ABSTRACT
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.
Subject(s)
Myocytes, Cardiac/drug effects , Peptidyl-Dipeptidase A/metabolism , Testosterone/pharmacology , Tumor Necrosis Factor-alpha/metabolism , Animals , Apoptosis/drug effects , Caspase 3/metabolism , Cell Line , Myocytes, Cardiac/metabolism , Rats , Renin-Angiotensin System/drug effects , Signal Transduction/drug effectsABSTRACT
RESUMO No Brasil, a família Malvaceae está representada por aproximadamente 200 espécies e algumas foram descritas como gastroproteroras. Pavonia alnifolia A.St.-Hil. (Malvaceae) foi selecionada após uma abordagem quimiossistemática, considerando-se sua potencial capacidade em prevenir lesões gástricas. Assim, a atividade gastroprotetora do extrato etanólico de caules de P. alnifolia foi avaliada utilizando o modelo de indução aguda da lesão gástrica por etanol acidificado em camundongos. Além disso, foram quantificados o teor de flavonóides, pelo método de cloreto de alumínio, e de polifenóis, pelo método Folin-Ciocalteu, uma vez que a relação desses componentes com a proteção gástrica foi evidenciada. Os ensaios apontaram redução acentuada das lesões gástricas em camundongos tratados com o extrato da planta em todas as doses ensaiadas (10, 100 e 300 mg/kg). Esse efeito pode estar relacionado com a presença de polifenóis, cujo teor encontrado foi 74,3 ± 7,5 µg equivalente de pirogalol/mg do material vegetal examinado e 82,7 ± 7,1 µg equivalente de pirogalol /mg da amostra no extrato preparado por percolação e teor de flavonoides totais, que por sua vez apresentou um resultado de 17,1 ± 1,4 µg/mg de extrato. O extrato apresentou proteção da mucosa gástrica e este efeito pode estar relacionado à presença dos polifenóis e flavonóides encontrados
ABSTRACT Gastro protective activity of the Pavonia alnifolia A.St.-Hil. extract. In Brazil, the Malvaceae family is represented by at about 200 species. Some of those species are known as gastro protective ones. The Pavonia alnifolia A.St.-Hil (Malvaceae) was selected after a chemosystematic approach. The gastro preventive activity of the ethanol extract of stems Pavonia alnifolia was evaluated through the use of the Ethanol:chlroridric acid model on mice. The quantification of the total flavonoids (aluminum chloride method) and total polyphenols (Folin-Ciocalteu method) was also performed since the relation of those components with gastric protection has been previously highlighted. The tests showed a significant reduction of the ulcer formation in the mice treated with the plant extract (10, 100 and 300 mg/kg). This effect may be related to the presence of polyphenols whose content was found to be 74.3 ± 7.5 µg/mg of vegetal material and 82.7 ± 7.1 µg/mg of crude extract and flavonoids, which in turn showed a content of 17.1 ± 1.4 µg/mg dry extract
Subject(s)
Plant Extracts/analysis , Malvaceae/classification , Flavonoids/analysis , Polyphenols/analysisABSTRACT
P/SL Healthcare System, Denver, just completed a five-year ordeal of consolidating two hospitals, expanding tertiary services and building and moving into a new $120 million facility, Presbyterian-St. Luke's Medical Center. The process was interrupted by the sale of the hospitals, which forced a construction halt. In this interview with Donald E.L. Johnson, editor and publisher of Health Care Strategic Management, Donald W. Lenz, president of P/SL Medical Center, discusses planning the merger, constructing the facility, managing the move and positioning the hospital for the future. The hospital's design is innovative, with parts of the facility resembling a fine hotel. The curved building is attractive and improves productivity by concentrating central services in easily accessible areas.