Effects of ABCA1 SNPs, including the C-105T novel variant, on serum lipids of Brazilian individuals

Background: ABCA1 plays an important role in HDL metabolism. Single nucleotide polymorphisms (SNPs) in ABCA1 gene were associated with variation in plasina HDL-c. Methods: The effect of the ABCA1 SNPs C-14T, R219K and of a novel variant C-105T on serum lipids was investigated in 367 unrelated Brazilian individuals (224 hypercholesterolemic and 143 normolipidemic). The relation between ABCA1 SNPs and the lipid-lowering response to atorvastatin (10 mg/day/4 weeks) was also evaluated in 141 hypercholesterolemic (HC) individuals. The polymorphisms were detected by PCRR_FLP and confirmed by DNA sequencing. Results: Linkage disequilibrium was found between the SNPs C-105T and C-14T in the HC group. HC individuals carrying - 105CT/TT genotypes had higher serum HDL-c and lower triglyceride and VLDL-c concentrations as well as lower TG/HDL-c ratio compared to the -105CC carriers (p<0.05). The R219K SNP was associated with reduced serum triglyceride, VLDL-c and TG/HDL-c ratio in the HC group (p<0.05), and with an increased serum apoAI in NL individuals. The effects of ABCA1 SNPs on basal serum lipids of HC individuals were not modified by atorvastatin treatment. Conclusions: The ABCA1 SNPs R219K and C-105T were associated with a less atherogenic lipid profile but not with the lowering-cholesterol response to atorvastatin in a Brazilian population. (C) 2007 Elsevier B.V. All rights reserved.

Influence of SCARB1 polymorphisms on serum lipids of hypercholesterolemic individuals treated with atorvastatin

Background: The SR-BI is a key component on the cholesterol metabolism. Polymorphisms in the SR-BI gene (SCARB1) were related with variations on plasma lipoprotein profile and other risk factors for cardiovascular disease. We tested the relationship of 3 SCARB1 single nucleotide polymorphisms (SNPs) with hypercholesterolemia in a Brazilian population and whether these variants can influence lipid-lowering response to atorvastatin. Methods: c.4G>A, c.726+54C>T and c.1050C>T SNPs and serum concentrations of lipid and apolipoproteins were evaluated in 147 hypercholesterolemic (HC) and 185 normolipidemic (NL) unrelated Brazilian subjects. HC patients were treated with atorvastatin (10 mg/day/4 weeks). Results: Frequencies of SCARB1 polymorphisms were similar between the HC and NL groups (p>0.05). The T allele for c.726+54C>T was associated with higher LDL-c in NL and with higher apoB and apoB/apoAI in HC (p<0.05). HC individuals carrying c.1050C allele carriers (CC and CT genotypes) had lower change of total cholesterol, LDL-c, apoB and apoB/apoAI ratio (p<0.05) than the TT genotype carriers in response to atorvastatin. Conclusion: The SCARB1 polymorphisms are related with variations in serum lipids in the Brazilian population and c.1050C>T SNP is associated with lipid-lowering atorvastatin response. (C) 2010 Elsevier B.V. All rights reserved.

Role of dietary fats in modulating cardiometabolic risk during moderate weight gain : a randomized double-blind overfeeding trial (LIPOGAIN study)

BACKGROUND: Whether the type of dietary fat could alter cardiometabolic responses to a hypercaloric diet is unknown. In addition, subclinical cardiometabolic consequences of moderate weight gain require further study. METHODS AND RESULTS: In a 7-week, double-blind, parallel-group, randomized controlled trial, 39 healthy, lean individuals (mean age of 27±4) consumed muffins (51% of energy [%E] from fat and 44%E refined carbohydrates) providing 750 kcal/day added to their habitual diets. All muffins had identical contents, except for type of fat; sunflower oil rich in polyunsaturated fatty acids (PUFA diet) or palm oil rich in saturated fatty acids (SFA diet). Despite comparable weight gain in the 2 groups, total: high-density lipoprotein (HDL) cholesterol, low-density lipoprotein:HDL cholesterol, and apolipoprotein B:AI ratios decreased during the PUFA versus the SFA diet (-0.37±0.59 versus +0.07±0.29, -0.31±0.49 versus +0.05±0.28, and -0.07±0.11 versus +0.01±0.07, P=0.003, P=0.007, and P=0.01 for between-group differences), whereas no significant differences were observed for other cardiometabolic risk markers. In the whole group (ie, independently of fat type), body weight increased (+2.2%, P<0.001) together with increased plasma proinsulin (+21%, P=0.007), insulin (+17%, P=0.003), proprotein convertase subtilisin/kexin type 9, (+9%, P=0.008) fibroblast growth factor-21 (+31%, P=0.04), endothelial markers vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and E-selectin (+9, +5, and +10%, respectively, P<0.01 for all), whereas nonesterified fatty acids decreased (-28%, P=0.001). CONCLUSIONS: Excess energy from PUFA versus SFA reduces atherogenic lipoproteins. Modest weight gain in young individuals induces hyperproinsulinemia and increases biomarkers of endothelial dysfunction, effects that may be partly outweighed by the lipid-lowering effects of PUFA. CLINICAL TRIAL REGISTRATION URL: http://ClinicalTrials.gov. Unique identifier: NCT01427140.

