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BACKGROUND: Isoflavones present in soybean may contribute to soy atheroprotective effects. AIM OF THE STUDY: To investigate the effect of soy isoflavones supplementation on the formation of electronegative LDL (LDL(-)) and its autoantibodies in blood plasma and aortic atheromas of rabbits fed an atherogenic casein-based diet enriched with isoflavones. METHODS: New Zealand male rabbits (n = 15) were fed an atherogenic diet (27% casein) supplemented with isoflavones (0.73 or 7.3 mg of isoflavones/kg/day, Low and High Iso groups, respectively) for 180 days. Monthly, blood samples were collected after 12-15 h fasting and at 180 days of treatment all animals were sacrificed. Isoflavones were analyzed in plasma and urine samples by HPLC. LDL(-) in plasma and atheromas was detected by ELISA and immunohistochemistry, respectively, with a monoclonal antibody reactive to LDL(-). Autoantibodies reactive to LDL(-) were analyzed in plasma and aorta by ELISA. RESULTS: Low and High Iso groups had decreased LDL-cholesterol, increased HDL-cholesterol and lower levels of LDL(-) in blood plasma and aortic atherosclerotic lesions than the non-supplemented Control group. IgG autoantibodies reactive to LDL(- )were higher in plasma of the Control group in comparison with the High and Low Iso groups. In contrast, the aortas from animals that consumed isoflavones showed higher levels of IgG reactive to LDL(- )than the Control group. CONCLUSION: Soy isoflavones showed hypolipidemic effects and decreased the pro-inflammatory LDL(-) subfraction in blood plasma and aorta of hypercholesterolemic rabbits. [ABSTRACT FROM AUTHOR]

The development of new methods to assess biomarkers of cardiovascular disease is currently a subject of scientific research. This article broadens our view of nonlinear optical responses of oxidized low density lipoprotein (LDL) evaluated using the Z-scan peak-valley distance and proposes a cutoff point. We investigated the association of peak-valley distance and some cardiovascular risk factors related with sociodemographic, clinical and anthropometric profiles and plasma biomarkers such as lipid and glucose profile, apolipoprotein, lipoprotein subfractions and omega 3 fatty acids. Z-scan analysis was performed using isolated LDL after ultracentrifugation in human blood samples collected after fasting. Peak-valley distance is a parameter that decreases directly depending on the oxidizability of LDL. As peak-valley distance was associated with relevant biomarkers of cardiovascular risk, we tested cutoff points for categorization and the best results were obtained using percentile < 75 (Low z-scan ) and percentile ≥ 75 (High z-scan ). The regression logistic models tested after establishing the cutoff point for peak-valley distance showed that increased levels of plasma high-density lipoprotein cholesterol, apolipoprotein A-I, large high-density lipoprotein subfractions and docosahexaenoic acid are directly associated with High Z-scan . Conversely, high levels of small LDL were associated with decreased odds of presenting High Z-scan. In conclusion, the cutoff point for peak-valley distance was able to identify atherogenic characteristics of LDL and its relationship with some parameters of high-density lipoprotein functionality., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background & Aims: Metabolic syndrome (MetS) is a cluster of interrelated risk factors for type 2 diabetes mellitus, and cardiovascular disease, with underlying inflammatory pathophysiology. Genetic variations and diet are well-known risk factor for MetS, but the interaction between these two factors is less explored. The aim of the study was to evaluate the influence of interaction between SNP of inflammatory genes (encoding interleukin (IL)-6, IL-1β and IL-10) and plasma fatty acids on the odds of MetS, in a population-based cross-sectional study., Methods: Among participants of the Health Survey - São Paulo, 301 adults (19-59 y) from whom a blood sample was collected were included. Individuals with and without MetS were compared according to their plasma inflammatory biomarkers, fatty acid profile, and genotype frequency of the IL1B (rs16944, rs1143623, rs1143627, rs1143634 and rs1143643), IL6 (rs1800795, rs1800796 and rs1800797) and IL10 (rs1554286, rs1800871, rs1800872, rs1800890 and rs3024490) genes SNP. The influence of gene-fatty acids interaction on MetS risk was investigated., Results: IL6 gene SNP rs1800795 G allele was associated with higher odds for MetS (OR = 1.88; p = 0.017). Gene-fatty acid interaction was found between the IL1B gene SNP rs116944 and stearic acid (p inter = 0.043), and between rs1143634 and EPA (p inter = 0.017). For the IL10 gene SNP rs1800896, an interaction was found for arachidonic acid (p inter = 0.007) and estimated D5D activity (p inter = 0.019)., Conclusion: The IL6 gene SNP rs1800795 G allele is associated with increased odds for MetS. Plasma fatty acid profile interacts with the IL1B and IL10 gene variants to modulate the odds for MetS. This and other interactions of risk factors can account for the unexplained heritability of MetS, and their elucidation can lead to new strategies for genome-customized prevention of MetS., (Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objective: HIV/AIDS is generally associated with dyslipidemia and oxidative imbalance, which are caused by the infection itself and by antiretroviral therapy (ART). The flavonoids, found in cocoa and yerba mate, have antioxidant and hypolipidemic properties. The aim of this study was to evaluate the effects of the consumption of dark chocolate and mate tea on the lipid profiles of individuals with HIV/AIDS who are undergoing ART., Methods: A randomized, double-blind, placebo-controlled crossover clinical trial was conducted with 92 patients receiving ART for ≥6 mo and with viral suppression. The participants were randomized to receive either 65 g of chocolate (with 2148 mg polyphenols) or placebo chocolate (without polyphenols) or 3 g of mate tea (with 107 mg total phenols and 84.24 mg chlorogenic acid) or placebo mate (without polyphenols) for 15 d each, separated by a washout period of 15 d. The lipid profile, including determination of electronegative low-density lipoprotein, was determined after each intervention. The data were analyzed by analysis of variance using the pkcross procedure of the Stata 11.0 software., Results: Analysis of variance revealed a significant overall difference in mean high-density lipoprotein cholesterol (HDL-C) between all supplements (P = 0.047). Using the paired t test, the effect was attributed to the consumption of dark chocolate (P = 0.046). The other parameters investigated were not improved., Conclusions: The consumption of dark chocolate for 15 d improved HDL-C concentrations of individuals with HIV/AIDS undergoing ART, possibly due to the presence of fatty acids (stearic acid), polyphenols, and theobromine. This fact is important for the cardiovascular protection of these individuals., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Under physiologic conditions, the human gut microbiota performs several activities essential to the body health. In contrast, their imbalances exacerbate some actions which can promote a cascade of metabolic abnormalities, and vice versa. Numerous diseases, including chronic kidney disease, are associated with gut microbiota imbalance, and among several strategies to re-establish gut symbiosis, prebiotics seem to represent an effective nonpharmacological approach. Prebiotics fermentation by gut microbiota produce short-chain fatty acids, which improve the gut barrier integrity and function, and modulate the glucose and lipid metabolism as well as the inflammatory response and immune system. Therefore, this literature review intends to discuss the beneficial effects of prebiotics in human health through short-chain fatty acids production, with a particular interest on chronic kidney disease.

