BackgroundThere is growing interest in sex differences and RAS components. However, whether gender influences cardiac angiotensin I-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) activity is still unknown. In the present work, we determined the relationship between ACE and ACE2 activity, left ventricular function and gender in spontaneously hypertensive rats (SHRs).Methodology / Principal FindingsTwelve-week-old female (F) and male (M) SHRs were divided into 2 experimental groups (n = 7 in each group): sham (S) and gonadectomized (G). Fifty days after gonadectomy, we measured positive and negative first derivatives (dP/dt maximum left ventricle (LV) and dP/dt minimum LV, respectively), hypertrophy (morphometric analysis) and ACE and ACE2 catalytic activity (fluorimetrically). Expression of calcium handling proteins was measured by western blot. Male rats exhibited higher cardiac ACE and ACE2 activity as well as hypertrophy compared to female rats. Orchiectomy decreased the activity of these enzymes and hypertrophy, while ovariectomy increased hypertrophy and ACE2, but did not change ACE activity. For cardiac function, the male sham group had a lower +dP/dt than the female sham group. After gonadectomy, the +dP/dt increased in males and reduced in females. The male sham group had a lower -dP/dt than the female group. After gonadectomy, the -dP/dt increased in the male and decreased in the female groups when compared to the sham group. No difference was observed among the groups in SERCA2a protein expression. Gonadectomy increased protein expression of PLB (phospholamban) and the PLB to SERCA2a ratio in female rats, but did not change in male rats.ConclusionOvariectomy leads to increased cardiac hypertrophy, ACE2 activity, PLB expression and PLB to SERCA2a ratio, and worsening of hemodynamic variables, whereas in males the removal of testosterone has the opposite effects on RAS components.

BackgroundThe beverage obtained by fermentation of milk with kefir grains, a complex matrix containing acid bacteria and yeasts, has been shown to have beneficial effects in various diseases. However, its effects on hypertension and endothelial dysfunction are not yet clear. In this study, we evaluated the effects of kefir on endothelial cells and vascular responsiveness in spontaneously hypertensive rats (SHR).MethodsSHR were treated with kefir (0.3 mL/100 g body weight) for 7, 15, 30 and 60 days and compared with non-treated SHR and with normotensive Wistar-Kyoto rats. Vascular endothelial function was evaluated in aortic rings through the relaxation response to acetylcholine (ACh). The balance between reactive oxygen species (ROS) and nitric oxide (NO) synthase was evaluated through specific blockers in the ACh-induced responses and through flow cytometry in vascular tissue.ResultsSignificant effects of kefir were observed only after treatment for 60 days. The high blood pressure and tachycardia exhibited by the SHR were attenuated by approximately 15 % in the SHR-kefir group. The impaired ACh-induced relaxation of the aortic rings observed in the SHR (37 ± 4 %, compared to the Wistar rats: 74 ± 5 %), was significantly attenuated in the SHR group chronically treated with kefir (52 ± 4 %). The difference in the area under the curve between before and after the NADPH oxidase blockade or NO synthase blockade of aortic rings from SHR were of approximately +90 and −60 %, respectively, when compared with Wistar rats. In the aortic rings from the SHR-kefir group, these values were reduced to +50 and −40 %, respectively. Flow cytometric analysis of aortic endothelial cells revealed increased ROS production and decreased NO bioavailability in the SHR, which were significantly attenuated by the treatment with kefir. Scanning electronic microscopy showed vascular endothelial surface injury in SHR, which was partially protected following administration of kefir for 60 days. In addition, the recruitment of endothelial progenitor cells was decreased in the non-treated SHR and partially restored by kefir treatment.ConclusionsKefir treatment for 60 days was able to improve the endothelial function in SHR by partially restoring the ROS/NO imbalance and the endothelial architecture due to endothelial progenitor cells recruitment.

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The objective of this study was to determine the impact of a pharmaceutical care (PC) program in a sample of public outpatients with metabolic syndrome (MS) who were being treated in Brazil's health system; the patients were randomized into PC or standard care. The pharmacotherapy follow-up (PF) was performed in a total of 120 patients with type 2 diabetes for 6 months. Adherence to treatment (measured with the Morisky test), negative outcomes associated with medication (NOM) and anthropometric and biochemical parameters were measured before and after PF. The Framingham scoring method was used to estimate changes in 10-year coronary heart disease risk scores in all patients. Ninety-six of 120 patients had characteristics of MS and were randomized into two groups (G): the control group (CG: 36) and the intervention group (IG: 38). Among the MS patients, 100% were taking a glucose-lowering drug; many were also taking anti-hypertensive drugs (CG: 72%; IG: 73%), and some patients were also taking hypolipemic drugs (CG: 12.0%; IG: 14.7%). Only 20.7% of the IG patients were considered adherent to their prescribed drugs. In the CG, an increase of coronary heart disease (CHD) risk (22±2 to 26±3; p<0.05) was observed, while in the IG, there was a reduction in CHD risk (22±2 to 14±2%; p<0.01). The PC program administered to patients with MS monitored through the primary healthcare services of the Brazilian public health system improved patient health, resulting in clinical improvements and a decrease in cardiovascular risk in IG patients over a period of ten years.
O objetivo deste estudo foi o de determinar o impacto de um Programa de atenção Farmacêutica (AF) em uma amostra de pacientes ambulatoriais de Sistema Público de Saúde do Brasil portadores de Síndrome Metabólica, randomizados em AF ou atenção à saúde usual. Realizou-se o seguimento farmacoterapêutico com 120 pacientes com diabetes tipo 2 durante seis meses. Avaliou-se o nível de aderência ao tratamento (teste Morisky), resultados clínicos negativos associados a medicamentos (RNM), parâmetros bioquímicos e antropométricos, antes e após o seguimento. O método de Framingham foi usado para calcular as variações no risco de doenças coronarianas em 10 anos em todos os pacientes. Dos 120 pacientes, 96 tiveram características de SM e foram então randomizados em dois grupos (G): Controle (GC: 36) e Intervenção (GI: 38). Entre os pacientes com SM, 100% faziam uso de medicamentos para diminuir a glicose, anti-hipertensivos (GC: 72%; GI: 73%) e hipoglicemiantes (GC: 12.0%; GI: 14.7%). Apenas 20,7% do GI foram considerados aderentes aos fármacos prescritos. No GC foi observado aumento do risco de Doença Arterial Coronariana (DAC) (22±2 para 26±3; p<0,05), enquanto no GI foi observado redução (22±2 para 14±2%; p<0,01). O Programa de AF para pacientes com SM monitorados na atenção primária do Sistema de Saúde Pública brasileiro melhora o funcionamento do serviço resultando na melhoria clínica dos pacientes com redução do risco de doença cardiovascular em um período de dez anos