Fatores associados ao controle metabólico em pacientes com diabetes melito tipo 2 não usuários de insulina

Introdução: a obtenção de um bom controle metabólico é essencial para a prevenção das complicações crônicas do Diabetes Melito (DM). O tratamento é complexo e depende da implementação efetiva das diferentes estratégias terapêuticas disponíveis. Para que isso seja possível, é necessário que o paciente entenda os princípios terapêuticos e consiga executá-los. A precária educação em diabetes é percebida como um dos obstáculos para o alcance das metas terapêuticas. Objetivo: analisar, os fatores associados ao controle metabólico, em pacientes com DM tipo 2 (DM2) não usuários de insulina. Métodos: foi realizado um estudo transversal em pacientes com DM2 não usuários de insulina, selecionados ao acaso entre aqueles que consultavam nos ambulatórios de Medicina Interna, Endocrinologia e Enfermagem do Hospital de Clínicas de Porto Alegre. Os pacientes foram submetidos à avaliação clínica, laboratorial e responderam um questionário que incluía o tipo de tratamento realizado para DM, outros medicamentos e co-morbidades, pesquisa de complicações em ano prévio e avaliação do conhecimento sobre DM. Os pacientes foram classificados em dois grupos, com bom ou mau controle glicêmico, de acordo com o valor da glico-hemoglobina de 1 ponto % acima do limite superior do método utilizado. As comparações entre variáveis contínuas, com distribuição normal, foram analisadas pelo teste t de Student para amostras não-pareadas e para as variáveis de distribuição assimétrica ou com variância heterogênea o teste U de Mann-Whitney. A comparação entre percentagem foi feita pelo teste de qui-quadrado ou exato de Fisher. Foi realizada uma análise logística múltipla para identificar os fatores mais relevantes associados ao controle metabólico (variável dependente). As variáveis independentes com um nível de significância de P < 0,1 na análise bivariada, foram incluídas no modelo. Resultados: foram avaliados 143 pacientes com DM2, idade de 59,3 ± 10,1 anos, duração conhecida do DM 7,5 ± 6,3 anos, índice de massa corporal (IMC) de 29,7 ± 5,2 kg/m².Destes, 94 pacientes (65,73%) apresentavam bom controle glicêmico. Os pacientes com mau controle glicêmico usavam mais anti-hiperglicemiantes orais como monoterapia (OR = 9,37; IC = 2,60-33,81; P=0,004) ou associados (OR = 31,08; IC = 7,42-130,15; P < 0,001). Da mesma maneira, não fizeram dieta em dias de festa (OR = 3,29; IC = 1,51-7,16; P = 0,012). A inclusão do conhecimento sobre diabetes não foi diferente entre os pacientes com bom ou mau controle glicêmico (OR = 1,08; IC = 0,97 - 1,21; P = 0,219). A análise multivariada demonstrou que a consulta com a enfermeira educadora (OR = 0,24; IC = 0,108-0,534; P = 0,003), com o endocrinologista (OR = 0,15 ; IC = 0,063-0,373; P = 0,001) e o uso de hipolipemiantes (OR = 0,10; IC = 0,016 - 0,72; P = 0,054) foram associados ao bom controle glicêmico, ajustados para a não realização de dieta em festas, uso de anti-hiperglicemiantes orais e conhecimento sobre diabetes. Conclusão: o controle metabólico em pacientes DM2 é influenciado pelas atividades de educação com enfermeira e endocrinologista. O tratamento do DM2 deve incluir atividades de educação de forma sistemática.

