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Background. HCV infection is associated with lipid disorders because this virus utilizes the host lipid metabolism to sustain its life cycle. Several studies have indicated that higher concentrations of serum cholesterol and LDL before treatment are important predictors of higher rates of sustained virological response (SVR). However, most of these studies involved patients infected with HCV genotype 1. Thus, we performed a multi-institutional clinical study to evaluate the impact of lipid profiles on SVR rates in patients with HCV genotype 2. Methods. A total of 100 chronic hepatitis C patients with HCV genotype 2 who received peg-IFN alfa-2b and ribavirin therapy were consecutively enrolled. The significance of age, sex, BMI, AST level, ALT level, WBC, hemoglobin, platelet count, gamma-glutamyltransferase, total cholesterol level (TC), LDL level, HCV RNA, and histological evaluation was examined for SVR using logistic regression analysis. Results. The 100 patients infected with HCV genotype 2 were divided into 2 groups, an SVR group and a non-SVR group. Characteristics of each group were subsequently compared. There was no significant difference in the level of HCV RNA, BMI, platelet, TG, or stage of fibrosis between the groups. However, there were significant differences in the levels of TC and LDL-C. In multivariate logistic regression analysis using baseline characteristics, high TC level was an independent and significant risk factor (relative risk 18.59, P = 0.015) for SVR. Conclusion. Baseline serum total cholesterol levels should be considered when assessing the likelihood of sustained treatment response following the course of peg-IFN and ribavirin therapy in patients with chronic HCV genotype 2 infection., Gastroenterology Research and Practice, 2012, 317580; 2012

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:26:01Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:36:24Z : No. of bitstreams: 1 2-s2.0-84860764467.pdf: 196567 bytes, checksum: dfbf5a17fbfae870901d52db68587ec2 (MD5) Made available in DSpace on 2014-05-27T11:26:01Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-10-01 Introduction: The lack of physical exercises generated by immobilization of the lower limbs leads to changes in body composition that are generally associated with the imbalance of metabolic rate coupled with a sedentary status, which can result in obesity, diabetes mellitus and cardiovascular disease. Therefore, the improvement of physical fitness can contribute to promoting health and quality of life for these patients. As there is a very small number of research in this direction, our purpose was to investigate the effects of an adapted swimming program in protocol interval, for people with spinal cord injury, aiming to verify the improvement of your fitness and, consequently, some biochemical variables important for health. Methodology: The study included 17 subjects with spinal cord injury, sedentary, divided into two groups: 11 participants in the training group (TG) and 6 in control group (CG). TG was applied by a protocol of interval training in swimming for eight consecutive weeks, three times a week. The protocol employed a stroke of breaststroke in work periods of moderate to severe, and stroke in the backstroke, in periods of active recovery. The CG has not participated in any physical activity. Both groups were collecting blood for biochemical analysis, before (evaluation) and after (revaluation) the swimming program. Results and Discussion: The concentrations of triglycerides, total cholesterol and LDL-cholesterol showed no significant changes in assessment for reassessment in both groups. However the TG, the level of HDL-cholesterol were significant differences (p=0,0110), showing an improvement in posttraining, which did not occur in the CG. With respect to the state of fitness, the results revealed a significant difference in relation to time and distance covered in water when compared with the pre-training (p

Objective We sought to investigate whether serum choline levels are increased across the spectrum of coronary artery disease (CAD) manifestations and correlate with the severity of coronary stenosis. Methods A total of 36 patients with acute coronary syndrome (ACS) [22 patients with non-ST-segment elevation ACS and 14 patients with ST-segment elevation acute myocardial infarction (STEMI)], 22 patients with stable angina pectoris (SAP), and 18 controls were recruited for the study. In ACS patients, serum choline levels were measured on admission, and at 24 and 48 h thereafter, using high-performance liquid chromatography. The severity of CAD was assessed using the Gensini score. Results Serum choline levels on admission were significantly higher in the entire group of patients with ACS than in controls. The highest level of choline was observed in the STEMI group, followed by the SAP, and the non-ST-segment elevation ACS groups. Serum choline levels decreased gradually in patients with STEMI over the 48-h period. Serum choline levels on admission, and at 24 or 48 h thereafter, did not correlate with the presence of CAD neither in patients with ACS (P = 0.78, 0.98 and 0.98, respectively) nor in those with SAP (P = 0.92). Conclusion Our results suggest that serum choline levels are increased in ACS patients. However, there was no clear correlation between levels of choline and the severity and extent of CAD in this patient group. Coron Artery Dis 21:466-471

Funding: The authors acknowledge Clinica Médica e Diagnóstico Dr Joaquim Chaves (Alge´s, Portugal) for the technical assistance regarding the serum lipids determination. The present study was supported by FCT POCTI/CVT/2002/44 750 and PTDC/CVT/2006/66 114 grants. S. V. M., P. A. L. and S. P. A. are the recipients of FCT individual fellowships SFRH/BD/2005/2256, SFRH/BPD/2005/23 931 and SFRH/ BD/2007/37 793, respectively. S. V. M., P. A. L. and C. M. A. performed the animal experiment, tissue sampling, laboratory work and prepared the manuscript. P. O. R. was responsible for Luminex xMAP analysis. S. P. A. and R. J. B. B. were responsible for fatty acid analysis. R. M. A. P. performed the biochemistry serum profile. S. V. M. and R. J. B. B. performed the statistical analysis. M. F. C. and J. A. M. P. were responsible for interpretation of the results, preparation of the manuscript and design of the study. Conjugated linoleic acid (CLA) has been reported as having body fat lowering properties and the ability to modulate the inflammatory system in several models. In the present study, the effects of CLA added to saturated fat diets, from vegetable and animal origins, on the serum adipokine profile of obese Zucker rats were assessed. In addition, the fatty acid composition of epididymal and retroperitoneal adipose tissues was determined and a principal component analysis (PCA) was used to assess possible relationships between fatty acids and serum metabolites. Atherogenic diets (2% cholesterol) were formulated with palm oil and ovine fat and supplemented or not with 1% of a mixture (1:1) of cis-9, trans-11 and trans-10, cis-12-CLA isomers. CLA-fed animals exhibited lower daily feed intake, final body and liver weights, and hepatic lipids content. Total and LDL-cholesterol levels were increased in CLA-supplemented groups. CLA also promoted higher adiponectin and lower plasminogen activator inhibitor-1 (PAI-1) serum concentrations. In contrast to palm oil diets, ovine fat increased insulin resistance and serum levels of leptin, TNF-α and IL-1β. Epididymal and retroperitoneal adipose tissues had similar deposition of individual fatty acids. The PCA analysis showed that the trans-10, cis-12-CLA isomer was highly associated with adiponectin and PAI-1 levels. Summing up, CLA added to vegetable saturated enriched diets, relative to those from animal origin, seems to improve the serum profile of adipokines and inflammatory markers in obese Zucker rats due to a more favourable fatty acid composition. © 2009 The Authors. publishersversion published

Aims/hypothesis To determine whether 6 weeks of daily, moderate alcohol consumption increases expression of the gene encoding adiponectin (ADIPOQ) and plasma levels of the protein, and improves insulin sensitivity in postmenopausal women. Methods In a randomised, open-label, crossover trial conducted in the Netherlands, 36 apparently healthy postmenopausal women who were habitual alcohol consumers, received 250 ml white wine (∼25 g alcohol/day) or 250 ml of white grape juice (control) daily during dinner for 6 weeks. Randomisation to treatment allocation occurred according to BMI. Insulin sensitivity and ADIPOQ mRNA and plasma adiponectin levels were measured at the end of both periods. Insulin sensitivity was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR). Levels of ADIPOQ mRNA in subcutaneous adipose tissue were determined by RT-PCR. Results All subjects completed the study. Six weeks of white wine consumption reduced fasting insulin (mean ± SEM 40.0 ± 3.4 vs 46.5 ± 3.4 pmol/l; p

