Eficácia e segurança da atorvastatina no tratamento de pacientes com hipercolesterolemia primária

Introduction: Hypercholesterolemia is an important risk factor for cardiovascular disease, the first cause of death and third reason for hospital admissions in Brazil. The reduction of serum cholesterol levels reduces morbidity and mortality from cardiovascular disease. The present study evaluated the efficacy and safety of atorvastatin in the treatment of Brazilian patients with primary hypercholesterolemia (types IIA and IIB dyslipidemias). Patients and methods: After a 4-week wash-out period, 152 patients were treated with atorvastatin at the initial dose of 10 mg/day. According to treatment efficacy within the first 8 weeks this dose could be increased to 20 mg/day. Treatment lasted for a total of 16 weeks, and its efficacy was evaluated by the reduction of serum levels of LDL-cholesterol, total cholesterol, HDL-cholesterol, and triglycerides, as well as by the propotion of patients that achieved the target levels recommended by the National Cholesterol Education Program - Adult Treatment Panel II (NCEP ATP II) Results: The analysis of efficacy was conducted in 145 patients. Atorvastatin led to significant reductions in the levels of LDL-cholesterol after 8 and 16 weeks of treatment (P<0.001 for both comparisons). The relative reduction of such levels was 38% (P<0.001 after 8 and 16 weeks). Atorvastatin also led to significant reductions of total cholesterol and triglycerides. At the end of the study, 81% of patients achieved the target LDL-cholesterol levels recommended by NCEP ATP II. Treatment was well tolerated, and was interrupted due to creatine phosphokinase elevation in only one patient. Conclusion: Atorvastatina is efficacious and safe in the treatment of patients with primary hypercholesteromia. © Copyright Moreira Jr. Editora. Todos os direitos reservados.

High cholesterol intake modifies chylomicron metabolism in normolipidemic young men

Whether the consumption of egg yolk, which has a very high cholesterol content without excess saturated fats, has deleterious effects on lipid metabolism is controversial. Absorbed dietary cholesterol enters the bloodstream as chylomicrons, but the effects of regular consumption of large amounts of cholesterol on the metabolism of this lipoprotein have not been explored even though the accumulation of chylomicron remnants is associated with coronary artery disease (CAD). We investigated the effects of high dietary cholesterol on chylomicron metabolism in normolipidemic, healthy young men. The plasma kinetics of a chylomicron-like emulsion, doubly-labeled with 14C-cholesteryl ester ( 14C-CE) and 3H-triolein ( 3H-TG) were assessed in 25 men (17-22 y old, BMI 24.1 ± 3.4 kg/m 2). One group (n = 13) consumed 174 ± 41 mg cholesterol/d and no egg yolk. The other group (n = 12) consumed 3 whole eggs/d for a total cholesterol intake of 804 ± 40 mg/d. The nutritional composition of diets was the same for both groups, including total lipids and saturated fat, which comprised 25 and 7%, respectively, of energy intake. Serum LDL and HDL cholesterol and apoprotein B concentrations were higher in the group consuming the high-cholesterol diet (P < 0.05), but serum triacylglycerol, apo AI, and lipoprotein (a) did not differ between the 2 groups. The fractional clearance rate (FCR) of the 14C-CE emulsion, obtained by compartmental analysis, was 52% slower in the high-cholesterol than in the low-cholesterol group (P < 0.001); the 3H-TG FCR did not differ between the groups. Finally, we concluded that high cholesterol intakes increase the residence time of chylomicron remnants, as indicated by the 14C-CE kinetics, which may have undesirable effects related to the development of CAD. © 2006 American Society for Nutrition.

