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  • 1
    ISSN: 0304-4165
    Keywords: Cyanine dyes ; Heavy atom effect ; Liposomes ; Photophysics ; Photosensitization ; Singlet oxygen
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 0303-7207
    Keywords: androgen receptor ; molybdate ; musculature ; prostate
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 0584-8547
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 0960-0760
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1041
    Keywords: Key words Fluticasone propionate ; Inhalation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: To evaluate the pharmacokinetic and systemic pharmacodynamic properties of inhaled fluticasone propionate (FP). Methods: Single doses of 0.25, 0.5, 1.0 and 3.0 mg FP were administered to groups of six healthy subjects. Serum concentration profiles of FP were monitored over 24 h by means of high-performance liquid chromatography/mass spectrometry (HPLC/MS–MS). Systemic pharmacodynamic effects were evaluated by measuring endogenous serum cortisol and circulating white blood cells, and analyzed with previously developed integrated pharmacokinetic/pharmacodynamic (PK/PD) models. Results: FP showed a dose-independent terminal half-life with a mean (SD) of 6.0 (0.7) h. Maximum serum concentrations occurred 1.0 (0.5) h after administration, ranging from 90 pg · ml−1 for the 0.25 mg dose to 400 pg · ml−1 for the 3.0 mg dose. This, together with an estimated mean absorption time of nearly 5 h and a known oral bioavailability of less than 1%, indicates prolonged residence at and slow absorption from the lungs. In the investigated dose range, the cumulative systemic effect was dose-dependent for both markers of pharmacodynamic activity. For doses of 0.25, 0.50, 1.0 and 3.0 mg FP, the PK/PD-based cumulative systemic-effect parameters were 159, 186, 257 and 372% · h for lymphocyte suppression, 107, 186, 202 and 348% · h for granulocyte induction and 23.6%, 33.8%, 51.0% and 73.6% for cortisol reduction, respectively. The time courses of lymphocytes, granulocytes and endogenous cortisol could be sufficiently characterized with the applied PK/PD models. The measured in vivo EC50 values, 30 pg · ml−1 and 7.3 pg · ml−1 for white blood cells and cortisol, respectively, were in good agreement with predictions based on the in vitro relative receptor affinity of FP. Conclusion: After inhalation, FP follows linear pharmacokinetics and exhibits dose-dependent systemic pharmacodynamic effects that can be described by PK/PD modeling.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1433-0563
    Keywords: Schlüsselwörter BPH ; Androgenmetabolismus ; Estrogene ; Alter ; Key words BPH ; Androgen metabolism ; Estrogens ; Aging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Although human benign prostatic hyperplasia (BPH) is the most common tumor in men, its etiology is still unclear. At present, it is only widely accepted that BPH is under the endocrine control of the testes and strongly associated with aging. Therefore, in the human prostate we describe the impact of aging on the activity of various androgen metabolizing enzymes as well as on the endogenous androgen and estrogen levels. Moreover, the inhibition of 5α-reductase by finasteride (Proscar®) will be reported. Among all androgen metabolizing enzymes, within the human prostate 5α-reductase is the most powerful one. Most of the androgen metabolizing enzymes undergo a significant age-dependent alteration. For distinct enzymes, the correlation with age is either negative (e. g. 5α-reductase), or positive. Despite a complex pattern of age-dependent alterations, the dominance of 5α-reductase among all androgen metabolizing enzymes is always maintained. This is underlined by a strong accordance between the age-dependent 5α-reductase activity and the corresponding age-dependent endogenous DHT level. In epithelium, both the 5α-reductase activity and the DHT level decrease with age, whereas in stroma not only the 5α-reductase activity is rather constant over the whole age range but the DHT level as well. In contrast to the relatively unaltered DHT content in the stroma of the human prostate, the estrogen content follows an age-dependent increase. On the other side, in epithelium such a positive correlation between the estrogen level and age is not found. Thus, the age-dependent decrease of the DHT accumulation in epithelium and the concomitant increase of the estrogen accumulation in stroma will lead to a tremendous increase with age of the estrogen/androgen ratio in the human prostate. This could be of pathogenetic importance for BPH development if in fact a balanced androgen/estrogen synergism is necessary for the integrity of the normal human prostate. Finally, it is remarkable that the inhibition of 5α- reductase activity by finasteride (Proscar®) is significantly stronger in epithelium than in stroma. Therefore, it is conceivable that the global size-reduction of BPH under finasteride treatment is primarily due to the regression of BPH epithelium.