1. Hypothyroidism is accompanied by hyperlipidaemia and oxidative stress and is associated with several complications, such as atherosclerosis. Paraoxonase activity has been reported to decrease in several situations associated with atherosclerosis and oxidative stress. In the present study, the effects of different doses of taurine on serum paraoxonase and arylesterase activities, as well as on the serum lipid profile, were investigated in hypothyroid rats. 2. Forty male Sprague-Dawley rats were randomly divided into five groups as follows: Group 1, rats received normal rat chow and tap water; Group 2, rats received standard rat chow + 0.05% propylthiouracil (PTU) in the drinking water; and Groups 3-5, taurine-supplemented PTU groups (standard rat chow + 0.5, 2 or 3% taurine in the drinking water, respectively, in addition to PTU). Paraoxon or phenylacetate were used as substrates to measure paraoxonase and arylesterase activity, respectively. Plasma and tissue malondialdehyde (MDA) levels, indicators of lipid peroxidation, were determined using the thiobarbituric-acid reactive substances method. Serum triglyceride, total cholesterol and high-density lipoprotein-cholesterol (following precipitation with dextran sulphate-magnesium chloride) were determined using enzymatic methods. 3. Serum paraoxonase and arylesterase activities were increased and plasma and tissue MDA levels and serum triglyceride levels were reduced in a dose-dependent manner in taurine-treated hypothyroid rats. Taurine concentrations were positively correlated with enzyme activities and negatively correlated with MDA and triglyceride levels. 4. Further studies are needed to investigate the role of taurine supplementation in hypothyroidism in human subjects.

To assess the effects of a moderately hypoenergetic Mediterranean diet (MHMD) and exercise program on body cell mass (BCM) and cardiovascular disease risk factors in obese women.Forty-seven obese women, 39.7+/-13.2 years of age, with a body mass index (BMI)=30.7+/-6.0 kg/m(2), completed the study. The following were measured at baseline, 2 and 4 months: BCM, BCM index (BCMI), body weight, BMI, fat-free mass (FFM), fat mass (FM), total body water (TBW), extracellular water (ECW) and intracellular water (ICW) using bioelectrical impedance analysis; fasting blood glucose (FBG), serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) concentrations; systolic (SBP) and diastolic (DBP) blood pressure.Body weight, BMI, FM, TC and TG significantly decreased (P0.001; P0.002 (TG)) at 2 and 4 months. FFM, TBW, ECW, FBG and DBP significantly decreased at 2 months (P0.05 (FFM); P0.001). LDL-C significantly decreased (P0.001), while HDL-C significantly increased (P0.002) at 4 months. BCM, BCMI, ICW and SBP remained stable over time.BCM was preserved and cardiovascular disease risk factors improved in obese women placed on a MHMD and exercise program for 4 months.

Background Vanadyl sulfate (VS) and taurine are two promising agents in the treatment of diabetes related to their antihyperglycemic, antihyperlipidemic, and hyperinsulinemic effects. Data about the effects of VS on the oxidant–antioxidant system is limited and controversial. However, taurine is a well-documented antioxidant agent and our aim was to investigate the effects of VS, taurine and VS and taurine combination on the oxidative–antioxidative systems in streptozotocin–nicotinamide (STZ-NA) diabetic rats. Methods Nicotinamide (230 mg/kg, i.p.) and streptozotocin (65 mg/kg, i.p.) were administered. VS (0.75 mg/mL) and taurine (1%) were added to drinking water for 5 weeks. Rats were divided as control (C), diabetes (D), diabetes + VS (D + VS), diabetes + taurine (D + T), diabetes + VS and taurine (D + VST). Plasma and tissue malondialdehyde (MDA) levels were measured by high-performance liquid chromatography and spectrophotometry, respectively. Paraoxonase and arylesterase activities were measured by spectrophotometric methods and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were determined using commercial kits. Results VS, taurine and VS and taurine combination treatments reduced the enhanced blood glucose, serum total cholesterol and triglyceride, tissue MDA and plasma MDA (except in the D + VS group) levels and increased the reduced serum insulin level, serum paraoxonase and arylesterase activities, GSH-Px activity and SOD activity (except in the D + VS group). Conclusions The findings of the present study suggest that VS and taurine exert beneficial effects on the blood glucose and lipid levels in STZ-NA diabetic rats. However, VS might exert prooxidative or antioxidative effects in various components of the body and taurine and VS combination might be an alternative for sole VS administration.

Background While the relationship between impaired glucose tolerance (IGT) and circulating interleukin-6 (IL-6) is well established, there is no information whether IL-6 levels are elevated in impaired fasting glucose (IFG). Methods To this end, we examined the relationship between plasma IL-6 concentration and different degrees of glucose homeostasis in a cohort of 470 Italian Caucasian subjects comprising 236 normal glucose tolerant (NGT), 49 IFG, 51 IGT, and 134 type 2 diabetic subjects. Results We observed that IL-6, CRP and fibrinogen levels were higher in subjects with IGT or type 2 diabetes as compared with NGT and IFG subjects. Univariate correlations between IL-6 concentrations and metabolic variables in the whole cohort showed that IL-6 levels were positively correlated with age, BMI, waist, systolic and diastolic blood pressure, fasting plasma glucose, triglycerides, CRP, fibrinogen, and negatively correlated with insulin sensitivity, IGF-I and HDL. In a subgroup analysis including NGT, IFG and IGT (n = 336), IL-6 levels were positively correlated with age, BMI, waist, systolic and diastolic blood pressure, triglycerides, CRP, fibrinogen, fasting insulin, 2 h post-load glucose, and negatively correlated with insulin sensitivity, IGF-I and HDL. Stepwise linear regression analysis in a model including gender, age, BMI, waist, glucose tolerance status, fasting plasma glucose, 2 h post-load glucose, triglycerides, HDL, fasting insulin, and insulin sensitivity revealed that waist was the only independent variable associated with IL-6 levels accounting for 21.0% of its variation (P < 0.0001). Conclusions These data show that IGT and type 2 diabetes, but not IFG, are associated with elevated plasma IL-6 levels. Copyright © 2006 John Wiley & Sons, Ltd.

The impact of apolipoprotein C-I (apoC-I) deficiency on hepatic lipid metabolism was addressed in mice in the presence or the absence of cholesteryl ester transfer protein (CETP). In addition to the expected moderate reduction in plasma cholesterol levels, apoCIKO mice showed significant increases in the hepatic content of cholesteryl esters (+58%) and triglycerides (+118%) and in biliary cholesterol concentration (+35%) as compared with wild-type mice. In the presence of CETP, hepatic alterations resulting from apoC-I deficiency were enforced, with up to 58% and 302% increases in hepatic levels of cholesteryl esters and triglycerides in CETPTg/apoCIKO mice versus CETPTg mice, respectively. Biliary levels of cholesterol, phospholipids, and bile acids were increased by 88, 77, and 20%, respectively, whereas total cholesterol, HDL cholesterol, and triglyceride concentrations in plasma were further reduced in CETPTg/apoCIKO mice versus CETPTg mice. Finally, apoC-I deficiency was not associated with altered VLDL production rate. In line with the previously recognized inhibition of lipoprotein clearance by apoC-I, apoCI deficiency led to decreased plasma lipid concentration, hepatic lipid accumulation, and increased biliary excretion of cholesterol. The effect was even greater when the alternate reverse cholesterol transport pathway via VLDL/LDL was boosted in the presence of CETP. Copyright ©2007 by the American Society for Biochemistry and Molecular Biology, Inc.

