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
-
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.
-
Translocation of bacteria and other luminal factors from the intestine following surgical injury can be a major driver of critical illness. Bile acids have been shown to play a key role in the loss of intestinal epithelial barrier function during states of host stress. Experiments to study the ability of nonionic block copolymers to abrogate barrier failure in response to bile acid exposure are described. ⋯ Preliminary transepithelial electrical resistance-based studies examining structure-function correlates of polymer protection against bile acid damage were performed with a small library of PEG-based copolymers. Polymer properties associated with optimal protection against bile acid-induced barrier disruption were PEG-based compounds with a molecular weight greater than 10 kd and amphiphilicity. The data demonstrate that PEG-based copolymer architecture is an important determinant that confers protection against bile acid injury of intestinal epithelia.
-
Sepsis is a poorly understood syndrome. Therefore, we examined the mechanisms underlying failed regeneration in sham-operated (SO), mildly septic (cecal ligation and single puncture [CLP]), and severely septic (cecal ligation with two punctures [2CLP]) C57Bl6 mice. Relative to no operation (T0) or SO, CLP, but not 2CLP, increased the number of cells staining for proliferating cell nuclear antigen, a marker for cell division. ⋯ Finally, CLP increased the steady-state abundance of the mRNAs encoding thymidine kinase, DNA polymerase α, and dihydrofolate reductase, all required for DNA replication. No changes were noted after 2CLP. We conclude that 2CLP impaired hepatocyte proliferation following 2CLP in part via impaired cyclin D1/cdk-4-induced phosphorylation of pRb, maintaining the association between pRb and E2F and inhibited E2F transcriptional activity.
-
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.
-
Stimulation of toll-like receptor 9 (TLR9) by CpG-C containing oligonucleotides attenuates ischemic injury in the brain and liver. In this study, we investigate whether any of the three classes of CpG (A, B, or C) mitigate ischemia-induced cardiac dysfunction. We measured left ventricular ejection fraction (LVEF) in C57BL/6 mice using transthoracic echocardiography. ⋯ Gene expression microarray of CpG-C-stimulated cells revealed upregulation of the nuclear factor κB pathway inhibitors TNFAIP3, NFKBIA, TRIM30, and TNIP1. These may play a role in attenuation of cardiac inflammation. The TLR9 ligand CpG-C attenuates the acute inflammatory cardiac dysfunction induced by both LPS and ischemia-reperfusion of the left anterior descending artery.