Renin-Angiotensin System Blockade Associated with Statin Improves Endothelial Function in Diabetics

Abstract Background: Studies suggest that statins have pleiotropic effects, such as reduction in blood pressure, and improvement in endothelial function and vascular stiffness. Objective: To analyze if prior statin use influences the effect of renin-angiotensin-aldosterone system inhibitors on blood pressure, endothelial function, and vascular stiffness. Methods: Patients with diabetes and hypertension with office systolic blood pressure ≥ 130 mmHg and/or diastolic blood pressure ≥ 80 mmHg had their antihypertensive medications replaced by amlodipine during 6 weeks. They were then randomized to either benazepril or losartan for 12 additional weeks while continuing on amlodipine. Blood pressure (assessed with ambulatory blood pressure monitoring), endothelial function (brachial artery flow-mediated dilation), and vascular stiffness (pulse wave velocity) were evaluated before and after the combined treatment. In this study, a post hoc analysis was performed to compare patients who were or were not on statins (SU and NSU groups, respectively). Results: The SU group presented a greater reduction in the 24-hour systolic blood pressure (from 134 to 122 mmHg, p = 0.007), and in the brachial artery flow-mediated dilation (from 6.5 to 10.9%, p = 0.003) when compared with the NSU group (from 137 to 128 mmHg, p = 0.362, and from 7.5 to 8.3%, p = 0.820). There was no statistically significant difference in pulse wave velocity (SU group: from 9.95 to 9.90 m/s, p = 0.650; NSU group: from 10.65 to 11.05 m/s, p = 0.586). Conclusion: Combined use of statins, amlodipine, and renin-angiotensin-aldosterone system inhibitors improves the antihypertensive response and endothelial function in patients with hypertension and diabetes.

Endothelial Effect of Statin Therapy at a High Dose Versus Low Dose Associated with Ezetimibe

Abstract Background: The effect of statins on the endothelial function in humans remains under discussion. Particularly, it is still unclear if the improvement in endothelial function is due to a reduction in LDL-cholesterol or to an arterial pleiotropic effect. Objective: To test the hypothesis that modulation of the endothelial function promoted by statins is primarily mediated by the degree of reduction in LDL-cholesterol, independent of the dose of statin administered. Methods: Randomized clinical trial with two groups of lipid-lowering treatment (16 patients/each) and one placebo group (14 patients). The two active groups were designed to promote a similar degree of reduction in LDL-cholesterol: the first used statin at a high dose (80 mg, simvastatin 80 group) and the second used statin at a low dose (10 mg) associated with ezetimibe (10 mg, simvastatin 10/ezetimibe group) to optimize the hypolipidemic effect. The endothelial function was assessed by flow-mediated vasodilation (FMV) before and 8 weeks after treatment. Results: The decrease in LDL-cholesterol was similar between the groups simvastatin 80 and simvastatin 10/ezetimibe (27% ± 31% and 30% ± 29%, respectively, p = 0.75). The simvastatin 80 group presented an increase in FMV from 8.4% ± 4.3% at baseline to 11% ± 4.2% after 8 weeks (p = 0.02). Similarly, the group simvastatin 10/ezetimibe showed improvement in FMV from 7.3% ± 3.9% to 12% ± 4.4% (p = 0.001). The placebo group showed no variation in LDL-cholesterol level or endothelial function. Conclusion: The improvement in endothelial function with statin seems to depend more on a reduction in LDL-cholesterol levels, independent of the dose of statin administered, than on pleiotropic mechanisms.

Adherence to statin treatment and associated factors in female users from the Unified Health System (SUS)

Objective: To identify the adherence rate of a statin treatment and possible related factors in female users from the Unified Health System. Method: Seventy-one women were evaluated (64.2 ± 11.0 years) regarding the socio-economic level, comorbidities, current medications, level of physical activity, self-report of muscular pain, adherence to the medical prescription, body composition and biochemical profile. The data were analyzed as frequencies, Chi-Squared test, and Mann Whitney test (p<0.05). Results: 15.5% of women did not adhere to the medical prescription for the statin treatment, whose had less comorbidities (p=0.01), consumed less quantities of medications (p=0.00), and tended to be younger (p=0.06). Those patients also presented higher values of lipid profile (CT: p=0.01; LDL-c: p=0.02). Musculoskeletal complains were not associated to the adherence rate to the medication. Conclusion: The associated factors to adherence of dyslipidemic women to statin medical prescription were age, quantity of comorbidities and quantity of current medication.