Context: Struthanthus vulgaris (Vell.) Mart. (Loranthaceae) has been widely used in traditional medicine in Brazil to bathe wounds. Objective: The objective of this study is to investigate the in vitro wound healing effects, together with the antioxidant and antimicrobial activities of S. vulgaris leaf and branch extracts. Material and methods: Ethanol leaf and branch extracts of S. vulgaris were investigated at 1-100 mg/ml concentrations in the scratch assay after 14 h. Antioxidant activity was investigated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging assay, and the antibacterial activity was tested at concentrations up to 1000 mg/ml against Gram-positive and Gramnegative bacteria by the microdilution test after 24 h. The total phenolic and flavonoid contents were determined by colorimetric methods. Results: Struthanthus vulgaris leaf and branch extracts at 100 mg/ml concentration stimulated migration and proliferation of fibroblasts and enhanced cell numbers by 56.2% and 18.6%, respectively. Antioxidant activity exhibited IC 50 values of 24.3 and 18.9 mg/ml for the leaf and branch extracts, respectively. The ethanol leaf extract showed antimicrobial activity against the Gram-positive Staphylococcus mutans and Staphylococcus aureus bacteria, exhibiting minimum inhibitory concentration values of 125 and 500 mg/ml, respectively. An appreciable total phenolic content in the leaves (813.6 ± 2.7 mg/g) and branches (462.8 ± 9.6 mg/g), and relatively low concentration of flavonoids in the leaves (13.3 ± 4.3 mg/g) and branches (1.9 ± 0.2 mg/g), was detected. Discussion and conclusion: The antioxidant and antibacterial activities, together with the strong ability to stimulate proliferation and migration of fibroblasts, provide some support for the traditional use of S. vulgaris.

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Aims: It has been previously shown that the probiotic kefir (a symbiotic matrix containing acid bacteria and yeasts) attenuated the hypertension and the endothelial dysfunction in spontaneously hypertensive rats (SHR). In the present study, the effect of chronic administration of kefir on the cardiac autonomic control of heart rate (HR) and baroreflex sensitivity (BRS) in SHR was evaluated.Methods: SHR were treated with kefir (0.3 mL/100 g body weight) for 60 days and compared with non-treated SHR and with normotensive Wistar-Kyoto rats. Cardiac autonomic vagal (VT) and sympathetic (ST) tones were estimated through the blockade of the cardiac muscarinic receptors (methylatropine) and the blockade of β1−adrenoceptor (atenolol). The BRS was evaluated by the tachycardia and bradycardia responses to vasoactive drug-induced decreases and increases in arterial blood pressure (BP), respectively. Additionally, spontaneous BRS was estimated by autoregressive spectral analysis.Results: Kefir-treated SHR exhibited significant attenuation of basal BP, HR, and cardiac hypertrophy compared to non-treated SHR (12, 13, and 21%, respectively). Cardiac VT and ST were significantly altered in the SHR (~40 and ~90 bpm) compared with Wistar rats (~120 and ~30 bpm) and were partially recovered in SHR-kefir (~90 and ~25 bpm). SHR exhibited an impaired bradycardic BRS (~50%) compared with Wistar rats, which was reduced to ~40% in the kefir-treated SHR and abolished by methylatropine in all groups. SHR also exhibited a significant impairment of the tachycardic BRS (~23%) compared with Wistar rats and this difference was reduced to 8% in the SHR-kefir. Under the action of atenolol the residual reflex tachycardia was smaller in SHR than in Wistar rats and kefir attenuated this abnormality. Spectral analysis revealed increased low frequency components of BP (~3.5-fold) and pulse interval (~2-fold) compared with Wistar rats and these differences were reduced by kefir-treatment to ~1.6- and ~1.5-fold, respectively. Spectral analysis also showed an impairment of spontaneous BRS in SHR, but kefir-treatment caused only a tendency to reverse this result.Conclusions: The novelty of this study is that daily chronic consumption of a low dose of kefir reduced the impairment of the cardiac autonomic control of HR and of the impaired BRS in SHR.

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