Nágila Raquel Teixeira Damasceno

Electronegative low-density lipoprotein: Origin and impact on health and disease

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.

Antioxidant and inflammatory aspects of lipoprotein-associated phospholipase A2 (Lp-PLA2 ): a review

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.

Validation of a food frequency questionnaire to assess the consumption of carotenoids, fruits and vegetables among adolescents: the method of triads

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.

Influence of obesity and cardiometabolic makers on lipoprotein-associated phospholipase A2 (Lp-PLA2) activity in adolescents: the healthy young cross-sectional study

BackgroundLipoprotein-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.ResultsThis 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.ConclusionsLp-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.

Casein and Soy Protein Isolate in Experimental Atherosclerosis: Influence on Hyperlipidemia and Lipoprotein Oxidation

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 β-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 (β-VLDL and LDL), which had beneficial effects over atherosclerosis progression in cholesterol-fed rabbits.

Neurobiochemical mechanisms of a ketogenic diet in refractory epilepsy

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.

Impacto da proteína-C reativa no risco cardiovascular de adolescentes

BACKGROUND Several studies suggest that C-reactive protein (CRP) is associated with coronary artery disease in adults. However, this association has not been thoroughly explored in cases of adolescents. OBJECTIVE To evaluate the association between CRP and cardiovascular risk factors in obese adolescents. METHODS Eighty-four adolescents (12.6 +/- 1.3 years) of both genders were divided into the following groups: Normal weight (n = 28), Overweight (n = 28), and Obese (n = 28), according to body mass index (BMI). CRP levels (ultrasensitive ELISA), the lipid profile, and anti-oxLDL antibody levels (ELISA) were determined after a 12-hour fast. RESULTS The groups were similar in age (p = 0.13) and gender (p = 0.83). Total cholesterol, HDL-C, TC/HDL-C, and LDL-C/HDL-C showed significant differences between Normal weight and Obese groups. There was no significant variation in anti-oxLDL levels. CRP values were different among the three groups (p < 0.01). CRP levels showed a significant association with BMI (beta = 2.533), AC (beta = 2.645), WC (beta = 2.945), TC (beta = 0.006), LDL-C (beta = 0.006), and anti-oxLDL antibodies (beta = 0.383), and a negative association with HDL-C (beta = -0.017). CONCLUSION The results indicate that CRP is significantly associated with markers of cardiovascular risk in adolescents.FUNDAMENTO: Varios estudos sugerem que a proteina-C reativa (PCR) se correlaciona com doenca arterial coronariana em adultos. Entretanto, essa associacao ainda e pouco explorada em adolescentes. OBJETIVO: Avaliar a associacao entre a PCR e os fatores de risco cardiovascular em adolescentes obesos. METODOS: Oitenta e quatro adolescentes (12,6 ± 1,3 anos), ambos os sexos, foram distribuidos nos grupos Eutrofico (n = 28), Sobrepeso (n = 28) e Obeso (n = 28), segundo o indice de massa corporea (IMC). A concentracao de PCR (ELISA ultrassensivel), o perfil lipidico e o conteudo de anticorpos anti-LDLox (ELISA) foram determinados apos jejum de 12h. RESULTADOS: Os grupos foram semelhantes quanto a idade (p = 0,13) e sexo (p = 0,83). Colesterol total, HDL-C, CT/HDL-C e LDL-C/HDL-C apresentaram diferencas significativas entre os grupos Eutrofico e Obeso. Nao houve variacao significativa no conteudo de anticorpos anti-LDLox. Os valores de PCR foram diferentes entre os tres grupos (p < 0,01). PCR apresentou associacao significativa com IMC (β = 2,533), CB (β = 2,645) e CC (β = 2,945), CT (β = 0,006), LDL-C (β = 0,006) e anticorpos anti-LDLox (β = 0,383) e negativa entre HDL-C (β = -0,017). CONCLUSAO: Os resultados indicam que a PCR se associa significativamente com marcadores de risco cardiovascular em adolescentes.

Effects of two lipid lowering therapies on immune responses in hyperlipidemic subjects

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.

Aversão alimentar adquirida e qualidade de vida em mulheres com neoplasia mamária

OBJECTIVE: The objective of this paper was to assess the eating behavior of women with breast cancer subjected to chemotherapy and its relation with the quality of life of these patients. METHODS: A total of 25 women receiving care at the Hospital AC Camargo (SP, Brazil) from October 2005 to April 2006 were selected based on a clinical assay of the before and after type. The patients included in the study were diagnosed with breast cancer, stages I and II and had indication of adjuvant chemotherapy. At the times T0 (before) and T1 (after chemotherapy), the eating behavior (food intake and aversion) was assessed by three 24-hour recalls and the Food Action questionnaire, respectively. Quality of life was monitored through the use of the Functional Assessment of Cancer Therapy - Breast questionnaire. RESULTS: After chemotherapy (T1), the intake of macro and micronutrients did not change significantly, but the intake of fruits and juices increased (p=0.03). The opposite was observed regarding the preference for black coffee (p=0.01) and for the beverages group (p<0.001). Fat-rich foods (38%), dairy (23%), black coffee (15%), tea (15%), chocolate (7%) and red meats (7%) were the main foods associated with patient discomfort. Analyses of the quality of life showed that chemotherapy caused a significant reduction of physical well-being (p<0.01). After chemotherapy, some eating behavior variables were significantly correlated with quality of life parameters. CONCLUSION: Chemotherapy caused the bilateral relationship between eating behavior and quality of life to change in a negative manner.

Anti-oxLDL autoantibodies and their correlation with lipid profile and nutritional status in adolescents

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 groups 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.