P. Yang

Diet-induced central obesity and insulin resistance in rabbits.

The present study was designed to examine whether rabbits fed a diet containing high fat and sucrose could develop obesity and insulin resistance (IR), the major pathophysiological features of metabolic syndrome. Male Japanese white rabbits were fed either a normal chow diet (control) or high fat and sucrose diet (HFSD) for 36 weeks. Plasma levels of triglycerides (TG), total cholesterol (TC), glucose and insulin were measured. To evaluate glucose metabolism, we performed an intravenous glucose tolerance test. In addition, we compared adipose tissue accumulation in HFSD-fed rabbits with that in normal rabbits. HFSD constantly and significantly led to an increase in body weight of HFSD-fed rabbits, caused by significantly higher visceral adipose tissue accumulation. Although there were no differences in plasma TG, TC, glucose, insulin levels and blood pressure between the two groups, HFSD-fed rabbits showed impaired glucose clearance associated with higher levels of insulin secretion compared to control rabbits. Our results showed that HFSD induced IR and increased adipose accumulation in rabbits, suggesting that HFSD-fed rabbits may become a model for research on human IR and obesity.

A practical method for quantifying atherosclerotic lesions in rabbits.

The rabbit has been widely used for the study of human atherosclerosis; however, the method for analysis of the atherosclerotic lesions has not been standardized between laboratories. The present study reports a practical method for quantifying the changes that occur in aortic atherosclerosis of rabbits. Male Japanese white rabbits were fed with either a standard chow or a diet containing 10% fat and 0.3% cholesterol for 16 weeks. Plasma concentrations of glucose, insulin, total cholesterol, triglycerides and high-density lipoprotein were measured. Aortic atherosclerotic lesions were assessed in quantitative fashion using an image analysis system that measured (1) the gross area of the entire aorta affected by atherosclerosis as defined by Sudan IV staining, (2) the microscopical intimal lesion defined by the elastic van Gieson stain and (3) the infiltration of macrophages and smooth muscle cell proliferation as determined immunohistochemically. The rabbits developed severe aortic atherosclerosis without apparent abnormality of glucose metabolism. The quantitative method described here will be useful for the further investigation of atherosclerosis in rabbits.

The effects of rosiglitazone on aortic atherosclerosis of cholesterol-fed rabbits

INTRODUCTION Thiazolidinedione (TZD) is widely used a drug for the treatment of type 2 diabetes and protects against cardiovascular events in human. However, it is not clear whether TZD can directly inhibit the progression of atherosclerosis. To test the hypothesis whether administration of TZD could reduce the development of atherosclerosis, we studied the effects of rosiglitazone on aortic atherosclerosis of rabbits fed a cholesterol diet. MATERIALS AND METHODS Male Japanese White rabbits were fed a diet containing either 0.3% cholesterol diet (control group, n=10) or 0.3% cholesterol with rosiglitazone (TZD-treated group, n=12) for 16 weeks. We compared the plasma lipids and the extent of aortic atherosclerosis between two groups. RESULTS AND CONCLUSIONS TZD treatment significantly resulted in the reduction of aortic atherosclerosis by 21% in the aortic arch (p<0.01), 20% in the thoracic aorta (p=0.14), and 28% in the abdominal aorta (p=0.25), without affecting the plasma levels of triglycerides, total cholesterol, high-density lipoprotein cholesterol, glucose and insulin. Immunohistochemical staining showed that the cellular components (macrophages and smooth muscle cells) of the lesions of TZD-treated rabbits were unchanged compared to those of control rabbits. In addition, TZD treatment also led to dramatic improvement of fatty liver in cholesterol-fed rabbits. Our results suggest that the activation of PPARgamma can be beneficial for the treatment of atherosclerosis and fatty liver independent upon the improvement of plasma lipids and glucose metabolism.

