Editorial: Vascular dysfunction beyond pathological pregnancies. An international effort addressed to fill the gaps in Latin America, Volume II

Q1Q1Mujeres en estado de embarazoRecent evidence suggests that vascular changes associated with pregnancy complications, such as preeclampsia; gestational diabetes; growth restriction; autoimmune diseases; among others, affect the function of the maternal and offspring vascular systems after delivery and may be extended until adult life (Giachini et al., 2017; Dayan et al., 2018; Honigberg et al., 2019). Furthermore, since the vascular system contributes to systemic homeostasis, defective development or function of blood vessels predisposes both mother and infant to future risk for chronic disease (Davis et al., 2012; Phipps et al., 2019).https://orcid.org/0000-0002-6804-0979Revista Internacional - IndexadaA1N

Glycosylation with O-linked β-N-acetylglucosamine (O-GlcNAc) induces vascular dysfunction via production of superoxide anion/reactive oxygen species

Overproduction of superoxide anion (•O2-) and O-linked β-N-acetylglucosamine (O-GlcNAc)-modification in the vascular system are contributors to endothelial dysfunction. This study tested the hypothesis that increased levels of O-GlcNAc-modified proteins contribute to •O2- production via activation of NADPH oxidase, resulting in impaired vasodilation. Rat aortic segments and vascular smooth muscle cell (VSMCs) were incubated with vehicle (methanol) or PUGNAc (100 µM). PUGNAc produced a time-dependent increase in O-GlcNAc levels in VSMC and decreased endothelium-dependent relaxation, which was prevented by apocynin and Tiron, suggesting that •O2- contributes to endothelial dysfunction under augmented O-GlcNAc levels. Aortic segments incubated with PUGNAc also exhibited increased levels of ROS, assessed by dihydroethidium fluorescence, and augmented •O2- production, determined by lucigenin-enhanced chemiluminescence. Additionally, PUGNAc treatment increased Nox1 and Nox4 protein expression in aorta and VSMCs. Translocation of p47phox subunit from the cytosol to the membrane was greater in aortas incubated with PUGNAc. VSMCs displayed increased p22phox protein expression after PUGNAc incubation, suggesting that NADPH oxidase is activated in conditions where O-GlcNAc protein levels are increased. In conclusion, O-GlcNAc levels reduce endothelium-dependent relaxation by overproduction of •O2- via activation of NADPH oxidase. This may represent an additional mechanism by which augmented O-GlcNAc levels impair vascular function

REPERCUSSÃO DO AMBIENTE UNIVERSITÁRIOS EM FATORES COMPORTAMENTAIS, BIOQUÍMICOS E PSICOLÓGICO NO CÂMPUS ARAGUAIA

A saúde favorece o desenvolvimento social, econômico e pessoal. O conhecimento de aspectos relacionados à saúde dos estudantes universitários garante a criação de condições para que possam desenvolver suas aptidões e capacidades individuais. Nesse sentido, a promoção da saúde se encontra estreitamente vinculada à eficácia da sociedade em garantir a implantação de políticas públicas voltadas para a qualidade de vida. O presente projeto teve como objetivo atuar na promoção de saúde no âmbito universitário visando à prevenção e diagnóstico de possíveis fatores de risco para o surgimento de doenças cardiovasculares (DCVs) em adolescentes universitários. É válido lembrar que segundo a Organização Mundial de Saúde as DCVs foram a maior causa de morte por doenças não transmissíveis em 2014. Em relação aos alunos envolvidos na elaboração deste projeto, a ação extensiva teve como intuito a aplicação prática e teórica com temas interdisciplinaridade, associados com as disciplinas de bioquímica, patologia, assistência farmacêutica, saúde pública, biossegurança e estatística. Já os alunos alvo deste projeto nos auxiliaram a melhor entender a relação entre a medicina baseada em evidencias clínicas, com os fatores de risco associados à DCVs, tais como: hipertensão, obesidade, consumo de álcool, estresse, dislipidemia, disfunção hepática, hábitos sociais e sedentarismo. Para atingirmos o objetivo deste projeto, foram realizadas 1037 análises em 61 universitários. Após as análises e reflexão, constatou-se a vulnerabilidade da população estudada, em relação à precária assistência estudantil, seja no aspecto de saúde física, como psicológica

Activation of STIM1/Orai1 mediates sex-differences in the calcium influx in vascular miocytes from hypertensive rats.