Objective: The aim of this study was to analyze whether ω-3 supplementation improves cardiometabolic profile in individuals with cardiovascular risk factors and to determine the effect of adiponectin levels on these changes., Methods: In this double-blind, placebo-controlled, 2-mo clinical trial, we randomized 80 individuals of both sexes (mean age 52 y) with at least one cardiovascular risk factor (excess weight, hypertension, dyslipidemia, diabetes, or smoking) into two groups: ω-3 (supplemented with 3 g/d of fish oil containing 37% eicosapentaenoic acid and 23% docosahexaenoic acid) and placebo (3 g/d of sunflower oil containing 65% linoleic acid). At baseline and after the intervention, we evaluated serum adiponectin, leptin, lipid profile, apolipoproteins (apo), electronegative low-density lipoprotein (LDL[-]), and glucose metabolism (glucose and insulin)., Results: After supplementation, the ω-3 group showed an increase in serum adiponectin. After stratifying the ω-3 group by adiponectin concentration at baseline, participants with lower adiponectin concentration showed a higher reduction of total cholesterol, LDL, LDL/high-density lipoprotein ratio, LDL/apo B, and LDL(-). Individuals with a higher variation of adiponectin concentration after ω-3 supplementation presented with reduced blood glucose. The variation of serum adiponectin induced by ω-3 supplementation was negatively correlated with the Framingham and Adult Treatment Panel IV scores (r = -0.4 and P < 0.05 for both)., Conclusions: Adiponectin is shown as one of the mechanisms by which ω-3 improves cardiometabolic profile in persons with cardiovascular risk. Moreover, the benefit varies according to the adiponectin basal level and adiponectin variation after supplementation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to evaluate the effects of the classic ketogenic diet (KD) on low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions in children and adolescents with refractory epilepsy., Methods: This prospective study recruited children and adolescents of either sex, whose epilepsy was refractory to treatment with multiple drugs. To be included, the patient had to have an indication for treatment with the KD and be treated as an outpatient. At baseline and after 3 and 6 mo of the KD, lipid profile (total cholesterol [TC], triacylglycerols [TG], LDL cholesterol [LDL-C], and HDL cholesterol [HDL-C]), apolipoproteins (apoA-I and apoB), 10 subfractions of HDL, 7 subfractions of LDL, LDL phenotype, and LDL size were analyzed using the Lipoprint system., Results: The lipid profile components (TC, TG, LDL-C, HDL-C, apoA-I, and apoB) increased during the 3-mo follow-up, and remained consistent after 6 mo of treatment. Similarly, non-HDL-C, TC/HDL-C, LDL-C/HDL-C, and apoB/apoA-I ratios, representing atherogenic particles, significantly increased. In contrast, qualitative lipoprotein characteristics progressively changed during the follow-up period. Small LDL subfractions increased, and this profile was related with reduced LDL size (27.3 nm to 26.7 nm). The LDL phenotype became worse; 52.1% of the patients had a non-A phenotype after 6 mo of the KD. Small HDL subfractions decreased only after 6 mo of the KD., Conclusions: KD treatment promotes negative changes in lipoprotein size and phenotype, contributing to atherogenic risk in these patients., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: The goal of this study was evaluate the conicity index (C index) in women and its association with hypertension (SAH) and diabetes mellitus (DM)., Subjects and Methods: This was a cross-sectional study, with 573 women between 20 and 59 years of age. After analysis of clinical and demographic characteristics, anthropometric variables were measured and used to calculate the C index. Plasma glucose and lipid profile were evaluated by standard methods. The analysis of the results was based on logistic regression and the odds ratio (OR) was calculated, which was used to assess the association of the variable outcome with the variable exposure using two logistic regression models that tested the possible influence of the C index in the chance of developing SAH or DM. A confidence interval of 95% was used., Results: In the crude and adjusted models, the OR confirmed the association of the C index with DM and SAH. Compared with women that showed C index p < 75, the risk of women with C index (p ≥ 75) developing DM and SAH was 1.72 and 1.75, respectively. Results demonstrated that the negative impact of age on these associations significantly raised the odds of women having DM and SAH. The high C index was also linked to low HDL-C., Conclusion: The C index is an important tool in estimating the risk of diabetes and hypertension in women. Besides, high C indexes are negatively associated with HDL-C, an important lipid marker related to cardiovascular risk.

