Exercise training accelerates the removal from plasma of LDL-like nanoemulsion in moderately hypercholesterolemic subjects

Objective: Exercise training improves plasma lipid profile and diminishes risk of coronary heart disease. Previously, we showed that training increases LDL plasma clearance, as tested by an artificial LDL-like nanoemulsion method, presumably by increasing LDL receptor activity. In this study, we investigated whether training could also improve LDL clearance in hypercholesterolemic subjects (HCh) that are exposed to increased risk of cardiovascular events. Methods: Twenty sedentary HCh and 20 normolipidemic (NL) sedentary volunteers were divided into four groups: 12 HCh submitted to 4-month training program, 8 HCh with no exercise program, 12 NL submitted to 4-month training and 8 NL with no exercise program. An LDL-like nanoemulsion labeled with 14C-cholesteryl ester was injected intravenously into all subjects and plasma samples were collected during 24h after injection to determine the fractional clearance rate (FCR, in h-1) by compartmental analysis. The study was performed on the first and on the last day of the 4-month study period. Results: In both, trained HCh and NL groups, training increased nanoemulsion FCR by 36% (0.0443 +/- 0.0126; 0.0602 +/- 0.0187, p=0.0187 and 0.0503 +/- 0.0203; 0.0686 +/- 0.0216, p=0.0827, respectively). After training, LDL cholesterol diminished in both HCh and NL groups. In HCh, but not in NL group, LDL susceptibility to oxidation decreased, but oxidized LDL was unchanged. In both non-trained groups FCR was the same for the last and the 4-month previous evaluation. Conclusion: In HCh, exercise training increased the removal of LDL as tested by the nanoemulsion, and this probably accounted for decreased LDL cholesterol and diminished LDL susceptibility to oxidation. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Effects of Green Tea Use on Wound Healing

Green tea, a product from Camellia sinensis, consists of over 200 componentes. The most known are the catechins, ou polyphenolic compounds, or flavonoids, but it contains also polysacharide conjugates, amino acids, caffeine and vitamins. Studies have suggested that the regular consumption of green tea reduces the risk of cancer, protecting agains initial events and progression of the disease, may act as antioxidant, has bactericidal properties, and that green tea consumption may be an adjuvant in the treatment of diabetes mellitus, hypertension and hypercholesterolemia. Our experimental study was carried out with male Wistar rats, separated in two groups, experimental and control. The animals in control group were given water ad libitum, and the animals in the experimental group received green tea instead of water. After 2 weeks of experimental period, all the animals, suffered surgical wounds on the dorsum. The animals were sacrificed on I, 3 and 7 days after surgery. Skin samples were used for light microscopy evaluation. Our results allowed us to observe that the experimental group (green tea drinking) presented accelerated epithelial neformation on day 3 after surgery, when epithelial neoformation is in the initial phases. The surgical areas presented 48.20% X 27.32% epithelial neoformation for green tea group and their controls respectivelly at this time. The results of the present study, along with other information about green tea in the literature, strongly suggests that regular use of green tea may be beneficial in surgery situations, when fast epithelial neoformation is desirable.

NMR structure and backbone dynamics of a concatemer of epidermal growth factor homology modules of the human low-density lipoprotein receptor