Estudo multicêntrico Brasileiro - Adesivo contraceptivo transdérmico semanal: Preferência e satisfação das usuárias

Background: To assess satisfaction with the weekly transdermal contraceptive patch, compared to the previous contraceptive method. Adhesion, cycle control, safety and efficacy were secondary outcomes. Methods: A multicenter, open label, descriptive study. Subjects received the weekly transdermal contraceptive patch for 6 cycles. At the baseline and after the 1 st, 3 rd and 6 th cycles, satisfaction with the method was assessed. The contraceptive efficacy was assessed by the Pearl Index and by life table analysis. Results: An ITT analysis was performed with 494 subjects. At the endpoint, 95.3% of women were satisfied with the patch compared to the previous method; 59.5%, 58.0% and 63.2% of women reported improvement in the physical and emotional well-being, and pre-menstrual symptoms, respectively. Pre-menstrual symptoms frequency decreased from 85.0% (CI 95%: 80.8-87.4%) to 55.0% (CI 95%: 49.9-66.0%). There was a significant increase in hemoglobin levels, and also a significant decrease in total serum cholesterol and tryglicerides.. There were no significant adverse events. The adjusted Pearl Index was 1.1 pregnancies per 100 women-years. Conclusions: The weekly contraceptive transdermal patch is a safe and effective method, and there was a high rate of satisfaction with its use among brazilian women. The patch was associated to a good cycle control, with easiness of use, improvement in the physical and emotional well-being and improvement in the premenstrual symptoms and lipid profile. © Copyright Moreira Jr. Editora. Todos os direitos reservados.

Bezafibrate for the treatment of hypertriglyceridemia in HIV1-infected patients on highly active antiretroviral therapy

The use of highly active antiretroviral therapy (HAART) in HIV-infected patients has been associated with the development of risk factors for cardiovascular diseases (CD) including dyslipidemia and insulin resistance, hypertriglyceridemia being the most frequent metabolic disturbance in these patients. Fibrates are indicated when hypertriglyceridemia is accentuated and persists for over six months. We evaluated the efficacy and safety of bezafibrate for the treatment of hypertriglyceridemia in HIV-infected individuals on HAART. All patients received 400mg/day of bezafibrate and were evaluated three times: Mo (pre-treatment), M1 (one month after treatment), and M2 (six months after treatment). Fifteen adult individuals, eight males and seven females with mean age = 41.2 ± 7.97 years and triglyceride serum levels ≥400mg/dL were included in the study. Smoking, alcohol ingestion and sedentarism rates were 50%, 6.66% and 60%, respectively. Family history of CD, hypertension and diabetes mellitus was reported in 33.3%, 40% and 46.7% of the cases, respectively, while dyslipidemia was reported by only 13.3%. More than half of the patients were using a protease inhibitor plus a nucleotide analog transcriptase inhibitor. Eutrophy and tendency toward overweight were observed at all three study time points. There were significant reductions in triglyceride serum levels from Mo to M1 and from Mo to M2. No significant changes were observed in the serum levels of creatine phosphokinase, hepatic enzymes, CD4 +, CD8 + and viral load. Therefore, bezafibrate seems to be safe and effective for the reduction of hypertriglyceridemia in HIV-infected patients on HAART. © 2006 by The Brazilian Journal of Infectious Diseases and Contexto Publishing. All rights reserved.

Efeito do extrato aquoso de Allium sativum L. sobre parâmetros bioquímicos de ratas com diabete induzido por Streptozotocin

Many plants, even without scientific confirmation, are used in Brazil as hypoglycemic. The objective of the present work was to study the influence of the Allium sativum treatment, plant known popularly as garlic, on characteristic biochemical parameters in streptozotocin-induced diabetic rats. Female Wistar rats were injected with 40 mg kg-1 streptozotocin (STZ). Oral administration of an aqueous extract of A. sativum was given to the diabetic animals in 2 doses: 200 and 400 mg kg-1 (n=6 animals/group). Diabetic rats given distilled water constituted the control group. After 28 days of treatment, the female rats were anesthetized and died by decapitation for collection of the blood for biochemical determinations and retreat of liver samples for hepatic glycogen dosage. The treatment with Allium sativum in the doses of 200 and 400 mg kg-1 alter no concentrations of total proteins, hepatic glycogen, triglycerides and VLDL, but it promoted reduction in the total cholesterol rate (control=280.5 ± 30.9; 200 mg kg-1 A. sativum =169.9 ± 19.5 and 400 mg kg-1 A. sativum =148.4 ± 26.6 mg dL-1) and LDL (control=128.8± 25.3; 200 mg kg-1 A. sativum = 41.4 ± 16.2 and 400 mg kg-1 A. sativum=42.0 ± 26.0 mg dL-1). The extract presented beneficial effect because it decreased 13.0% of glycemia in the highest dose. Therefore, the of garlic extract reduced the HDL concentration in two tested doses (control= 81.4 ± 30.2; 200 mg kg-1 A. sativum=49.6 ± 14.3 and 400 mg kg-1 A. sativum=41.7 ± 16.1 mg dL -1), presenting impaired effect. Thus, the garlic extract showed efficiency in the analyzed experimental conditions, and it could be used as complementary therapy to diabetic patients.