Introduction: Quality Indicators for Nutritional Therapy (QINT) allow a practical assessment of nutritional therapy (NT) quality., Objective: To apply and monitor QINT for critically ill patients at nutritional risk., Methods: Cross sectional study including critically ill patients > 18 years old, at nutritional risk, on exclusive enteral (ENT) or parenteral nutritional therapy (PNT) for > 72 hours. After three consecutive years, 9 QINT were applied and monitored. Statistical analysis was performed with SPSS version 17.0., Results: A total of 145 patients were included, 93 patients were receiving ENT, among then 65% were male and the mean age was 55.7 years (± 17.4); 52 patients were receiving PNT, 67% were male and the mean age was 58.1 years (± 17.4). All patients (ENT and PNT) were nutritionally screened at admission and their energy and protein needs were individually estimated. Only ENT was early initiated, more than 70% of the prescribed ENT volume was infused and there was a reduced withdrawal of enteral feeding tube. The frequency of diarrhea episodes and digestive fasting were not adequate in ENT patients. The proper supply of energy was contemplated only for PNT patients and there was an expressive rate of oral intake recovery in ENT patients., Conclusion: After three years of research, the percentage of QINT adequacy varied between 55%-77% for ENT and 60%-80% for PNT. The results were only made possible by the efforts of a multidisciplinary team and the continuous re-evaluation of the procedures in order to maintain the nutritional assistance for patients at nutritional risk.

Scope: Interactions between adiponectin genetic variants and plasma fatty acid profile can modulate plasma inflammatory biomarker concentration and the risk for metabolic diseases. The aim of this study was to investigate the interaction between single nucleotide polymorphisms of the adiponectin gene and plasma fatty acid profile in modulating the odds for systemic inflammation in a cross-sectional population-based study., Methods and Results: Inflammatory patterns comprised 11 inflammatory biomarkers. Among participants of the Health Survey of São Paulo, 262 adults (19-59 years) met the inclusion criteria. Anthropometric parameters, blood pressure, plasma inflammatory biomarker concentration, and fatty acid profile were measured and five single nucleotide polymorphisms of the adiponectin gene (rs2241766, rs1501299, rs16861209, rs17300539, and rs266729) genotyped. Individuals in the upper 50th percentile for plasma araquidonic acid, n-3 highly unsaturated fatty acid and estimated delta-5-desaturase activity, had reduced odds of being in the inflammatory cluster (OR (95% CI) = 0.55 (0.32-0.95), 0.50 (0.28-0.88) and 0.48 (0.28-0.83), respectively). Gene-plasma fatty acid profile interaction was found between rs2241766 and n-3 (p = 0.019), rs16861209 and araquidonic acid and docosapentaenoic acid (p = 0.044, p = 0.037, respectively), and rs17300539 and saturated fatty acid (p = 0.019)., Conclusion: Plasma fatty acid profile can interact with adiponectin gene variants to modulate the risk for systemic inflammatory state., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background/objectives: Breast cancer is a disease characterised by both oxidative reactions and inflammation. However, few studies have focused on the oxidative and inflammatory biomarkers. The aim of the present study was to evaluate the association between oxidative stress markers and adiposity and clinical staging, as well as the association between the oxidative and the antioxidant biomarkers of women with breast cancer., Subjects/methods: A total of 135 cases of breast cancer occurring in 2011 and 2012 were assessed. After exclusions, 101 pre- and post-menopausal women with clinical staging I to IV were eligible to participate in the study. The anthropometric evaluation was performed by collecting data on waist circumference, body mass index and body composition. The socioeconomic and clinical profiles were determined using a standard questionnaire. For the oxidative biomarkers, thiobarbituric acid reactive substances (TBARS), oxidative DNA damage (8-hydroxy-2-deoxyguanosine (8-OHdG)), low-density lipoprotein(-) (LDL(-)), autoantibody anti-LDL(-) and liposoluble antioxidants (α-tocopherol, retinol and β-carotene) were analysed. The data were analysed using differences in the mean values, correlation tests and multiple linear regression., Results: The antioxidant levels were higher in postmenopausal women with clinical staging I and II and negative lymph nodes. The TBARS level was associated with clinical staging. Adiposity was associated with levels of retinol and 8-OHdG, whereas LDL(-), 8-OHdG and TBARS were correlated with liposoluble antioxidants after adjusting for the confounders., Conclusions: The adiposity and clinical staging of patients were associated with oxidative stress. The oxidative and antioxidant biomarkers showed a negative correlation in patients with breast cancer.