Os distúrbios na regulação da concentração de cálcio (Ca2+) citoplasmático contribuem para a patogênese da hipertensão arterial. Evidências sugerem que as moléculas de interação estromal (STIM) atuam como sensores dos estoques intracelulares de Ca2+, enquanto as proteínas Orai representam as subunidades que formam os canais de Ca2+ ativados pela liberação de Ca2+ (CRAC). Neste estudo avaliamos a participação de STIM1/Orai1 na regulação das concentrações de Ca2+ citoplasmático e na ativação da contração vascular em aortas de ratos hipertensos. Nossos resultados sugerem que a ativação de STIM1/Orai1 pode representar um novo mecanismo que modula alterações vasculares nos níveis de Ca2+ intracelular na hipertensão arterial e que contribui para as diferenças sexuais de reatividade vascular em animais hipertensos.Disturbance in the regulation of cytoplasmic calcium (Ca2+) concentration contributes to the pathogenesis of hypertension. Evidences suggest that the stromal interaction molecule (STIM) acts as a sensor of intracellular Ca2+ stores, whereas Orai proteins are the subunits that form CRAC channels. In this study, we evaluated the role of STIM1/Orai1 in the regulation of cytoplasmic Ca2+ concentrations and in the activation of contraction in aortas from hypertensive rats. We also studied how the differential activation of this pathway contributes to sex differences observed between hypertensive rats, as well as the protective effects of the female sex hormones in the vasculature. Our results suggest that activation of STIM1/Orai1 may represent a new mechanism that modulates intracellular Ca2+ concentration during hypertension and contributes to sex differences in the vascular reactivity of hypertensive animals

POTENCIAIS INTERAÇÕES ENTRE MEDICAMENTOS E ALIMENTOS EM IDOSOS HOSPITALIZADOS NO MÉDIO ARAGUAIA

Introdução e objetivos: O idoso possui alterações em seu organismo que resultam em alterações tanto na farmacocinética como na farmacodinâmica, tornando esses indivíduos mais vulneráveis a desenvolverem interações medicamentosas. Outro aspecto de interesse é a interação ocasionada pela associação entre medicamentos e alimentos, fator que nem sempre é considerado no momento da prescrição. O objetivo deste trabalho foi avaliar prontuários de pacientes idosos hospitalizados no sistema público de saúde da região do Médio Araguaia, no ano de 2010, identificando possíveis interações entre medicamento-alimento. Metodologia: A amostra foi composta de 264 pacientes, onde foram identificadas informações como idade, gênero, motivo e dias de internação, bem como os medicamentos prescritos durante este período. Resultados e discussões: Foi observado que 82,2% das prescrições analisadas apresentavam possíveis interações entre medicamento-alimento, e destas possíveis interações, 71% foram classificadas como moderadas. Observou-se que 26,9% dos pacientes utilizaram dieta hipossódica. Os medicamentos mais envolvidos nas possíveis interações entre medicamento-alimento foram a aminofilina (27,8%) e furosemida (23,3%). Entre os medicamentos que causaram possíveis interações com suco de laranja, destacam-se o diazepam (43,4%) e a nifedipina (22,1%). Conclusões: Esses dados demonstram a importância em se adotar uma conduta mais cautelosa para a prescrição de medicamentos, devendo sempre oferecer instruções ao paciente sobre o uso correto de medicamento, destacando os alimentos que não devem ser ingeridos concomitantemente com a medicação

POTENCIAIS INTERAÇÕES MEDICAMENTOSAS EM PACIENTES PORTADORES DE DOENÇA RENAL CRÔNICA EM TRATAMENTO DE HEMODIÁLISEDOI: http://dx.doi.org/10.5892/ruvrd.v15i2.3087

