its relation to autoimmune disease has not been elucidated. Here, we focused on interleukin (IL)-17, which is closely related to the pathogenesis of multiple sclerosis, and investigated the effect of ET receptor blockers on the production of IL-17 by T lymphocytes. Main methods: Lymph node cells from mice at 8 days post-immunization with MOG(35-55) were stimulated in vitro with MOG(35-55) in the presence or absence of an ET receptor blocker (BQ123 for ETA or BQ788 for ETB). Naive T cells from mice were subjected to an in vitro model of Th17 differentiation, and ET-mediated IL-17 production
was investigated under the states of Th17 differentiation and activation. Key findings: Fosbretabulin concentration ELISA revealed that MOG(35-55)-induced IL-17 production was significantly inhibited by BQ123 but check details not BQ788. Consistent with the ELISA results for IL-17. the frequency of CD4(+) T cells producing IL-17 but not IFN-gamma was reduced by BQ123. Under the differentiating state from naive T cells to Th17 cells, the spontaneous release of IL-17 from CD4(+) T cells was increased, which was insensitive to BQ123, indicating that ET/ETA signaling
did not affect Th17 differentiation. After the time period of Th17 differentiation, however, the increase in IL-17 production by restimulation of the cells with anti-CD3 plus anti-CD28 antibodies was significantly inhibited by BQ123. Significance: We demonstrated that ET/ETA signaling plays a crucial role in IL-17 production by Th17. BQ123 might be expected to be a future therapeutic drug for multiple sclerosis. (C) 2014 The Authors. Published by Elsevier Inc.”
“Matrix metalloproteinases (MMPs) are enzymes thought to be involved in tumor invasion. We selleck screening library hypothesized that MMP-2 and MHP-11 overexpression was associated with the aggressiveness of ovarian carcinoma. This study was performed on samples from 100 patients with stage III ovarian carcinomas treated surgically between 1990 and 2000. Immunohistochemical staining was performed on ovarian tumors and peritoneal implants using
monoclonal antibodies. Overexpression was defined as more than 10% of cells expressing the marker Multivariate analyses showed that only MMP-2 overexpression by cancer cells in peritoneal implants was associated with a significant risk of death by disease (hazard ratio, 2.65; 95% confidence interval, 1.41-4.97; P =.003). MMP-11 overexpression was not predictive of survival. These results suggest that MMP-2 overexpression by cancer cells in peritoneal implants and not in the primary ovarian cancer is predictive of ovarian cancer prognosis and more likely reflects the presence of particularly aggressive clones of cancer cells.”
“Background: The aim of this study was to evaluate efficacy and tolerability of levetiracetam (LEV) in patients with different epilepsy syndromes. Methods: We evaluated epileptic patients seen in the previous 18 months, including all patients with present or past exposure to LEV.