Introduction: the inflammatory response caused by sepsis leads to metabolic changes, which may result in significant lean mass loss in septic patient. Because of this, when digestive tract is functional, nutritional therapy (NT) must be initiated within 48 hours of intensive treatment to reduce protein loss., Objective: to evaluate enteral nutritional therapy (ENT) in adult septic patients with exclusive ENT for ≥ 72 hours and length of stay ≥7 days in Intensive Care Unit and its relationship with clinical prognosis., Methods: we prospectively analyzed the adequacy of enteral nutrition administered, factors associated with non-conformity, gastrointestinal tolerance and outcome. Statistical tests of chi-square and Student's t as well as Mann-Whitney and Spearman and Pearson correlations (p < 0.05) were used. A multiple logistic regression model has been done by using the stepwise method to evaluate the association between predictors of clinical outcome., Results: 53 patients, 67.9% male and 52.8% elderly were enrolled in this study. The average time for starting ENT was 30 (23.5) hours, and 88.7% of patients achieved nutritional goal in 48 hours. The mean volume delivered in relation to prescribed was 78.9%. When the sample was stratified according to administered/ prescribed calories, patients who received < 80% had a higher mortality rate (p = 0.001) and the caloric intake ≥ 80% was the determining factor in patients' clinical prognosis (p = 0.021)., Conclusion: septic patients received early enteral nutrition. The nutritional goal and the mean volume delivered in relation to the prescribed volume meet the intensive care guidelines. The nutritional support was associated with clinical outcome, and caloric intake ≥ 80% determining the clinical prognosis. The pauses caused by reflux were significant in the group of patients who died and it may be related to disease severity., (Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)

Background: studies have investigated the relationship between the transition through menopause and cardiovascular diseases. White population, generally, have lower levels of traditional coronary heart risk factors, particularly dyslipidemia, hypertension, obesity, and diabetes, and lower rates of coronary heart disease mortality, than black population. Furthermore many studies have shown the cardioprotective and anti-inflammatory effects of omega-3 polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic acid) of marine origin. The aim of this study was to investigate the effect of omega-3 supplementation, combined or not with vitamin E, on oxidative biomarkers and lipid profiles in nonwhite and white women with dyslipidemia transitioning through menopause., Methods: a randomized, double-blind, placebo-controlled trial was conducted. Seventy-four eligible women were assigned to receive: fish oil, fish oil plus vitamin E and placebo for three months. At baseline, 45 and 90 days blood sample for biochemical variables and biomarkers of oxidative stress were taken. Socioeconomic and lifestyle variables were collected with standardized questionnaires., Results: after 90 days the fish oil plus vitamin E treated group had a significant decrease in total cholesterol and LDL-C. Furthermore, there was a decrease in anti- LDL- autoantibodies after 45 days. Plasma TBARS concentrations were increased after 90 days in the group receiving only fish oil when compared to the placebo and fish oil-vitamin E groups. All of the effects observed were independent of ethnic group., Conclusion: supplementation with fish oil and vitamin E reduced total cholesterol and LDL-C, but had opposite effects on oxidative stress compared to supplementation with fish oil alone., (Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)

Objectives: Ketogenic diet (KD) is an important therapy used in the control of drug-refractory seizures. The major goal of this review is to update the knowledge about the adverse effects of KD on lipoproteins, lipid profile, and cardiometabolic risk., Methods: Articles on the effect of the KD on plasma lipoproteins of children and adolescents with refractory epilepsy, which were published in the past 15 years and indexed in the PubMed and MedLine databases, were included., Results: Dyslipidemia was recurrent in children, and adolescents treated with KD. Evidence suggests that hypercholesterolemia promotes structural modifications in low-density lipoprotein particles. Such modifications possibly favor oxidative processes and contribute to changes in the size of lipoproteins, particularly related to small and denser LDL. However, oxidative modifications in LDL of children on KD are not described in the literature., Discussion: The positive effects of KD on the health of children and adolescents with refractory epilepsy are unquestionable. Conversely, this positive role is associated with significant and negative changes in lipid metabolism. Moreover, the positive effects are possibly related to oxidative reactions and unbalance of antioxidants that can contribute to an increased cardiometabolic risk. Therefore, this review invites clinicians and researchers to investigate the lipid and oxidative metabolism in their clinical practice and trials, respectively.

Dietary glycemic index (GI) and glycemic load (GL) are indicators of carbohydrate consumption and widely used in studies evaluating the risk for breast cancer. However, the effect of chemotherapy on these indices has been scarcely studied. The aim of this study was to evaluate dietary levels of GI and GL in women with breast cancer during chemotherapy treatment and their relationships to body fat and phase angle. Twenty-five patients were assessed according to demographic, clinical, anthropometric, and food consumption data. Dietary intake was assessed by 24-h dietary recalls applied on nonconsecutive days. Anthropometric measures and body composition were determined at all study timepoints: prior to the first chemotherapy cycle (T0), immediately after the last chemotherapy cycle (T1), and 2 months after T1 (T2). There was no difference in mean GI and GL among study timepoints. However, a high prevalence of inadequate GI and GL values was noted, independent of study timepoint. GI and GL were associated with phase angle at T1. GI was associated with percentage fat at T0 only. Dietary GI and GL were unchanged during chemotherapy, but were associated with indicators of clinical outcome, such as percentage fat and phase angle.

