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Anti-inflammation strategy is one of the proposed therapeutic approaches to hepatic fibrosis. IL-17 is critical in inflammation, but the role of IL-17 in liver fibrosis has not yet been elucidated. In this study, we investigate the role of IL-17 on bile duct ligation-induced liver injury and fibrosis in C57BL/6 mice. Animals were sacrificed at designated times, and serum and liver tissues were collected for analysis of liver function and serum IL-6, IL-1β, tumour necrosis factor-alpha ( TNF-α) and transforming growth factor-β ( TGF-β) levels. IL-17 blockade with anti- IL-17A mAb significantly improved liver function and decreased hepatocellular necrosis, pro-inflammatory cytokines, neutrophils and macrophages influx. Furthermore, CD3 + and CD8 + lymphocytes, neutrophils and macrophages were found to express IL-17, and neutrophils are the principal IL-17-producing cells after BDL-induced liver injury. These data indicated that IL-17 signal contributes to the pathogenesis of cholestatic liver injury and blocked of IL-17 could potentially benefit patients with cholestatic liver disease. [ABSTRACT FROM AUTHOR]

Background Interventional treatment for overt hepatic encephalopathy (OHE), includes non-absorbable disaccharides, neomycin, rifaximin, L-ornithine-L-aspartate and branched chain amino acids (BCAA). However, the optimum regimen remains inconclusive. Aim To compare interventions in terms of patients' adverse events and major clinical outcomes. Methods Literature search of PubMed, Embase, Scopus, and Cochrane Library studies published up to July 31 2014. RCTs of above interventions in OHE patients were included. Network meta-analysis combined direct and indirect evidence to estimate odds ratios (ORs) and mean difference (MD) between treatments and the probabilities of ranking for treatment based on clinical outcomes. Results Twenty eligible RCTs were included. When compared with observation, only L-ornithine-L-aspartate (OR 3.71, P < 0.001) and BCAA (OR 3.37, P < 0.001) improved clinical efficacy significantly. However, when L-ornithine-L-aspartate was compared with BCAA, non-absorbable disaccharides and neomycin, there was a trend suggesting that L-ornithine-L-aspartate may be the most effective intervention with respect to clinical improvement (OR 1.10), rifaximin (OR 1.31), non-absorbable disaccharides (OR 2.75), neomycin (OR 2.22). In addition, L-ornithine-L-aspartate (MD 20.18, 95% CI 40.12 to 0.27) provided a significant reduction in blood ammonia concentration compared with observation. Neomycin appeared to be associated with more adverse events in comparison with non-absorbable disaccharides (OR 10.15), rifaximin (OR 17.31), L-ornithine-L-aspartate (OR 3.16) or BCAA (OR 7.69). Conclusions L-ornithine-L-aspartate treatment may show a trend in superiority for clinical efficacy among standard interventions for OHE. Rifaximin shows the greatest reduction in blood ammonia concentration, and treatment with neomycin demonstrates a higher probability in causing adverse effects among the five compared interventions. [ABSTRACT FROM AUTHOR]

Excessive sympathetic activity contributes to the pathogenesis of hypertension and the progression of the related organ damage. Adipose afferent reflex ( AAR) is a sympatho-excitatory reflex that the afferent activity from white adipose tissue ( WAT) increases sympathetic outflow and blood pressure. Hypothalamic paraventricular nucleus ( PVN or PVH) is one of the central sites in the control of the AAR, and ionotropic glutamate receptors in the nucleus mediate the AAR. The AAR is enhanced in obesity and obesity hypertension. Enhanced WAT afferent activity and AAR contribute to the excessive sympathetic activation and hypertension in obesity. Blockage of the AAR attenuates the excessive sympathetic activity and hypertension. Leptin may be one of sensors in the WAT for the AAR, and is involved in the enhanced AAR in obesity and hypertension. This review focuses on the neuroanatomical basis and physiological functions of the AAR, and the important role of the enhanced AAR in the pathogenesis of obesity hypertension. [ABSTRACT FROM AUTHOR]

Purpose: A significant limitation of adenoviral mediated suicide gene therapy is poor gene distribution in vivo. The choice of vehicle has been demonstrated to affect the level of adenoviral delivered gene transduction. We examined the hypotheses that 1) adenovirus suspended in PEG400 improves gene expression in the naïve canine prostate model, 2) improved transgene expression with PEG400 results in improved tumor control and 3) vehicle affects the initial adenoviral spread from a single intratumor injection. Materials and Methods: The magnitude and volume of gene expression were measured 24 hours following intraprostatic injection of adenovirus suspended in PEG400 (12.5% weight per volume) or saline as vehicle. Tumor growth delay was measured in mice bearing human tumor xenografts following the injection of adenovirus in PEG400 and saline. The initial spread of adenovirus was measured by confocal microscopy following a single injection of fluorescently labeled adenoviral particles in human tumor xenografts using each vehicle. Results: Adenovirus suspended in PEG400 provided an average of twice the level of gene expression in the canine prostate and significantly better tumor control relative to saline in preclinical tumor models (p = 0.046 and 0.036, respectively). The initial spread of adenovirus with PEG400 was superior to that of adenovirus in saline and the latter was largely limited to the needle tract. Conclusions: Adenoviral gene therapy vectors suspended in PEG400 results in improved tumor control because of greater initial adenoviral spread, and the increased volume and magnitude of gene expression in vivo. [Copyright &y& Elsevier]

Summary Background To evaluate the clinical efficacies and toxicities of induction chemotherapy followed by concomitant cisplatin-chemoradiotherapy (CRT) or cetuximab-radiotherapy (ERT) in locally advanced nasopharyngeal carcinoma (NPC). Methods Previously untreated patients with stage III–IVb NPC were eligible. They were randomized to CRT arm: intensity modulated radiation therapy (IMRT) with weekly cisplatin (30 mg/m 2 /w) or ERT arm: IMRT with weekly cetuximab (loading dose of 400 mg/m 2 followed by weekly doses of 250 mg/m 2 ). Two cycles of induction chemotherapy (docetaxel 75 mg/m 2 d1 and cisplatin 80 mg/m 2 d1) were administered to both arms. Endpoints were survivals, toxicities and quality of life (QoL). Results Because of the unexpectedly high rates of grade 3/4 mucositis observed in the ERT arm, the study was closed ahead of schedule. A total of 44 patients (23 in CRT arm and 21 in ERT arm) were enrolled. All patients completed the scheduled induction chemotherapy and radical radiotherapy. The results showed better compliance ( P < 0.001) with more oral mucositis, acneiform rash and dysphagia ( P < 0.05) of cetuximab. The 3-year disease-free survival (DFS) were achieved as 78.3% and 85.7% ( P = 0.547) in CRT and ERT arm, respectively. In the analysis of QoL, the addition of cetuximab to radiotherapy temporarily increased the adverse symptoms but did not result in long-term dysfunction. Conclusions ERT was not more efficacious than CRT but was more likely to cause acute adverse events in LA NPC. The recommended treatment modality was still concurrent cisplatin-IMRT. The combination of TP induction chemotherapy and concurrent cetuximab-radiotherapy should only be used in selected patients. [ABSTRACT FROM AUTHOR]