The ligand-binding region of the low-density lipoprotein (LDL) receptor is formed by seven N-terminal, imperfect, cysteine-rich (LB) modules. This segment is followed by an epidermal growth factor precursor homology domain with two N-terminal, tandem, EGF-like modules that are thought to participate in LDL binding and recycling of the endocytosed receptor to the cell surface. EGF-A and the concatemer, EGF-AB, of these modules were expressed in Escherichia coli. Correct protein folding of EGF-A and the concatemer EGF-AB was achieved in the presence or absence of calcium ions, in contrast to the LB modules, which require them for correct folding. Homonuclear and heteronuclear H-1-N-15 NMR spectroscopy at 17.6 T was used to determine the three-dimensional structure of the concatemer. Both modules are formed by two pairs of short, anti-parallel beta -strands. In the concatemer, these modules have a fixed relative orientation, stabilized by calcium ion-binding and hydrophobic interactions at the interface. N-15 longitudinal and transverse relaxation rates, and {H-1}-N-15 heteronuclear NOEs were used to derive a model-free description of the backbone dynamics of the molecule. The concatemer appears relatively rigid, particularly near the calcium ion-binding site at the module interface, with an average generalized order parameter of 0.85 +/- 0.11. Some mutations causing familial hypercholesterolemia may now be rationalized. Mutations of D41, D43 and E44 in the EGF-B calcium ion-binding region may affect the stability of the linker and thus the orientation of the tandem modules. The diminutive core also provides little structural stabilization, necessitating the presence of disulfide bonds. The structure and dynamics of EGF-AB contrast with the N-terminal LB modules, which require calcium ions both for folding to form the correct disulfide connectivities and for maintenance of the folded structure, and are connected by highly mobile linking peptides. (C) 2001 Academic Press.

Repeated three-dimensional magnetic resonance imaging of atherosclerosis development in innominate arteries of low-density lipoprotein receptor-knockout mice

Background-In vivo methods to evaluate the size and composition of atherosclerotic lesions in animal models of atherosclerosis would assist in the testing of antiatherosclerotic drugs. We have developed an MRI method of detecting atherosclerotic plaque in the major vessels at the base of the heart in low-density lipoprotein (LDL) receptor-knockout (LDLR-/-) mice on a high-fat diet. Methods and Results-Three-dimensional fast spin-echo magnetic resonance images were acquired at 7 T by use of cardiac and respiratory triggering, with approximate to140-mum isotropic resolution, over 30 minutes. Comparison of normal and fat-suppressed images from female LDLR-/- mice I week before and 8 and 12 weeks after the transfer to a high-fat diet allowed visualization and quantification of plaque development in the innominate artery in vivo. Plaque mean cross-sectional area was significantly greater at week 12 in the LDLR-/- mice (0.14+/-0.086 mm(2) [mean+/-SD]) than in wild-type control mice on a normal diet (0.017+/-0.031 mm(2), p

Effects of combined low-density lipoprotein apheresis and aggressive statin therapy on coronary calcified plaque as measured by computed tomography

Eight patients with heterozygous familial hypercholesterolemia who received combined long-term low-density lipoprotein apheresis and high-dose statin therapy showed a significant decrease in volume of coronary calcium over a period of 29 months as measured by, computed tomography. This suggests that the effects of aggressive lipid-lowering therapy can be assessed non-invasively and may be used as surrogate end points when testing new therapies.

Independent contribution of plaque complexity to myocardial ischemia during Dobutamine stress echocardiography

The influence of complex plaque morphology on the extent of demand-induced ischemia in unselected patients is not well defined. We sought to investigate the functional significance of lesion morphology in patients who underwent coronary angiography and dobutamine stress echocardiography (DSE).,Angiography and DSE were performed within a 6-month period (mean 1 +/- 1 month) in 196 patients. Angiographic assessments involved quantification of stenosis severity, assessment of the extent of jeopardized myocardium, and categorization of plaque morphology according to the Ambrose classification. DSE was interpreted by separate investigators with respect to wall motion score index (WMSI) and number of coronary territories involved. A general linear model was constructed to assess,the independent contribution of patient characteristics and angiographic and DSE results with respect to extent of ischemic myocardium. Complex lesion morphology was seen in 62 patients (32%). Patients with complex lesions were more likely to have had prior myocardial infarction (p < 0.001) and be current smokers (p = 0.03). During angiography, they exhibited a trend toward a greater number of diseased vessels, had a greater coronary jeopardy score (p < 0.001) and more frequent collateral flow (p = 0.03). During echocardiography, patients had a higher stress WMSI (p < 0.001) and were more likely to show ischemia in all 3 arterial territories (p < 0.01). On multivariate regression, the coronary artery jeopardy score and the presence of complex plaque morphology were independent predictors of the extent of ischemic myocardium (R 2 = 34%, p < 0.001). Thus, patients with complex plaque morphology are older, more likely to smoke, and more likely to have had prior myocardial. infarction. They exhibit more extensive disease with higher coronary jeopardy scores and a higher resting and peak stress WMSI. Despite these differences, complex plaque morphology remains an independent predictor of the extent of ischemia during stress. (C) 2003 by Excerpta Medica, Inc.