A comparison of peginterferon α-2a and α-2b for treatment-naive patients with chronic hepatitis C virus: A meta-analysis of randomized trials

BACKGROUND The standard treatments for chronic infection with the hepatitis C virus (HCV) are peginterferon α-2a or α-2b plus ribavirin, but it remains unclear if one has a better efficacy and safety profile. OBJECTIVE The aim of this study was to perform a meta-analysis of randomized controlled trials (RCTs) comparing peginterferon α-2a and α-2b (in combination with ribavirin) treatments for chronic HCV. METHODS The Cochrane Central Register of Controlled Trials, MEDLINE, Science Citation Index, and EMBASE were searched (1966-April 2010) to identify RCTs that evaluated the sustained virologic response (SVR) to peginterferon α-2a and peginterferon α-2b in patients with chronic HCV. The inclusion criteria were: RCT studies designed to compare the therapeutic effects of peginterferon α-2a (180 μg/wk) and peginterferon α-2b (1.5 μg/kg/wk) for treatment-naive patients with chronic HCV; patients treated for ≥24 weeks if infected with HCV genotypes 2 or 3 and for ≥48 weeks if infected with genotypes 1 or 4, with 24-week follow-ups; and publications written in any language. Reports of duplicated studies were excluded by examining the author list, parent institution, sample size, and results. The primary outcome was the SVR, and the other measures included the liver-related morbidity, all-cause mortality, and adverse events leading to treatment discontinuation. RESULTS The literature search yielded 5580 studies, and 7 RCTs comprising 3212 patients matched the inclusion/exclusion criteria. Overall, the SVR rate was significantly higher in patients treated with peginterferon α-2a than in patients treated with peginterferon α-2b (50% vs 46%, respectively; relative risk [RR] = 1.11; 95% CI, 1.02-1.20; P < 0.05) and varying levels of ribavirin treatment. The subgroup analysis found that, in patients with genotypes 1 or 4, the difference between SVR rate in patients treated with peginterferon α-2a and patients treated with peginterferon α-2b was not statistically significant (43% vs 39%; RR = 1.25; 95% CI, 0.99-1.57). A significantly higher SVR rate was achieved in the HCV patients with genotypes 2 or 3 treated with peginterferon α-2a compared with the patients treated with peginterferon α-2b (86% vs 77%; RR = 1.11; 95% CI, 1.02-1.22; P = 0.02). The meta-analysis of adverse events leading to treatment discontinuation revealed no significant differences between the 2 treatments. CONCLUSIONS The evidence reviewed in this meta-analysis suggests that peginterferon α-2a treatment was associated with a higher SVR rate than peginterferon α-2b treatment in patients with chronic HCV also treated with ribavirin. However, the available evidence on adverse events was insufficient to make recommendations.

Fat and cholesterol diet induced lipid metabolic disorders and insulin resistance in rabbit.

BACKGROUND Lipid disorder has been found to result in insulin resistance (IR). IR often is associated with other cardiovascular risk factors. However, the pathogenesis of human IR is not completely understood. METHODS The present study was designed to examine if rabbits were fed with a diet containing high fat and high-cholesterol diet (HFCD) could develop lipid disorder and subsequently IR. Male Japanese white rabbits were fed either a normal chow diet or HFCD for 20 weeks. Plasma levels of triglycerides (TG), total cholesterol (TC), glucose, and insulin were measured. To evaluate glucose metabolism, we performed an intravenous glucose tolerance test. In addition, we compared adipose tissue accumulation and aortic atherosclerosis lesions in HFCD-fed rabbits with those in control rabbits. RESULTS In HFCD-fed rabbits there was an increase in plasma levels of TC and TG as well as visceral adipose tissue accumulation. Severe aortic atherosclerotic lesions were found in HFCD-fed rabbits. Although there were no differences in body weight, plasma insulin and blood pressure between the two groups, HFCD-fed rabbits showed higher insulin IR index compared to control rabbits. CONCLUSION Our results showed that HFCD induced IR, increased adipose accumulation and atherosclerotic lesions in rabbits, suggesting that the HFCD-fed rabbits can serve as a model for the research on human IR and lipid metabolism abnormalities.

Interferon plus Chinese herbs are associated with higher sustained virological response than interferon alone in chronic Hepatitis C: a meta-analysis of randomised trials.