Risk factors for vascular dementia in elderly psychiatric outpatients with preserved cognitive functions

The aim of the study was to assess risk factors for vascular dementia (VaD) in elderly psychiatric outpatients without dementia, and to determine to what extent clinical interventions targeted such risk factors. Out of 250 clinical charts, 78 were selected of patients over 60 years old, who showed no signs of dementia. Information was obtained regarding demographics, clinical conditions (diagnosis according to ICD-10), complementary investigation, cognitive functions (via CAMCOG), neuroimaging, and the presence of risk factors for VaD. Depression was the most prevalent psychiatric disorder (74%). A great majority of the patients (86%) had at least one risk factor for VaD. One-third of the sample showed three or more risk factors for VaD. The clinical conditions related to risk factors for VaD were hypertension (48.7%), heart disease (30.8%), hypercholesterolemia (25.6%), diabetes mellitus (23.1%), stroke (12.8%), tryglyceride (12.8%), and obesity (5.1%). In terms of lifestyle, smoking (19.2%), alcohol abuse (16.7%), and sedentarism (14.1%) were other risk factors found. Definite risk factors for VaD were found in 83.3% of the patients. Previous interventions targeting risk factors were found in only 20% of the cases. The high rates of risk factors for VaD identified in this sample suggest that psychiatrists should be more attentive to these factors for the prevention of VaD. © 2007 Elsevier B.V. All rights reserved.

Production and partial characterization of keratinase produced by a microorganism isolated from poultry processing plant wastewater

A Streptomyces was isolated from poultry plant wastewater, showed high keratinolytic activity when cultured on feather meal medium. Optimum keratinolytic activity was observed at 40°C and pH 8.0. The enzyme also showed to be stable between 40 and 60°C. The keratinolytic activity was not inhibited by EDTA, DMSO and Tween 80. On the other hand, CaCl2, ZnCl2, and BaCl2 slightly inhibited the keratinolytic activity. The Streptomyces isolated might be useful in leather, keratin waste treatment, animal feeding industry, and also cosmetic industry. © 2008 Academic Journals.

Exercise training improves relaxation response and SOD-1 expression in aortic and mesenteric rings from high caloric diet-fed rats

Background. Obesity has been associated with a variety of disease such as type II diabetes mellitus, arterial hypertension and atherosclerosis. Evidences have shown that exercise training promotes beneficial effects on these disorders, but the underlying mechanisms are not fully understood. The aim of this study was to investigate whether physical preconditioning prevents the deleterious effect of high caloric diet in vascular reactivity of rat aortic and mesenteric rings. Methods. Male Wistar rats were divided into sedentary (SD); trained (TR); sedentary diet (SDD) and trained diet (TRD) groups. Run training (RT) was performed in sessions of 60 min, 5 days/week for 12 weeks (70-80% VO2max). Triglycerides, glucose, insulin and nitrite/nitrate concentrations (NOx -) were measured. Concentration- response curves to acetylcholine (ACh) and sodium nitroprusside (SNP) were obtained. Expression of Cu/Zn superoxide dismutase (SOD-1) was assessed by Western blotting. Results. High caloric diet increased triglycerides concentration (SDD: 216 ± 25 mg/dl) and exercise training restored to the baseline value (TRD: 89 ± 9 mg/dl). Physical preconditioning significantly reduced insulin levels in both groups (TR: 0.54 ± 0.1 and TRD: 1.24 ± 0.3 ng/ml) as compared to sedentary animals (SD: 0.87 ± 0.1 and SDD: 2.57 ± 0.3 ng/ml). On the other hand, glucose concentration was slightly increased by high caloric diet, and RT did not modify this parameter (SD: 126 ± 6; TR: 140 ± 8; SDD: 156 ± 8 and TRD 153 ± 9 mg/dl). Neither high caloric diet nor RT modified NO x - levels (SD: 27 ± 4; TR: 28 ± 6; SDD: 27 ± 3 and TRD: 30 ± 2 μM). Functional assays showed that high caloric diet impaired the relaxing response to ACh in mesenteric (about 13%), but not in aortic rings. RT improved the relaxing responses to ACh either in aortic (28%, for TR and 16%, to TRD groups) or mesenteric rings (10%, for TR and 17%, to TRD groups) that was accompanied by up-regulation of SOD-1 expression and reduction in triglycerides levels. Conclusion. The improvement in endothelial function by physical preconditioning in mesenteric and aortic arteries from high caloric fed-rats was directly related to an increase in NO bioavailability to the smooth muscle mostly due to SOD-1 up regulation. © 2008 de Moraes et al; licensee BioMed Central Ltd.

