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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 67 (1989), S. 707-712 
    ISSN: 1432-1440
    Keywords: Ketoconazole ; Androgens ; Inhibition of adrenal androgen secretion ; Hirsutism ; Hyperandrogenism therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of ketoconazole on adrenal androgen secretion was examined in 15 patients with elevated serum androgens. In a dose of 600 mg per day orally ketoconazole inhibited the biosynthesis of all measured androgens. The mean reduction in serum levels of dehydroepiandrosterone sulfate was 32%, of dehydroepiandrosterone 54%, of androstenedione 52%, and of testosterone 43%; mean serum levels of cortisol only fell by 19%. The reduction in serum androgen levels was first significant 24 h after beginning of treatment and persisted as long as the drug was administered. We conclude that ketoconazole inhibits adrenal androgen biosynthesis more pronouncedly than cortisol biosynthesis. This might be of clinical benefit in the treatment of hirsutism and other states of androgen hypersecretion.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1440
    Keywords: Etomidate ; Ketoconazole ; Steroid biosynthesis ; Adrenal gland ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The narcotic agent etomidate and the antimycotic drug ketoconazole are known to block steroid biosynthesis in man. To study the different effects of these imidazole derivatives on human adrenal steroid biosynthesis we incubated slices of human adrenal glands with 3H-labeled precursors and increasing concentrations of etomidate or ketoconazole (0-2000 μM). After extraction the labeled metabolites were separated by thin-layer chromatography and quantified by scintillation counting. Etomidate inhibited most potently 11β-hydroxylase activity by suppressing the formation of corticosterone from 11-deoxycorticosterone to 1 % of control [50% inhibitory concentration (IC50) 0.03 μM] while ketoconazole suppressed 11β-hy-droxylase to only 39% of control activity (IC50 15 μM). Ketoconazole however, most potently blocked the conversion of 17α-hydroxy-proges-terone to androstenedione by C17,20-desmolase to about 15% of control activity (IC50 1 μM) while etomidate showed a much weaker effect on this enzyme with a suppression to 50% of C17,20-desmolase control activity at a concentration of 380 μM. Both imidazole drugs showed a similar strong inhibitory effect on the activity of 17α-hy-droxylase (IC50 6-18 μM) and 16α-hydroxylase (IC50 4–8 μM) and did not affect 21-hydroxylase. These in vitro data indicate a predominant inhibitory effect of etomidate on corticosteroid biosynthesis by relative selective inhibition of 11β-hydroxylase and of ketoconazole on the adrenal androgen biosynthesis by a predominant inhibition of C17,20-desmolase. This differential inhibitory effect of etomidate and ketoconazole on human steroid biosynthesis may be of clinical importance for a possible therapeutic use of these imidazole derivatives in endocrine disorders.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1434-601X
    Keywords: 21.10.Ft ; 25.70.Np ; 27.40.+z
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract At the projectile-fragment separator FRS of GSI, relativistic secondary beams of about 520 MeV/nucleon were produced by fragmentation of a primary beam of58Ni at 650 MeV/nucleon in a beryllium target. By means of aΔE—Bρ—TOF measurement, the fragments were identified and their charge-changing probabilities in targets of (CH2) n , C, Al, and Pb placed at the exit of the FRS were determined. Whereas a first article dealt with the total charge-changing cross sections, we describe in this second article the element distributions of these secondary fragments, which are found to depend strongly on the isospin of the secondary projectile as well as on the target material. In the case of the lead target, the influence of the electromagnetic dissociation is clearly visible in the one-proton and two-proton removal channels. The preference for the formation of even-Z fragments is much more pronounced for exotic secondary projectiles than for projectiles close to stability. Calculations with a geometrical abrasion-ablation model allow to understand the global features of the experimental data. However, far from stability, the discrepancies between calculations and experimental data increase.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1434-601X
    Keywords: 21.10.Ft ; 25.70.Np ; 27.40.+Z
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract At the projectile-fragment separator FRS of GSI, relativistic secondary beams of about 520 MeV/nucleon were produced by fragmentation of a primary beam of58Ni at 650 MeV/nucleon in a beryllium target. By means of aΔE—Bρ—TOF measurement, the fragments have been identified and their charge-changing probabilities in targets of CH2, C, Al, and Pb have been determined. We describe the results for the total charge-changing cross sections in this first paper, whereas a second article deals with the partial charge-changing cross sections. At the drip line, the measured charge-changing cross sections exhaust close to 100% of the total interaction cross sections as calculated with semiempirical models. The measurements at the proton drip line with low-Z targets indicate that only a very small increase of the cross sections may be observed, whereas the measurements with a lead target show that no significant increase of the total charge-changing cross sections is present which would be a hint for low-lying dipole strength. Our experimental data are compared to Glauber-type calculations.
    Type of Medium: Electronic Resource
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