatment reduced LPS-induced lung, liver, and kidney injury. Both early and late 2ME2 treatment prolonged survival in LPS- and CLP-induced sepsis. 2-Methoxyestradiol significantly reduced IL-1β, IL-6, TNF-α, and NO levels in septic mice as well as in LPS-stimulated peritoneal macrophages. 2-Methoxyestradiol treatment also reduced the LPS-induced expression of HIF-1α, iNOS, and pNF-κB in RAW264.7 cells, as well as iNOS and pNF-κB expression in siHIF-1α-RAW264.7 cells. 2-Methoxyestradiol prolongs survival and reduces lung, liver, and kidney injury in septic mice by inhibiting iNOS/NO and cytokines through HIF-1α and NF-κB signaling.
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The objective of the study was to investigate pulmonary responses to Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) using ovine and mice models of sepsis with emphasis on lung cytokine expression, asymmetric dimethylarginine (ADMA) concentration, and the arginase pathway. Sheep were instilled with either MRSA, P. aeruginosa, or saline under deep anesthesia; mechanically ventilated; resuscitated with fluid; and killed after 24 h. Mice were instilled with either MRSA, P. aeruginosa, or saline under deep anesthesia and killed after 8 h. ⋯ In the mice model, P. aeruginosa significantly increased lung cytokine expression (IL-1 and IL-13), protein oxidation, and arginase activity compared with MRSA. Our data suggest that the greater expression of cytokines and ADMA concentrations may be responsible for severity of acute lung injury in P. aeruginosa sepsis. The lack of arginase activity may explain the greater nitric oxide production in MRSA sepsis.
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Fluid resuscitation is essential in the treatment of septic shock. This study examined the effect of resuscitative fluids (RFs) on sepsis-induced neutrophil-endothelial cell interactions. The RFs studied were 0.9% saline (NS), Ringer's lactate (RL), 7.5% saline and dextran-70 (DHS), 5% albumin (AL), and 6% hydroxyethyl starch (HS). ⋯ These data suggest that fluids used in the resuscitation of septic shock vary in their effects on sepsis-induced neutrophil-endothelial cell interactions. Ringer's lactate amplifies the effects of sepsis, while NS appears to have minimal impact. Dextran-70 and 7.5% saline, AL, and HS in varying degrees decrease sepsis-related neutrophil-endothelial cell interactions and activation.