G-protein-coupled receptor MAS deletion produces a preeclampsia-like phenotype in FVB/N mice.

BACKGROUND: An unbalance in the renin-angiotensin (Ang) system (RAS) between the Ang II/AT1 and Ang-(1-7)/Mas axis appears to be involved in preeclampsia (PE), in which a reduction in Ang-(1-7) was observed. Here, we tested whether the reduction in the activity of the Ang-(1-7)/Mas axis could be a contributing factor for the development of PE, using Mas-deficient (Mas-/-) mice. METHODS AND RESULTS: Cardiovascular parameters were evaluated by telemetry before, during pregnancy and 4 days postpartum in 20-week-old Mas-/- and wild-type (WT) female mice. Mas-/- mice presented reduced arterial blood pressure (BP) at baseline (91.3 ± 0.8 in Mas-/- vs. 94.0 ± 0.9 mmHg in WT, Diastolic, P<0.05). However, after the 13th day of gestation, BP in Mas-/- mice started to increase, time-dependently, and at day 19 of pregnancy, these animals presented a higher BP in comparison with WT group (90.5 ± 0.7 in Mas-/- vs. 80.3 ± 3.5 mmHg in WT, Diastolic D19, P<0.0001). Moreover, pregnant Mas-/- mice presented fetal growth restriction, increase in urinary protein excretion as compared with nonpregnant Mas-/-, oliguria, increase in cytokines, endothelial dysfunction and reduced ACE, AT1R, ACE2, ET-1A, and eNOS placental mRNA, similar to some of the clinical manifestations found in the development of PE. CONCLUSIONS: These results show that Mas-deletion produces a PE-like state in FVB/N mice.

A funcionalidade da órtese TQJTP na esclerose múltipla / Functionality of THKLF orthosis in multiple sclerosis

A esclerose múltipla (EM) é uma doença desmielinizante que causa uma degeneração difusa no sistema nervoso central, gerando limitações funcionais graves. O objetivo do estudo foi avaliar a funcionalidade e a qualidade de vida (QV) de um adulto com EM, antes e após o uso da órtese Tronco Quadril Joelho Tíbia e Pé (TQJTP), assim como avaliar a satisfação da paciente com o seu uso. Trata-se de um estudo de caso, realizado com um adulto jovem com diagnóstico de EM da forma remitente-remissiva. Foram avaliadas as seguintes medidas de interesse: teste cronometrado de subir e descer escadas (TCSDE); Timed up and go (TUG); teste de caminhada de seis minutos (TC6M); escala de determinação funcional da qualidade de vida em pacientes com esclerose múltipla (DEFU) e um questionário de satisfação do uso da órtese TQJTP. De acordo com os resultados observados, a órtese teve um efeito positivo na realização das atividades funcionais que envolvem mobilidade funcional (TUG) e em atividades mais desafiadoras como no TCSDE. O tempo de descida reduziu 40% com o uso da órtese. Não foram observadas melhora na capacidade de exercício, avaliada pelo TC6M, e na avaliação da qualidade de vida. A satisfação com o uso da órtese TQJTP foi determinante nos critérios relacionados com a marcha, material, conforto e para a realização de tarefas gerais. Conclui-se que a órtese TQJTP foi determinante para diminuir as limitações impostas pelas tarefas do dia a dia, destacando a satisfação da paciente com o seu uso. (AU)

Multiple sclerosis (MS) is a demyelinating disease that causes a diffuse degeneration of the central nervous system, causing severe functional limitations. The aim of this study was to evaluate the functionality and quality of life (QOL) of an adult with MS, before and after Trunk Hip Knee Leg and Foot (THKLF) Orthosis use, and to measure the satisfaction with the orthosis use. This is a case study performed with a young adult diagnosed with relapsing-remitting MS form. The outcome measures were assessed by: timed stair test (TST); Timed up and go (TUG); the six-minute walk test (6MWT); Functional Assessment of Multiple Sclerosis (FAMS) and a satisfaction questionnaire related to the TQJTP orthosis use. According to the results, the orthosis had a positive effect on the achievement of functional activities involving functional mobility (TUG) and challenging activities like TST. The time of climbing down the stairs reduced 40% with orthosis use. No improvement was observed in exercise capacity, measured by the 6MWT, and in the quality of life evaluation. The satisfaction with the TQJTP orthosis use was important in the questions related to walk, material, comfort and to do different tasks. We concluded that the TQJTP orthosis was crucial to reduce the limitations imposed by the tasks of everyday life, highlighting patient satisfaction with their use. (AU)

Identification of a Novel Agonist-Like Autoantibody in Preeclamptic Patients.