A ketogenic diet is an important therapy used in the control of drug-refractory seizures. Many studies have shown that children and adolescents following ketogenic diets exhibit an over 50% reduction in seizure frequency, which is considered to be clinically relevant. These benefits are based on a diet containing high fat (approximately 90% fat) for 24 months. This dietary model was proposed in the 1920s and has produced variable clinical responses. Previous studies have shown that the mechanisms underlying seizure control involve ketone bodies, which are produced by fatty acid oxidation. Although the pathways involved in the ketogenic diet are not entirely clear, the main effects of the production of ketone bodies appear to be neurotransmitter modulation and antioxidant effects on the brain. This review highlights the impacts of the ketogenic diet on the modulation of neurotransmitters, levels of biogenic monoamines and protective antioxidant mechanisms of neurons. In addition, future perspectives are proposed.

Objective: To determine the factors that influence the adequacy of enteral nutritional therapy in an intensive care unit., Methods: This prospective observational study was conducted in an intensive care unit between 2010 and 2012. Patients >18 years of age underwent exclusive enteral nutritional therapy for ≥72 hours. The energy and protein requirements were calculated according to the ICU protocols. The data regarding enteral nutrition, the causes of non-compliance, and the biochemical test results were collected daily., Results: Ninety-three patients admitted to the intensive care unit were evaluated. Among these patients, 82% underwent early enteral nutritional therapy, and 80% reached the nutritional goal in <36 hours. In addition, 81.6%±15.4% of the enteral nutrition volume was infused, with an adequacy of 82.2%±16.0% for calories, 82.2%±15.9% for proteins, and a mean energy balance of -289.9±277.1 kcal/day. A negative correlation of C-reactive protein with the volume infused and the energy and protein balance was observed. In contrast, a positive correlation was found between C-reactive protein and the time required to reach nutritional goals. Extubation was the main cause for interrupting the enteral nutritional therapy (29.9% of the interruption hours), and the patients >60 years of age exhibited a lower percentage of recovery of the oral route compared with the younger patients (p=0.014)., Conclusion: Early enteral nutritional therapy and the adequacy for both energy and protein of the nutritional volume infused were in accordance with the established guidelines. Possible inadequacies of energy and protein balance appeared to be associated with an acute inflammatory response, which was characterized by elevated C-reactive protein levels. The main cause of interruption of the enteral nutritional therapy was the time spent in extubation.

Aims: To compare the effects of two of the most effective lipid-lowering therapies with similar LDL-cholesterol reduction capacity on the innate and adaptive immune responses through the evaluation of autoantibodies anti-oxidized LDL (anti-oxLDL Abs) and electronegative LDL [LDL(-)] levels., Main Methods: We performed a prospective, randomized, open label study, with parallel arms and blinded endpoints. One hundred and twelve subjects completed the study protocol and received rosuvastatin 40 mg or ezetimibe/simvastatin 10/40 mg for 12 weeks. Lipids, apolipoproteins, LDL(-), and anti-oxLDL Abs (IgG) were assayed at baseline and end of study., Key Findings: Main clinical and laboratory characteristics were comparable at baseline. Lipid modifications were similar in both treatment arms, however, a significant raise in anti-oxLDL Abs levels was observed in subjects treated with rosuvastatin (p=0.026 vs. baseline), but not in those receiving simvastatin/ezetimibe. (p=0.233 vs. baseline), thus suggesting modulation of adaptive immunity by a potent statin. Titers of LDL(-) were not modified by the treatments., Significance: Considering atherosclerosis as an immune disease, this study adds new information, showing that under similar LDL-cholesterol reduction, the choice of lipid-lowering therapy can differently modulate adaptive immune responses., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: The PREDIMED trial showed that Mediterranean diets supplemented with either extra-virgin olive oil or nuts reduced incident cardiovascular events compared to a control diet. Consumption of both supplemental foods has been associated with reduced LDL-cholesterol, but it is unknown whether they can shift lipoprotein subfractions to a less atherogenic pattern. We investigated changes in adiposity and lipoprotein subfractions after consumption of the PREDIMED diets., Methods: In a PREDIMED sub-cohort (n = 169), lipoprotein subclasses (particle concentrations and size) were determined by nuclear magnetic resonance spectroscopy at baseline and after intervention for 1 year., Results: Participants allocated to the Mediterranean diet supplemented with nuts showed significant reductions from baseline of waist circumference (mean [95% CI]; -5 cm [-7; -3]) and concentrations of medium-small (-27 nmol/l [-46; -8]) and very small LDL (-111 nmol/l [-180; -42]); decreased LDL particle number (a nuclear magnetic resonance-specific measurement) (-98 nmol/l [-184; -11]); and an increase of large LDL concentrations (54 nmol/l [18; 90]), with a net increase (0.2 nmol/l [0.1; 0.4]) of LDL size. The Mediterranean diets with olive oil and nuts increased large HDL concentrations (0.6 μM [0.0; 1.1] and 1.0 μM [0.4; 1.5], respectively). Compared to the other two intervention groups, participants in the nut-enriched diet showed significantly reduced waist circumference (p ≤ 0.006, both) and increased LDL size (p < 0.05, both)., Conclusion: Lipoprotein subfractions are shifted to a less atherogenic pattern by consumption of Mediterranean diets enriched with nuts. The results contribute mechanistic evidence for the reduction of cardiovascular events observed in the PREDIMED trial., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Lipoprotein-associated phospholipase A2 activity (Lp-PLA2) is a good marker of cardiovascular risk in adults. It is strongly associated with stroke and many others cardiovascular events. Despite this, the impact of obesity on this enzyme activity and its relation to biomarkers of cardiovascular disease in adolescents is not very well investigated. The purpose of this article is to evaluate the influence of obesity and cardiometabolic markers on Lp-PLA2 activity in adolescents., Results: This cross-sectional study included 242 adolescents (10-19 years) of both gender. These subjects were classified in Healthy Weight (n = 77), Overweight (n = 82) and Obese (n = 83) groups. Lipid profile, glucose, insulin, HDL size, LDL(-) and anti-LDL(-) antibodies were analyzed. The Lp-PLA2 activity was determined by a colorimetric commercial kit. Body mass index (BMI), waist circumference and body composition were monitored. Food intake was evaluated using three 24-hour diet recalls. The Lp-PLA2 activity changed in function to high BMI, waist circumference and fat mass percentage. It was also positively associated with HOMA-IR, glucose, insulin and almost all variables of lipid profile. Furthermore, it was negatively related to Apo AI (β = -0.137; P = 0.038) and strongly positively associated with Apo B (β = 0.293; P < 0.001) and with Apo B/Apo AI ratio (β = 0.343; P < 0.001). The better predictor model for enzyme activity, on multivariate analysis, included Apo B/Apo AI (β = 0.327; P < 0.001), HDL size (β = -0.326; P < 0.001), WC (β = 0.171; P = 0.006) and glucose (β = 0.119; P = 0.038). Logistic regression analysis demonstrated that changes in Apo B/Apo AI ratio were associated with a 73.5 times higher risk to elevated Lp-PLA2 activity., Conclusions: Lp-PLA2 changes in function of obesity, and that it shows important associations with markers of cardiovascular risk, in particular with waist circumference, glucose, HDL size and Apo B/Apo AI ratio. These results suggest that Lp-PLA2 activity can be a cardiovascular biomarker in adolescence.

