Evaluation of Sexual Dimorphism in the Efficacy and Safety of Simvastatin/Atorvastatin Therapy in a Southern Brazilian Cohort

Background: Dyslipidemia is the primary risk factor for cardiovascular disease, and statins have been effective in controlling lipid levels. Sex differences in the pharmacokinetics and pharmacodynamics of statins contribute to interindividual variations in drug efficacy and toxicity. Objective: To evaluate the presence of sexual dimorphism in the efficacy and safety of simvastatin/atorvastatin treatment. Methods: Lipid levels of 495 patients (331 women and 164 men) were measured at baseline and after 6 ± 3 months of simvastatin/atorvastatin treatment to assess the efficacy and safety profiles of both drugs. Results: Women had higher baseline levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) compared with men (p < 0.0001). After treatment, women exhibited a greater decrease in plasma TC and LDL-C levels compared with men. After adjustment for covariates, baseline levels of TC and LDL-C influenced more than 30% of the efficacy of lipid-lowering therapy (p < 0.001), regardless of sex. Myalgia [with or without changes in creatine phosphokinase (CPK) levels] occurred more frequently in women (25.9%; p = 0.002), whereas an increase in CPK and/or abnormal liver function was more frequent in in men (17.9%; p = 0.017). Conclusions: Our results show that baseline TC and LDL-C levels are the main predictors of simvastatin/atorvastatin therapy efficacy, regardless of sex. In addition, they suggest the presence of sexual dimorphism in the safety of simvastatin/atorvastatin. The effect of sex differences on receptors, transporter proteins, and gene expression pathways needs to be better evaluated and characterized to confirm these observations.

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.

High levels of LDL-C combined with low levels of HDL-C further increase platelet activation in hypercholesterolemic patients

High levels of low-density lipoprotein cholesterol (LDL-C) enhance platelet activation, whereas high levels of high-density lipoprotein cholesterol (HDL-C) exert a cardioprotective effect. However, the effects on platelet activation of high levels of LDL-C combined with low levels of HDL-C (HLC) have not yet been reported. We aimed to evaluate the platelet activation marker of HLC patients and investigate the antiplatelet effect of atorvastatin on this population. Forty-eight patients with high levels of LDL-C were enrolled. Among these, 23 had HLC and the other 25 had high levels of LDL-C combined with normal levels of HDL-C (HNC). A total of 35 normocholesterolemic (NOMC) volunteers were included as controls. Whole blood flow cytometry and platelet aggregation measurements were performed on all participants to detect the following platelet activation markers: CD62p (P-selectin), PAC-1 (GPIIb/IIIa), and maximal platelet aggregation (MPAG). A daily dose of 20 mg atorvastatin was administered to patients with high levels of LDL-C, and the above assessments were obtained at baseline and after 1 and 2 months of treatment. The expression of platelets CD62p and PAC-1 was increased in HNC patients compared to NOMC volunteers (P<0.01 and P<0.05). Furthermore, the surface expression of platelets CD62p and PAC-1 was greater among HLC patients than among HNC patients (P<0.01 and P<0.05). Although the expression of CD62p and PAC-1 decreased significantly after atorvastatin treatment, it remained higher in the HLC group than in the HNC group (P<0.05 and P=0.116). The reduction of HDL-C further increased platelet activation in patients with high levels of LDL-C. Platelet activation remained higher among HLC patients regardless of atorvastatin treatment.

The combination of atorvastatin and ethanol is not more hepatotoxic to rats than the administration of each drug alone

Animal studies and premarketing clinical trials have revealed hepatotoxicity of statins, primarily minor elevations in serum alanine aminotransferase levels. The combined chronic use of medicines and eventual ethanol abuse are common and may present a synergistic action regarding liver injury. Our objective was to study the effect of the chronic use of atorvastatin associated with acute ethanol administration on the liver in a rat model. One group of rats was treated daily for 5 days a week for 2 months with 0.8 mg/kg atorvastatin by gavage. At the end of the treatment the livers were perfused with 72 mM ethanol for 60 min. Control groups (at least 4 animals in each group) consisted of a group of 2-month-old male Wistar EPM-1 rats exposed to 10% ethanol (v/v) ad libitum replacing water for 2 months, followed by perfusion of the liver with 61 nM atorvastatin for 60 min, and a group of animals without chronic ethanol treatment whose livers were perfused with atorvastatin and/or ethanol. The combination of atorvastatin with ethanol did not increase the release of injury marker enzymes (alanine aminotransferase, aspartate aminotransferase, and lactic dehydrogenase) from the liver and no change in liver function markers (bromosulfophthalein clearance, and oxygen consumption) was observed. Our results suggest that the combination of atorvastatin with ethanol is not more hepatotoxic than the separate use of each substance.