Effects of simvastatin in abdominal sepsis in rats

Statins are widely recognized as hypolipemic drugs, but some studies have observed anti-inflammatory and immunomodulatory effects, known as pleiotropic. The aims of this work was to study possible anti-inflammatory effects of simvastatin in abdominal sepsis. Serum pro-inflammatory cytokines and leukocytes count were determined in an experimental model of abdominal sepsis, using cecal ligation and puncture (CLP) in rats. Methods: Twenty eigth Wistar rats weighing 285±12g were randomly divided in: CLP/Sinvastatin rats (n=7), treated with 10 mg/Kg of oral simvastatin 18 and 2 hs berofe CLP; CLP/Saline group rats (n=7), treated with oral saline; group Sham/Simvastatin (n=7), treated with simvastatin, and group Sham/Saline (n=7), treated with saline. Serum TNF-α, IL-1β and IL-6 by ELISA and total leukocytes, neutrophils, lymphocytes, and eosinophils were determined 24 hs after CLP. ANOVA and Tukey test were used considering significant p<0.05. Results: It was demonstrated that serum TNF-α, IL-1β and IL-6 were respectively 364,8±42pg/mL; 46,3±18pg/mL and 28,4±13pg/mL in CLP/Sinvastatin rats, significantly lower (p<0.05) than in group CLP/Saline (778,5±86pg/ml; 176,9±46pg/ ml; 133,6±21 pg/ml, respectively). The same results were observed in total leukocytes and neutrophils counts. Conclusion: These results clearly demonstrate that simvastatin is an effective agent that reduces cytokines levels and leukocyte count in sepsis, independently of its well-known lipid-lowering effects. Thus, HMG-CoA reductase inhibitors like simvastatin have important anti-inflammatory effects in abdominal sepsis in rats

Intake of isoflavone-supplemented soy yogurt fermented with Enterococcus faecium lowers serum total cholesterol and non-HDL cholesterol of hypercholesterolemic rats

The aim of this study was to obtain an isoflavone-supplemented soy yogurt, fermented with Enterococcus faecium CRL 183 and Lactobacillus helveticus ssp jugurti, with suitable sensory properties and to assess the effects of the final product on blood lipids in hypercholesterolemic rats. Four isoflavone supplementation procedures were tested, in which the isoflavone was added at these stages: (1) before heat-treatment; (2) after heating and before fermentation; (3) after fermentation and (4) in the okara (by-product of soy milk) flour stirred into the fermented product when consumed. The products were subjected to a test of sensory acceptability. To assess their potential hypocholesterolemic properties in vivo, four groups of rats were used: control (C), hypercholesterolemic (H), hypercholesterolemic plus fermented product (HF) and hypercholesterolemic plus isoflavone-supplemented fermented product (HFI). Hypercholesterolemia was induced in rats of groups H, HF and HFI by feeding them on a commercial rat chow to which cholesterol and cholic acid had been added. Total, HDL and non-HDL cholesterol and triglycerides were measured in the blood of the rats. No significant sensorial differences were detected among the samples of soy yogurt supplemented with isoflavones at various processing stages. Rats fed a fermented soy product enriched with isoflavones (HFI group) had significantly (P < 0.05) less serum total cholesterol (15.5%) compared with rats fed a hypercholesterolemic diet (H group). Non-HDL cholesterol was less (P < 0.05) in rats fed a fermented soy product enriched or not with isoflavones (27.4 and 23.2%) compared to H group. The HDL-C and triglyceride concentrations did not differ significantly among the groups. It was possible to obtain an isoflavone-supplemented soy yogurt with satisfactory sensory characteristics. The resulting supplemented soy yogurt was capable of producing a lipid-lowering effect in hypercholesterolemic rats, relative to the animals that did not consume this product.

