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Aims:The aim of this study was to investigate the antihypertensive effect of leaves Mangifera indica L. using in vitro and in vivo assays. Methodology: The ethanol extract of leaves of M. indica was fractionated to dichloromethanic, n-butyl alcohol and aqueous fractions. The chemical composition of ethanolic extract and dichloromethanic fraction were evaluated by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Antioxidant activity was evaluated in the DPPH scavenging activity assay. Angiotensin-converting enzyme (ACE) inhibitory activity was investigated using in vitro and in vivo assays. The chronic antihypertensive assay was performed in spontaneously hypertensive rats (SHRs) and Wistar rats treated with enalapril (10 mg/kg), dichloromethanic fraction (100 mg/kg; twice a day) or vehicle control for 30 days. The baroreflex sensitivity was evaluated through the use of sodium nitroprusside and phenylephrine. Cardiac hypertrophy was evaluated by morphometric analysis. Results: The dichloromethanic fraction exhibited the highest flavonoid, total phenolic content and high antioxidant activity. Dichloromethanic fraction elicited ACE inhibitory activity in vitro (99 ± 8%) similar to captopril. LC-MS/MS analysis revealed the presence of ferulic acid (48.3 ± 0.04 µg/g) caffeic acid (159.8 ± 0.02 µg/g), gallic acid (142.5 ± 0.03 µg/g), apigenin (11.0 ± 0.01 µg/g) and quercetin (203.3 ± 0.05 µg/g). The chronic antihypertensive effects elicited by dichloromethanic fraction were similar to those of enalapril, and the baroreflex sensitivity was normalized in SHR. Plasma ACE activity and cardiac hypertrophy were comparable with animals treated with enalapril. Conclusions: Dichloromethanic fraction of M. indica presented an antihypertensive effect, most likely by ACE inhibition, with benefits in baroreflex sensitivity and cardiac hypertrophy. Altogether, the results of the present study suggest that the dichloromethanic fraction of M. indica leaves may have potential as a promoting antihypertensive agent.

The germline R337H mutation in the TP53 gene is considered to be responsible for the increased incidence of adrenocortical tumors (ACTs) in children from Brazil. High level production of hormones in ACTs (>95%) cause virilization alone (60%), Cushing syndrome (<5%), the mixed type (30%), or other rarer manifestations. ACT probably develops owing to events occurring during the final stages of intrauterine life based on the very common early onset of signs and symptoms shortly after birth. In this study, we determined by immunohistochemistry and enzyme assays whether placental alkaline phosphatase (PLAP) is expressed in pediatric ACTs. Immunohistochemical analysis revealed positive p53 expression in 88% of the tested ACTs (29 of 33). PLAP was detected at a slightly lower frequency based on immunohistochemical (17 of 33, 51%) and enzyme activity analyses (9 of 16, 56%). In conclusion, probably at a certain time point during adrenocortical development (end of gestation to early postnatal period), some fetal zone cells survive owing to defective apoptosis and develop into childhood ACT, maintaining some characteristics of the embryonal period, such as PLAP expression. Further studies of PLAP should investigate the functional role, if any, of PLAP in such tumors.

Anabolic androgenic steroids lead to cardiac complications and have been shown to exhibit proapoptotic effects in cardiac cells; however, the mechanism involved in those effects is unclear. The aim of this study was to assess whether apoptosis and the activation of caspase-3 (Casp-3) induced by testosterone in high concentrations involves increments in tumor necrosis factor-α (TNF-α) concentrations and angiotensin-converting enzyme (ACE) activity in cardiomyocytes (H9c2) cell cultures. Cardiomyocytes were treated with testosterone (5 × 10−6 mol/L), doxorubicin (9.2 × 10−6 mol/L), testosterone + etanercept (Eta; 6.67 × 10−5 mol/L), testosterone + losartan (Los; 10−7 mol/L), and testosterone + AC-DEVD-CHO (10−5 mol/L; Casp-3 inhibitor). Apoptosis was determined by flow cytometry and by the proteolytic activity of Casp-3. We demonstrated that incubation of H9c2 cells for 48 h with testosterone causes the apoptotic death of 60–70% of the cells and co-treatments with Eta, Los, or AC-DEVD-CHO reduced this effect. Testosterone also induces apoptosis (concentration dependent) and increases the proteolytic activity of Casp-3, which were reduced by co-treatments. TNF-α and ACE activities were elevated by testosterone treatment, while co-treatment with Los and Eta reduced these effects. We concluded that an interaction between testosterone, angiotensin II, and TNF-α induced apoptosis and Casp-3 activity in cultured cardiomyocytes, which contributed to the reduced viability of these cells induced by testosterone in toxic concentrations.

A score of quality (SQ) was calculated using variables such as impact factor and the frequency of the citations. We included 3265 articles published in 544 journals. We found that there was a steady increase in scientific production since 1990 and that the USA had a higher quality of scientific production than Spain, whereas the Spain produced the highest quantity of articles. In comparison, the Brazilian production of scientific publications on PC is low in terms of both quality and quantity but has increased steadily since 2002. Nevertheless, Brazil has not yet reached the level of the USA or Spain. In conclusion, Brazil's scientific production has evolved over the second decade studied in this work, with particularly high levels of production in the last five years. However, an increase in the quantity and quality of the publications should be encouraged.Uniterms: Pharmaceutical care/scientific production. Brazil/pharmaceutical care/scientific production. Spain/pharmaceutical care/scientific production. United States of America/pharmaceutical care/scientific production.O objetivo deste estudo foi estimar a evolução da área de atenção farmacêutica (AF) através da medição da qualidade e quantidade da produção científica na área de AF no Brasil, comparando-a com os países pioneiros no ramo: Estados Unidos da América (EUA) e Espanha. Os bancos de dados Web of Science, Scopus, Medline, Lilacs e SciELO foram usados como fontes para a pesquisa. AF ou as respectivas traduções foram usadas como descritor para a pesquisa bibliográfica sendo incluídos artigos publicados no período de 1990 a 2009. A pontuação da qualidade (PQ) foi calculada, utilizando variáveis como fator de impacto e frequência das citações. Foram cincluídos 3.265 artigos publicados em 544 revistas. Verificou-se um aumento constante na produção científica desde 1990 sendo que os EUA possuíam maior qualidade, enquanto a maior quantidade de artigos foi produzida na Espanha. Em comparação, a produção brasileira na AF é baixa em qualidade e quantidade, mas tem aumentado desde 2002. Apesar disso, o Brasil ainda não atingiu o nível dos EUA ou Espanha. Em conclusão, o Brasil apresentou expressiva evolução na última década com maior desenvolvimento nos últimos cinco anos. Entretanto, melhoria na quanitdade e qualidade das publicações deve ser incentivada.Unitermos: Atenção Farmacêutica/produção científica. Brasil/atenção farmacêutica/produção científica. Espanha/atenção farmacêutica/produção científica. Estados Unidos da América/atenção farmacêutica/ produção científica.