Gladiolus development in response to bulb treatment with different concentrations of humic acids

Gladiolus is an ornamental species produced for cut flowers and propagated by corms. The early flowering and increase in the number of flower buds, besides the production of commercial corms are constant challenges to be addressed in the crop improvement. Commercial production of ornamentals is technologically accelerated by means of growth regulators. Among them, the auxins stand out for their key role in the adventitious rooting and cell elongation. Alternatively, the humic substances present in the organic matter also have biostimulating effect, which is very similar to the auxinic effect. Therefore, this work aimed to study the growth and development of gladiolus in response to application of different concentrations of humic acids (HA) isolated from vermicompost. Corms were soaked for 24 hours in solutions containing 0, 10, 20, 30 and 40 mmol L-1 of C from HA. The corms were planted in 10-dm³ plastic bags filled with substrate and kept in a greenhouse. Growth of shoots and roots was evaluated. The results showed that the use of HA accelerates growth, and anticipates and increases flowering of Gladiolus.

Chemical treatment of papaya seeds aiming at long-term storage and control of damping off

Damping off is a nursery disease of great economic importance in papaya and seed treatment may be an effective measure to control. The aim of this work was to evaluate the quality of papaya seeds treated with fungicides and stored under two environmental and packaging conditions. Additionally, the efficiency of fungicide treatments in the control of damping-off caused by Rhizoctonia solani was evaluated. Papaya seeds were treated with the fungicides Captan, Tolylfluanid and the mixture Tolylfluanid + Captan (all commercial wettable powder formulations). Seeds of the control group were not treated. The seeds were stored for nine months in two conditions: packed in aluminum coated paper and kept at 7 ± 1ºC and in permeable kraft paper and kept in non-controlled environment. At the beginning of the storage and every three months the seed quality (germination and vigor tests), emergence rate index, height, dry mass and damping of plants in pre and post-emergence (in contaminated substrate and mycelia-free substrate) were analyzed. Both storage conditions as well as the fungicide treatments preserved the germination and seed vigor. In the infested substrate, seedling emergence was favored by fungicides, but in post-emergence, fungicides alone did not control the damping off caused by R. solani. Symptoms of damping off were not observed in the clean substrate. The results showed that the fungicide treatments may be used to pretreat papaya seed for long-term storage and commercialization.

Initial performance of corn in response to treatment of seeds with humic acids isolated from bokashi

ABSTRACT The humified organic matter presents bioactivity similar to the auxinic effect. As bokashi is produced by a special process of humification, information is needed about the bioactive potential of its humic acids. The objective of this work was studying the initial performance of corn-indicator plants in response to the application of different concentrations of humic acids isolated from bokashi. The corn seeds were treated for 16 hours with solutions containing 0, 10, 20, 30, 40 and 80 mmol L-1 of C in the form of humic acids. Then, the seeds were planted in pots of 1 dm3 containing corrected and fertilized soil, in greenhouse. Growth characteristics of shoot and root systems were evaluated. The results showed that the humic acids extracted from bokashi had positive effects on the initial performance of corn.

Popular beliefs regarding the treatment of senile cataract

OBJECTIVE: To identify popular beliefs regarding the treatment of senile cataract in patients enrolled in the community health programs on eye rehabilitation. METHODS: A cross-sectional survey was carried out using an interview questionnaire that was applied to 776 subjects drawn from a non-probabilistic sample in five cities of the state of São Paulo. The sample was made up of 47.2% males and 52.8% females, aged 50 to 96 years (average age 71.6 years). RESULTS: Of the total of subjects studied, 41.9% had never attended school, and 78.5% were no longer in the employment market. Most (85.1%) credited the sight restoration to cataract surgery. Among those unconvinced, 47.4% asserted that sight restoration depended only on God's will. A greater proportion of women than men (p 0.0000) believed in the association of cataract and menopause, maternity, and menstrual periods and they admitted using herbal and rose teas for treating cataract. CONCLUSIONS: Misbeliefs related to the causes and treatment of senile cataract were identified, most probably of sociocultural basis, indicating the need of education on the subject.