A Brazilian family with hereditary inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia

Inclusion body myopathy associated with Paget disease and frontotemporal dementia (IBMPFD) is a progressive and usually misdiagnosed autosomal dominant disorder. It is clinically characterized by a triad of features: proximal and distal myopathy, early onset Paget disease of bone (PDB), and frontotemporal dementia (FTD). It is caused by missense mutations in the valosin-containing protein (VCP) gene. We describe here the clinical and molecular findings of the first Brazilian family identified with IBMPFD. Progressive myopathy affecting the limb girdles was detected by clinical examination followed by muscle biopsy and creatine kinase measurement. PDB was suggested after anatomopathological bone examination and FTD was diagnosed by clinical, neuropsychological and language evaluations. Brain magnetic resonance revealed severe atrophy of the anterior temporal lobes, including the hippocampi. A R93C mutation in VCP was detected by direct sequencing screening in subject W (age 62) and in his mother. Four more individuals diagnosed with "dementia" were reported in this family. We also present a comprehensive genotype-phenotype correlation analysis of mutations in VCP in 182 patients from 29 families described in the literature and show that while IBM is a conspicuously penetrant symptom, PDB has a lower penetrance when associated with mutations in the AAAD1 domain and FTD has a lower penetrance when associated with mutations in the Junction (L1-D1) domain. Furthermore, the R93C mutation is likely to be associated with the penetrance of all the clinical symptoms of the triad.

Role of microRNAs 221/222 on Statin Induced Nitric Oxide Release in Human Endothelial Cells

Background: Nitric oxide (NO) has been largely associated with cardiovascular protection through improvement of endothelial function. Recently, new evidence about modulation of NO release by microRNAs (miRs) has been reported, which could be involved with statin-dependent pleiotropic effects, including anti-inflammatory properties related to vascular endothelium function. Objective: To evaluate the effects of cholesterol-lowering drugs including the inhibitors of cholesterol synthesis, atorvastatin and simvastatin, and the inhibitor of cholesterol absorption ezetimibe on NO release, NOS3 mRNA expression and miRs potentially involved in NO bioavailability. Methods: Human umbilical vein endothelial cells (HUVEC) were exposed to atorvastatin, simvastatin or ezetimibe (0 to 5.0 μM). Cells were submitted to total RNA extraction and relative quantification of NOS3 mRNA and miRs -221, -222 and -1303 by qPCR. NO release was measured in supernatants by ozone-chemiluminescence. Results: Both statins increased NO levels and NOS3 mRNA expression but no influence was observed for ezetimibe treatment. Atorvastatin, simvastatin and ezetimibe down-regulated the expression of miR-221, whereas miR-222 was reduced only after the atorvastatin treatment. The magnitude of the reduction of miR-221 and miR-222 after treatment with statins correlated with the increment in NOS3 mRNA levels. No influence was observed on the miR-1303 expression after treatments. Conclusion: NO release in endothelial cells is increased by statins but not by the inhibitor of cholesterol absorption, ezetimibe. Our results provide new evidence about the participation of regulatory miRs 221/222 on NO release induction mediated by statins. Although ezetimibe did not modulate NO levels, the down-regulation of miR-221 could involve potential effects on endothelial function.