Statins may exert pleiotropic effects in coronary artery disease (CAD), diabetes mellitus, and familial hypercholesterolemia. We evaluated the effects of statins on the neutrophil–lymphocyte ratio (NLR) and mean platelet volume (MPV) in 261 consecutive patients with hypercholesterolemia having CAD or at high cardiovascular (CV) risk and 50 healthy participants who were retrospectively included in this study. Patients were treated with 10 to 80 mg atorvastatin or 10 to 40 mg rosuvastatin for 24 weeks according to baseline levels of cholesterol, triglycerides, and CV risk. Baseline NLR and MPV were significantly higher in patients with CAD or at high risk compared to the control group (1.89 [0.37-6.78]) vs 1.44 [0.75-2.41], P < .001 and 8.8 [6.27-18.6] vs 8.45 [6-11] fL, P = .038, respectively). The NLR, MPV, and lipid parameters were also compared in the patient group after statin treatment for 24 weeks. Lipid levels decreased but the NLR and MPV did not change significantly after the statin therapy. Further studies are needed to clarify the effect of statin therapy on NLR and MPV in patients with CAD or at high CV risk.

Brown adipose tissue (BAT) combusts high amounts of fatty acids, thereby lowering plasma triglyceride levels and reducing obesity. However, the precise role of BAT in plasma cholesterol metabolism and atherosclerosis development remains unclear. Here we show that BAT activation by β3-adrenergic receptor stimulation protects from atherosclerosis in hyperlipidemic APOE*3-Leiden.CETP mice, a well-established model for human-like lipoprotein metabolism that unlike hyperlipidemic Apoe−/− and Ldlr−/− mice expresses functional apoE and LDLR. BAT activation increases energy expenditure and decreases plasma triglyceride and cholesterol levels. Mechanistically, we demonstrate that BAT activation enhances the selective uptake of fatty acids from triglyceride-rich lipoproteins into BAT, subsequently accelerating the hepatic clearance of the cholesterol-enriched remnants. These effects depend on a functional hepatic apoE-LDLR clearance pathway as BAT activation in Apoe−/− and Ldlr−/− mice does not attenuate hypercholesterolaemia and atherosclerosis. We conclude that activation of BAT is a powerful therapeutic avenue to ameliorate hyperlipidaemia and protect from atherosclerosis.

The present study is the first intervention study in a well-established, translational mouse model for hyperlipidaemia and atherosclerosis showing that anacetrapib dose-dependently reduces atherosclerosis development and adds to the anti-atherogenic effects of atorvastatin. This effect is mainly ascribed to the reduction in non-HDL-C despite a remarkable increase in HDL-C and without affecting HDL functionality. In addition, anacetrapib improves lesion stability., Background The residual risk that remains after statin treatment supports the addition of other LDL-C-lowering agents and has stimulated the search for secondary treatment targets. Epidemiological studies propose HDL-C as a possible candidate. Cholesteryl ester transfer protein (CETP) transfers cholesteryl esters from atheroprotective HDL to atherogenic (V)LDL. The CETP inhibitor anacetrapib decreases (V)LDL-C by ∼15–40% and increases HDL-C by ∼40–140% in clinical trials. We evaluated the effects of a broad dose range of anacetrapib on atherosclerosis and HDL function, and examined possible additive/synergistic effects of anacetrapib on top of atorvastatin in APOE*3Leiden.CETP mice. Methods and results Mice were fed a diet without or with ascending dosages of anacetrapib (0.03; 0.3; 3; 30 mg/kg/day), atorvastatin (2.4 mg/kg/day) alone or in combination with anacetrapib (0.3 mg/kg/day) for 21 weeks. Anacetrapib dose-dependently reduced CETP activity (−59 to −100%, P < 0.001), thereby decreasing non-HDL-C (−24 to −45%, P < 0.001) and increasing HDL-C (+30 to +86%, P < 0.001). Anacetrapib dose-dependently reduced the atherosclerotic lesion area (−41 to −92%, P < 0.01) and severity, increased plaque stability index and added to the effects of atorvastatin by further decreasing lesion size (−95%, P < 0.001) and severity. Analysis of covariance showed that both anacetrapib (P < 0.05) and non-HDL-C (P < 0.001), but not HDL-C (P = 0.76), independently determined lesion size. Conclusion Anacetrapib dose-dependently reduces atherosclerosis, and adds to the anti-atherogenic effects of atorvastatin, which is mainly ascribed to a reduction in non-HDL-C. In addition, anacetrapib improves lesion stability.

BACKGROUND: The nature and underlying mechanisms of an inverse association between adult height and the risk of coronary artery disease (CAD) are unclear. METHODS: We used a genetic approach to investigate the association between height and CAD, using 180 height-associated genetic variants. We tested the association between a change in genetically determined height of 1 SD (6.5 cm) with the risk of CAD in 65,066 cases and 128,383 controls. Using individual-level genotype data from 18,249 persons, we also examined the risk of CAD associated with the presence of various numbers of height-associated alleles. To identify putative mechanisms, we analyzed whether genetically determined height was associated with known cardiovascular risk factors and performed a pathway analysis of the height-associated genes. RESULTS: We observed a relative increase of 13.5% (95% confidence interval [CI], 5.4 to 22.1; P

Background: This study investigated the possible effects of metabolic syndrome on bone mineral density (BMD) and bone turnover markers in Turkish postmenopausal women. Method: This prospective case-control study included a total of 230 postmenopausal women, between 45 and 65 years old, including 63 with metabolic syndrome and 167 without metabolic syndrome on the basis of the International Diabetes Federation criteria. The height, weight, body mass index (BMI), waist circumference, hip circumference, and waist-to-hip ratio of each subject were measured. Fasting and nonfasting blood glucose, triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), parathyroid hormone (PTH), thyroid-stimulating hormone (TSH), calcium, phosphorus, glycated hemoglobin (HbA1c), bone-specific alkaline phosphatase (ALP), 25-hydroxyvitamin D3 [25(OH) D], osteocalcin, and the β-isomerized form carboxy-terminal telopeptide of type I collagen (β-CTx) were measured. Bone mineral densities in the lumbar spine and femoral neck were measured by dual energy X-ray absorptiometry. Results: The mean age was 58.49±5.7 years in metabolic syndrome patients and 56.13±5.0 years in patients without metabolic syndrome. There was a statistically significant difference in the age of the patients. The mean BMI was 33.96±5.3 and 30.867±3.8 kg/m2 in metabolic syndrome patients and patients without metabolic syndrome, respectively, indicating a statistically significant difference. Serum calcium, osteocalcin, and β-CTx were statistically significantly lower in metabolic syndrome patients. There was no significant difference in the levels of phosphorus, 25-hydroxyvitamin D3, and bone-specific ALP, TSH, and PTH among the patients with metabolic syndrome and without metabolic syndrome. The statistical analysis, after adjusting for age and BMI, revealed no significant difference between the two groups in terms of lumbar and femoral BMD. When the patients in the metabolic syndrome group were split into two groups on the basis of those with a T score-2.5 or less and those with a normal score, a statistically significant difference was identified between the two groups in terms of the fasting blood glucose (FBG) and HbA1c values (P

Brown adipose tissue (BAT) combusts high amounts of fatty acids, thereby lowering plasma triglyceride levels and reducing obesity. However, the precise role of BAT in plasma cholesterol metabolism and atherosclerosis development remains unclear. Here we show that BAT activation by b3-adrenergic receptor stimulation protects from atherosclerosis in hyperlipidemic APOE3-Leiden.CETP mice, a well-established model for human-like lipoprotein metabolism that unlike hyperlipidemic Apoe-/-and Ldlr-/-mice expresses functional apoE and LDLR. BAT activation increases energy expenditure and decreases plasma triglyceride and cholesterol levels. Mechanistically, we demonstrate that BAT activation enhances the selective uptake of fatty acids from triglyceride-rich lipoproteins into BAT, subsequently accelerating the hepatic clearance of the cholesterol-enriched remnants. These effects depend on a functional hepatic apoE-LDLR clearance pathway as BAT activation in Apoe-/-and Ldlr-/-mice does not attenuate hypercholesterolaemia and atherosclerosis. We conclude that activation of BAT is a powerful therapeutic avenue to ameliorate hyperlipidaemia and protect from atherosclerosis. © 2015 Macmillan Publishers Limited.