Estado nutricional e estilo de vida em vegetarianos e onívoros, Grande Vitória-ES

Objetivo: Descrever e analisar o estado nutricional e aspectos do estilo de vida de vegetarianos e onívoros residentes na Grande Vitória/ES, na faixa etária de 35 a 64 anos de idade. Material E Métodos: Trata-se de estudo observacional híbrido de casos prevalentes com avaliação retrospectiva da exposição. Os grupos de expostos (134) e não expostos à dieta onívora típica ocidental (67) foram determinados no início da investigação. Foram coletados dados antropométricos, bioquímicos, de atividade física e alimentação através de questionário e 3 recordatórios de 24 horas e diagnosticados sobrepeso, Razão Cintura Quadril (RCQ) inadequada e hipercolesterolemia. Colesterol total e frações, triglicerídeos, ácido úrico, sódio e potássio urinários foram comparados entre os grupos, através do teste t de Student. Foi usado o teste qui-quadrado para comparar proporções, com =0,05. Resultados: Foram encontradas diferenças significativas em relação à ocupação. Duração da atividade física e tempo assistindo televisão e/ou utilizando computador foram maiores entre os onívoros. Os vegetarianos relataram práticas alimentares mais saudáveis e menor consumo de lipídios, proteínas e sódio. Os onívoros apresentaram maior risco de sobrepeso, RCQ inadequada e hipercolesterolemia (valores de P<0,0001). HDL-colesterol não foi diferente nos grupos. Conclusão: Os vegetarianos apresentaram perfil nutricional mais adequado e menor risco para os agravos crônicos estudados, apesar de pequena diferença no padrão de atividade física regular entre os grupos estudados.

Smoking, consumption of alcohol and sedentary life style in population grouping and their relationships with lipemic disorders

The study, part of the project "Atherosclerotic cardiovascular diseases, lipemic disorders, hypertension, obesity and diabetis mellitus in a population of the metropolitan area of the southeastern region of Brazil", had the following objectives: a) the characterization and distribution among typical human socio-economic groupings, of the prevalence of some particular habits which constitute aspects of life-style-the use of tobacco, the use of alcohol and sedentary activity; b) the establishment of the interrelation between the above-mentioned habits and some lipemic disorders. The prevalence of the habits cited behaved in the following manner: the use of tobacco predominated among men, distributed uniformly throughout the social strata; among the women the average percentage of smokers was 18,9%, a significant difference occurring among the highest socio-economic class, where the average was of 40.2%. The sedentary style of life presented high prevalence, among both men and women with exception of the women of the highest socio-economic level and of the skilled working class. The use of alcohol, as one would expect, is a habit basically practised by the men, without any statistically significant differences between classes. For the purpose of establishing associations between these risk fictors and lipemic conditions four situations were chosen, of the following characteristics: 1- total cholesterol > or = 220 mg/dl and triglycerides > or = 150 mg/dl; 2- HDL cholesterol <35 mg/dl for men and <45 mg/dl for women and triglycerides levels > or = 150 mg/dl; 3- HDL cholesterol <35 mg/dl for men and <45 mg/dl for women and triglycerides levels <150 mg/dl; 4- total cholesterol 220 mg/dl with triglycerides levels <150 mg/dl. Six models of multiple (backward) regression were established, with seven independent variables- age, sex, use of tobacco, consumption of alcohol, light physical activity, hypertension and obesity. Significant associations (P<0,05) were revealed with hypercholesterolemia, accompanied by triglyceride levels > or = 150 mg/dl, and the following independent variables: age, use of tobacco and the interactions between obesity and smoking, age and sedentary lifestyle, sex and obesity (R2=22%); the standardized B coefficient showed that the variables with the greatest weight in the forecasting of the variation in the levels of cholesterol were smoking and the interaction between obesity and smoking. The hypercholesterolemia accompanied by triglycerides levels <150 mg/dl showed a positive association between total cholesterol and sex and the interactions obesity/smoking and sex/obesity. As regards HDL cholesterol accompanied by triglyceride/ levels > or = 150 mg/dl was inversely associated with obesity and the interaction smoking/ age and directly with age (R=31%). The standardized B coeffients, indicated that the variables obesity and the interactions smoking/age possessed a weight three times greater than age alone in accounting for the variation in the serum levels of HDL cholesterol. When accompanied by triglycerides <150 mg/dl there was no association between and the independent variables and the set of them presented R equal to 22%. The sum of top, in the population stutied in this project, the component habits of life-style (smoking, alcohol consumption and sedentary activity) which constitute risk factors which determine morbidity from atherosclerotic cardiovascular diseases are be found distributed through all the typical social groupings of this particular form of social organization. On the other hand, the seven independent variables used in the multiple regression models for the explanation of the lipemic conditions considered presented multiple determination coefficients which varied, approximately, between 20% and 30%. Thus it is important that in the genetic epidemiology the study of the morbidities in question be emphasized.