Inoculation with Azospirillum, associated with nitrogen fertilization in maize

The biological nitrogen fixation is an alternative to supply the nitrogen needed for maize. The objective of this study was to evaluate the development and yield of maize in response to inoculation with Azospirillum associated with nitrogen fertilization. We conducted two field experiments in the summer harvest, the first in the 2000/2001 crop year in the region of Marechal Cândido Rondon, under conventional tillage, and second in the 2002/2003 agricultural year in the region of Cascavel, under no tillage. The experimental design in both experiments was a randomized complete block, with four replications, 2x2x2 factorial, with two levels of nitrogen at sowing (zero and 20 kg ha-1), two levels of inoculum (zero and 200 g ha-1) and two levels of nitrogen in topdressing (zero and 100 kg ha-1). There was evaluated the height of ear insertion, total plant height, leaf N content, shoot dry biomass and grain yield. The height of ear insertion and total plant height were not influenced by the factors under study. Nitrogen fertilization at sowing increased the leaf N content, causing the opposite effect when combined with inoculation. Inoculation with Azospirillum in the absence of nitrogen, provide productivity increases of 15.4% and 7.4% for 2000/2001 and 2002/2003 crops, respectively. The inoculation provided productivity similar to that obtained with 100 kg ha-1 in topdressing in crop 2000/2001, while in association with the topdressing, reduced productivity and shoot dry biomass in crop 2002/2003.

Nutritional status of pregnant women: prevalence and associated pregnancy outcomes

INTRODUCTION: Although obesity is well recognized as a current public health problem, its prevalence and impact among pregnant women have been less investigated in Brazil. The objective of the study was to evaluate the impact of pre-obesity and obesity among pregnant women, describing its prevalence and risk factors, and their association with adverse pregnancy outcomes. METHODS: A cohort of 5,564 pregnant women, aged 20 years or more, enrolled at aproximately 20 to 28 weeks of pregnancy, seen in prenatal public clinics of six state capitals in Brazil were followed up, between 1991 and 1995. Prepregnancy weight, age, educational level and parity were obtained from a standard questionnaire. Height was measured in duplicate and the interviewer assigned the skin color. Nutritional status was defined using body mass index (BMI), according to World Health Organization (WHO) criteria. Odds ratios and 95% confidence interval were calculated using logistic regression. RESULTS: Age-adjusted prevalences (and 95% CI) based on prepregnancy weight were: underweight 5.7% (5.1%-6.3%), overweight 19.2% (18.1%-20.3%), and obesity 5.5% (4.9%-6.2%). Obesity was more frequently observed in older black women, with a lower educational level and multiparous. Obese women had higher frequencies of gestational diabetes, macrosomia, hypertensive disorders, and lower risk of microsomia. CONCLUSIONS: Overweight nutritional status (obesity and pre-obesity) was seen in 25% of adult pregnant women and it was associated with increased risk for several adverse pregnancy outcomes, such as gestational diabetes and pre-eclampsia.

Outpatient health service utilization and associated factors: a population-based study

OBJECTIVE: To identify factors that lead people to visit a doctor in Brazil and assess differences between socioeconomic groups. METHODS: A cross-sectional study comprising 1,260 subjects aged 15 or more was carried out in southern Brazil. Demographic, socioeconomic, health needs and regular source of care data were analyzed concerning visits to a doctor within two months from the interview. Adjusted prevalence ratios and 95% confidence intervals were calculated using Poisson regression. RESULTS: Adjusted PR showed that women having stressful life events, health insurance, and a regular doctor increased the outcome. A dose-related response was found with self-reported health, and the probability of visiting a doctor increased with health needs. Analysis in the chronic disease group revealed that uneducated lower income subjects had a 62% reduction in the chance of visiting a doctor compared to uneducated higher income ones. However, as it was seen a significant interaction between income and education, years of schooling increased utilization in this group. CONCLUSIONS: Results suggest the existence of health inequity in the poorest group that could be overcome with education. Specific measures reinforcing the importance of having a regular doctor may also improve access in the underserved group.

HTLV-I/II and blood donors: determinants associated with seropositivity in a low risk population

OBJECTIVE: Blood donors in Brazil have been routinely screened for HTLV-I/II since 1993. A study was performed to estimate the prevalence of HTLV-I/II infection in a low risk population and to better understand determinants associated with seropositivity. METHODS: HTLV-I/II seropositive (n=135), indeterminate (n=167) and seronegative blood donors (n=116) were enrolled in an open prevalence prospective cohort study. A cross-sectional epidemiological study of positive, indeterminate and seronegative HTLV-I/II subjects was conducted to assess behavioral and environmental risk factors for seropositivity. HTLV-I/II serological status was confirmed using enzyme-linked immunosorbent assay (EIA) and Western blot (WB). RESULTS: The three groups were not homogeneous. HTLV-I/II seropositivity was associated to past blood transfusion and years of schooling, a marker of socioeconomic status, and use of non-intravenous illegal drugs. CONCLUSIONS: The study results reinforce the importance of continuous monitoring and improvement of blood donor selection process.

