Effects of turmeric extract supplementation on the lipid and lipoprotein subfraction profile in hemodialysis patients: A randomised, double-blind, crossover and controlled trial.

Dyslipidemia is common in patients with chronic kidney disease. Curcumin, a bioactive polyphenol from Curcuma longa, can improve lipid profile. This study aims to analyze the effects of Curcuma Longa extract supplementation on lipid profile and lipoprotein subfractions in hemodialysis (HD) patients. This is a longitudinal, double-blind, washout-period randomized clinical trial. The patients were randomized into two groups: the curcumin group (n = 10) (orange and carrot juice with 2.5 g of Curcuma Longa extract) and the control group (n = 11) (juice without curcumin) 3x/w during HD sessions for 3 months. After the washout period, patients continued the supplementation as a crossover for the same period. The lipid profile was measured using enzymatic assays. The high-density lipoprotein and low-density lipoprotein subfractions analyses were performed using LipoprintTM. In the curcumin group, the triglyceride values tended to decrease with a different triglyceride variation between the pre and post-intervention for the control and curcumin groups of 38.5 (19.8) mg/dL (p = 0.06). There was no statistical difference in the others parameters. In conclusion, Curcuma longa extract may be a good nutritional strategy to reduce triglyceride plasma levels in hemodialysis patients, but it seems ineffective for the other parameter.

Tumor aggressiveness is associated with cell integrity changes in breast cancer-surviving women: a follow-up study / La agresividad tumoral está asociada a las alteraciones de la integridad celular en las mujeres que sobreviven al cáncer de mama: estudio de seguimiento

Introduction: cell integrity and fat mass had been studied as a prognostic marker for cancer survival. Objective: our aim was to evaluate the association between tumor aggressiveness and cell integrity changes and adiposity in breast cancer (BC) survivors. Methods: women with BC (n = 114) were evaluated at diagnosis and 5 years later. Percentage of lean mass, fat mass, phase angle (PA), resistance (R) and reactance (Xc) were obtained by bioimpedance (450-50 kHz). Plasma leptin was assessed by immunoassay. Changes in body composition were assessed by the paired t-test or Wilcoxon's test. The disease effect associated with the time of diagnosis was assessed by a generalized linear model. Regression models were structured to assess the prevalence ratio between tumor aggressiveness and body composition changes adjusted for age, income, and level of schooling. Results: patients with N+ (p = 0.02) and % Ki67 > 14 (p = 0.00) show a reduction in Xc. Patients with advanced clinical staging (CS) (p = 0.02), tumors > 2 cm (p = 0.01), N+ (p = 0.01), non-luminal tumors (p = 0.02), ER- (p = 0, 00) and PR- (p = 0.02) show a PA reduction, and N+ patients (p = 0.01) show a reduction in leptin during follow-up. Tumors ≤ 2 cm (CI: 0.33-0.95; p = 0.03), initial CS (CI: 0.20-0.93; p = .0.03), and luminal tumors (CI: 0.01-0.95; p = 0.04) are related to a lower reduction in PA. Initial CS (CI: 0.00-0.00; p = 0.00) are related to increased leptin. Conclusion: tumor aggressiveness is associated with cell integrity changes in women who are BC survivors (AU)

Introducción: se han estudiado la integridad celular y la masa grasa como marcadores pronósticos de supervivencia al cáncer. Objetivo: nuestro objetivo fue evaluar la asociación entre la agresividad del tumor y los cambios en la integridad celular y la adiposidad en supervivientes de cáncer de mama (CM). Métodos: las mujeres con CM (n = 114) se evaluaron al diagnóstico y 5 años después. El porcentaje de masa magra, masa grasa, ángulo de fase (PA), resistencia (R) y reactancia (Xc) se obtuvo mediante bioimpedancia (450-50 kHz). La leptina plasmática se evaluó mediante inmunoensayo. Los cambios en la composición corporal se evaluaron mediante la prueba de la t pareada o la prueba de Wilcoxon. El efecto de la enfermedad asociado con el momento del diagnóstico se evaluó mediante un modelo lineal generalizado. Los modelos de regresión se estructuraron para evaluar la razón de prevalencia entre la agresividad del tumor y los cambios en la composición corporal ajustados por edad, ingresos y nivel de escolaridad. Resultados: las pacientes con N+ (p = 0,02) y % Ki67 > 14 (p = 0,00) muestran una reducción de Xc. Las pacientes con estadificación clínica (EC) avanzada (p = 0,02), tumores > 2 cm (p = 0,01), N+ (p = 0,01), tumores no luminales (p = 0,02), ER- (p = 0, 00) y PR- (p = 0,02) muestran una reducción de la AP, y los pacientes N+ (p = 0,01) muestran una reducción de la leptina durante el seguimiento. Los tumores ≤ 2 cm (IC: 0,33-0,95; p = 0,03), el EC inicial (IC: 0,20-0,93; p = 0,03) y los tumores luminales (IC: 0,01-0,95; p = 0,04) se relacionan con un menor reducción de la PA. Los EC iniciales (IC: 0,00-0,00; p = 0,00) están relacionados con un aumento de leptina. Conclusión: la agresividad del tumor se asocia con cambios en la integridad celular en las mujeres que sobreviven al CM (AU)