Obesity has increased in children and adolescents. What is reflected in the early occurrence of cardiometabolic alterations, like hypertension and type 2 diabetes, where the oxLDL formation is stimulated. Various studies have shown that plasma α-tocopherol (α-TP) can protect LDL against oxidation. Nevertheless, the action of plasma α-TP in cardiovascular diseases remains controversial. We conducted a cross-sectional study to evaluate plasma α-TP and its impact on the concentration of LDL(-). Adolescents (n=150) of both sexes were classified into three groups: healthy weight (HW; 50%), overweight (OV; 22%), and obese (OB; 28%). Lipid profile, LDL(-), anti-oxLDL and anti-LDL(-) antibodies, CRP (ELISA) and plasma α-TP (HPLC) were analyzed. Demographic, anthropometric, and food intake data were evaluated. Crude and energy-adjusted intake of vitamin E in the OB group were higher than in the HW group (p<0.001). Crude and energy-adjusted vitamin E intakes were not correlated with plasma α-TP (r=-0.07; p=0.412 and r=-0.064; p=0.467, respectively). Subjects in the OB group had higher TC and LDL-C and lower HDL-C than in the HW and OV groups. C-reactive protein and anti-oxLDL antibodies changed as a function of BMI. The impact of obesity was reinforced by high values for LDL(-) and low content of plasma α-TP in comparison with the HW (p<0.001) and OV groups (p=0.03). This negative profile was maintained for the ratio between α-TP and TC or LDL-C. Plasma α-TP, α-TP/TC and α-TP/LDL-C were negatively associated with LDL(-) and other cardiometabolic risk factors (BMI, WC, AC and anti-oxLDL). Our results demonstrate that obesity in adolescents is associated with high levels of LDL(-) and low plasma α-TP content.

The association of cardiovascular events with Lp-PLA2 has been studied continuously today. The enzyme has been strongly associated with several cardiovascular risk markers and events. Its discovery was directly related to the hydrolysis of the platelet-activating factor and oxidized phospholipids, which are considered protective functions. However, the hydrolysis of bioactive lipids generates lysophospholipids, compounds that have a pro-inflammatory function. Therefore, the evaluation of the distribution of Lp-PLA2 in the lipid fractions emphasized the dual role of the enzyme in the inflammatory process, since the HDL-Lp-PLA2 enzyme contributes to the reduction of atherosclerosis, while LDL-Lp-PLA2 stimulates this process. Recently, it has been verified that diet components and drugs can influence the enzyme activity and concentration. Thus, the effects of these treatments on Lp-PLA2 may represent a new kind of prevention of cardiovascular disease. Therefore, the association of the enzyme with the traditional assessment of cardiovascular risk may help to predict more accurately these diseases.

