Peripheral 5-HT7 receptors as a new target for prevention of lung injury and mortality in septic rats.

Sepsis is a complex pathophysiological event involving metabolic acidosis, systemic inflammatory response syndrome, tissue damage and multiple organ dysfunction syndrome. Although many new mechanisms are being investigated to enlighten the pathophysiology of sepsis, there is no effective treatment protocol yet. Presence of 5-HT7 receptors in immune tissues prompted us to hypothesize that these receptors have roles in inflammation and sepsis. We investigated the effects of 5-HT7 receptor agonists and antagonists on serum cytokine levels, lung oxidative stress, lung histopathology, nuclear factor κB (NF-κB) positivity and lung 5-HT7 receptor density in cecal ligation and puncture (CLP) induced sepsis model of rats. Agonist administration to septic rats increased survival time; decreased serum cytokine response against CLP; decreased oxidative stress and increased antioxidant system in lungs; decreased the tissue NF-κB immunopositivity, which is high in septic rats; and decreased the sepsis-induced lung injury. In septic rats, as a result of high inflammatory response, 5-HT7 receptor expression in lungs increased significantly and agonist administration, which decreased inflammatory response and related mortality, decreased the 5-HT7 receptor expression. In conclusion, all these data suggest that stimulation of 5-HT7 receptors may be a new therapeutic target for prevention of impaired inflammatory response related lung injury and mortality.

Association between hepatic alveolar echinococcosis and frequency of human leukocyte antigen class I and II alleles in Turkish patients.

BACKGROUND: Human alveolar echinococcosis (AE) is a potentially fatal, chronically progressive hepatic infestation that is characterized by a long asymptomatic period in which an invasive tumor-like lesion develops. Several studies have suggested that genetic susceptibility to AE may be linked to HLA class II alleles. We investigated the association between AE and antigen HLA-A, B, C, DR and DQ profiles of patients with hepatic AE (HAE) in the eastern part of Turkey. METHODS: This case-controlled study was performed on 44 unrelated patients with HAE and 76 control subjects. The diagnosis was supported by clinical, radiological, and histopathological evidence. The association of class I and class II HLA antigens was examined in the patients with HAE and control subjects. RESULTS: There was an increase in the antigen frequencies of HLA-DRB1*15, HLA-DQB1*02, 06, 07 in the HAE patientscompared with those in the control group (P < 0.05, P < 0.001, P < 0.01, P < 0.05, respectively). HLA-DQB1*02, 06, 07 were more frequent in patients with stages III and IV who were classified according to the PNM staging system. CONCLUSIONS: The present study indicates that susceptibility to HAE in the Turkish population is essentially HLA class II and poorly class I mediated, with HLA-26, and DRB1*015, DQB1* 02, 06, 07 with more allele distribution in the patient group. Our results are not similar to those of other studies, but contribute to the discussions on the association of HLA class I and class II alleles with AE.