Comparison of effects of bezafibrate and fenofibrate on circulating proprotein convertase subtilisin/kexin type 9 and adipocytokine levels in dyslipidemic subjects with impaired glucose tolerance or type 2 diabetes mellitus: Results from a crossover study
Noguchi T.,Kanazawa University |
Kobayashi J.,Kanazawa University |
Nohara A.,Kanazawa University |
Oka R.,Hokuriku Chuo Hospital |
And 2 more authors.
Atherosclerosis | Year: 2011
Background: Bezafibrate and fenofibrate show different binding properties against peroxisome proliferator-activated receptor subtypes, which could cause different clinical effects on circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and on various metabolic markers. Methods: An open, randomized, four-phased crossover study using 400mg of bezafibrate or 200mg of fenofibrate was performed. Study subjects were 14 dyslipidemia with impaired glucose tolerance or type 2 diabetes mellitus (61±16 years, body mass index (BMI) 26±3kg/m 2, total cholesterol (TC) 219±53mg/dL, triglyceride (TG) 183±83mg/dL, high-density lipoprotein-cholesterol (HDL-C) 46±8mg/dL, fasting plasma glucose 133±31mg/dL and HbA1c 6.2±0.8%). Subjects were given either bezafibrate or fenofibrate for 8 weeks, discontinued for 4 weeks and then switched to the other fibrate for 8 weeks. Circulating PCSK9 levels and other metabolic parameters, including adiponectin, leptin and urine 8-hydroxy-2′-deoxyguanosine (8-OHdG) were measured at 0, 8, 12 and 20 weeks. Results: Plasma PCSK9 concentrations were significantly increased (+39.7% for bezafibrate and +66.8% for fenofibrate, p<. 0.001) in all patients except for one subject when treated with bezafibrate. Both bezafibrate and fenofibrate caused reductions in TG (-38.3%, p<. 0.001 vs. -32.9%, p<. 0.01) and increases in HDL-C (+18.0%, p<. 0.001 vs. +11.7%, p<. 0.001). Fenofibrate significantly reduced serum cholesterol levels (TC, -11.2%, p<. 0.01; non-HDL-C, -17.3%, p<. 0.01; apolipoprotein B, -15.1%, p<. 0.01), whereas bezafibrate significantly improved glucose tolerance (insulin, -17.0%, p<. 0.05) and metabolic markers (γ-GTP, -38.9%, p<. 0.01; adiponectin, +15.4%, p<. 0.05; urine 8-OHdG/Cre, -9.5%, p<. 0.05). Conclusion: Both bezafibrate and fenofibrate increased plasma PCSK9 concentrations. The addition of a PCSK9 inhibitor to each fibrate therapy may achieve beneficial cholesterol lowering along with desirable effects of respective fibrates. © 2011 Elsevier Ireland Ltd.
Huang C.-H.,Chang Gung University |
Huang C.-H.,Institute of Preventive Medicine |
Yen C.-T.,Institute of Preventive Medicine |
Yu C.-P.,Institute of Preventive Medicine |
And 8 more authors.
Journal of Infectious Diseases | Year: 2013
Background. Reassortment within polymerase genes causes changes in the pathogenicity of influenza A viruses. We previously reported that the 2009 pH1N1 PA enhanced the pathogenicity of seasonal H1N1. We examined the effects of the PA gene from the HPAI H5N1 following its introduction into currently circulating seasonal influenza viruses. Methods. To evaluate the role of H5N1 PA in altering the virulence of seasonal influenza viruses, we generated a recombinant seasonal H3N2 (3446) that expressed the H5N1 PA protein (VPA) and evaluated the RNP activity, growth kinetics, and pathogenicity of the reassortant virus in mice. Results. Compared with the wild-type 3446 virus, the substitution of the H5N1 PA gene into the 3446 virus (VPA/3446) resulted in increased RNP activity and an increased replication rate in A549 cells. The recombinant VPA/3446 virus also caused more severe pneumonia in Casp 1-/- mice than in IL1β-/- And wild-type B6 mice. Conclusions. Although the PA from H5N1 is incidentally compatible with a seasonal H3N2 backbone, the H5N1 PA affected the virulence of seasonal H3N2, particularly in inflammasome-related innate immunity deficient mice. These findings highlight the importance of monitoring PA reassortment in seasonal flu, and confirm the role of the Caspase-1 gene in influenza pathogenesis. © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
Moulton A.D.,Laboratory Science |
Albright A.L.,National Center for Chronic Disease Prevention and Health Promotion |
Gregg E.W.,National Center for Chronic Disease Prevention and Health Promotion |
Goodman R.A.,DHHS Office of the Assistant Secretary for Health
American Journal of Preventive Medicine | Year: 2013
The prevalence of new cases of diabetes continues to increase, and the health burden for those with diabetes remains high. This is attributable, in part, to low adoption of evidence-based interventions for diabetes prevention and control. Law is a critical tool for health improvement, yet assessments reported in this paper indicate that federal, state, and local laws give only partial support to guidelines and evidence-based interventions relevant to diabetes prevention and control. Public health practitioners and policymakers who are concerned with the human, fiscal, and economic costs of the epidemic can explore new ways to translate the evidence base for diabetes prevention and control into effective laws and policies. © 2013 American Journal of Preventive Medicine.
Jain R.K.,Laboratory Science |
Mehta R.,Laboratory Science |
Dimitrov R.,Laboratory Science |
Larsson L.G.,Laboratory Science |
And 7 more authors.
Modern Pathology | Year: 2011
Interobserver reproducibility in the diagnosis of benign intraductal proliferative lesions has been poor. The aims of the study were to investigate the inter- and intraobserver variability and the impact of the addition of an immunostain for high- and low-molecular weight keratins on the variability. Nine pathologists reviewed 81 cases of breast proliferative lesions in three stages and assigned each of the lesions to one of the following three diagnoses: usual ductal hyperplasia, atypical ductal hyperplasia and ductal carcinoma in situ. Hematoxylin and eosin slides and corresponding slides stained with ADH-5 cocktail (cytokeratins (CK) 5, 14. 7, 18 and p63) by immunohistochemistry were evaluated. Concordance was evaluated at each stage of the study. The interobserver agreement among the nine pathologists for diagnosing the 81 proliferative breast lesions was fair (κ-value=0.34). The intraobserver-value ranged from 0.56 to 0.88 (moderate to strong). Complete agreement among nine pathologists was achieved in only nine (11%) cases, at least eight agreed in 20 (25%) cases and seven or more agreed in 38 (47%) cases. Following immunohistochemical stain, a significant improvement in the interobserver concordance (overall-value=0.50) was observed (P=0.015). There was a significant reduction in the total number of atypical ductal hyperplasia diagnosis made by nine pathologists after the use of ADH-5 immunostain. Atypical ductal hyperplasia still remains a diagnostic dilemma with wide variation in both inter- and intraobserver reproducibility among pathologists. The addition of an immunohistochemical stain led to a significant improvement in the concordance rate. More importantly, there was an 8% decrease in the number of lesions classified as atypical ductal hyperplasia in favor of usual hyperplasia; in clinical practice, this could lead to a decrease in the number of surgeries carried out for intraductal proliferative lesions. © 2011 USCAP, Inc. All rights reserved.