Background and Aims: Virgin olive oil (VOO) and nuts are basic components of the Mediterranean diet, a heart-healthy dietary pattern. Nuts have well known cholesterol lowering effects, while evidence is unclear for VOO. We designed a study in hypercholesterolemic patients to assess the effects on serum lipids and other intermediate markers of cardiovascular risk of replacing 40% of the fat in the background diet with VOO, walnuts or almonds., Methods and Results: After a 4 week run-in period with a healthy diet, eligible candidates were randomized into three diet sequences in a crossover design, with a common background diet enriched with VOO, walnuts or almonds, lasting 4 weeks each. Outcomes were changes of serum lipids and oxidation and inflammation markers, measured by standard methods. Plasma fatty acids were determined by gas chromatography to assess compliance. In 18 participants completing the study (9 women, mean age 56 y, BMI 25.7 kg/m(2)), LDL-cholesterol was reduced from baseline by 7.3%, 10.8% and 13.4% after the VOO, walnut and almond diets, respectively (P = 0.001, Friedman test). Total cholesterol and LDL/HDL ratios decreased in parallel. LDL-cholesterol decreases were greater than predicted from dietary fatty acid and cholesterol exchanges among diets. No changes of other lipid fractions, oxidation analytes or inflammatory biomarkers were observed. Plasma fatty acid changes after each diet sequence supported good compliance., Conclusion: The results confirm the cholesterol lowering properties of nut-enriched diets. They also suggest that phenolic-rich VOO has a cholesterol lowering effect independently of its fatty acid content, which clearly deserves further study., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Oxidative modifications in lipoproteins (LP), especially in low-density lipoproteins (LDL), are associated with initiation and progression of atherosclerosis. The levels of a sub-fraction of LDL with oxidative characteristics, named electronegative LDL [LDL(-)], minimally oxidized LDL, and minus LDL, are known to be increased in subjects with familial hypercholesterolemia, hypertriglyceridemia, nonalcoholic steatohepatitis, diabetes mellitus, coronary artery disease, patients undergoing hemodialysis, and athletes after aerobic exercise. In addition to the oxidative profile, physical and biological characteristics of LDL(-) consist of nonenzymatic glycosylation, increased expression and activity of platelet-activating factor acetylhydrolase (PAF-AH) and phospholipase A(2) (PLA(2)), enriched NEFA content, hemoglobin and ApoB-100 cross-linking, and increase in ApoC-III and ApoE in LDL. Herein, we summarize the state of the art of the up-to-date body of knowledge on the possible origin and impact of LDL(-) in health and disease. Further, the potential perspectives of using LDL(-) as a biomarker in conditions under metabolic stress are also discussed., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

The aim of this study was to validate the intake of carotenoids, fruits and vegetables estimated by the Food Frequency Questionnaire for Adolescents (FFQA) using the method of triads. Blood samples were collected from 80 elementary school adolescents to assess serum levels of β-carotene. Partial correlation coefficients (r) were calculated between an estimated intake of carotenoids, fruits and vegetables and the serum levels of β-carotene. Validity coefficients were calculated using the method of triads. With the exception of carotenoids, partial r from the food frequency questionnaire (FFQ) were greater than those of the 24-hour recall (24hR). The fruit/vegetable group showed the highest partial r for the FFQ (r = 0.235) and the 24hR (r = 0.137). The highest validity coefficient was obtained for the vegetable group, as assessed by the FFQ (r = 0.873). On average, the validity coefficient values for the FFQ were greater than those obtained for the 24hR or the β-carotene serum levels. The FFQA is an accurate tool for estimating the intake of carotenoids, fruits and vegetables in this population group.

Dyslipidemias and physicochemical changes in low-density lipoprotein (LDL) are very important factors for the development of coronary artery disease (CAD). However, pathophysiological properties of electronegative low-density lipoprotein [LDL(-)] remain a controversial issue. Our objective was to investigate LDL(-) content in LDL and its subfractions (phenotypes A and B) of subjects with different cardiovascular risk. Seventy-three subjects were randomized into three groups: normolipidemic (N; n = 30) and hypercholesterolemic (HC; n = 33) subjects and patients with CAD (n = 10). After fasting, blood samples were collected and total, dense and light LDL were isolated. LDL(-) content in total LDL and its subfractions was determined by ELISA. LDL(-) content in total LDL was lower in the N group as compared to the HC (P < 0.001) and CAD (P = 0.006) groups. In the total sample and in those of the N, HC, and CAD groups, LDL(-) content in dense LDL was higher than in light LDL (P = 0.001, 0.001, 0.001, and 0.033, respectively) The impact of LDL(-) on cardiovascular risk was reinforced when LDL(-) content in LDL showed itself to have a positive association with total cholesterol (beta = 0.003; P < 0.001), LDL-C (beta = 0.003; p < 0.001), and non-HDL-C (beta = 0.003; P < 0.001) and a negative association with HDL-C (beta = -0.32; P = 0.04). Therefore, LDL(-) is an important biomarker that showed association with the lipid profile and the level of cardiovascular risk.

Objective: To investigate whether levels of autoantibodies to oxidized LDL (anti-oxLDL) in the plasma of adolescents correlates with their anthropometric measurements and lipid profiles., Methods: The study enrolled 150 adolescents aged between 10 and 15 years, recruited from the obesity clinic at Universidade Federal de São Paulo (SP) and from public schools in Piracicaba, SP, Brazil. Anthropometric measurements such as body mass index and waist and arm circumferences were used to classify the adolescents as having healthy weight, overweight or obesity. Colorimetric enzymatic methods were used for biochemical lipid profile analysis and ELISA was used to determine anti-oxLDL autoantibody levels., Results: Analysis of anthropometric variables indicated that the obese group's profile was abnormal compared to the healthy weight and overweight groups (p < 0.01), indicating cardiovascular risk. Analysis of the lipid profiles demonstrated statistically significant differences in concentrations of total cholesterol (p = 0.011), HDL-cholesterol (p = 0.001) and LDL-cholesterol (p < 0.042) between the healthy weight group and the obese group. Analysis of plasma anti-oxLDL autoantibodies demonstrated that the overweight (p = 0.012) and obese groups (p < 0.001) had higher values than the healthy weight group. There were also correlations between anti-oxLDL autoantibody levels and anthropometric variables., Conclusions: In adolescents the presence of anti-oxLDL autoantibodies and metabolic changes to the lipid profile vary in proportion with anthropometric parameters, which makes anti-oxLDL concentration a potential biochemical indicator of risk of metabolic syndrome.