Effect of 6-months of physical exercise on the nitrate/nitrite levels in hypertensive postmenopausal women

Background: Evidences have showed that the incidence of arterial hypertension is greater in postmenopausal women as compared to premenopausal. Physical inactivity has been implicated as a major contributor to weight gain and abdominal obesity in postmenopausal women and the incidence of cardiovascular disease increases dramatically after menopause. Additionally, more women than men die each year of coronary heart disease and are twice as likely as men to die within the first year after a heart attack. A healthy lifestyle has been strongly associated with the regular physical activity and evidences have shown that physically active subjects have more longevity with reduction of morbidity and mortality. Nitric oxide (NO) produced by endothelial cells has been implicated in this beneficial effect with improvement of vascular relaxing and reduction in blood pressure in both laboratory animals and human. Although the effect of exercise training in the human cardiovascular system has been largely studied, the majority of these studies were predominantly conducted in men or young volunteers. Therefore, the aim of this work was to investigate the effects of 6 months of dynamic exercise training (ET) on blood pressure and plasma nitrate/nitrite concentration (NOx-) in hypertensive postmenopausal women. Methods: Eleven volunteers were submitted to the ET consisting in 3 days a week, each session of 60 minutes during 6 months at moderate intensity (50% of heart rate reserve). Anthropometric parameters, blood pressure, NOx- concentration were measured at initial time and after ET. Results: A significant reduction in both systolic and diastolic blood pressure values was seen after ET which was accompanied by markedly increase of NOx- levels (basal: 10 ± 0.9; ET: 16 ± 2 μM). Total cholesterol was significantly reduced (basal: 220 ± 38 and ET: 178 ± 22 mg/dl), whereas triglycerides levels were not modified after ET (basal: 141 ± 89 and ET: 147 ± 8 mg/dl). Conclusion: Our study shows that changing in lifestyle promotes reducftion of arterial pressure which was accompanied by increase in nitrite/nitrate concentration. Therefore, 6-months of exercise training are an important approach in management arterial hypertension and play a protective effect in postmenopausal women. © 2009 Zaros et al; licensee BioMed Central Ltd.

Metabolic syndrome signs in Wistar rats submitted to different high-fructose ingestion protocols

In search of an adequate model for the human metabolic syndrome, the metabolic characteristics of Wistar rats were analysed after being submitted to different protocols of high fructose ingestion. First, two adult rat groups (aged 90 d) were studied: a control group (C1; n 6) received regular rodent chow (Labina, Purina) and a fructose group (F1; n 6) was fed on regular rodent chow. Fructose was administered as a 10 % solution in drinking water. Second, two adult rat groups (aged 90 d) were evaluated: a control group (C2; n 6) was fed on a balanced diet (AIN-93G) and a fructose group (F2; n 6) was fed on a purified 60 % fructose diet. Finally, two young rat groups (aged 28 d) were analysed: a control group (C3; n 6) was fed on the AIN-93G diet and a fructose group (F3; n 6) was fed on a 60 % fructose diet. After 4-8 weeks, the animals were evaluated. Glucose tolerance, peripheral insulin sensitivity, blood lipid profile and body fat were analysed. In the fructose groups F2 and F3 glucose tolerance and insulin sensitivity were lower, while triacylglycerolaemia was higher than the respective controls C2 and C3 (P < 0.05). Blood total cholesterol, HDL and LDL as well as body fat showed change only in the second protocol. In conclusion, high fructose intake is more effective at producing the signs of the metabolic syndrome in adult than in young Wistar rats. Additionally, diet seems to be a more effective way of fructose administration than drinking water.