BACKGROUND: Recent studies have shown that preeclampsia (PE) is associated with the presence of autoantibodies (AABs) that activate the angiotensin II AT1 receptor, which could contribute to many of the symptoms of PE. METHODS: To investigate the frequency and the targets of AABs in preeclamptic women (31 cases) and healthy pregnant normotensive women (29 cases) in Brazil, antibodies from serum samples were detected by a bioassay using spontaneously beating neonatal rat cardiomyocytes in culture. In the cardiomyocytes, the agonistic AABs induce a positive or negative chronotropic response, mimicking the corresponding receptor agonists. The specificity of the AAB response was identified by specific receptor antagonists. RESULTS: Thirty preeclamptic patients (97%) presented AABs against the angiotensin II AT1 receptor. The agonistic effect of the AAB was blocked by irbesartan and neutralized by a peptide corresponding to the second extracellular loop of this receptor. Strikingly, we discovered that all sera from the severe preeclamptic patients (16 cases) contained a novel agonist-like AAB directed against the endothelin-1 ETA receptor in addition to the AABs against the angiotensin II AT1 receptor. This AAB was selectively blocked by the antagonist BQ-123, antagonized by the protein kinase C (PKC) inhibitor Calphostin C and neutralized by peptides corresponding to the second extracellular loop of the endothelin-1 ETA receptor subtype. CONCLUSIONS: We described, for the first time, the presence of endothelin-1 ETA receptor AABs in PE. Our results suggest that the presence of both agonistic AABs may be involved in the pathogenesis of severe PE.

Resposta materno-fetal resultante da prática de exercício físico durante a gravidez: uma revisão sistemática / Maternal-fetal response resulting from the practice of physical exercise during pregnancy: a systematic review

Introdução: a gravidez determina modificações adaptativas locais e sistêmicas, com o objetivo principal de promover o crescimento e o desenvolvimento fetal. Essas adaptações são fisiológicas e ocorrem em reação à presença do concepto e seus tecidos, modulados pela ação crescente de vários hormônios trofoblásticos/ placentários, fetais e maternos. A despeito dessas adaptações fisiológicas, as grávidas beneficiam-se do exercício físico regular. Entretanto, ainda existem controvérsias tanto em relação à realização do exercício físico regular na gestação quanto ao risco fetal imposto pelos exercícios. Objetivos: realizar pesquisa bibliográfica sobre as alterações fisiológicas e exercícios físicos na gravidez bem como a resposta fetal aos seus efeitos. Metodologia: revisão sistematizada abordando as alterações fisiológicas e exercícios físicos na gravidez, desde a década de 80 até os dias atuais. Resultados: houve significativo aumento da FC (frequência cardíaca) fetal após o protocolo de exercícios sem ocorrer sofrimento fetal (SF). Porém, quando a FC materna ultrapassou os 140 bpm houve SF. Conclusão: a prática de exercícios físicos na intensidade moderada (até 140 bpm de FC materna) parece benéfica para a mãe e o feto em gestações não complicadas.

Introduction: pregnancy determines adaptive systemic and local modifications, with the main objective to promote fetal growth and development. These are physiological adaptations and occur in reaction to the presence of a fetus and his tissues, modulated by the enhanced action of several trophoblastic/placental, fetal, and maternal hormones. In spite of these physiological adaptations, pregnant women benefit from regular exercise. However, there are still controversies, both in relation to the practice of regular exercise during pregnancy and fetal risk imposed by exercises. Objectives: to carry out a bibliographic research on the physiological alterations and physical exercise in pregnancy and fetal responses to its effects. Methodology: a systematic review addressed physiological alterations and physical exercises in pregnancy, from the 80s to the present. Results: there was significant increase in fetal HR (heart rate) after the protocol of exercises without fetal distress (SF). However, when the maternal HR exceeded 140 bpm, SF happened. Conclusion: the practice of physical exercise at moderate intensity (up to 140 bpm of maternal HR) seems beneficial to the mother and fetus in non-complicated pregnancies.

Activation of angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas axis attenuates the cardiac reactivity to acute emotional stress.

Recent data indicate the brain angiotensin-converting enzyme/ANG II/AT1 receptor axis enhances emotional stress responses. In this study, we investigated whether its counterregulatory axis, the angiotensin-converting enzyme 2 (ACE2)/ANG-(1-7)/Mas axis, attenuate the cardiovascular responses to acute emotional stress. In conscious male Wistar rats, the tachycardia induced by acute stress (air jet 10 l/min) was attenuated by intravenous injection of ANG-(1-7) [Δ heart rate (HR): saline 136 ± 22 vs. ANG-(1-7) 61 ± 25 beats/min; P < 0.05]. Peripheral injection of the ACE2 activator compound, XNT, abolished the tachycardia induced by acute stress. We found a similar effect after intracerebroventricular injections of either ANG-(1-7) or XNT. Under urethane anesthesia, the tachycardia evoked by the beta-adrenergic agonist was markedly reduced by ANG-(1-7) [ΔHR: saline 100 ± 16 vs. ANG-(1-7) 18 ± 15 beats/min; P < 0.05]. The increase in renal sympathetic nerve activity (RSNA) evoked by isoproterenol was also abolished after the treatment with ANG-(1-7) [ΔRSNA: saline 39% vs. ANG-(1-7) -23%; P < 0.05]. The tachycardia evoked by disinhibition of dorsomedial hypothalamus neurons, a key nucleus for the cardiovascular response to emotional stress, was reduced by ∼45% after intravenous injection of ANG-(1-7). In cardiomyocyte, the incubation with ANG-(1-7) (1 µM) markedly attenuated the increases in beating rate induced by isoproterenol. Our data show that activation of the ACE2/ANG-(1-7)/Mas axis attenuates stress-induced tachycardia. This effect might be either via the central nervous system reducing anxiety level and/or interfering with the positive chronotropy mediated by activation of cardiac ß adrenergic receptors. Therefore, ANG-(1-7) might contribute to reduce the sympathetic load to the heart during situations of emotional stress, reducing the cardiovascular risk.