| 3 | Obese zebrafish: A small fish for a major human health condition显示文摘Obesity is becoming a silent worldwide epidemic, with a steady increase in both adults and children. To date, even though several drugs have been licensed for long-term obesity treatment, none of them are yet used in routine clinical practice. So far the only successful intervention has been behavioral therapy. A suitable and economic experimental model mimicking the human condition would therefore be extremely useful to evaluate preventive measures and novel treatments. Zebrafish are emerging as an important model system to study obesity and related metabolic disease. Remarkable similarities have been reported in lipid metabolism and the adipogenic pathway between zebrafish and mammals. Moreover, the zebrafish possesses a number of features—the relative inexpensiveness of animal husbandry, its optical transparency and the ability to produce a large number of offspring at low cost—that make it ideal for large-scale screening and for testing drugs and intervention. In this review, we summarize recent progress in using zebrafish as a model system to study obesity and obesity-related metabolic disorders. We describe several zebrafish models(in both larvae and adult animals) that develop obesity and non-alcoholic fatty liver disease(NAFLD) using different approaches, including gene manipulation, diet manipulation and modification of microbiota composition. For these models, we have outlined the specific aspects related to obesity and its development and we have summarized their advantages and limitations. | Francesca Faillaci Fabiola Milosa Rosina Maria Critelli Elena Turola Filippo Schepis Erica Villa | 2018 | Animal Models and Experimental Medicine2018，1，4： | 1 |
| 8 | Boceprevir is highly effective in treatment-experienced hepatitis C virus-positive genotype-1 menopausal women显示文摘AIM: To investigate the safety/efficacy of Boceprevirbased triple therapy in hepatitis C virus(HCV)-G1 menopausal women who were historic relapsers, partial-responders and null-responders. METHODS: In this single-assignment, unblinded study, we treated fifty-six menopausal women with HCV-G1, 46% F3-F4, and previous PEG-α/RBV failure(7% null, 41% non-responder, and 52% relapser) with 4 wk lead-in with PEG-IFNα2b/RBV followed by PEGIFNα2b/RBV+Boceprevir for 32 wk, with an additional 12 wk of PEG-IFN-α-2b/RBV if patients were HCV-RNApositive by week 8. In previous null-responders, 44 wk of triple therapy was used. The primary objective of retreatment was to verify whether a sustained virological response(SVR)(HCV RNA undetectable at 24 wk of follow-up) rate of at least 20% could be obtained. The secondary objective was the evaluation of the percent of patients with negative HCV RNA at week 4(RVR), 8(RVR BOC), 12(EVR), or at the end-of-treatment(ETR) that reached SVR. To assess the relationship between SVR and clinical and biochemical parameters, multiple logistic regression analysis was used.RESULTS: After lead-in, only two patients had RVR; HCV-RNA was unchanged in all but 62% who had ≤1 log10 decrease. After Boceprevir, HCV RNA became undetectable at week 8 in 32/56(57.1%) and at week 12 in 41/56(73.2%). Of these, 53.8% and 52.0%, respectively, achieved SVR. Overall, SVR was obtained in 25/56(44.6%). SVR was achieved in 55% previous relapsers vs. 41% non-responders(P = 0.250), in 44% F0-F2 vs 54% F3-F4(P = 0.488), and in 11/19(57.9%) of patients with cirrhosis. At univariate analysis for baseline predictors of SVR, only previous response to antiviral therapy(OR = 2.662, 95%CI: 0.957-6.881, P = 0.043), was related with SVR. When considering 'on treatment' factors, 1 log10 HCV RNA decline at week 4(3.733, 95%CI: 1.676-12.658, P = 0.034) and achievement of RVR BOC(7.347, 95%CI: 2.156-25.035, P = 0.001) were significantly related with the SVR, although RVR BOC only(6.794, 95%CI: 1.596-21.644, P = 0.010) maintained significance at multivariate logistic regression analysis. Anemia and neutropenia were managed with Erythropoietin and Filgrastim supplementation, respectively. Only six patients discontinued therapy. CONCLUSION: Boceprevir obtained high SVR response independent of previous response, RVR or baseline fibrosis or cirrhosis. RVR BOC was the only independent predictor of SVR. | Veronica Bernabucci Alessia Ciancio Salvatore Petta Aimilia Karampatou Laura Turco Silvia Strona Rosina Critelli Paola Todesca Caterina Cerami Caterina Sagnelli Mario Rizzetto Calogero Cammà Erica Villa | 2014 | World Journal of Gastroenterology2014，20，44： | 0 |
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