Plasma lipid profile of experimentally induced hyperlipidemic New Zealand white rabbits is not affected by resveratrol

Hyperlipidemia is well recognized as an important risk factor in the development of atherosclerosis. Low-density lipoproteins (LDL) are components of cholesterol that are highly associated to an increased risk of cardiovascular diseases. Hypercholesterolemia induces proteolytic and oxidative changes in vasculature, leading to a local inflammatory response. Since dietary antioxidants have attracted considerable attention as preventive and therapeutic agents, the polyphenolic compound resveratrol seems to play an important role in prevention of human atherosclerosis. Researches show that resveratrol inhibits LDL oxidation and platelet aggregation, as well as vascular prolifer ation of smooth muscle cells. However, recent findings in animal models reveal conflicting results regarding its effects on plasma lipid levels. The aim of the present study was to evaluate the effect of resveratrol on plasma biochemistry profile in New Zealand white rabbits submitted to a hypercholesterolemic diet. Twenty healthy, male, adult New Zealand white rabbits were fed with ordinary diet for one week before being divided into four treatment groups, containing five animals each. Group CT received maintenance diet; group R received maintenance diet and resveratrol (3mg/kg/day) given orally; group CL received maintenance diet enriched with 1.5% cholesterol; and group CR received maintenance diet enriched with 1.5% cholesterol and resveratrol (3mg/kg/day) given orally. During the experiment, from each animal, samples of 3mL venous blood were collected in heparin twice monthly for measurements of total cholesterol, triglycerides, and low- and high-density lipoproteins. The data analysis revealed that resveratrol did not have a hypolipidemic effect in experimentally induced hypercholesterolemic New Zealand white rabbits.

Dietary, anthropometric, and biochemical determinants of plasma high-density lipoprotein-cholesterol in free-living adults

The level of high-density lipoprotein is thought to be critical in inhibiting lesion formation as well as reducing the lipid load of preexisting atherosclerotic lesions. With the aim of determining the main determinants of plasma HDL-cholesterol (HDL-c) in free-living adults, 997 individuals (52.3 10 years, 67 females) were selected for a descriptive cross-sectional study. The used data corresponded to the baseline obtained from participants clinically selected for a lifestyle modification program. Covariables of clinical, anthropometry, food intake, aerobic fitness, and plasma biochemistry were analyzed against plasma HDL-c either as continuous or categorized variables. After adjustments for age, gender, and BMI the excess of abdominal fat along with high carbohydrate-energy intake and altered plasma triglycerides were the stronger predictors of reduced plasma HDL-c. In conclusion lifestyle interventions aiming to normalize abdominal fatness and plasma triglycerides are recommended to restore normal levels of HDL-c in these free-living adults. Copyright © 2011 Erick Prado de Oliveira et al.

Efeitos da prática da natação adaptada sobre o perfil bioquímico e o estado de condicionamento físico de indivíduos com lesão medular