INTRODUÇÃO: O paciente portador de doença renal crônica (DRC) faz uso de uma ampla gama de medicamentos, potencializando a ocorrência de possíveis interações medicamentosas (IM)s. OBJETIVO: Identificar potencias IMs nos prontuários dos pacientes portadores de DRC do estágio 5, em tratamento de hemodiálise, classificando-as quanto a sua gravidade e separando a sua ocorrência quanto as co-morbidades de cada paciente. METODOLOGIA: Foram analisados os prontuários dos pacientes portadores de DRC de estágio 5, que estavam em tratamento de hemodiálise no município de Barra do Garças MT.  Para identificar as possíveis IMs foi consultado o MICROMEDEX®, software que possui um sistema interativo para checar sua ocorrência. RESULTADOS: Foram analisados o prontuário de 49 pacientes, com faixa etária entre 25 e 80 anos, sendo 24 mulheres e 25 homens. A maioria dos pacientes utilizavam mais que 5 medicamentos simultaneamente, obtendo uma média de 8 medicamentos por paciente. Todos os pacientes analisados são hipertensos e 28% também possuem diabetes. Dentre os pacientes avaliados, 78% dos prontuários apresentaram potenciais IMs, com um total de 123 interações; observou-se a ocorrência de IMs graves, embora a maior parte das IMs sejam classificadas como moderadas. Pacientes hipertensos apresentaram maior número de ocorrência de IMs que os pacientes hipertensos e diabéticos. CONCLUSÃO: Os resultados mostram que os pacientes analisados apresentam um número significativo de IMs. Diante desses resultados nota-se a necessidade da conscientização dos profissionais da saúde quanto à possível ocorrência destas, e um estudo mais aprofundado sobre as consequências das IMs em pacientes de hemodiálise.

Evaluation of drug prescriptions for pregnant women in the Legal Amazon Region

Abstract Objectives: to evaluate the drug prescriptions for pregnant women in the Legal Amazon during prenatal care. Methods: this is a pharmacoepidemiological, descriptive, retrospective and cross-sectional study. Medical records included sociodemographic variables, prenatal care, most frequent pharmacological classes prescribed, risk classification of drugs and possible drug-drug interactions among pregnant women. Results: a total of 159 records from pregnant women, enrolled in the Unified Health System were used. Most pregnant women began prenatal consultations in the first trimester of pregnancy (53.3%) whereas most of the drugs were prescribed in the second gestational trimester (55.5%). The most used pharmacological classes, classified according to the National List of Essential Drugs were: antianemic preparations (52.9%), vitamins (12.5%) and analgesic (10.6%). According to the risk classification, the highest prevalence of prescribed drugs belongs to category A (46.8%), followed by category C (28.9%), category B (20.0%) and category D (4.3%). Eight possible drug-drug interactions were found, being considered with mild severity, and six classified with moderate risk. Conclusions: the results demonstrate a lack of information regarding prescription drugs for pregnant women and this may endanger maternal and fetal health. It is essential that medical records be an effective therapeutic tool, which should be read, analyzed and reviewed in order to ensure effective and safe medical treatment

Anti-Platelet therapy with clopidogrel prevents endothelial dysfunction and vascular remodeling in aortas from hypertensive rats.

The aim was to investigate the beneficial effects of clopidogrel in thoracic aorta function and structure and to characterize if P2Y12 receptors contribute to these effects. Male Sprague Dawley rats were infused with angiotensin II [(Ang II) 60 ng.min21, 14 days] or saline (control rats) and were simultaneously treated with clopidogrel (10 mg.kg21.day21) or vehicle. After 14 days, systolic blood pressure (mmHg) was similar in Ang II-hypertensive rats treated with clopidogrel or vehicle (19969 vs. 190611, respectively). Systolic blood pressure in control rats was not altered by clopidogrel treatment (12861 vs. vehicle, 13462). Endothelium-dependent relaxation induced by 2-MeS-ADP was decreased in aortas from vehicle-treated Ang II-hypertensive rats, compared to vehicle-treated control rats. This response was elicited via activation of P2Y1 and P2Y12 receptors. In the presence of L-NAME and indomethacin, 2-MeS-ADP induced contraction and this response was augmented in vehicle-treated Ang II-hypertensive rats, compared to vehicle-treated control rats. The contraction to 2-MeS-ADP was evoked by P2Y13 and P2Y12 receptor activation. Clopidogrel-treatment did not normalize relaxation or contractile responses induced by 2-MeS-ADP in aortas from Ang II-hypertensive rats. P2Y1 and P2Y12 protein expression was increased, whereas P2Y13 receptor expression was reduced in aorta from vehicle-treated Ang II-hypertensive rats. Endothelium-dependent relaxation upon acetylcholine-stimulation was reduced in vehicle-treated Ang II-hypertensive rats, and clopidogrel treatment was effective in improving endothelial function. Clopidogrel also prevented vascular remodeling, evidenced by augmented media thickness in aortas from Ang II-hypertensive rats. Clopidogrel has beneficial effects on the aortic endothelium of Ang II-hypertensive rats, but its effects do not seem to be directly related to the presence of P2Y12 receptors in this vessel