This study sought to evaluate the probiotic potential of lactic acid bacteria (LAB) isolated from traditionally fermented south Indian koozh and gherkin (cucumber). A total of 51 LAB strains were isolated, among which four were identified as Lactobacillus spp. and three as Weissella spp. The strains were screened for their probiotic potential. All isolated Lactobacillus and Weissella strains were capable of surviving under low pH and bile salt conditions. GI9 and FKI21 were able to survive at pH 2.0 and 0.50% bile salt for 3h without losing their viability. All LAB strains exhibited inhibitory activity against tested pathogens and were able to deconjugate bile salt. Higher deconjugation was observed in the presence of sodium glycocholate (. P

Familial hypercholesterolemia (FH) is a common genetic disorder, clinically manifested since birth, and associated with very high levels of plasma LDL-cholesterol (LDL-c), xanthomas, and premature coronary heart disease. Its early detection and treatment reduces coronary morbidity and mortality. Despite effective treatment being available, FH is underdiagnosed and under-treated. Identification of index cases and cascade screening using LDL-c levels and genetic testing are the most cost-effective strategies for detecting new cases and starting early treatment. Long-term treatment with statins has decreased the vascular risk to the levels of the general population. LDL-c targets are < 130 mg/dL for children and young adults, < 100 mg/dL for adults, and < 70 mg/dL for adults with known coronary heart disease or diabetes. Most patients do not to reach these goals, and combined treatments with ezetimibe or other drugs may be necessary. When the goals are not achieved with the maximum tolerated drug treatment, a reduction = 50% in LDL-c levels can be acceptable. Lipoprotein apheresis can be useful in homozygous, and in treatment-resistant severe heterozygous, cases. This Consensus Paper gives recommendations on the diagnosis, screening, and treatment of FH in children and adults, and specific advice to specialists and general practitioners with the objective of improving the clinical management of these patients, in order to reduce the high burden of coronary heart disease. © 2013 Elsevier España, S.L.U. All rights reserved.

HDL-increasing drugs such as fenofibrate and niacin have failed to decrease the cardiovascular risk in patients with type 2 diabetes. Drug-mediated quantitative and qualitative HDL modifications could be involved in these negative results. To evaluate the quantitative and qualitative effects of niacin and fenofibrate on HDL in patients with type 2 diabetes, a prospective, randomised controlled intervention trial was conducted. Thirty type 2 diabetic patients with low HDL were randomised to receive either fenofibrate (FFB) or niacin broken vertical bar laropiprant (ERN/LPR) as an add-on to simvastatin treatment for 12 weeks according to a crossover design. At the basal point and after each intervention period, physical examinations and comprehensive standard biochemical determinations and HDL metabolomics were performed. Thirty nondiabetic patients with normal HDL were used as a basal control group. ERN/LRP, but not FFB, significantly increased HDL cholesterol. Neither ERN/LRP nor FFB reversed the HDL particle size or particle number to normal. ERN/LRP increased apoA-I but not apoA-II, whereas FFB produced the opposite effect. FFB significantly increased Pre beta 1-HDL, whereas ERN/LRP tended to lower Pre beta 1-HDL. CETP and LCAT activities were significantly decreased only by ERN/LRP. PAF-AH activity in HDL and plasma decreased with the use of both agents. Despite their different actions on antioxidant parameters, none of the treatments induced detectable antioxidant improvements. ERN/LRP and FFB had strikingly different effects on HDL quantity and quality, as well as on HDL cholesterol concentrations. When prescribing HDL cholesterol increasing drugs, this differential action should be considered. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

Introduction: Low Carbohydrate High Protein diet represents a popular strategy to achieve weight loss. Objective: The aim of this study was to characterize effects of low carbohydrate, high protein diet (LCHP) on atherosclerotic plaque development in brachiocephalic artery (BCA) in $apoE/LDLR^{-/-}$ mice and to elucidate mechanisms of proatherogenic effects of LCHP diet. Materials and Methods: Atherosclerosis plaques in brachiocephalic artery (BCA) as well as in aortic roots, lipoprotein profile, inflammation biomarkers, expression of SREBP-1 in the liver as well as mortality were analyzed in Control diet (AIN-93G) or LCHP (Low Carbohydrate High Protein) diet fed mice. Results: Area of atherosclerotic plaques in aortic roots or BCA from LCHP diet fed mice was substantially increased as compared to mice fed control diet and was characterized by increased lipids and cholesterol contents (ORO staining, FT-IR analysis), increased macrophage infiltration (MOMA-2) and activity of MMPs (zymography). Pro-atherogenic phenotype of LCHP fed $apoE/LDLR^{-/-}$ mice was associated with increased plasma total cholesterol concentration, and in LDL and VLDL fractions, increased TG contents in VLDL, and a modest increase in plasma urea. LCHP diet increased SCD-1 index, activated SREBP-1 transcription factor in the liver and triggered acute phase response as evidence by an increased plasma concentration of haptoglobin, CRP or AGP. Finally, in long-term experiment survival of $apoE/LDLR^{-/-}$ mice fed LCHP diet was substantially reduced as compared to their counterparts fed control diet suggesting overall detrimental effects of LCHP diet on health. Conclusions: The pro-atherogenic effect of LCHP diet in $apoE/LDLR^{-/-}$ mice is associated with profound increase in LDL and VLDL cholesterol, VLDL triglicerides, liver SREBP-1 upregulation, and systemic inflammation.

Non-HDL-cholesterol is well recognised as a primary causal risk factor in cardiovascular disease. However, despite consistent epidemiological evidence for an inverse association between HDL-C and coronary heart disease, clinical trials aimed at raising HDL-C (AIM-HIGH, HPS2-THRIVE, dal-OUTCOMES) failed to meet their primary goals. This systematic review and meta-analysis investigated the effects of established and novel treatment strategies, specifically targeting HDL, on inhibition of atherosclerosis in cholesteryl ester transfer protein-expressing animals, and the prevention of clinical events in randomised controlled trials. Linear regression analyses using data from preclinical studies revealed associations for TC and non-HDL-C and lesion area (R2=0.258, P=0.045; R2=0.760, P

In terms of stereochemistry, catechins are divided into two groups: (-) epi forms (2R, 3R) and (-) forms (2S, 3R). Most of the catechins present in green tea are (-) epi forms (2R, 3R). Under the influence of high temperatures, in anaerobic conditions, as a result of epimerization the proportion of the (-) form (2S, 3R) increases. The data indicate that the presence of thermally modified catechins in the diet more efficiently reduces the development of atherosclerosis in apoE knockout mice than the presence of native catechins. The addition of the thermally modified formulations to the high-fat diet resulted in a reduction of the area of atherosclerotic lesions by about 28% (en face method) and 45% (cross-section method) compared to the group fed the high-fat diet without catechins. Furthermore, the body weight gain and plasma TBARS concentration in mice fed a diet with the addition of catechins depends on the degree of epimerization of catechins and decreases with increasing content of catechins belonging to the (-) form (2S, 3R). Moreover, plasma HDL cholesterol concentration in mice depends on catechins' stereoisomerism and increases along with the increasing content of catechins belonging to the (-) form (2S, 3R).

