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ABSTRACT Introduction: The use of oral contraceptives increases women's risk of developing cardiovascular and thromboembolic diseases, due to alterations in hemostatic and lipid profile. Objectives: Analyze the association between the use of different types of oral contraceptives with lipid profile and levels of serum high-sensitivity C-reactive protein (hsCRP) and plasma D-dimer. Methods: One hundred fifty-four participants were divided into the following groups: control nonusers (n = 41), medium-dose users (n= 32), third-generation low-dose users (n = 40), and fourth-generation low-dose users (n = 41). Triglycerides and total cholesterol serum levels were determined by colorimetric enzymatic method; high-density lipoprotein (HDL) cholesterol levels, by precipitation method; low-density lipoprotein (LDL) cholesterol levels, by Friedewald equation; hsCRP levels, by immunoturbidimetric method; and D-dimer levels, by fluorescence immunoassay. Results: Oral contraceptive users had higher serum levels of triglycerides, total cholesterol, HDL cholesterol (HDL-C), HDL/LDL index and hsCRP compared to controls. Medium-dose users had higher D-dimer plasma levels than controls and higher triglycerides serum levels than low-dose users. Triglycerides, hsCRP and D-dimer were positively correlated to each other. Conclusion: The use of combined oral contraceptives was associated with an unfavorable lipid profile and a chronic subclinical inflammation, with atherogenic potential. Furthermore, medium-dose contraceptives induced a higher thrombogenic potential, since they were associated with increased D-dimer levels in comparison to low-dose ones.
RESUMO Introdução: O uso de anticoncepcionais orais aumenta o risco de desenvolvimento de doenças cardiovasculares e tromboembólicas devido a alterações no perfil lipídico e hemostático. Objetivo: Analisar a associação entre o uso de diferentes tipos de anticoncepcionais orais com o perfil lipídico e os níveis da proteína C reativa ultrassensível (PCRus) e do dímero D. Métodos: Cento e quarenta e cinco participantes foram divididas em: não usuárias (n = 41), usuárias de média dose (n = 32), usuárias de terceira geração de baixa dose (n = 40) e usuárias de quarta geração de baixa dose (n = 41). Níveis de triglicerídeos e colesterol total foram determinados pelo método enzimático colorimétrico; colesterol da lipoproteína de alta densidade (HDL), pelo método de precipitação; colesterol da lipoproteína de baixa densidade (LDL), pela equação de Friedewald; PCRus, por imunoturbidimetria; e dímero D, por imunoensaio fluorescente. Resultados: As usuárias de anticoncepcionais orais apresentaram maiores níveis de triglicerídeos, colesterol total, HDL, índice HDL/LDL e PCRus do que as não usuárias. As usuárias de anticoncepcionais de média dose apresentaram maiores níveis de dímero D do que as não usuárias, e maiores níveis de triglicerídeos do que as usuárias de anticoncepcionais de baixa dose. Triglicerídeos, PCRus e dímero D apresentaram correlação positiva uns com os outros. Conclusão: O uso de anticoncepcionais orais combinados está associado ao perfil lipídico desfavorável e à inflamação crônica subclínica, com potencial aterogênico. Além disso, os anticoncepcionais orais de média dose induziram maior potencial trombogênico, já que foram relacionados com níveis maiores de dímero D em comparação com os de baixa dose.
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Cardiotonic steroids (CS), natural compounds with traditional use in cardiology, have been recently suggested to exert potent anticancer effects. However, the repertoire of molecules with Na,K-ATPase activity and anticancer properties is limited. This paper describes the synthesis of 6 new digoxin derivatives substituted (on the C17-butenolide) with γ-benzylidene group and their cytotoxic effect on human fibroblast (WI-26 VA4) and cancer (HeLa and RKO) cell lines as well as their effect on Na,K-ATPase activity and expression. As digoxin, compound BD-4 was almost 100-fold more potent than the other derivatives for cytotoxicity with the three types of cells used and was also the only one able to fully inhibit the Na,K-ATPase of HeLa cells after 24h treatment. No change in the Na,K-ATPase α1 isoform protein expression was detected. On the other hand it was 30-40 fold less potent for direct Na,K-ATPase inhibition, when compared to the most potent derivatives, BD-1 and BD-3, and digoxin. The data presented here demonstrated that the anticancer effect of digoxin derivatives substituted with γ-benzylidene were not related with their inhibition of Na,K-ATPase activity or alteration of its expression, suggesting that this classical molecular mechanism of CS is not involved in the cytotoxic effect of our derivatives.
