28 research outputs found

    Glucagon-producing cells are increased in Mas-deficient mice

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    It has been shown that Angiotensin-(1-7) [Ang-(1-7)] produces several effects related to glucose homeostasis. In this study, we aimed to investigate the effects of genetic deletion of Ang-(1-7), the GPCR Mas, on the glucagon -producing cells. C57BL6/N Mas-/- mice presented a significant and marked increase in pancreatic {alpha}-cells (number of cells: 146 +/- 21 vs. 67 +/- 8 in WT - p<0.001) and the percentage per islet (17.9±0.91 vs. 12.3 +/- 0.9% in WT - p<0.0001) with subsequent reduction of {beta}-cells percentage (82.1 +/- 0.91 vs. 87.7 +/- 0.9% in WT - p<0.0001). Accordingly, glucagon plasma levels were increased (516.7 +/- 36.35 vs 390.8 +/- 56.45 pg/mL in WT, p<0.05 ) and insulin plasma levels were decreased in C57BL6/N Mas-/- mice (0.25 +/- 0.01 vs 0.31 +/- 56.45 pg/mL in WT- p=0.02). In order to eliminate the possibility of a background-related phenotype we determined the number of glucagon-producing cells in FVB/N Mas-/- mice. In keeping with the observations in C57BL6/N Mas-/- mice, the number and percentage of pancreatic {alpha}-cells were also significantly increased in these mice (number of {alpha}-cells: 260 +/- 22 vs. 156 +/- 12 in WT, p<0.001; percentage per islet: 16 +/- 0.8 vs. 10 +/- 0.5% in WT, p<0.0001). These results suggest that Mas has a previously unexpected role on the pancreatic glucagon production

    Quality evaluation of minoxidil topical solutions obtained from magistral pharmacies

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    The objective of this study was to evaluate quality parameters of magistral topical solutions containing minoxidil (A, B and C), comparing the results with the ones obtained for the industrial formulation. Organoleptic tests, evaluation of the pH and density, centrifuge test, drug content determination, comparison of indicated dosages and in vitro follicular penetration of minoxidil were performed. Regarding the organoleptic properties, differences in color and viscosity were observed between the magistral (composed of minoxidil sulfate) and the industrial formulations (composed of minoxidil base). For pH values, the magistral solutions presented considerably more acidic pH, compared to the industrial sample. For the density test, the samples with the highest ethanol percentages (B and C) presented lower density. In the centrifuge test, none of the samples showed changes. Considering the drug content test, only the industrial sample and the magistral sample C showed drug percentage within the expected (90-110%), indicating lack of correction factor determination by the magistral pharmacies. Furthermore, it was observed that the dosage indicated by the magistral pharmacies do not correspond to the dose indicated by the industry, being significantly lower. All topical solutions tested presented hair follicle penetration of minoxildil, without statistical difference. The results indicate that there is a failure in the magistral pharmacies regarding the production and the indication of dosage of minoxidil topical solutions

    Increased vascular sympathetic modulation in mice with Mas receptor deficiency

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    Introduction: The angiotensin-converting enzyme 2 (ACE2)/angiotensin (Ang)-(1–7)/Mas axis could modulate the heart rate (HR) and blood pressure variabilities (BPV) which are important predictors of cardiovascular risk and provide information about the autonomic modulation of the cardiovascular system. Therefore we investigated the effect of Mas deficiency on autonomic modulation in wild type and Mas-knockout (KO) mice. Methods: Blood pressure was recorded at high sample rate (4000 Hz). Stationary sequences of 200–250 beats were randomly chosen. Frequency domain analysis of HR and BPV was performed with an autoregressive algorithm on the pulse interval sequences and on respective systolic sequences. Results: The KO group presented an increase of systolic arterial pressure (SAP; 127.26±11.20 vs 135.07±6.98 mmHg), BPV (3.54±1.54 vs 5.87±2.12 mmHg2), and low-frequency component of systolic BPV (0.12±0.11 vs 0.47±0.34 mmHg2). Conclusions: The deletion of Mas receptor is associated with an increase of SAP and with an increased BPV, indicating alterations in autonomic control. Increase of sympathetic vascular modulation in absence of Mas evidences the important role of Ang-(1–7)/Mas on cardiovascular regulation. Moreover, the absence of significant changes in HR and HRV can indicate an adaptation of autonomic cardiac balance. Our results suggest that the Ang-(1–7)/Mas axis seems more important in autonomic modulation of arterial pressure than HR
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