    Notes: Zusammenfassung Es wird über altersabhängige Veränderungen der Enzyme des Androgenstoffwechsels und der endogenen Steroidkonzentrationen in der Prostata berichtet. Darüber hinaus wird die Hemmung der 5α-Reduktase durch Finasterid dargestellt. Die 5α-Reduktase besitzt von allen androgenmetabolisierenden Enzymen die höchste Aktivität. Die meisten der Enzyme unterliegen einer signifikanten altersabhängigen Veränderung. Eine Dominanz der 5α-Reduktase gegenüber allen anderen Enzymen bleibt trotz dieser altersabhängigen Veränderungen über den gesamten Altersbereich gewahrt. Dies wird dadurch unterstrichen, daß die endogene DHT-Konzentration den gleichen altersabhängigen Veränderungen unterliegt wie die 5α-Reduktaseaktivität. Berücksichtigt man die ebenfalls gemessenen Estrogenspiegel in der Prostata, so zeigt sich mit zunehmendem Alter ein deutlicher Anstieg des Estrogen-Androgen-Quotienten im Epithel und Stroma. Sollte die Integrität der normalen Prostata einen ausbalancierten Synergismus zwischen Androgenen und Estrogenen voraussetzen, ist ein kausaler Zusammenhang zwischen der altersbedingten Zunahme des Estrogen-Androgen-Quotienten und der BPH-Entwicklung denkbar. Therapeutisch von Interesse ist, daß die 5α-Reduktaseaktivität im Epithel durch Finasterid signifikant stärker gehemmt wird als im Stroma. Somit ist wahrscheinlich die unter Finasteridtherapie erzielbare Volumenreduktion der BPH primär auf eine Regression des Epithels zurückzuführen.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1433-2965
    Keywords: Quantitative ultrasound ; Bone ; Institutionalized elderly
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Quantitative ultrasound of bone is a promising method for bone assessment: radiation-free, portable and predictive of hip fracture. Its portability allowed us to study the relationships between ultrasonic parameters of bone with age and with non-vertebral fractures in elderly women living in 19 nursing homes. Broadband ultrasound attenuation (BUA) and speed of sound (SOS) of the calcaneus were measured (and the stiffness index calculated) in a sample of 270 institutionalized women, aged 85±7 years, using an Achilles bone densitometer (Lunar). The effects of age, history of non-vertebral and non-traumatic fractures, body mass index, triceps skinfold and arm circumference were assessed on BUA, SOS and stiffness index. Furthermore, to evaluate longitudinally the influence of aging on the ultrasound parameters of bone, 60 subjects from the same group had a second ultrasound measurement after 1 year. The cross-sectional analysis of the data on all 270 women showed a significant decrease (p〈0.001) with age in BUA, SOS and stiffness index (−0.47%, −0.06%, and −1.01% respectively per year). In the 94 women (35%) with a history of previous non-vertebral fractures, ultrasound parameters were significantly lower (p〈0.0001) than in the 176 women with no history of fracture (−8.3% for BUA, −1.3% for SOS, −18.9% for stiffness index). In contrast, there was no significant difference in anthropometric measurements between the groups with and without previous non-vertebral fractures, although the measurements decreased significantly with age. In the longitudinal study, repeated quantitative ultrasound after 11.4±0.8 months showed no significant decrease in BUA (−1%) but a significant decrease in SOS (−0.3%,p〈0.0001) and in stiffness index (−3.6%,p〈0.0002). In conclusion, quantitative ultrasound of the calcaneus measures properties of bone which continue to decline in institutionalized elderly women, and is able to discriminate women with previous non-vertebral fractures.
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  • 8
    ISSN: 1433-2965
    Keywords: Key words:Institutionalized elderly – Secondary hyperparathyroidism – Ultrasound of bone – Vitamin D deficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: Supplementation of elderly institutionalized women with vitamin D and calcium decreased hip fractures and increased hip bone mineral density. Quantitative ultrasound (QUS) measurements can be performed in nursing homes, and easily repeated for follow-up. However, the effect of the correction of vitamin D deficiency on QUS parameters is not known. Therefore, 248 institutionalized women aged 62–98 years were included in a 2-year open controlled study. They were randomized into a treated group (n = 124), receiving 440 IU of vitamin D3 combined with 500 mg calcium (1250 mg calcium carbonate, Novartis) twice daily, and a control group (n = 124). One hundred and three women (42%), aged 84.5 ± 7.5 years, completed the study: 50 in the treated group, 53 in the controls. QUS of the calcaneus, which measures BUA (broadband ultrasound attenuation) and SOS (speed of sound), and biochemical analysis were performed before and after 1 and 2 years of treatment. Only the results of the women with a complete follow-up were taken into account. Both groups had low initial mean serum 25-hydroxyvitamin D levels (11.9 ± 1.2 and 11.7 ± 1.2 mg/l; normal range 6.4–40.2 mg/l) and normal mean serum parathyroid hormone (PTH) levels (43.1 ± 3.2 and 44.6 ± 3.5 ng/l; normal range 10–70 ng/l, normal mean 31.8 ± 2.3 ng/l). The treatment led to a correction of the metabolic disturbances, with an increase in 25-hydroxyvitamin D by 123% (p50.01) and a decrease in PTH by 18% (p50.05) and of alkaline phosphatase by 15% (p50.01). In the controls there was a worsening of the hypovitaminosis D, with a decrease of 25-hydroxyvitamin D by 51% (p50.01) and an increase in PTH by 51% (p50.01), while the serum calcium level decreased by only 2% (p5 0.01). After 2 years of treatment BUA increased significantly by 1.6% in the treated group (p50.05), and decreased by 2.3% in the controls (p50.01). Therefore, the difference in BUA between the treated subjects and the controls (3.9%) was significant after 2 years (p50.01). However, SOS decreased by the same amount in both groups (approximately 0.5%). In conclusion, BUA, but not SOS, reflected the positive effect on bone of supplementation with calcium and vitamin D3 in a population of elderly institutionalized women.
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  • 9
    ISSN: 1434-601X
    Keywords: 23.40.−s ; 29.25.Cy ; 32.80.RM
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract A chemically selective laser ion source based on resonance ionization of atoms in a hot cavity has been applied for the study of short-lived silver isotopes at CERN/ ISOLDE. Silver atoms were ionized by two resonant excitations and final laser ionization into the continuum. Decay properties of the neutron-rich isotopes121–127Ag were studied with a neutron long-counter and aβ-detector.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Journal of Steroid Biochemistry 17 (1982), S. lxxxi 
    ISSN: 0022-4731
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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