Metabolic changes associated with antiretroviral therapy in HIV-positive patients

OBJECTIVE: To evaluate metabolic changes associated with highly active antiretroviral therapy (HAART) in HIV-positive patients, and to identify risk factors associated. METHODS: Retrospective study that included 110 HIV-positive patients who where on HAART in the city of Porto Alegre (Southern Brazil) between January 2003 and March 2004. Data on demographic variables, cigarette smoking, diabetes mellitus, cholesterol and triglyceride levels, stage of HIV infection, antiretroviral therapy and HCV coinfection were collected. General linear models procedure for repeated measures was used to test the interaction between HAART and HCV coinfection or protease inhibitor treatment. RESULTS: Total cholesterol, triglycerides, and glucose levels significantly increased after receiving HAART (p<0.001 for all variables), but no interaction with protease inhibitors was seen for total cholesterol, glucose and triglyceride levels (interaction treatment*protease inhibitors p=0.741, p=0.784, and p=0.081, respectively). An association between total cholesterol levels and HCV coinfection was found both at baseline and follow-up (effect of HCV coinfection, p=0.011). Glucose levels were increased by HAART (treatment effect, p=0.036), but the effect was associated to HCV coinfection (treatment*HCV effect, p=0.018). Gender, smoking habit, intravenous drug use and age were not significantly associated with cholesterol, triglyceride and glucose changes. CONCLUSIONS: HCV-infected patients at baseline were significantly less likely to develop hypercholesterolemia. The results provide further evidence of the role of HAART for the development of metabolic disturbances.

Avaliação do risco cardiovascular numa população da zona Norte do País

As doenças cardiovasculares lideram as causas de mortalidade no mundo e em Portugal. Alguns dos fatores de risco (FR) associados são sexo masculino, idade avançada, hipertensão arterial, hipercolesteremia, tabagismo, obesidade e sedentarismo, cuja sinergia amplifica o risco cardiovascular. Realizou-se um rastreio em indivíduos da região norte de Portugal, com o objetivo de determinar, pela tabela derivada do projeto SCORE, o Risco Cardiovascular Absoluto e o Risco Cardiovascular Relativo e Risco Cardiovascular Absoluto Projetado aos 60 anos. Verificou-se a presença de vários FR na amostra em estudo. A avaliação do risco permite estimar a interação de FR individuais, fundamentando a definição de estratégias interventivas, com potenciais ganhos em saúde.