Adiponectin predicts the antioxidant capacity and size of high-density lipoprotein (HDL) in individuals with diabetes mellitus.

AIMS: The relationship between adiponectin and type 2 diabetes mellitus (T2DM) is established; however the evidence on its role in high-density lipoprotein (HDL) functionality is still scant. The aim of this study was to assess the association of adiponectin with HDL functionality especially on the antioxidant capacity and HDL subfractions in individuals with T2DM. METHODS: This case-control study enrolled 356 individuals who were divided into two groups: diabetics [T2DM (n = 188)] and non-diabetic [nT2DM (n = 168)]. The association of adiponectin level on HDL functionality parameters was done in function of the cut-off point for adiponectin [percentile p < 75 = 12.9 µg/mL versus p ≥ 75 = 12.9 µg/mL] and multiple adjustments applied in the logistic regression models. RESULTS: Body mass index (BMI), waist circumference (WC) and body fat mass (FM) were higher in T2DM. The larger HDL particles (HDLLARGE) were lower in T2DM group in comparison with nT2DM (28.20% versus 30.40%; p = 0.016). Individuals with T2DM and simultaneous highest adiponectin (p ≥ 75) had 2.25 OR (95% CI = 1.03-4.91) and 5.14 OR (95% CI = 2.37-11.15) to present higher HDL-C and HDLLARGE concentrations. After adjustment for multiple confounders, high level of adiponectin was independently related with improvement of the HDL antioxidant capacity (OR = 2.78; 95% CI = 1.16-6.67). CONCLUSIONS: High adiponectin level associates with a lesser negative impact of T2DM on HDL functionality by increase in APO AI, particles size, and cholesterol content. On the same token, higher adiponectin was associated with greater odds to have high antioxidant capacity.

Association of oxidative stress biomarkers with adiposity and clinical staging in women with breast cancer.

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 ß-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.

Crossover study of diets enriched with virgin olive oil, walnuts or almonds. Effects on lipids and other cardiovascular risk markers.

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.

Biomarcador da modificaçäo oxidativa da LDL in vivo / Biomarker LDL's oxidative modification in vivo

As modificaçöes oxidativas da lipoproteína de baixa densidade (LDL) säo consideradas um fator importante para o desenvolvimento da aterosclerose. Estas modificaçöes ocorrem in vivo, originando uma sub-traçäo denominada de LDL, eletronegativa (LDL-). O monitoramento clínico da LDL- é de extrema importância, mas estava sendo limitado pela dificuldade para detecçäo desta partícula em fluídos biológicos. Neste estudo desenvolveu-se novas metodologias para detectar a LDL- no plasma, utilizando-se um anticorpo monoclonal anti-LDL- humana (3D1036) e avaliar a resposta imune humoral relacionada à LDL-. A LDL- plasmática foi analisada através de um ELISA com detecçäo por quimioluminescência com boa sensibilidade (<1,0µg/mL) e precisäo (CVintra=6,44 ñ 1,15 porcento e CVinter=8,59 ñ 3,42 porcento). As análises dos auto-anticorpos anti-LDL- evidenciaram a presença de uma resposta imune específica para LDL- em humanos e em coelhos. A determinaçäo da LDL-, abre novas perspectivas para o monitoramento das modificaçöes oxidativas endógenas da LDL em estudos clínicos e de intervençäo que utilizam um elevado número de amostras. Além disto, a detecçäo dos auto-anticorpos anti-LDL- demonstra o potencial imunogênico desta partícula. Portanto, a detecçäo da LDL- e dos auto-anticorpos anti-LDL- abre novas perspectivas para o monitoramento dos fatores de risco para a aterosclerose vinculados às reaçöes oxidativas

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 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.

Soy protein isolate reduces the oxidizability of LDL and the generation of oxidized LDL autoantibodies in rabbits with diet-induced atherosclerosis.

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.

Monoclonal antibodies against low density lipoprotein with various degrees of oxidative modifications.

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.

Monoclonal antibodies against low density lipoprotein with various degrees of oxidative modifications

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.