BACKGROUND/AIMS Traditional Chinese herbal therapies are widely used for the treatment of chronic hepatitis C (CHC) in Asia. The aim of this study was to perform a meta-analysis of randomised controlled trials (RCTs) comparing interferon therapies with Chinese herbal therapies and/or interferon plus Chinese herb therapies for the treatment of CHC. METHODS The Cochrane Central Register of Controlled Trials, Medline, Science Citation Index, EMBASE, China National Knowledge Infrastructure, Wanfang Database and China Biomedical Database were searched to identify RCTs that evaluated the virological response to interferon therapies, Chinese herbal therapies and interferon plus Chinese herb therapies in CHC patients. We statistically combined data using a random-effect meta-analysis according to the intention-to-treat principle. RESULTS The literature search yielded 770 studies, and 26 RCTs comprising 1905 patients matched the selection criteria. Overall, the sustained virological response (SVR) was significantly higher in patients treated with interferon plus Chinese herbs than in patients treated with interferon alone (49% vs 33%, relative risk, 1.52; 95% confidence interval: 1.23-1.89; p<0.05). Combined therapies of interferon plus Chinese herb therapies were also superior to interferon therapies alone in achieving the end-of-treatment viral response (ETVR), and resulted in fewer relapses, fewer adverse events and more rapid alanine transaminase normalisation. Interferon therapies achieved higher ETVR than Chinese herbal therapies, but they yielded a similar SVR. CONCLUSIONS The current evidence suggests that combined therapies of interferon plus Chinese herbs yielded a higher SVR, and resulted in fewer relapses and fewer adverse events than interferon therapies.

Treatment with peginterferon plus ribavirin vs. interferon plus ribavirin for 48 weeks in Chinese patients with chronic hepatitis C

Introduction: Virological responses to interferon (IFN) treatment for chronic hepatitis C (CHC) have been found to be correlated with racial differences. Furthermore, higher sustained virological response (SVR) rates were obtained in many randomised clinical trials (RCT) in Caucasian patients with CHC after treating with peg‐IFN than those with IFN. However, it is not clear whether this conclusion can be adapted to patients of Chinese descent.

Association between TaqIB polymorphism of cholesteryl ester transfer protein and coronary artery disease in the Chinese population

ObjectiveTo assess whether the TaqIB polymorphism of cholesteryl ester transfer protein (CETP) is associated with coronary artery disease (CAD) in Chinese population, we performed a meta-analysis in this paper.MethodsWe searched PubMed, Embase, the Science Citation Index (SCI), the China Biological Medicine database (CBM), the China National Knowledge Infrastructure (CNKI), and the Wanfang database for relevant articles. Data were extracted, and pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.ResultsThe literature search yielded 448 studies, in which 10 case-control studies including 1 694 cases and 1 456 controls matched the selection criteria. The combined B1 and B2 allele frequencies were 0.587 and 0.413, respectively. The pooled OR was 1.10 (95% CI, 0.89–1.34) for comparing the B1B1 or B1B2 carriers with B2B2 carriers, and was 1.27 (95% CI, 1.09–1.49) in the B1B1 carriers versus B2B2 or B1B2 carriers.ConclusionsIn the present study, the TaqIB polymorphism of CETP was found to be associated with CAD in the Chinese population.

Treatment with peginterferon versus interferon in Chinese patients with chronic hepatitis C

Higher sustained virological response (SVR) rates after treating with peginterferon than after treating with interferon have been obtained in some randomized clinical trials (RCTs) in Chinese patients with chronic hepatitis C (CHC). However, the numbers of patients included in these clinical trials were too small to draw a clear conclusion. Therefore, a new meta-analysis including a large number of patients was needed to compare peginterferon with interferon in the treatment of Chinese CHC patients. A search of Medline, the China National Knowledge Infrastructure, the Wanfang Database, and the China Biomedical Database for relevant articles published between 1966 and 2009 was performed. RCTs comparing the use of peginterferon and interferon for the treatment of Chinese patients with CHC were assessed. Of the 236 studies screened, 18 RCTs including 1,148 patients (659 treated with peginterferon therapy and 489 treated with interferon therapy) were analyzed. The total SVR rates obtained in patients treated with peginterferon were significantly higher than those obtained in patients treated with interferon (64% vs. 40%; relative risk, 1.56; 95% confidence interval: 1.28–1.91; p < 0.01), but the difference between the peginterferon α-2b and interferon α-2b treatments was not significant. Withdrawal rates were similar between patients treated with peginterferon and interferon. Chinese patients with CHC have a greater likelihood of achieving an SVR with peginterferon α-2a.