Pleiotropic effects of statins may improve outcomes in atherosclerotic renovascular disease

BACKGROUNDAtherosclerotic renovascular disease (ARD) coexists with arterial obstructive disease in the coronary, cerebral, and peripheral arteries that may remain underdiagnosed and untreated.METHODSThis retrospective study compares overall survival and renal survival (i.e., time to doubling of serum creatinine or end-stage renal disease (ESRD)) over an 11-year period in 104 ARD patients of whom 68 received statin therapy (group S) because of elevated lipid levels and 36 had no statin (group NS) because of normal lipid profile at entry.RESULTSAtherosclerosis in another vascular bed was documented in 84%. Lipid profiles at end point were virtually identical in both the groups Group S had mean survival 123 months (confidence interval (CI) 113-134) with four deaths, and mean renal survival 122 months (CI 113-131). Group NS had mean survival 33 months (CI 23-42) with 13 deaths, and mean renal survival 27 months (CI 17-37).CONCLUSIONSStatin therapy was associated with lesser rate of progression of renal insufficiency (with 7.4% of S patients reaching renal end points vs. 38.9% of NS patients) and lower overall mortality (5.9% in S vs. 36.1% in NS patients), P < 0.001 for both. Although both groups received what was deemed optimal therapy, they did have other differences that may have affected the outcomes (a limitation addressed by Cox multiple regression analysis). These results suggest the need for prospective randomized controlled studies in ARD patients in order to explore potential benefits of statins that may not be attributable solely to lipid lowering.

Modulation of the Pharmacological Activities of Secretory Phospholipase A2 from Crotalus durissus cascavella Induced by Naringin

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Soybean glycinin (11S) increases HDL-cholesterol in hypercholesterolemic rats

Purpose: The purpose of this paper is to determine the effects of isolated soy glycinin (11S) on lipid metabolism in animals subjected to a hypercholesterolemic diet. Design/methodology/approach: Male Wistar rats were kept in individual cages under appropriate conditions. The animals were divided into three groups (n=9): normal diet (STD) given a diet containing casein as protein source, recommended in AIN-93M; hypercholesterolemic (HC) fed a normal diet with 1 per cent cholesterol and 0.5 per cent cholic acid; and hypercholesterolemic+glycinin (HC+11S), fed a hypercholesterolemic diet, plus 11S soy protein (300 mg/kg/day), dissolved in saline and administered by gavage. After 28 days, the animals were sacrificed and blood and liver removed for biochemical analysis of total cholesterol (TC), HDL-cholesterol (HDL-C) and triglycerides (TG) in the plasma, hepatic TC and TG. Findings: A single daily dose of glycinin given to the hypercholesterolemic group demonstrated its functional role, particularly in raising HDL-C and reducing triglycerides in the liver. Originality/value: This study demonstrates the action of the 11S globulin in soybean as a serum lipid lowering agent, in addition to its nutritional properties, especially in raising the HDL-C. © Emerald Group Publishing Limited.

Avaliação da participação dos ácidos graxos nas adaptações das ilhotas pancreáticas à resistência periférica à insulina pelo tratamento com dexametasona

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Avaliação da toxicidade reprodutiva da sinvastatina em Ratos machos adultos

Pós-graduação em Biologia Geral e Aplicada - IBB

Atividade hipolidêmica e protetora da bixina no fígado de ratos tratados com dieta hipercalórica

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Influence of daily consumption of synbiotic soy-based product supplemented with okara soybean by-product on risk factors for cardiovascular diseases

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Red-fleshed sweet orange juice improves the risk factors for metabolic syndrome

Orange juice consumption can promote lower levels of oxidative stress and inflammation due to the antioxidant activity of citrus flavonoids and carotenoids. In addition, red-fleshed sweet orange juice (red orange juice) also contains lycopene. This study investigated the effects of red orange juice consumption on risk factors for metabolic syndrome. Volunteers consumed red orange juice daily for 8 weeks, with clinical and biochemical assessments performed at baseline and on the final day. There was no change in the abdominal obesity, but low-density lipoprotein cholesterol, C-reactive protein decreased, while there was an increase of the antioxidant activity in serum after red orange juice consumption. Insulin resistance and systolic blood pressure were reduced in normal-weight volunteers, while diastolic blood pressure decreased in overweight volunteers after intervention. Red orange juice showed anti-inflammatory, antioxidant, and lipid-lowering properties that may prevent the development of metabolic syndrome.

Desenvolvimento de um embutido cárneo fermentado, com teores reduzidos de gordura e sais de cura, através da utilização de culturas probióticas

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)