Background Acromegaly is characterized by excess growth hormone and insulin-like growth factor-1 concentrations. There is conflicting evidence as to whether acromegaly is associated with an increased risk of atherosclerosis. Apelin is an adipose tissue-derived peptide that may be associated with hyperinsulinemia. Fetuin-A is a hepatocyte produced plasma glycoprotein that has an important role as a calcification inhibitor. The aim of this study was to examine apelin, fetuin-A, and procalcitonin concentrations and to assess their relationship with carotid intima medial thickness (cIMT) in subjects with acromegaly. Methods Apelin, fetuin-A, and procalcitonin serum concentrations were measured in 37 (20 inactive and 17 active) subjects with acromegaly and 30 control subjects, along with carotid intima medial thickness. Results The concentrations of apelin, fetuin-A, and procalcitonin were increased in subjects with acromegaly. There were significant correlations between apelin, fetuin-A, and procalcitonin in subjects with acromegaly. Carotid intima medial thickness values were similar between control subjects and subjects with acromegaly. Conclusions Carotid intima medial thickness was not increased in subjects with acromegaly. It is possible that the increased apelin and fetuin-A concentrations observed play a protective role against the development of atherosclerosis in subjects with acromegaly.

Non-HDL-cholesterol is well recognised as a primary causal risk factor in cardiovascular disease. However, despite consistent epidemiological evidence for an inverse association between HDL-C and coronary heart disease, clinical trials aimed at raising HDL-C (AIM-HIGH, HPS2-THRIVE, dal-OUTCOMES) failed to meet their primary goals. This systematic review and meta-analysis investigated the effects of established and novel treatment strategies, specifically targeting HDL, on inhibition of atherosclerosis in cholesteryl ester transfer protein-expressing animals, and the prevention of clinical events in randomised controlled trials. Linear regression analyses using data from preclinical studies revealed associations for TC and non-HDL-C and lesion area (R2=0.258, P=0.045; R2=0.760, P

Objective— To demonstrate, quantify, and mechanistically dissect antiatherosclerotic effects of fenofibrate besides lowering plasma cholesterol per se. Methods and Results— ApoE*3Leiden transgenic mice received either a high-cholesterol diet (HC) or HC containing fenofibrate (HC+FF) resulting in 52% plasma cholesterol-lowering. In a separate low-cholesterol diet (LC) control group, plasma cholesterol was adjusted to the level achieved in the HC+FF group. Low plasma cholesterol alone (assessed in LC) resulted in reduced atherosclerosis (lesion area, number and severity) and moderately decreased plasma serum amyloid-A (SAA) concentrations. Compared with LC, fenofibrate additively reduced lesion area, number and severity, and the total aortic plaque load. This additional effect in HC+FF was paralleled by an extra reduction of aortic inflammation (macrophage content; monocyte adhesion; intercellular adhesion molecule-1 [ICAM-1], soluble vascular cell adhesion molecule-1, granulocyte-macrophage colony-stimulating factor (GM-CSF), MCP-1, and NF-κB expression), systemic inflammation (plasma SAA and fibrinogen levels), and by an upregulation of plasma apoE levels. Also, enhanced expression of ABC-A1 and SR-B1 in aortic macrophages may contribute to the antiatherosclerotic effect of fenofibrate by promoting cholesterol efflux. Conclusion— Fenofibrate reduces atherosclerosis more than can be explained by lowering total plasma cholesterol per se. Impaired recruitment of monocytes/macrophages, reduced vascular and systemic inflammation, and stimulation of cholesterol efflux may all contribute to these beneficial effect of fenofibrate.

Xanthophylls have attracted a lot of interest since their health benefits were documented. Unfortunately, studying their intestinal absorption is often affected by high baseline levels present in the fasting plasma. As a-cryptoxanthin is rarely found in the traditional European diet, its concentration in human plasma is extremely low. A pilot human intervention study was designed using a-cryptoxanthin for the first time as a marker xanthophyll in a minimally formulated cellulose-based supplement. a-Cryptoxanthin was administered in gelatin soft-gel capsules in multiple doses of 156mg/ d to three male volunteers (age 27·3 (SD 4·7) years; BMI 21·6 (SD 0·3) kg/m 2 ) for 16 d after a 2-week carotenoid depletion period. Fasting blood samples were taken before the intervention and after 3, 6, 9, 13 and 16 d. Plasma HPLC analyses allowed for determination of the concentration; liquid chromatography – MS in the single ion monitoring mode was used to confirm peak assignment. The concentrations of a-cryptoxanthin increased significantly after only 3 d of supplementation. The concentration-time plots showed a characteristic shape with a first maximum after day 6, a decline until day 9 and a gradual second rise until the end of the study. Standardisation of plasma a-cryptoxanthin concentrations to triacylglycerol or total cholesterol did not influence the characteristics. The maximum concentrations reached at the end of the intervention period ranged from 0·077 to 0·160mmol/l. These results suggest a high intestinal absorption and an enrichment of a-cryptoxanthin in the plasma even from a minimally formulated cellulose-based supplement. a-Cryptoxanthin: Plasma xanthophyll response: Liquid chromatography–mass spectroscopy in the single ion monitoring mode: Pilot studies

1-{7-[(1-(3,5-Diethoxyphenyl)-3-{[(3,5-difluorophenyl)(ethyl)amino]carbo nyl}-4-oxo-1,4-dihydroquinolin-7-yl)oxy]heptyl}-1-methylpiperidinium bromide, R-146224, is a potent, specific ileum apical sodium-dependent bile acid transporter (ASBT) inhibitor; concentrations required for 50% inhibition of [3H]taurocholate uptake in human ASBT-expressing HEK-293 cells and hamster ileum tissues were 0.023 and 0.73 μM, respectively. In bile-fistula rats, biliary and urinary excretion 48 h after 10 mg/kg [14C]R-146224, were 1.49 ± 1.75% and 0.14 ± 0.05%, respectively, demonstrating extremely low absorption. In hamsters, R-146224 dose-dependently reduced gallbladder bile [3H]taurocholate uptake (ED50: 2.8 mg/kg). In basal diet-fed hamsters, 14-day 30-100 mg/kg R-146224 dose-dependently reduced serum total cholesterol (∼ 40%), high density lipoprotein (HDL) cholesterol (∼ 37%), non-HDL cholesterols (∼ 20%), and phospholipids (∼ 20%), without affecting serum triglycerides, associated with reduced free and esterified liver cholesterol contents. In normocholesterolemic cynomolgus monkeys, R-146224 specifically reduced non-HDL cholesterol. In human ileum specimens, R-146224 dose-dependently inhibited [3H]taurocholate uptake. Potent non-systemic ASBT inhibitor R-146224 decreases bile acid reabsorption by inhibiting the ileal bile acid active transport system, resulting in hypolipidemic activity. © 2006 Elsevier B.V. All rights reserved. Chemicals / CAS: carbon 14, 14762-75-5; cholesterol, 57-88-5; taurocholic acid, 145-42-6, 59005-70-8, 81-24-3; tritium, 10028-17-8; carrier protein, 80700-39-6; sodium, 7440-23-5; 1-(7-((1-(3,5-diethoxyphenyl)-3-(((3,5-difluorophenyl)(ethyl)amino)carbonyl)-4-oxo-1,4-dihydroquinolin-7-yl)oxy)heptyl)-1-methylpiperidinium bromide; Anticholesteremic Agents; Bile Acids and Salts; Cholesterol, 57-88-5; Membrane Transport Proteins; Organic Anion Transporters, Sodium-Dependent; Piperidines; Quinolines; Sodium, 7440-23-5; sodium-bile acid cotransporter, 145420-23-1; Symporters; Taurocholic Acid, 81-24-3

This longitudinal, controlled clinical study was conducted to compare the effects of resistance exercise (RE) and aerobic exercise (AE) on body mass index (BMI), weight, fat mass (FM), serum lipid profile, and insulin resistance in obese women who cannot adhere to energy-restricted diets. A total of 60 obese women with severe eating disorders were evaluated. Patients were randomly divided into 3 groups: control group with no exercise (n=20), group 1 with AE (n=20), and group 2 with RE (n=20). Demographic and anthropometric measurements were taken. Serum lipid fractions and fasting (FGIc) and postprandial glucose insulin (PGlc) levels were measured. Insulin resistance was calculated with use of homeostasis model assessment (HOMA-IR). Total body FM was measured by bioelectric impedance analysis. After 12 wk of exercise, significant decreases in BMI, waist and weight measurements, and FGlc, PGlc, triglyceride, and total cholesterol levels were noted in each of the study groups. Reduced low-density lipoprotein cholesterol level and FM and HOMA-IR measurements were observed only in group 1 (with AE). This study indicated that AE and RE training induces improvement in body fat composition and has a favorable metabolic effect in obese women with severe eating disorders. ©2006 Health Communications Inc.

