Phase Of Sepsis Research Articles

Non-hepatic Hyperammonemia: A Potential Therapeutic Target for Sepsis-associated Encephalopathy.

Sepsis-Associated Encephalopathy (SAE) is a common complication in the acute phase of sepsis, and patients who develop SAE have a higher mortality rate, longer hospital stay, and worse quality of life than other sepsis patients. Although the incidence of SAE is as high as 70% in sepsis patients, no effective treatment is available for this condition. To develop an effective treatment for SAE, it is vital to explore its pathogenesis. It is known that hyperammonemia is a possible factor in the pathogenesis of hepatic encephalopathy as ammonia is a potent neurotoxin. Furthermore, our previous studies indicate that non-hepatic hyperammonemia seems to occur more often in sepsis patients; it was also found that >50% of sepsis patients with non-hepatic hyperammonemia exhibited encephalopathy and delirium. Substatistical analyses indicate that non-hepatic hyperammonemia is an independent risk factor for SAE. This study updates the definition, clinical manifestations, and diagnosis of SAE; it also investigates the possible treatment options available for non-hepatic hyperammonemia in patients with sepsis and the mechanisms by which non-hepatic hyperammonemia causes encephalopathy.

Heat shock treatment decreases the mortality of sepsis in rats.

Sepsis is an increasingly common and lethal diagnosis in hospitalized patients. In spite of the advances in antibiotics and medical equipment, the mortality rate has not been improved in the last decade. Recently, heat shock proteins (Hsps) have been well documented to play a self-protective role in almost all living cells under various pathological and physiological stresses through a mechanism known as thermotolerance or cross tolerance. The present study was designed to investigate the expression of Hsp72 and the protective role of pre-induction of Hsps in the mortality during different phases of sepsis. Adult male Sprague-Dawley rats were employed in the study. Sepsis was induced by cecal ligation and puncture (CLP). Heat shock treatment was performed 16 hrs before sepsis induction by heating the rats whole-bodily with an electric heating pad under general anesthesia. The mortality rates with time in both control and preheated groups were monitored. Hsp72 was detected by SDS-PAGE, Western blotting and immunostaining in the brain, heart, liver, kidney, lung, adrenal gland, muscle and lymphocytes. The results show that both early (9 hrs post-CLP) and late (18 hrs post-CLP) sepsis failed to increase the synthesis of Hsp72. Previous induction of Hsps by heat shock treatment significantly decreased the mortality rate of late sepsis. Applying a sufficient inducer to lymphocytes of late sepsis reversed the synthesis of Hsp72 from inactive state into an over-expressive situation in vitro. These results suggest that Hsps are involved in the pathogenesis of sepsis and the involvement of Hsps during the progression of sepsis could add to a first line of host defense against invasive pathogens. Searching for an acceptable agent or less invasive method that leads to increased Hsps expression may provide a means for better treatment of severe infection.

Group II phospholipase A2 gene expression is transcriptionally regulated in rat liver during sepsis.

Changes in group II phospholipase A2 (PLA2) gene expression in rat liver during different phases of sepsis were studied. Sepsis was induced by cecal ligation and puncture (CLP). The results show that PLA2 activity was increased by 41 and 92% during early hyperdynamic phase (9 h after CLP) and late hypodynamic phase (18 h after CLP) of sepsis, respectively. Western blot analysis reveals that group II PLA2 protein levels were elevated by 53 and 95% during early and late sepsis, respectively. Northern blot analysis depicts that the steady-state levels of group II PLA2 mRNA were enhanced by 39 and 114% during early and late sepsis, respectively. Nuclear run-off assay shows that the transcription rates of group II PLA2 gene transcript were stimulated by 36 and 74% during early and late sepsis, respectively. The actinomycin D pulse chase study indicates that the half-life of group II PLA2 mRNA remained unaffected during early and late phases of sepsis. These results demonstrate that group II PLA2 gene transcripts were overexpressed in rat liver during the progression of sepsis and that the overexpression was a result of the enhanced synthesis of group II PLA2 mRNA. Because PLA2 plays an important role in the maintenance of cell membrane integrity, our findings may contribute to the understanding of the pathogenesis of hepatic dysfunction during the progression of sepsis.