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ABSTRACT Caryocar brasiliense Cambess., Caryocaraceae (pequi) is a typical Brazilian Cerrado tree. A previous study showed that the butanolic fraction of pequi leaves promotes endothelium-dependent relaxation mediated by nitric oxide and that it causes reversible hypotension in rats. In the present study, we investigated the cell signaling pathways associated with the butanolic fraction-induced nitric oxide release, and we characterized the chemical composition of its fraction. Vascular reactivity tests, a western blotting analysis, and a chemiluminescence assay were used to investigate the signaling pathways involved in the vasorelaxant effect of the butanolic fraction. Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry was used to characterize the butanolic fraction chemical composition. Vasorelaxation was mediated through the activation of the calmodulin and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways, leading to subsequent endothelial nitric oxide synthase phosphorylation and nitric oxide production, as evidenced by western blotting and chemiluminescence assays, respectively. The chemical characterization of the butanolic fraction revealed the presence of 72 oxygenated compounds, whose molecular formulae are compatible with phenolic compounds, suggesting a potential contribution of these compounds for the butanolic fraction vasorelaxant effect. These findings show that the calmodulin and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways are involved in the butanolic fraction-induced endothelial nitric oxide synthase activation and are promoted by polyphenol compounds present in the C. brasiliense leaves.
ABSTRACT
Abstract INTRODUCTION: Acquired immunodeficiency syndrome is an advanced stage of a human immunodeficiency virus infection. The antiretroviral therapy aims to improve the life quality of HIV patients and a good adherence is essential for a better prognosis. This study aimed to evaluate the adherence of human immunodeficiency virus/acquired immunodeficiency syndrome patients to antiretroviral therapy recommended by the Brazilian health system in Anápolis/Goiás, and correlate the level of adherence with sociodemographic data and clinical-laboratory variables. METHODS Adherence to antiretroviral therapy was assessed using the Questionnaire for Evaluation of Adherence to Antiretroviral Therapy. The sociodemographic data were collected using a standardized questionnaire and the clinical-laboratory records were reviewed. RESULTS: Among 220 patients included, 59% (129/220) were men and the average age was 41 years. Infection was acquired primarily through sexual contact (92%, 202/220), and 69% (152/220) of the patients were heterosexual. Approximately 86% (188/220) of the patients had good or strict adherence to antiretroviral therapy. In our study, the use of illicit drugs was associated with low adherence to antiretroviral therapy (p=0.0004), and no significant association was observed between adherence levels and other sociodemographic data (p>0.05). The logistic regression indicated that adverse effects (p=0.0018) and sexual orientation (p=0.0152) were associated with the level of adherence to antiretroviral therapy. Patients with good or strict adherence had higher CD4+T lymphocyte count (p<0.0001) and undetectable viral load (p<0.0001). Patients with low adherence (14%, 32/220) had higher frequency of adverse events (p=0.0009). The frequency of coinfections was 25% (55/220), with syphilis and tuberculosis being the most common coinfections. CONCLUSIONS: Adherence was related to use of illicit drugs, adverse effects, and sexual orientation.