The aim of the study was to assess the interaction between occupational and leisure time physical activities (LTPA) as well as socioeconomical status (SES), lifestyles and dietary habits on the prevalences of overweight and obesity in employed and unemployed (housewife) urban premenopausal Turkish women. Among 1209 women surveyed 508 premenopausal ones between 20 and 45 years of age were included in the study. Overweight prevalence in the employed (47.3% versus 36.2%) and obesity prevalence in the unemployed women (housewives) were higher (42.2% versus 11.6%). The ratio of family history for obesity, comorbid diseases, habit of < 30 min of walking/day, consuming meals twice/day, preference of vegetables were higher in the housewives. Employed women had a higher SES scoring, education level, percentage of no habit of walking, consuming meals thrice per day, preference for protein, smoking and alcohol consumption. Housewife group had a higher glucose level measured while employed group higher total cholesterol. Age, waist circumference (WaC), having one or two meals/day versus three or four meals/day, having lunch at home versus outdoor lunch, having one parity versus none were the main predictors of obesity. Our results indicated that lifestyle interventions should be afforded for increasing LTPA for both employed and unemployed women since overweight and obesity prevalences are high in both.

Objective: To determine the gastrointestinal (GI) tolerance of NUTRIOSE®FB in men. Design: A randomized, placebo-contro lled, parallel, double-blind study. Setting: The metabolic ward of TNO Quality of Life. Subjects: Forty-eight subjects started the study: 16 men participated in one of the three treatments. Subjects consumed either 22.5 g of pure maltodextrin (Glucidex®6), or 30 or 45 g of the dextrin NUTRIOSE®FB daily for 4-5 weeks. Forty-three subjects completed the study (age: 34.7±8.2 years; BMI 24.9±3.3 kg m2). Measurements: Tolerance of NUTRIOSE®FB was examined with a GI complaints questionnaire; effectiveness on colonic flora was examined by faecal analysis; fermentation by breath hydrogen excretion measurement. Furthermore, the effect on body weight (BW), energy intake and blood parameters were examined in the study. Results: Both doses of NUTRIOSE®FB were very well tolerated and GI complaints hardly differed from the placebo treatment. No diarrhoea was reported due to NUTRIOSE®FB supplementation. In the course of the study, some habituation and adaptation of GI symptoms were found. Fermentation and faecal characteristics (pH and enzyme activity) were significantly positively affected with NUTRIOSE®FB treatment. Body weight in both NUTRIOSE®FB groups remained stable over time, although the placebo-treated group showed a small increase in BW (Δday35-1 0.8±1.0 kg) (P=0.07). However, total food intake and macronutrient composition of the diet remained the same throughout the study. No significant differences were found between the three treatment groups in hunger and satiety scores and food preferences. Conclusions: Long-term supplementation of 30 or 45 g of the dextrin NUTRIOSE®FB per day was well tolerated, and may act as a pre-biotic supplement. © 2006 Nature Publishing Group. All rights reserved.

The increased consumption of fruits and vegetables is associated with reduced cardiovascular disease. The molecular basis of this health effect is not fully understood, yet dietary flavonoids are thought to play an important role. Genetic engineering has enabled us to overexpress specific flavonoids (flavones and flavonols) in tomato fruit. Human C-reactive protein transgenic (CRPtg) mice express markers of cardiovascular risk that allow us to study of the putative health effects of wild-type tomato (wtTom) and flavonoid-enriched tomato (flTom). In this study, we analyzed whether consumption of wtTom, at a dose achievable with a human diet, has beneficial effects on cardiovascular risk markers and whether flTom may enhance such effects. CRPtg mice were fed a diet containing 4 g/kg wtTom, flTom peel, vehicle, or 1 g/kg fenofibrate, which reportedly reduces cardiovascular risk, for 7 wk. Markers of general health (bodyweight, food intake, and plasma alanine aminotransferase activities) and of cardiovascular risk (plasma CRP, fibrinogen, E-selectin, and cholesterol levels) were analyzed. All groups had comparable food intakes and body-weight gains. Plasma alanine aminotransferase activities increased significantly in vehicle and fenofibrate-treated mice. Compared with baseline, wtTom and flTom significantly reduced basal human CRP concentrations by 43 and 56%, respectively. The CRP-lowering effect of flTom significantly exceeded that of wtTom. The effects of flTom on CRP were reversed within a 2-wk washout period. WtTom and flTom did not affect fibrinogen, but comparably repressed E-selectin expression and upregulated HDL cholesterol. Tomato peel consumption improved cardiovascular risk factors in CRPtg mice, a beneficial effect that was further enhanced by enrichment of the flavonoid content. © 2006 American Society for Nutrition.

This study was designed to determine serum human leukocyte antigen-G (HLA-G) levels and establish whether serum HLA-G level is related with insulin resistance, oxidative stress, dyslipidemia and ovarian hyperandrogenism in women with polycystic ovary syndrome (PCOS). Twenty-five patients with PCOS and 23 healthy control women were evaluated in this study. Serum HLA-G, lipid fractions, glucose, insulin, malondialdehyde (MDA), glutathione (GSH), white blood cell (WBC), sex hormone-binding globulin (SHBG) and other hormone (gonadotropins and androgens) levels were measured. The estimate of insulin resistance was calculated by homeostasis model assessment (HOMA-IR). Serum luteinizing hormone (LH), total testosterone, fasting insulin, WBC levels and LH/follicle-stimulating hormone (FSH) ratio, free androgen index (FAI) and HOMA-IR values were significantly higher in patients with PCOS compared with healthy women. However, the women with PCOS had considerably lower serum FSH, SHBG, MDA, GSH and HLA-G levels than healthy subjects. HLA-G was inversely related with HOMA-IR, FAI, LH/FSH ratio and WBC, but positively with high-density lipoprotein cholesterol. Decreased serum HLA-G level may be related with insulin resistance, ovarian hyperandrogenism and oxidative stress in women with PCOS. Nevertheless, the exact role of HLA-G in the pathogenesis of the disease remains to be elucidated. © 2014 Informa UK Ltd.

Background/Aim: Evaluation of cardiovascular risk profile in 154 German vegans. Methods: Cross-sectional study, Germany. Study instruments: 2 FFQ, 2 questionnaires, analyses of fasting venous blood samples. Results: The total study population had a low BMI (mean: 22.3 kg/m2), a moderate blood pressure (mean: 120/75 mm Hg), an extremely low consumption of alcohol (mean: 0.77 g/day) and 96.8% were nonsmokers. Moderate physical activity (PAL) was reported by nearly 50%, whereas 22.7% declared to have a high PAL (>3 h/week). Median triacylglycerol (TG) was 0.81 mmol/l, total cholesterol (TC) was 4.33 mmol/l, HDL was 1.34 mmol/l. The mean TC/HDL-ratio was 3.3. Lipoprotein(a) (Lp(a)) was 8.13 mg/dl, concentrations of >30 mg/dl were prevalent in 25% of the participants. In general, status of folate and pyridoxine were sufficient, while 49.7% showed cobalamin concentrations Conclusion: Although TC and LDL concentrations were favorable, low HDL and elevated homocysteine and Lp(a) concentrations were unfavorable. Overall, these results confirm the notion that a vegan diet is deficient in vitamin B12, which may have an unfavorable effect on CHD risk.

