There are varieties of murine models of nonalcoholic steatohepatitis (NASH) with different pathophysiologic characteristics. For preclinical assessment, a standardized model would allow comparisons of various pharmacotherapeutic candidates in efficacy, pharmacokinetics, pharmaco-metabolism, and adverse effects under a same system. The present study aims to characterize murine NASH models by comparing end-points of major abnormalities. NASH was induced by feeding high fructose/glucose in drinking water (HF/G), high-fat/calorie diet (HFCD), and in combination (HFCD-HF/G) in mice for 8 or 16 weeks. HF/G feeding caused a minimal fat accumulation and increase in free fatty acids (FFA). In contrast, HFCD-HF/G feeding resulted in a remarkable increase in body weight, subcutaneous and visceral adipose tissue, macrosteatosis with a nearly seven-fold increase in triglyceride and FFA content, accompanied with marked hepatocellular injury, inflammatory responses, fibrosis, and insulin resistance, and represented as typical NASH in histopathology, metabolic, and adipokine profiles in a progressive manner. Meanwhile, mice fed HFCD displayed significant steatosis, necroptosis, fibrosis, insulin resistance, metabolic, and adipokine profiles, and the extent is less than those fed HFCD-HF/G. Significant MCP-1, CCR-2, and NLRP-1/3 activation were found in mice fed HFCD and HFCD-HF/G for 16 weeks, whereas gene expression of CPT-1 and ACOX-1 was down-regulated in these two groups in comparison to the controls. Nuclear receptors, such as SREBP-1c, FXR, LXR-α, PPAR-α, and PPAR-γ, were strikingly elevated in the HFCD-HF/G group. In conclusion, feeding HFCD-HF/G resulted in a reliable NASH model in mice with remarkable necroptosis, steatosis, fibrosis, and insulin resistance as well as a disordered profile of lipid metabolism and adipokine, and HFCD caused significant NASH features in histopathology and metabolic profiles only at a late stage. Whereas HF/G feeding barely led to minimal fat accumulation, some changes at molecular levels and metabolic disturbance in mice.
BackgroundThe clinical efficacy of furosemide administration in preventing contrast-induced nephropathy (CIN) remains uncertain. This meta-analysis was designed to update data on the incidence of CIN with additional furosemide treatment beyond saline hydration in comparison with hydration alone in patients undergoing percutaneous coronary intervention (PCI).Material/MethodsA computerized literature search of MEDLINE, EMBASE, and Cochrane databases was performed. Trials were eligible if they enrolled patients undergoing coronary angiography and randomly allocated participants to receive furosemide administration in addition to saline hydration or saline hydration alone. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for combinations of studies.ResultsFive trials involving 1294 patients (640 for additional furosemide treatment and 654 for hydration alone) were included in the meta-analysis. In the synthesis of data, additional furosemide administration had little impact on the incidence of CIN post-PCI compared with peri-procedural saline hydration alone (OR=0.96; 95% CI 0.33–2.84, p=0.95). Moreover, as for the subsequent need for dialysis, there was no statistical significant difference between the 2 groups (OR=1.01; 95% CI 0.38–2.67, p=0.99). Sensitivity analyses did not show any relevant influence on the overall results. There was no publication bias in the meta-analysis.ConclusionsFurosemide administration did not achieve additional benefit beyond saline hydration in reducing the incidence of CIN in patients undergoing PCI.
BackgroundLong-term outcomes of drug-eluting stents (DES) versus bare-metal stents (BMS) in patients with ST-segment elevation myocardial infarction (STEMI) remain uncertain.ObjectiveTo investigate long-term outcomes of drug-eluting stents (DES) versus bare-metal stents (BMS) in patients with ST-segment elevation myocardial infarction (STEMI).MethodsWe performed search of MEDLINE, EMBASE, the Cochrane library, and ISI Web of Science (until February 2013) for randomized trials comparing more than 12-month efficacy or safety of DES with BMS in patients with STEMI. Pooled estimate was presented with risk ratio (RR) and its 95% confidence interval (CI) using random-effects model.ResultsTen trials with 7,592 participants with STEMI were included. The overall results showed that there was no significant difference in the incidence of all-cause death and definite/probable stent thrombosis between DES and BMS at long-term follow-up. Patients receiving DES implantation appeared to have a lower 1-year incidence of recurrent myocardial infarction than those receiving BMS (RR = 0.75, 95% CI 0.56 to 1.00, p= 0.05). Moreover, the risk of target vessel revascularization (TVR) after receiving DES was consistently lowered during long-term observation (all p< 0.01). In subgroup analysis, the use of everolimus-eluting stents (EES) was associated with reduced risk of stent thrombosis in STEMI patients (RR = 0.37, p=0.02).ConclusionsDES did not increase the risk of stent thrombosis in patients with STEMI compared with BMS. Moreover, the use of DES did lower long-term risk of repeat revascularization and might decrease the occurrence of reinfarction.
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