Objectives: To produce a monoclonal antibody (MAb) against electronegative LDL (LDL-) for detecting this modified lipoprotein in blood plasma and tissues., Design and Methods: LDL- was isolated from human blood plasma and used as an antigen for immunization of Balb/c mice. Lymphocytes of immunized mice were fused with myeloma cells (SP2/0) to obtain the hybridomas. LDL- was detected in blood plasma and atherosclerotic lesions of humans and rabbits by MAb-based ELISA and immunohistochemistry, respectively., Results: LDL- concentrations were higher (P < 0.05) in the blood plasma of hypercholesterolemic subjects (HC, 248 +/- 77 mg/dL of total cholesterol) than in normolipidemic subjects (NL, 173 +/- 82 mg/dL of total cholesterol) and rabbits (HC, 250 +/- 15 mg/dL of cholesterol versus NL, 81 +/- 12 mg/dL of cholesterol). Moreover, LDL- was detected in the atherosclerotic lesions of humans and rabbits., Conclusion: These MAb-based immunoassays are adequate to detect LDL- in biological samples and represent an important tool for investigating the role of LDL- in atherosclerosis.

Background/aims: Nutrients able to modify the susceptibility of lipoproteins to oxidation and/or reduce the cholesterol levels of blood plasma are important for prevention and/or treatment of atherosclerosis. The influence of animal and vegetable proteins on hypercholesterolemia and atherogenesis has been studied, concerning the mechanisms able to modify the digestion, absorption and bioavailability of lipids. In this study, the influence of casein and soy protein isolate on lipoprotein oxidation and atherosclerosis progression was investigated in cholesterol-fed rabbits., Methods: During 2 months, 20 New Zealand rabbits were fed with diets containing 1% cholesterol and 27% casein or 27% soy protein isolate. Blood samples were collected at baseline, 15, 30, 45 and 60 days of feeding., Results: Casein feeding contributed to increasing cholesterol and triglyceride concentrations, lipoprotein oxidation and the area of aorta atherosclerotic lesions. In contrast, the soy protein isolate reduced, when compared to casein, the concentrations of cholesterol and lipid peroxides of beta-VLDL and LDL fractions during the experimental time course, as well as the area of atherosclerotic lesions at the end of the study., Conclusion: Soy protein isolate, in comparison with casein, promoted a decrease of lipid peroxides, cholesterol and triglyceride content of atherogenic lipoproteins (beta-VLDL and LDL), which had beneficial effects over atherosclerosis progression in cholesterol-fed rabbits., (Copyright 2001 S. Karger AG, Basel.)

The incidence of atherosclerosis can be modified by diet, and plant-derived proteins have a beneficial effect, but the underlying mechanisms remain unclear. It has been suggested that oxidized LDL (oxLDL) and autoantibodies against oxLDL are important in the development of atherosclerosis. We analyzed these factors in rabbits fed a nonpurified diet supplemented with high cholesterol (10.0 g/kg) containing either 270.0 g/kg casein (CAS, n = 10) or 270.0 g/kg soy protein isolate (SPI, n = 10) for 2 mo. Plasma and purified serum LDL from rabbits were analyzed at d 0, 15, 30, 45 and 60 of treatment, and the size of atherosclerotic lesions was evaluated at d 60 of treatment. CAS-fed rabbits had significantly higher plasma cholesterol at d 15-45 and LDL cholesterol levels at d 15 and 30. Levels of trilinolein and phosphatidylcholine hydroperoxides were higher in the LDL fraction of rabbits fed CAS than in those fed SPI. Also, CAS-fed rabbits had higher levels of highly oxidized LDL [monoclonal antibody (mAb) 24-reactive oxLDL] in plasma at d 60, whereas SPI-fed rabbits had higher levels of minimally oxidized LDL (mAb 28-reactive oxLDL) at d 45. These results were consistent with the earlier formation of anti-oxLDL antibodies and the presence of a larger area of atherosclerotic lesion in rabbits fed the CAS diet. These data indicate the importance of both the type of dietary protein used in the induction of atherosclerosis and the relevance of immunologic mechanisms in addition to biochemical and physiologic factors in the pathogenesis of atherosclerosis.

Oxidative processes leading to the generation of oxidized low density lipoprotein (oxLDL) particles have been suggested to be an important factor in the pathogenesis of atherosclerosis. After initiation of the oxidative process, LDL undergoes a progressive protein and lipid fragmentation. To understand this process and the role of oxLDL in various diseases of inflammatory origin, we have generated mouse monoclonal antibodies against copper-oxidized human LDL. Mice were immunized intrasplenically and after one intravenous boost the spleen cells were fused with the Sp2/0 hybridoma fusion partner. The hybridoma clones obtained after selection and cloning were analyzed for reactivity against oxLDL with various degrees of copper-mediated oxidative modifications. Three hybridoma clones were purified and further characterized. The following observations were made: 1) the intrasplenic route of immunization, avoiding the use of mycobacterial adjuvants, yielded a high frequency of positive clones; 2) the individual hybridomas reacted against LDL with various degrees of oxidative modifications; 3) the monoclonal antibodies could be used in ELISA and to detect oxLDL in immunohistochemical tissue staining, and 4) the monoclonal antibodies also detected oxLDL from hamsters and rabbits. We conclude that these monoclonal antibodies could be useful to further investigate the role of oxLDL in inflammation and in the immune response.