Diptera of sanitary importance associated with composting of biosolids in Argentina

OBJECTIVE: Odorous compounds produced at the biosolids composting plant in Bariloche (NW Patagonia) attract a variety of insects, mainly belonging to the order Diptera. In order to characterize these flies, collected specimens were taxonomically identified, their community characteristics were described and their sanitary and synanthropic importance and autochthonous or introduced character were determined. METHODS: Sampling was performed from October 1999 until March 2000. Adults were collected using an entomological net, and larvae and puparia were obtained from the composting material and incubated to obtain adults. Richness, abundance and sex ratio were calculated. RESULTS: A total of 9 taxa of Diptera were identified: Sarconesia chlorogaster, Phaenicia sericata, Calliphora vicina, Cochliomya macellaria, Ophyra sp, Muscina stabulans, Musca domestica, Sarcophaga sp and Fannia sp. Specimens of Anthomyiidae, Acaliptratae and one larva of Eristalis tenax were also found. Ophyra sp. was the most abundant taxa. All the captured Diptera belonged to introduced taxa. Most of them are considered to be eusynanthropic and/or hemisynanthropic and have sanitary importance as they may cause myiasis and pseudomyiasis. The high number of females registered and the finding of immature stages indicated that flies can develop their complete life cycle on biosolid composting windrows. CONCLUSIONS: The characterization of flies obtained in this study may be useful for defining locations of urban or semi-urban composting facilities. It also highlights the importance of sanitary precautions at such plants.

Factors associated with infant feeding practices after hospital discharge

OBJECTIVE: To assess factors associated with infant feeding practices on the first day at home after hospital discharge. METHODS: A total of 209 women, who had a child aged four months or less and were living in Itapira, Brazil, were interviewed during the National Immunization Campaign Day in 1999. Statistical analysis was performed using the Chi-square test and a logistic regression model was used for verifying an association between dependent and independent variables. RESULTS: Women aged 25.5 years on average and 18.2% were teenagers. Fifty-three percent of the women delivered vaginally and most vaginal deliveries (78.5%) took place in the public hospital. The prevalence of exclusive breastfeeding on the first day at home was 78.1% and 11.6% of the infants were receiving formula at this time. The only factor associated with EBF on the first day at home was being a teenaged-primiparous mother (OR=9.40; 95% CI: 1.24-71.27). This association remained statistically significant even after controlling for type of delivery and hospital where the birth took place. Feeding formula on the first day at home was only significantly associated with the hospital (i.e., birth at the city hospital was a protective factor (OR=0.33; 95% CI: 0.13-0.86), even after controlling for vaginal delivery. CONCLUSIONS: On the first day at home after hospital discharge, teenaged-primiparous mothers were more likely to exclusive breastfeeding as well as those infants born in the municipal public hospital. Further studies are needed from a multidisciplinary approach.

Factors associated to smoking habit among older adults (The Bambuí Health and Aging Study)

OBJECTIVE: To describe the characteristics and associated factors of the smoking habit among older adults. METHODS: A population-based study was carried out comprising 1,606 (92.2%) older adults (>60 years old) living in the Bambuí town, Southeastern Brazil in 1997. Data was obtained by means of interview and socio-demographic factors, health status, physical functioning, use of healthcare services and medication were considered. The multiple multinomial logistic regression was used to assess independent associations between smoking habits (current and former smokers) and the exploratory variables. RESULTS: The prevalence of current and past smoking was 31.4% and 40.2% among men, and 10.3% and 11.2% among women, respectively (p<0.001). Among current smokers, men consumed a larger number of cigarettes per day and started the habit earlier than women. Among men, current smoking presented independent and negative association with age (>80 years) and schooling (>8 years) and positive association with poor health perception and not being married. Among women, independent and negative associations with current smoking were observed for age (75-79 and >80 years) and schooling (4-7 and >8 years). CONCLUSIONS: Smoking was a public health concern among older adults in the studied community, particularly for men. Yet, in a low schooling population, a slightly higher level was a protective factor against smoking for both men and women. Programs for reducing smoking in the elderly population should take these findings into consideration.