Preeclampsia association of placental nucleotide variations in eNOS, VEGFA, and FLT-1 genes in Latin American pregnant women

Q2Q1Mujeres con preeclampsiaIntroduction: Preeclampsia is a leading cause of maternal and fetal morbidity in low- and middle-income countries, including those in Latin America. Placental vascular alterations are crucial in the pathophysiology of preeclampsia and few studies have evaluated nucleotide variations on genes associated with vascular regulation in the human placenta. This study aimed to evaluate whether placental nucleotide variations on eNOS, VEGFA, and FLT-1 genes are more frequently associated with preeclampsia in the Latin American population. Methods: This case-control study included placental tissue from 88 controls and 82 cases that were genotyped through Taqman probes for eNOS, VEGFA, and FLT-1 genes. The intergroup comparisons were analyzed with the Mann-Whitney U test. Genotype and allele frequencies were compared by the X2 test. The association between the nucleotide variants with preeclampsia was evaluated through logistic regression analysis. Results: A significant association was observed for VEGFA SNV rs2010963 (OR 1.95; CI 95% 1.13–3.37), after adjusting for population substructure. The allele combination T, G, G, C, C, C (rs2070744, rs1799983, rs2010963, rs3025039, rs699947 and rs4769613 respectively), showed a negative association with preeclampsia (OR 0.08; CI 95% 0.01–0.93). results. Discussion: Placental SNV rs2010963 in the VEGFA gene was a risk factor for preeclampsia, while the allele combination T, G, G, C, C, C may represent potential protective factors for preeclampsia within Latin American women.https://orcid.org/0000-0002-6804-0979https://orcid.org/0000-0002-0141-1149Revista Internacional - IndexadaA1N

Activation of the ET-1/ETA pathway contributes to erectile dysfunction associated with mineralocorticoid hypertension.

Introduction. The cavernosal tissue is highly responsive to endothelin-1 (ET-1), and penile smooth muscle cells not only respond to but also synthesize ET-1. Aim. Considering that ET-1 is directly involved in end-organ damage in salt-sensitive forms of hypertension, we hypothesized that activation of the ET-1/ETA receptor pathway contributes to erectile dysfunction (ED) associated with mineralocorticoid hypertension. Methods. Wistar rats were uninephrectomized and submitted to deoxycorticosterone acetate (DOCA)-salt treatment for 5 weeks. Control (Uni [uninephrectomized control]) animals were uninephrectomized and given tap water. Uni and DOCA-salt rats were simultaneously treated with vehicle or atrasentan (ETA receptor antagonist, 5 mg/ Kg/day). Cavernosal reactivity to ET-1, phenylephrine (PE), ETB receptor agonist (IRL-1620) and electric field stimulation (EFS) were evaluated in vitro. Expression of ROCKa, ROCKb, myosin phosphatase target subunit 1 (MYPT-1), and extracellular signal-regulated kinase 1/2 (ERK 1/2) were evaluated by western blot analysis. ET-1 and ETA receptor mRNA expression was evaluated by real-time reverse-transcriptase polymerase chain reaction. Voltage-dependent increase in intracavernosal pressure/mean arterial pressure (ICP/MAP) was used to evaluate erectile function in vivo. Main Outcome Measure. ETA receptor blockade prevents DOCA-salt-associated ED. Results. Cavernosal strips from DOCA-salt rats displayed augmented preproET-1 expression, increased contractile responses to ET-1 and decreased relaxation to IRL-1620. Contractile responses induced by EFS and PE were enhanced in cavernosal tissues from DOCA-salt hypertensive rats. These functional changes were associated with increased activation of the RhoA/Rho-kinase and ERK 1/2 pathways. Treatment of rats with atrasentan completely prevented changes in cavernosal reactivity in DOCA-salt rats and restored the decreased ICP/MAP, completely preventing ED in DOCA-salt rats. Conclusion. Activation of the ET-1/ETA pathway contributes to mineralocorticoid hypertension-associated ED. ETA receptor blockade may represent an alternative therapeutic approach for ED associated with salt-sensitive hypertension and in pathological conditions where increased levels of ET-1 are present