Household members and health care workers as supervisors of tuberculosis treatment

OBJECTIVE: To compare tuberculosis cure rates among patients supervised by household members or health care workers. METHODS: Prospective cohort study of 171 patients treated by the program in Vitoria, Southeastern Brazil, from 2004 to 2007. Each patient was followed-up for six months until the end of the treatment. Of the patients studied, a household member supervised 59 patients and healthcare workers supervised 112 patients. Patients' sociodemographic and clinic data were analyzed. Differences between groups were assessed using chi-square test or Student's t-test. Significance level was set at 5%. RESULTS: Most patients had smear positive, culture confirmed pulmonary tuberculosis. Two patients were HIV-positive. There were more illiterate patients in the healthcare-supervised group, in comparison to those supervised by their families (p=0.01). All patients supervised by a household member were cured compared to 90% of the patients supervised by health care workers (p = 0.024). CONCLUSIONS: Successful tuberculosis treatment was more frequent when supervised by household members.

Direct treatment costs of HIV/AIDS in Portugal

OBJECTIVE To analyze the direct medical costs of HIV/AIDS in Portugal from the perspective of the National Health Service. METHODS A retrospective analysis of medical records was conducted for 150 patients from five specialized centers in Portugal in 2008. Data on utilization of medical resources during 12 months and patients’ characteristics were collected. A unit cost was applied to each care component using official sources and accounting data from National Health Service hospitals. RESULTS The average cost of treatment was 14,277 €/patient/year. The main cost-driver was antiretroviral treatment (€ 9,598), followed by hospitalization costs (€ 1,323). Treatment costs increased with the severity of disease from € 11,901 (> 500 CD4 cells/µl) to € 23,351 (CD4 count ≤ 50 cells/ µl). Cost progression was mainly due to the increase in hospitalization costs, while antiretroviral treatment costs remained stable over disease stages. CONCLUSIONS The high burden related to antiretroviral treatment is counterbalanced by relatively low hospitalization costs, which, however, increase with severity of disease. The relatively modest progression of total costs highlights that alternative public health strategies that do not affect transmission of disease may only have a limited impact on expenditure, since treatment costs are largely dominated by constant antiretroviral treatment costs.

Biological drugs for the treatment of psoriasis in a public health system

OBJECTIVE To analyze the access and utilization profile of biological medications for psoriasis provided by the judicial system in Brazil.METHODSThis is a cross-sectional study. We interviewed a total of 203 patients with psoriasis who were on biological medications obtained by the judicial system of the State of Sao Paulo, from 2004 to 2010. Sociodemographics, medical, and political-administrative characteristics were complemented with data obtained from dispensation orders that included biological medications to treat psoriasis and the legal actions involved. The data was analyzed using an electronic data base and shown as simple variable frequencies. The prescriptions contained in the lawsuits were analyzed according to legal provisions.RESULTS A total of 190 lawsuits requesting several biological drugs (adalimumab, efalizumab, etanercept, and infliximab) were analyzed. Patients obtained these medications as a result of injunctions (59.5%) or without having ever demanded biological medication from any health institution (86.2%), i.e., public or private health services. They used the prerogative of free legal aid (72.6%), even though they were represented by private lawyers (91.1%) and treated in private facilities (69.5%). Most of the patients used a biological medication for more than 13 months (66.0%), and some patients were undergoing treatment with this medication when interviewed (44.9%). Approximately one third of the patients discontinued treatment due to worsening of their illness (26.6%), adverse drug reactions (20.5%), lack of efficacy, or because the doctor discontinued this medication (13.8%). None of the analyzed medical prescriptions matched the legal prescribing requirements. Clinical monitoring results showed that 70.3% of the patients had not undergone laboratory examinations (blood work, liver and kidney function tests) for treatment control purposes.CONCLUSIONS The plaintiffs resorted to legal action to get access to biological medications because they were either unaware or had difficulty in accessing them through institutional public health system procedures. Access by means of legal action facilitated long-term use of this type of medication through irregular prescriptions and led to a high rate of adverse drug reactions as well as inappropriate clinical monitoring.