Body dissatisfaction in Brazilian schoolchildren: prevalence and associated factors

OBJECTIVE: To examine the prevalence of body dissatisfaction and associated factors in 8- to 11-year-old schoolchildren. METHODS: A cross-sectional study including children aged 8- to 11-years enrolled in public and private schools in Porto Alegre, Southern Brazil, was carried out from August to December, 2001. A total of 901 subjects were selected through cluster sampling. Participants answered a questionnaire aimed at measuring body dissatisfaction and self-esteem and questions about family and social pressures on weight change. Height and weight were measured. The relationship between body dissatisfaction and the variables studied was measured by logistic regression. RESULTS: The prevalence of body dissatisfaction was 82%. Fifty-five percent of the girls wanted a thinner body size, and 28% desired a larger one; the estimates for the boys were 43% and 38%, respectively. Children with the lowest self-esteem (OR=1.80; 95% CI: 1.13-2.89) and who thought their parents (OR=6.10; 95% CI: 2.95-12.60) and friends (OR=1.81; 95% CI: 1.02-3.20) expected them to be thinner showed a higher chance of presenting body dissatisfaction. CONCLUSIONS: Body dissatisfaction was highly prevalent among the evaluated schoolchildren, especially in those with lower self-esteem and who thought their parents and friends expected them to be thinner.

Prevalence of alcohol abuse and associated factors in a population-based study

OBJECTIVE: To estimate the prevalence of alcohol abuse/dependence and identify associated factors among demographic, family, socioeconomic and mental health variables. METHODS: A household survey was carried out in the urban area of Campinas, southeastern Brazil, in 2003. A total of 515 subjects, aged 14 years or more were randomly selected using a stratified cluster sample. The Self-Report Questionnaire and the Alcohol Use Disorder Identification Test were used in the interview. Prevalences were calculated, and univariate and multivariate logistic analyses performed by estimating odds ratios and 95% confidence intervals. RESULTS: The estimated prevalence of alcohol abuse/dependence was 13.1% (95% CI: 8.4;19.9) in men and 4.1% (95% CI: 1.9;8.6) in women. In the final multiple logistic regression model, alcohol abuse/dependence was significantly associated with age, income, schooling, religion and illicit drug use. The adjusted odds ratios were significantly higher in following variables: income between 2,501 and 10,000 dollars (OR=10.29); income above 10,000 dollars (OR=10.20); less than 12 years of schooling (OR=13.42); no religion (OR=9.16) or religion other than Evangelical (OR=4.77); and illicit drug use during lifetime (OR=4.47). Alcohol abuse and dependence patterns were different according to age group. CONCLUSIONS: There is a significantly high prevalence of alcohol abuse/dependence in this population. The knowledge of factors associated with alcohol abuse, and differences in consumption patterns should be taken into account in the development of harm reduction strategies.

Factors associated with depression symptoms in high school students in São Paulo, Brazil

OBJECTIVE: To assess factors associated with depression symptoms in high school students. METHODS: A cross-sectional study involving high school students was conducted in the city of São Paulo, Brazil, 2001. A total of 724 students aged 14-18 years answered questionnaires on life and health conditions. Another questionnaire was applied to working (44.8%) and unemployed (22.9%) students to collect information on working conditions. Factors associated to depressive disorders were analyzed using multiple logistic regression controlled for occupational status. RESULTS: Overall prevalence rate of depression was 7.5%. Rates according to gender were 39 (10.3%) in females and 15 (4.3%) in males. The multiple logistic regression analysis showed that factors associated with depressive disorders were: poor self-perception of health (OR=5.78), being female (OR = 2.45), and alcohol consumption (OR=2.35). CONCLUSIONS: The study results showed that sociodemographic, lifestyle and health variables were associated with symptoms of depression in this population. These ndings suggest that it is important to have mental health professionals available in high schools for early detection of mental conditions and student counseling.