ERICA: prevalence of dyslipidemia in Brazilian adolescents

ABSTRACT OBJECTIVE To determine the distribution of total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides in Brazilian adolescents, as well as the prevalence of altered levels of such parameters. METHODS Data from the Study of Cardiovascular Risks in Adolescents (ERICA) were used. This is a country-wide, school-based cross-sectional study that evaluated 12 to 17-year old adolescents living in cities with over 100,000 inhabitants. The average and distribution of plasma levels of total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides were evaluated. Dyslipidemia was determined by levels of total cholesterol ≥ 170 mg/dl, LDL cholesterol ≥ 130 mg/dl, HDL cholesterol < 45 mg/dL, or triglycerides ≥ 130 mg/dl. The data were analyzed by gender, age, and regions in Brazil. RESULTS We evaluated 38,069 adolescents – 59.9% of females, and 54.2% between 15 and 17 years. The average values found were: total cholesterol = 148.1 mg/dl (95%CI 147.1-149.1), HDL cholesterol = 47.3 mg/dl (95%CI 46.7-47.9), LDL cholesterol = 85.3 mg/dl (95%CI 84.5-86.1), and triglycerides = 77.8 mg/dl (95%CI 76.5-79.2). The female adolescents had higher average levels of total cholesterol, LDL cholesterol, and HDL cholesterol, without differences in the levels of triglycerides. We did not observe any significant differences between the average values among 12 to 14 and 15- to 17-year old adolescents. The most prevalent lipid alterations were low HDL cholesterol (46.8% [95%CI 44.8-48.9]), hypercholesterolemia (20.1% [95%CI 19.0-21.3]), and hypertriglyceridemia (7.8% [95%CI 7.1-8.6]). High LDL cholesterol was found in 3.5% (95%CI 3.2-4.0) of the adolescents. Prevalence of low HDL cholesterol was higher in Brazil’s North and Northeast regions. CONCLUSIONS A significant proportion of Brazilian adolescents has alterations in their plasma lipids. The high prevalence of low HDL cholesterol and hypertriglyceridemia, especially in Brazil’s North and Northeast regions, must be analyzed in future studies, to support the creation of strategies for efficient interventions.

ELEVATED ALANINE AMINOTRANSFERASE (ALT) IN BLOOD DONORS: AN ASSESSMENT OF THE MAIN ASSOCIATED CONDITIONS AND ITS RELATIONSHIP TO THE DEVELOPMENT OF HEPATITIS C

The determination of aminotranferases levels is very useful in the diagnosis of hepatopathies. In recent years, an elevated serum ALT level in blood donors has been associated with an increased risk of post-transfusion hepatitis (PTH). The purpose of the study was to research the factors associated with elevated ALT levels in a cohort of voluntary blood donors and to evaluate the relationship between increased ALT levels and the development of hepatitis C (HCV) infection. 166 volunteer blood donors with elevated ALT at the time of their first donation were studied. All of the donors were questioned about previous hepatopathies, exposure to hepatitis, exposure to chemicals, use of medication or drugs, sexual behaviour, contact with blood or secretions and their intake of alcohol. Every three months, the serum levels of AST, ALT, alkaline phosphatase, gamma glutamyl transpeptidase, cholesterol, triglyceride and glycemia are assessed over a two year follow-up. The serum thyroid hormone levels as well as the presence of auto-antibodies were also measured. Abdominal ultrasound was performed in all patients with persistently elevated ALT or AST levels. A needle biopsy of liver was performed in 9 donors without definite diagnostic after medical investigation. The presence of anti-HCV antibodies in 116 donors were assayed again the first clinical evaluation. At the end of follow-up period (2 years later) 71 donors were tested again for the presence of anti-HCV antibodies. None of donors resulted positive for hepatitis B or hepatitis C markers during the follow-up. Of the 116 donors, 101 (87%) had persistently elevated ALT serum levels during the follow-up. Obesity and alcoholism were the principal conditions related to elevated ALT serum levels in 91/101 (90.1%) donors. Hypertriglyceridemia, hypercholesterolemia, hypothyroidism and diabetes mellitus also were associated with increased ALT levels. Only 1/101 (0.9%) had mild chronic active non A-G viral hepatitis and 3/101 (2.9%) had liver biopsy with non-specific reactive hepatitis. The determination of ALT levels was not useful to detect donors infected with HCV at donation in Brazil, including the initial seronegative anti-HCV phase.