Economic analysis of surgical treatment of hip fracture in older adults

OBJECTIVE To analyze the incremental cost-utility ratio for the surgical treatment of hip fracture in older patients.METHODS This was a retrospective cohort study of a systematic sample of patients who underwent surgery for hip fracture at a central hospital of a macro-region in the state of Minas Gerais, Southeastern Brazil between January 1, 2009 and December 31, 2011. A decision tree creation was analyzed considering the direct medical costs. The study followed the healthcare provider’s perspective and had a one-year time horizon. Effectiveness was measured by the time elapsed between trauma and surgery after dividing the patients into early and late surgery groups. The utility was obtained in a cross-sectional and indirect manner using the EuroQOL 5 Dimensions generic questionnaire transformed into cardinal numbers using the national regulations established by the Center for the Development and Regional Planning of the State of Minas Gerais. The sample included 110 patients, 27 of whom were allocated in the early surgery group and 83 in the late surgery group. The groups were stratified by age, gender, type of fracture, type of surgery, and anesthetic risk.RESULTS The direct medical cost presented a statistically significant increase among patients in the late surgery group (p < 0.005), mainly because of ward costs (p < 0.001). In-hospital mortality was higher in the late surgery group (7.4% versus 16.9%). The decision tree demonstrated the dominance of the early surgery strategy over the late surgery strategy: R$9,854.34 (USD4,387.17) versus R$26,754.56 (USD11,911.03) per quality-adjusted life year. The sensitivity test with extreme values proved the robustness of the results.CONCLUSIONS After controlling for confounding variables, the strategy of early surgery for hip fracture in the older adults was proven to be dominant, because it presented a lower cost and better results than late surgery.

Spatial analysis of the tuberculosis treatment dropout, Buenos Aires, Argentina

OBJECTIVE Identify spatial distribution patterns of the proportion of nonadherence to tuberculosis treatment and its associated factors.METHODS We conducted an ecological study based on secondary and primary data from municipalities of the metropolitan area of Buenos Aires, Argentina. An exploratory analysis of the characteristics of the area and the distributions of the cases included in the sample (proportion of nonadherence) was also carried out along with a multifactor analysis by linear regression. The variables related to the characteristics of the population, residences and families were analyzed.RESULTS Areas with higher proportion of the population without social security benefits (p = 0.007) and of households with unsatisfied basic needs had a higher risk of nonadherence (p = 0.032). In addition, the proportion of nonadherence was higher in areas with the highest proportion of households with no public transportation within 300 meters (p = 0.070).CONCLUSIONS We found a risk area for the nonadherence to treatment characterized by a population living in poverty, with precarious jobs and difficult access to public transportation.

Profile of women who carried out smoking cessation treatment: a systematic review

OBJECTIVE Analyze the profile of women, in health services, who carry out treatment for smoking cessation.METHODS Systematic review that used the following sources of information: Cummulative Index to Nursing and Allied Health Literature (CINAHL), PubMed,Biblioteca Virtual em Saúde (BVS), Scopus and Web of Science. We included quantitative studies that addressed the characterization of women, in health services, who carried out treatment for smoking cessation, resulting in 12 articles for analysis. The assessment of the methodological quality of the studies was performed using the instrument MAStARI from Joanna Briggs Institute.RESULTS The predominant profile of women who carried out treatment for smoking cessation in health services was composed of white, married, employed, and highly level educated women. Women who carried out the treatment for smoking cessation in specialized services had a more advanced age, were white, were married and had a diagnosis of depression. The quality level of most studies was moderate.CONCLUSIONS The profile of women who carry out treatment for smoking cessation, either in general or specialized health services, is composed of white, married, and highly level educated women. Publications about smoking women are scarce and the lack of Brazilian studies characterizing the profile of women who start treatment for smoking cessation shows the need for studies that explore this subject.

Treatment of depression in older adults beyond fluoxetine

This review aimed to discuss the importance of the comprehensive treatment of depression among older adults in Brazil. The abuse of selective serotonin reuptake inhibitors, including fluoxetine hydrochloride, as antidepressants has been considered a serious public health problem, particularly among older adults. Despite the consensus on the need for a comprehensive treatment of depression in this population, Brazil is still unprepared. The interface between pharmacotherapy and psychotherapy is limited due to the lack of healthcare services, specialized professionals, and effective healthcare planning. Fluoxetine has been used among older adults as an all-purpose drug for the treatment of depressive disorders because of psychosocial adversities, lack of social support, and limited access to adequate healthcare services for the treatment of this disorder. Preparing health professionals is a sine qua non for the reversal of the age pyramid, but this is not happening yet.