Introduction: The lack of physical exercises generated by immobilization of the lower limbs leads to changes in body composition that are generally associated with the imbalance of metabolic rate coupled with a sedentary status, which can result in obesity, diabetes mellitus and cardiovascular disease. Therefore, the improvement of physical fitness can contribute to promoting health and quality of life for these patients. As there is a very small number of research in this direction, our purpose was to investigate the effects of an adapted swimming program in protocol interval, for people with spinal cord injury, aiming to verify the improvement of your fitness and, consequently, some biochemical variables important for health. Methodology: The study included 17 subjects with spinal cord injury, sedentary, divided into two groups: 11 participants in the training group (TG) and 6 in control group (CG). TG was applied by a protocol of interval training in swimming for eight consecutive weeks, three times a week. The protocol employed a stroke of breaststroke in work periods of moderate to severe, and stroke in the backstroke, in periods of active recovery. The CG has not participated in any physical activity. Both groups were collecting blood for biochemical analysis, before (evaluation) and after (revaluation) the swimming program. Results and Discussion: The concentrations of triglycerides, total cholesterol and LDL-cholesterol showed no significant changes in assessment for reassessment in both groups. However the TG, the level of HDL-cholesterol were significant differences (p=0,0110), showing an improvement in posttraining, which did not occur in the CG. With respect to the state of fitness, the results revealed a significant difference in relation to time and distance covered in water when compared with the pre-training (p<0,001), showing a great improvement in the ability to shift with the stroke of breaststroke and a significant improvement in cardiorespiratory function. Conclusion: The swimming program interval used, with moderate to severe intensity, can even in a short period of time, promote positive changes in HDLcholesterol in individuals with spinal cord injury studied, and substantially improve your fitness.

β-conglycinin combined with fenofibrate or rosuvastatin have exerted distinct hypocholesterolemic effects in rats

Background: There is increasing interest in non-pharmacological control of cholesterol and triglyceride levels in the plasma and diet-drug association represent an important area of studies. The objective of this study was to observe the hypocholesterolemic effect of soybean β-conglycinin (7S protein) alone and combined with fenofibrate and rosuvastatin, two hypolipidemic drugs. Methods. The protein and drugs were administered orally once a day to rats and the effects were evaluated after 28 days. Wistar rats were divided into six groups (n = 9): hypercholesterolemic diet (HC), HC+7S protein (300 mg.kg-1 day-1) (HC-7S), HC+fenofibrate (30 mg.kg-1 day-1)(HC-FF), HC+rosuvastatin (10 mg.kg-1 day-1)(HC-RO), HC+7S+fenofibrate (HC-7S-FF) and HC+7S+rosuvastatin (HC-7S-RO). Results: Animals in HC-7S, HC-FF and HC-RO exhibited reductions of 22.9, 35.8 and 18.8% in total plasma cholesterol, respectively. In HC-7S-FF, animals did not show significant alteration of the level in HC+FF while the group HC-7S-RO showed a negative effect in comparison with groups taking only protein (HC-7S) or drug (HC-RO). The administration of the protein, fenofibrate and rosuvastatin alone caused increases in the plasma HDL-C of the animals, while the protein-drug combinations led to an increase compared to HC-FF and HC-RO. The plasma concentration of triacylgycerides was significantly reduced in the groups without association, while HC-7S-FF showed no alteration and HC-7S-RO a little reduction. Conclusion: The results of our study indicate that conglycinin has effects comparable to fenofibrate and rosuvastatin on the control of plasma cholesterol, HDL-C and triacylglycerides, when given to hypercholesterolemic rats, and suggests that the association of this protein with rosuvastatin alters the action of drug in the homeostasis of cholesterol. © 2012 Ferreira et al; licensee BioMed Central Ltd.

High-sucrose effect on bone structure, hardness and biomechanics in an obesity model using Wistar male rats

Introduction: Excessive consumption of sugar-sweetened beverage is positively related to overweight. Despite the epidemic of childhood obesity, body mass can have a positive or negative effect on bone health. Material and methods: Wistar rats 8 weeks olds were randomly assigned to consume water (Control group, n = 10), sucrose 30% (HS group, n = 10) and water + sucrose 30% (WHS group, n = 14) for 8 weeks. All animals received standard laboratory chow ad libitum. Femur measurements included microhardness, bone mineral density (BMD) by DXA, mechanical compression test and microcomputed tomography (microCT) analysis. Results: We observed significant difference in final body weight in HS and WHS groups, significant increase in triacylglycerol/fructosamine in HS and WHS groups, significantly high BMD in WHS group, increased periosteal/endosteal cortical microhardness in WHS group. Compared with control, microCT parameters evidenced lower amount of connected trabecular bone, decreased bone volume, lower trabecular number with high trabecular separation in distal epiphysis in WHS animals. Conclusion: High-sucrose consumption causes obesity induced by a liquid diet with negative effects on cancellous bone.