“Despite recent advances in antibiotic therapy and intensive care, sepsis is still considered to be the most common cause of death in intensive care units. Excessive production of reactive oxygen species plays an important role in the pathogenesis
of sepsis. Recently, it has been suggested that molecular hydrogen (H(2)) exerts a therapeutic antioxidant activity by selectively reducing hydroxyl radicals (center dot OH, the most cytotoxic reactive oxygen species) and effectively protects against organ damage induced by I/R. Therefore, we hypothesized that H(2) treatment had a beneficial effect on sepsis. In the present study, we found that H(2) inhalation buy BEZ235 starting at 1 and 6 h after cecal ligation and puncture (CLP) or sham operation significantly improved the survival rate of septic mice with moderate or severe CLP in a concentration-and time-dependent manner. Furthermore, moderate or severe CLP mice showed significant multiple organ damage characterized by the increases of lung myeloperoxidase activity, wet-to-dry weight ratio, protein concentration in bronchoalveolar lavage, serum biochemical parameters, and organ histopathologic scores at 24 h after CLP operation, which was significantly attenuated by 2% H(2) treatment. In addition, we found that the beneficial effects of H(2) treatment on sepsis and sepsis-associated
organ damage were associated with the decreased levels of oxidative product, increased activities of antioxidant enzymes, and reduced levels of high-mobility group box 1 in serum and selleck chemical tissue. Thus, H(2) eFT-508 mw inhalation may be an effective therapeutic strategy
for patients with sepsis.”
“Background: The IALT, JBR. 10, ANITA and Cancer and Leukemia Group B 9633 trials compared adjuvant chemotherapy with observation for patients with resected non-small-cell lung cancer (R-NSCLC). Data from the metastatic setting suggest high tumor class III beta-tubulin (TUBB3) expression is a determinant of insensitivity to tubulin-targeting agents (e.g. vinorelbine, paclitaxel). In 265 patients from JBR.10 (vinorelbine-cisplatin versus observation), high TUBB3 was an adverse prognostic factor and was associated (nonsignificantly) with ‘greater’ survival benefit from chemotherapy. We explored this further in additional patients from JBR.10 and the other three trials.\n\nPatients and methods: TUBB3 immunohistochemical staining was scored for 1149 patients on the four trials. The original JBR.10 cut-off scores were used to classify tumors as TUBB3 high or low. The prognostic and predictive value of TUBB3 on disease-free survival (DFS) and overall survival (OS) was assessed by Cox models stratified by trial and adjusted for clinical factors.\n\nResults: High TUBB3 expression was prognostic for OS [hazard ratio (HR) = 1.27 (1.07-1.51), P = 0.008) and DFS [HR = 1.30 (1.11-1.53), P = 0.001).