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
-
Expression of inflammatory cytokines is regulated by transcriptional and posttranscriptional mechanisms. We previously showed that NADPH oxidase-derived superoxide induces inflammatory mediators in response to tumor necrosis factor α (TNF-α) and lipopolysaccharide (LPS). In this study, we examined the role of endothelial NADPH oxidase in the regulation of mRNA stability of three inflammatory mediators: interleukin (IL) 8, IL-6, and intercellular adhesion molecule 1 (ICAM-1). ⋯ In conclusion, NADPH oxidase contributes to destabilization of IL-8 mRNA stability and propose a model for the complex underlying mechanism, which is dependent upon agonist (LPS vs. TNF-α) and target molecule (IL-8 vs. IL-6 and ICAM-1) and involves tristetraprolin, p38, and extracellular signal-regulated kinase 1/2 MAPK.
-
Despite our increasing ability to support vital organs and resuscitate patients, the morbidity and mortality of acute kidney injury (AKI) remain high in the intensive care unit (ICU). The ability to predict the occurrence of AKI is crucial for the development of preventive strategies. Early diagnosis of AKI requires markers that are sensitive and easily applicable in clinical practice. ⋯ The Doppler-based renal resistive index, which is a simple, rapid, noninvasive, and repeatable marker, could be a promising tool to prematurely detect the patients most at risk of developing AKI in the ICU and to distinguish transient from persistent AKI. Moreover, the resistive index could also be useful to adjust preventive or therapeutic modalities for the kidney perfusion at the bedside. The recent progress in ultrasound with contrast-enhanced ultrasound gives the opportunity to assess not only the kidney macrocirculation but also the kidney microcirculation in the ICU.
-
The influence of estrogen signaling on infectious diseases is not fully known. Males seem to be more susceptible to infections than females. This has also been noted for the Scandinavian form of hemorrhagic fever with renal syndrome caused by Puumala hantavirus (PUUV). ⋯ None or very small amounts of ERβ were detected, and ERα and ERβ2 mRNA were elevated in the patient group. The samples from the males were correlated with ERβ2; the female samples, with ERα. Furthermore, the female and male samples are partly separated using multivariate statistic analysis (principal component analysis), supporting findings that clinical symptoms differ depending on sex.
-
Cirrhosis increases the risk of kidney injury and sepsis, leading to increased mortality. Elevated levels of plasma asymmetric dimethylarginine (ADMA) occur in patients critically ill with cirrhosis, renal failure, and sepsis. We used a rat model of cirrhosis with superimposed sepsis to assess the relationship of plasma and tissue ADMA profiles with acute kidney injury and survival. ⋯ Lipopolysaccharide increased hepatic AAR, decreased renal AAR, and paradoxically mediated the expression of neuronal nitric oxide synthase-β in the liver and kidneys. A novel mechanism underlies the LPS-mediated L-arginine-ADMA-nitric oxide pathway activation and exacerbation of kidney injury and mortality in our BDL model. In the presence of cirrhosis with superimposed sepsis, simultaneous lowering of ADMA levels and enhancement of L-arginine levels to restore plasma and renal AARs may be an optimal strategy for the treatment of kidney injury.
-
Experimental sepsis was induced in male C57BL/6j, adiponectin-deficient mice (ADPNKO), and wild-type littermates by i.p. injection of 16 mg/kg lipopolysaccharide or cecal ligation and puncture. Blood and tissue samples were harvested 24 h after model induction. Circulating adiponectin is reduced in mice with endotoxemic challenge and after cecal ligation and puncture compared with healthy control mice. ⋯ Adiponectin-deficient mice have reduced survival following cecal ligation and puncture and increased blood levels of interleukin 6, soluble vascular endothelial growth factor receptor 1, and soluble endothelial adhesion molecules E-selectin and intercellular adhesion molecule 1. Finally, ADPNKO promoted end-organ injury in the liver and kidney, whereas the lungs were not affected. These data suggest a protective role of adiponectin in diminishing microvascular organ-specific endothelial cell activation during sepsis.