1,721,191 research outputs found
The Effect of SEX/Gender on Cardiovascular Pharmacology
No full textAbstract: Cardiovascular diseases differ between men and women as do outcomes after therapeutic interventions. Management of these
diseases, however, is generally guided by evidence from trials conducted predominantly in men, with few studies focused on women
alone. Our goal is to review the sex/gender differences in cardiovascular therapies, which show many areas of uncertainty regarding
women due to their small enrolment in clinical trials; thus, in some cases, firm conclusions about efficacy in women are difficult to obtain.
Nevertheless, female gender appears to suffer from more adverse drug effects (ADE) than the male gender. For example, women are
significantly more likely to experience drug-induced QT-prolongation and torsade de pointes arrhythmia and many other types of ADE.
The major sex-specific differences present in pharmacokinetics, especially for the major drug metabolizing enzymes, the cytochromes
P450 family, but also for phase II reactions such as glucuronidation, are discussed. Pharmacodynamic mechanisms underlying sex/gender
differences are not clearly elucidated yet; however, this highlights the need for more studies focusing on women in order to optimize
sex/gender-specific therapy and, therefore, improve clinical outcomes in women with cardiovascular diseases
Redox state, cell death and autoimmune diseases: A gender perspective. Autoimmun Rev 7:579-84. 2008
No full textCYTOSKELETON AS A TARGET IN MENADIONE-INDUCED OXIDATIVE STRESS IN CULTURED-MAMMALIAN-CELLS .1. BIOCHEMICAL AND IMMUNOCYTOCHEMICAL FEATURES
No full textCytoskeletal abnormalities occurring during oxidative stress generated by the metabolism of the redox cycling compound 2-methyl-1,4-naphtoquinone (menadione) have been investigated in different mammalian cells in culture. Extraction of the whole cytoskeleton as well as the intermediate filament- and the microtubule-enriched fractions from menadione-treated cells revealed a marked depletion of protein sulfhydryl groups. The analysis of the whole cytoskeletal fraction by PAGE showed a menadione-dependent and thiol-sensitive oxidation of actin, leading to the formation of high-molecular-weight aggregates. In addition, the extraction of this fraction with high concentrations of KCl entailed only a partial solubilization of actin. The comparative cytochemical analysis performed on treated cells showed a menadione-dependent clustering of actin microfilaments. The metabolism of menadione induced microtubule depolymerization and inhibition of GTP-induced microtubule assembly from soluble cytosolic components. The latter phenomenon was prevented by previously treating the cytosolic fraction with thiol reductants such as dithiothreitol. Menadione increased the protein content of the intermediate-size filament fraction, partially purified by one or more cycles of disassembly/assembly, and particularly enriched in polypeptides reacting with antikeratin antibodies. Furthermore, a reversible and oxidation-dependent change of the electrophoretic mobility of some polypeptides in this fraction was detected. The immunocytochemical investigation of intermediate-size filament distribution in menadione-treated cells, however, revealed only minor modifications mainly consisting of perinuclear condensation of cytokeratin structures. These findings suggest that cytoskeletal structures (actin microfilaments, microtubules, and intermediate-size filaments) are actually significant targets in quinone-induce
Cytoskeleton as a target in menadione-induced oxidative stress in cultured mammalian cells. I. Biochemical and immunocytochemical features
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Gender specific features of plasmatic and circulating cell alterations as risk factors in cardiovascular disease
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