Estudo Comparativo, Aleatorizado, em Dupla Ocultação, de Orlistat Versus Placebo, de Eficácia e Segurança, em Doentes Obesos com Hipercolesterolemia Ligeira a Moderada

INTRODUCTION: Obesity is a chronic disease and a serious health problem that leads to increased prevalence of diabetes, hypertension, dyslipidemia and gallbladder disease. OBJECTIVE: To evaluate the efficacy of orlistat for weight loss and improved lipid profile compared to placebo in obese patients with hypercholesterolemia, treated over a period of 6 months. METHODOLOGY: In a 6-month, multicenter (10 centers in Portugal), double-blind, parallel, placebo-controlled study, 166 patients, aged 18-65 years, body mass index (BMI) > or = 27 kg/m2, LDL cholesterol > 155 mg/dl, were randomized to a reduced calorie diet (600 kcal/day deficit) plus orlistat three times a day or placebo. Exclusion criteria included triglycerides > 400 mg/dl, severe cardiovascular disease, uncontrolled hypertension, type 1 or 2 diabetes under pharmacological treatment, and gastrointestinal or pancreatic disease. RESULTS: The mean difference in weight from baseline was 5.9% (5.6 kg) in the orlistat group vs. 2.3% (2.2 kg) in the placebo group. In the orlistat group 49% of patients achieved 5-10% weight loss and 8.8% achieved > 10%. The orlistat group showed a significant reduction in total and LDL cholesterol, with similar changes for HDL in both treatment groups. The frequency of gastrointestinal adverse events was slightly higher in the orlistat group than in the placebo group, leading to discontinuation in 7 patients. CONCLUSION: Treatment with orlistat plus a reduced calorie diet for 6 months achieved significant reductions in weight, BMI and lipid parameters.

Neuropsychiatric Features of a Cohort of Patients with Systemic Lupus Erythematosus

In order to establish if neuropsychiatric systemic lupus erythematosus (NPSLE) can be identified by any characteristic other than those used to diagnose the neuropsychiatric (NP) disease itself, we retrospectively reviewed 98 systemic lupus erythematosus (SLE) patients followed over a mean period of 10 years. NPSLE was identified in 22 patients. Stroke and generalized seizures were the most frequent NP manifestations. The NPSLE and non-NPSLE groups were similar with regard to demographic characteristics, ACR criteria, serum autoantibodies, and frequency of hypertension and hypercholesterolemia. Of note, compared to the non-NPSLE group, NPSLE was associated with a higher frequency of smoking (78 versus 26%), organ damage (73 versus 34%), and cumulative mortality rate (14 versus 7%). The series of patients was further analysed according to the presence of antiphospholipid syndrome (APS). Significantly, the interval between the onset of NP disease and SLE diagnosis was shorter in the APS(-) (0.3 ± 1 years) than in the APS(+) (5 ± 7 years) groups. Recurrence and/or persistence of NP events were only documented in the APS(-) group. Overall cumulative mortality was highest in NPSLE and in APS(+) patients with inadequate anticoagulation control, identifying an aspect that requires improved vigilance and the development of novel therapeutic modalities.

Hand, Foot, and Mouth Syndrome in an Immunocompetent Adult: a Case Report

BACKGROUND: Hand, foot, and mouth syndrome (HFMS) is a common acute illness. It is characterized by mild clinical symptoms including fever, blisters, and sores in the mouth and on the palms and soles following a 3- to 7-day incubation period. This syndrome is rarely seen in adults. CASE PRESENTATION: A 35-year-old male Caucasian patient had a history of multiple episodes of acute pharyngitis, hypertension, hypercholesterolemia, and occasional abdominal pain. He presented with polyarthralgia in the knees and hands and odynophagia, followed by fever, oral mucosal aphthous lesions, and vesicles on the palms and soles. Three weeks after presentation, he was admitted to the emergency room with acute myocarditis. The in-hospital evaluation revealed positive serology for coxsackie A9 (1:160), positive anti-transglutaminase and anti-gliadin antibodies, normal immunoglobulins, and human immunodeficiency virus negativity. CONCLUSION: We herein describe a case of HFMS that was associated with coxsackie A9 infection complicated by acute myocarditis. Although an association between celiac disease and HFMS has not been described, this patient's immunologic disruption could have favored the development of infection and ultimately HFMS.