The present study was designed to investigate the lipid-lowering properties and mechanisms of action of a new HMG-CoA reductase inhibitor, rosuvastatin, in female ApoE*3-Leiden transgenic mice. Mice received a high fat/cholesterol (HFC) diet containing either rosuvastatin (O [control], 0.00125%, 0.0025%, or 0.005% [w/w]) or 0.05% (w/w) lovastatin. The highest dose of rosuvastatin reduced plasma cholesterol and triglyceride levels by 39% and 42%, respectively, compared with the HFC control. Lovastatin had no effect on plasma cholesterol and triglyceride levels. In ApoE*3-Leiden mice on a chow diet, rosuvastatin (0.005% [w/w]) decreased plasma cholesterol levels by 35% without having an effect on triglyceride levels. On a chow diet, expression of genes involved in cholesterol biosynthesis and uptake in the liver was increased by rosuvastatin. Further mechanistic studies in HFC-fed mice showed that rosuvastatin treatment resulted in decreased hepatic VLDL-triglyceride and VLDL-apolipoprotein B production. VLDL lipid composition remained unchanged, indicating a reduction in the number of VLDL particles secreted. Lipolytic activity and expression of genes involved in cholesterol and triglyceride synthesis and β-oxidation of fatty acids in the liver were not affected by rosuvastatin treatment, and hepatic lipid content did not change. However, activity of hepatic diacylglycerol acyltransferase was significantly decreased by 25% after rosuvastatin treatment. Moreover, biliary excretion of cholesterol, phospholipids, and bile acids was increased during treatment. The results indicate that rosuvastatin treatment in ApoE*3-Leiden mice on a HFC diet leads to redistribution of cholesterol and triglycerides in the body, both by reduced hepatic VLDL production and triglyceride synthesis and by enhanced hepatobiliary removal of cholesterol, bile acids, and phospholipids, resulting in substantial reductions in plasma cholesterol and triglyceride levels. Chemicals / CAS: diacylglycerol acyltransferase, 9029-98-5; mevinolin, 75330-75-5; rosuvastatin, 147098-18-8, 147098-20-2; apolipoprotein E3 (Leidein); Apolipoprotein E3; Apolipoproteins B; Apolipoproteins E; Bile Acids and Salts; Cholesterol, 57-88-5; Cholesterol, VLDL; Fluorobenzenes; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pyrimidines; RNA, Messenger; rosuvastatin, 287714-41-4; Sterols; Sulfonamides; Triglycerides

Objective-The beneficial effect of dietary fish oil, rich in omega-3 polyunsaturated fatty acids (PUFAs), on cardiovascular disease is multifactorial and may partly rely on their anticoagulant action. We studied how fish oil intake influenced thrombin generation in plasma and which factors were involved herein. Methods and Results-Twenty-five healthy males with borderline overweight received 3.0 g omega-3 PUFAs daily for 4 weeks. Fish oil intake reduced plasma triglycerides and lowered platelet integrin activation, as well as plasma levels of fibrinogen and factor V, but had no effect on vitamin K-dependent coagulation factors. Before fish oil intake, thrombin generation (reflecting the coagulant potential) considerably varied between plasmas from individual subjects, which were partly explained by variation in prothrombin, antithrombin, fibrinogen, and factor V levels. Fish oil intake reduced thrombin generation in the presence and absence of platelets. This reduction correlated with the fish oil effect on fibrinogen and factor V levels. Interestingly, the lowering effect of fish oil on thrombin generation and fibrinogen clustered around subjects with high fibrinogen carrying a structural fibrinogen α-chain polymorphism. Conclusions-Dietary omega-3 PUFAs provoke a hypocoagulant, vitamin K-independent effect in humans, the degree of which may depend on fibrinogen level. Chemicals / CAS: antithrombin, 9000-94-6; blood clotting factor 5, 9001-24-5, 9013-23-4; cholesterol, 57-88-5; fibrinogen, 9001-32-5; fish oil, 8016-13-5; protein C, 60202-16-6; prothrombin, 9001-26-7; thrombin, 9002-04-4; vitamin K group, 12001-79-5; Cholesterol, LDL; Factor V, 9001-24-5; Fatty Acids, Omega-3; Fibrinogen, 9001-32-5; Fish Oils; Peptide Fragments; Thrombin, 3.4.21.5; Triglycerides; thrombin receptor peptide (42-47)

Background: Treatment of persons at high risk for coronary heart disease (CHD) should include nutritional counselling, but little is known about the effects of different types of education. Methods: In a quasi-experimental study design the effects of a nutritional education programme (1st year: three group sessions by a dietitian; 2nd year: one group session; 3rd year: additional focus on saturated fat; reinforcement by written nutritional messages annually) (intervention group; n=103) are compared with the effects of a posted leaflet containing standard dietary guidelines (control group; n=163). Participants had hypercholesterolemia (6-8 mmol/l) and at least two other CHD risk factors. Results: After 3 years, no significant differences existed in established CHD risk factors between intervention and control groups (adjusted mean net differences: total cholesterol (0 mmol/l), diastolic blood pressure (-1.1 mm Hg; NS), and body weight (+0.3 kg, NS)). Regarding dietary intake, the intervention group had a lower intake of total (net difference -2.0% of energy, SEM 0.9) and saturated fat (-1.2% of energy, SEM 0.4) and a higher fish (+11 g/day, SEM 4) and vegetables consumption (+21 g/day, SEM 10) during the study period (p

Objective: Changes in lipid profiles, Lp(a) lipoprotein, and acute phase reactants are associated with early atherosclerosis in rheumatoid arthritis (RA). The associations of Lp(a) levels with atherosclerotic disorders, diabetes, RA, and renal diseases suggest that Lp(a) might be involved in autoimmune reactions. Methods: Eighty-seven women with RA diagnosed according to American Rheumatism Association criteria (mean age 45.4±9.4 years) were recruited and 50 healthy women (mean age 44±10.7 years) included as a control group. Serum Lp(a), total cholesterol (TC), triglyceride (TG), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), and C-reactive protein levels were analyzed. Results: In the RA and C groups, serum Lp(a) levels were 39.2±20.6 mg/dl and 14.8±9.7 mg/dl, respectively (P0.05), TG levels were 124.5±50.1 mg/dl and 94.6±24.9 mg/dl (P0.05). While serum CRP levels showed a positive correlation with Lp(a), they correlated negatively with HDL-C levels (r=0.83 and P

Obese obob mice with strong overexpression of the human apolipoprotein C1 (APOC1) exhibit excessive free fatty acid (FFA) and triglyceride (TG) levels and severely reduced body weight (due to the absence of subcutaneous adipose tissue) and skin abnormalities. To evaluate the effects of APOC1 overexpression on hepatic and peripheral insulin sensitivity in a less-extreme model, we generated obob mice with mild overexpression of APOC1 (obob/APOC1+/-) and performed hyperinsulinemic clamp analysis. Compared with obob littermates, obob/APOC1+/- mice showed reduced body weight (-25%) and increased plasma levels of TG (+632%), total cholesterol (+134%), FFA (+65%), glucose (+73%, and insulin (+49%). Hyperinsulinemic clamp analysis revealed severe whole-body and hepatic insulin resistance in obob/APOC1+/- mice and, in addition, increased hepatic uptake of FFA and hepatic TG content. Treatment of obob/APOC1+/- mice with rosiglitazone strongly improved whole-body insulin sensitivity as well as hepatic insulin sensitivity, despite a further increase of hepatic fatty acid (FA) uptake and a panlobular increase of hepatic TG accumulation. We conclude that overexpression of APOC1 prevents rosiglitazone-induced peripheral FA uptake leading to severe hepatic steatosis. Interestingly, despite rosiglitazone-induced hepatic steatosis, hepatic insulin sensitivity improves dramatically. We hypothesize that the different hepatic fat accumulation and/or decrease in FA intermediates has a major effect on the insulin sensitivity of the liver. Chemicals / CAS: glucose, 50-99-7, 84778-64-3; insulin, 9004-10-8; rosiglitazone, 122320-73-4, 155141-29-0; Apolipoprotein C-I; Apolipoproteins C; Blood Glucose; Fatty Acids; Insulin, 11061-68-0

Background: The study was carried out to evaluate the effects of short-term transdermal hormone replacement therapy (HRT) on glycaemic control, lipid metabolism, C-reactive protein (CRP) and proteinuria in high-risk post-menopausal women. Methods: A total of 20 well-controlled type 2 diabetic, hypertensive and 21 well-controlled glucose-tolerant, hypertensive postmenopausal women were prospectively enrolled. After 12 weeks of transdermal HRT, the changes in serum lipid sub-fractions, fasting glucose, fructosamine, glycated haemoglobin (HbA1c), CRP, creatinine, 24 h urine protein levels, creatinine clearance and blood pressure were evaluated. Results: After 12 weeks of treatment, serum total-cholesterol and low-density cholesterols (LDL-cholesterol) appeared slightly reduced and serum triglyceride slightly elevated, although non-significantly so in both groups. The increase in HDL-cholesterol (P < 0.05) and reduction in very low density (VLDL)-cholesterol (P < 0.05) levels were significant in hypertensive patients. Elevation in the Apolipoprotein A1 (P < 0.05) and reduction in the Apolipoprotein B (P < 0.05) levels were statistically significant in all patients. HRT was associated with significant decreases in serum fasting glucose (P < 0.05) and fructosamine (P < 0.05) levels in diabetic patients. Serum HbA1c, CRP, creatinine, 24 h urine protein levels, creatinine clearance and systolic and diastolic blood pressure did not change significantly in either group. Conclusions: There were no detrimental effects of transdermal HRT on lipid profile, glucose metabolism, CRP and urine protein levels in our well-controlled diabetic or hypertensive patients. A decision regarding HRT use should be taken on a case-by-case basis., Results:All of the patients completed the study. The mean body mass index (BMI) was 31.27 and 30.95 kg/m2 in the DM-HRT and HT-HRT groups respectively. Estraderm TTS plus NETA was associated with statistically significant decreases in serum mean fasting glucose and fructosamine levels, and with a non-significant reduction in serum mean HbA1c level in the DM-HRT group. Significant changes were seen in mean serum VLDL (decreased) and HDL-cholesterol (increased) levels in the HT-HRT group. The increase in mean serum Apo-A1 level and the reduction in mean serum Apo-B level were statistically significant in both treatment groups. Serum CRP, creatinine, 24 h urine protein levels, creatinine clearance and systolic and diastolic blood pressure did not change significantly during 12 weeks of transdermal HRT in both groups. High-risk postmenopausal women did not have any adverse effect on proteinuria and serum creatinine levels after 3 months of Estraderm TTS plus NETA treatment., TypeofStudy:A prospective, open study evaluating the effects of short-term hormone replacement therapy (HRT) Estraderm TTS plus norethisterone acetate (NETA) (=Estracombi TTS) on glycemic control, lipid metabolism, C-reactive protein (CRP) and proteinuria in high-risk postmenopausal women with diabetes and/or hypertension., DosageDuration:17beta-estradiol 0.05 mg daily and sequential norethisterone acetate 0.25 mg daily transdermally. Duration was 12 weeks., AdverseEffects:2 subjects (10%) in the DM-HRT group and 1 subject (4.7%) in the HT-HRT group complained about abnormal vaginal bleeding such as metrorrhagia and 4 patients (19%) reported breast tenderness in the HT-HRT group. No patient experienced detrimental effects on lipid profile, glucose metabolism, CRP and urine protein levels., AuthorsConclusions:Additional research will be necessary to determine the effects of long-term transdermal HRT in high-risk postmenopausal women. We conclude that decisions about HRT should be taken on a case-by-case basis, and in doing so it is important to include the potential personal benefits and risk profile, especially in high-risk postmenopausal women., FreeText:In order to maintain their glucose levels in an acceptable range, women with type 2 diabetes were on dietary management alone (2 patients) or taking oral antidiabetic drugs that consisted of metformin and sulfonylureas (18 patients). Each diabetic patient received a diabetic diet with, Indications:20 patients with diabetes type 2 and hypertension and 21 patients with hypertension., Patients:41 postmenopausal women. Type 2 diabetes and hypertension group (DM-HRT group): n=20, mean age was 50.9 years. Hypertension group (HT-HRT group): n=21, mean age was 52.6 years.

Background: Tamoxifen has favorable effects on the serum lipid profile. It has been suggested that the apolipoprotein (Apo) E phenotype can influence serum lipid parameters; the ApoE allele 4 (ApoE4) is associated with higher total and low-density lipoprotein (LDL) cholesterol levels. The ApoE phenotype also affects lipid responses to diets or treatment with statins. However, the effect of tamoxifen on the lipid profile in different ApoE phenotypes is unknown. Patients and Methods: In the present study, we evaluated the effects of tamoxifen on the serum lipid profile in 11 ApoE4-positive postmenopausal women with breast cancer (phenotypes 3/4 and 4/4) compared with 33 ApoE4-negative women (phenotypes 3/2 and 3/3). Serum lipid parameters [high-density (HDL), LDL and total cholesterol, triglycerides, ApoAI, ApoB and lipoprotein (a)] were measured after an overnight fast before treatment and after 3 and 12 months. ApoE isoforms were determined by isoelectric focusing of delipidated very-low-density lipoproteins (VLDL). Results: During the follow-up period, serum levels of total and LDL cholesterol and ApoB decreased significantly in both groups, but no significant differences were found. Concentrations of serum HDL cholesterol were not significantly different between both groups. However, serum ApoAI levels increased significantly in ApoE4-negative subjects (p = 0.00005), but no significant changes in ApoE4-positive women were observed. Serum triglyceride levels increased by 23.2% (p < 0.05) in ApoE4-positive patients, but they did not change significantly in ApoE4-negative patients. The LDL/HDL cholesterol ratio decreased similarly in the two groups, but the ApoAI/ApoB ratio, which may be a better predictor of cardiovascular events, significantly changed in the ApoE4-negative subjects. Finally, the median level of Lp(a) decreased by 43.4% in the ApoE4-negative patients, whereas it did not change significantly in the ApoE4-positive group. Conclusion: In postmenopausal Greek women with breast cancer, the levels of Lp(a) and triglycerides and the ApoAI/ApoB ratio respond more favorably to tamoxifen treatment in ApoE4-negative than in ApoE4-positive patients.

This study assessed the effects of individual conjugated linoleic acid isomers, c9t11-CLA and t10c12-CLA, on nonalcoholic fatty liver disease (NAFLD) and systemic endothelial dysfunction in rats fed for four weeks with control or high-fructose diet. The high-fructose diet hampered body weight gain (without influencing food intake), increased liver weight and glycogen storage in hepatocytes, upregulated expression of fatty acid synthase (FAS) and stearoyl-CoA desaturase-1 (SCD-1), and increased saturated fatty acid (SFA) content in the liver. Both CLA isomers prevented excessive accumulation of glycogen in the liver. Specifically, t10c12-CLA decreased concentration of serum triacylglycerols and LDL + VLDL cholesterol, increased HDL cholesterol, and affected liver lipid content and fatty acid composition by downregulation of liver SCD-1 and FAS expression. In turn, the c9t11-CLA decreased LDL+VLDL cholesterol in the control group and downregulated liver expression of FAS without significant effects on liver weight, lipid content, and fatty acid composition. In summary, feeding rats with a high-fructose diet resulted in increased liver glycogen storage, indicating the induction of gluconeogenesis despite simultaneous upregulation of genes involved inde novolipogenesis. Although both CLA isomers (c9t11 and t10c12) display hepatoprotective activity, the hypolipemic action of the t10c12-CLA isomer proved to be more pronounced than that of c9t11-CLA.