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  • 1
    ISSN: 1432-1041
    Keywords: triamcinolone acetonide ; triamcinolone acetonide phosphate ; pharmacokinetics ; high dose ; glucocorticoids ; renal excretion ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Triamcinolone acetonide in the form of its phosphate ester was given intravenously in two different doses (10 mg/kg and 80 mg). Plasma levels of the ester and triamcinolone acetonide were measured and pharmacokinetic parameters were calculated. The pharmacokinetics both of the phosphate and the free alcohol were dose-dependent. No unchanged ester was found in the urine, indicating complete conversion of the pro-drug. Triamcinolone was not a major metabolite of triamcinolone acetonide in humans. Renal clearance was low and independent of the dose. Only about 1% of the dose was found in the urine as triamcinolone acetonide.
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  • 2
    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.
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  • 3
    ISSN: 1432-2013
    Keywords: Physical Exercise ; Enzyme Activities ; Liver Alterations ; Microscopic Observations ; Körperliches Training ; Enzymaktivität ; Leberveränderungen ; Mikroskopische Beobachtungen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Licht- und elektronenmikroskopische Längsschnittuntersuchungen des Leberparenchyms untrainierter und trainierter Ratten vor und nach körperlicher Belastung ergaben bei paralleler Bestimmung von verschiedenen Fermentaktivitäten im Serum einen signifikanten Zusammenhang zwischen Training und Leistungssteigerung. Durch die schonende transcutane Leberblindpunktion waren mehrere Versuchsfolgen an ein und demselben Tier möglich. Bei untrainierten Ratten wurden nach Belastung durch den Schwimmtest destruktive Veränderungen des Leberzellgefüges, Umbauvorgänge im Bereich der meta- und paraplasmatischen Substrukturen sowie statistisch gesicherte Abweichungen der Serumenzymspiegel gegenüber 10 Tage vorher ermittelten morphologischen und enzymologischen Normalbefunden beobachtet. Nach einer Trainingsphase von ca. 4 Wochen kam es zu einer Adaptation des Leberstoffwechsels auf den unphysiologischen Belastungsreiz, die sich in einer deutlichen Vermehrung von Zellorganellen (Mitochondrien, Ribosomen) und einer leichten Steigerung der Fermentaktivitäten von Glutamat-Oxalacetat-Transaminase (GOT), Glutamat-Pyruvat-Transaminase (GPT), Lactat-Dehydrogenase (LDH) und Abnahme der Aldolase (ALD) erkennbar machte und dazu führte, daß bei einer weiteren Schwimmbelastung neben einer erheblichen Leistungssteigerung die ohne vorheriges Training beobachteten schweren fermentativen und Leberzellveränderungen nicht mehr auftraten. Ursachen der beschriebenen Reaktionen in den Leberzellen und im enzymatischen Status sowie der Einfluß des Trainings auf den Leberstoffwechsel nach körperlicher Belastung werden diskutiert.
    Notes: Summary Light- and electron-microscopic longitudinal sections of the hepatic tissue of trained and untrained rats before and after physical exercise revealed a significant relationship between training and performance. The same results were found by parallel determination of different enzyme activities. Using an indulgent transcutaneous liver puncture, numerous experiments using the same animal were possible. Untrained rats showed after a strenuous program of swimming destructive alterations of the liver cell framework and alterations in the area of meta- and paraplasmatic substructures. Statistically significant differences were observed in serum enzyme levels, compared with results obtained 10 days before. After prolonged exercise of four weeks an adaptation of the liver metabolism to the unphysiological strain was found. This was revealed by augmentation of cell organelles (mitochondria, ribosomes) and a slight increase of serum enzyme activities of glutamic oxalacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), lactic dehydrogenase (LDH), and decrease of aldolase (ALD). A large increase in swimming performance was noticed and no great liver cell alterations could be observed after swimming as in untrained rats. Reasons for the described reactions in the liver cells, the differences in serum enzyme values, and the influence of training on liver metabolism after physical exercise are discussed.
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  • 4
    ISSN: 1432-0878
    Keywords: Carotid body ; Adrenal medulla ; Rabbit ; Osmiophilic vesicles ; Cat ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Zusammenfassung Die organspezifischen Strukturen im Glomus caroticum und Nebennierenmark zeigen unter verschiedenen experimentellen Bedingungen ein unterschiedliches Bild. So läßt sich unter anderem durch Modifizierung der Fixationsmedien (Glutaraldehyd, Osmiumsäure in Kombination mit verschiedenen Puffern) eine optimale Differenzierung der zellulären Strukturelemente von Glomuszellen erreichen. An den osmiophilen Vesikeln fällt eine starke Variabilität ihres Erscheinungsbildes auf. Feinstrukturelle Unterschiede werden in Elektronendichte des Vesikelinhaltes, Größe und Ausbildung des Hofes sowie in Aufbau und Verlauf der Membran deutlich. Auf Grund dieser Kriterien lassen sich im wesentlichen 4 Haupttypen der Granula von seltener vorkommenden Sonderformen abgrenzen.
    Notes: Summary The organospecific structures of the carotid body and the adrenal medulla show a different appearance under various experimental conditions. Thus, it is possible to obtain an optimal differentiation of the cellular structure elements of the carotid body cells by modifying the fixatives (glutaraldehyde, osmic acid, in combination with various buffer systems). Especially the osmiophilic vesicles show a great variability in their appearance. Ultrastructural differences become evident in the electron-density of the vesicle content, in the size of the electron-lucent space (halo of the dense core), as well as in the structure and conduct of the membrane. Based on these criteria four main types of granules can be said to occur in the carotid body. These can be distinguished from more uncommon special types.
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  • 5
    ISSN: 1432-1041
    Keywords: diclofenac sodium ; triamcinolone acetate ; pharmacokinetics ; drug interactions ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Seventy-five mg diclofenac sodium were given intramuscularly to 15 subjects alone and in combination with 40 mg triamicinolone acetate. Plasma levels of diclofenac were measured and pharmacokinetic parameters were calculated. The results indicate no statistically significant differences for most of the parameters. The maximum plasma concentrations (Cpmax) was increased by about 20% in combination with the glucocorticoid, whereas terminal elimination rate did not change significantly.
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  • 6
    ISSN: 1432-055X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 7
    ISSN: 1433-8580
    Keywords: Glucocorticoid receptor ; Adult human lung ; Lung cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A dexamethasone-binding protein was detected in cytosol of five normal and three neoplastic lung tissue samples. The apparent dissociation constant of the dexamethasone protein complex ranged from 5.8 to 21 nM (11.4±5.7 nM for normal tissue cytosol, 12.1±7.7 nM for the neoplastic tissue cytosol). The binding protein sedimented at 8 S in sucrose density gradient at low ionic strength and showed a high specifity for glucocorticoids. It was concluded that the dexamethasone-binding protein had the characteristics of a glucocorticoid receptor. The glucocorticoid receptor content was determined to be 12–77 fmol/mg protein (37.1±18.9 fmol/mg protein for the normal tissue cytosol, 51.9±23.9 fmol/mg protein for the neoplastic tissue cytosol).
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  • 8
    ISSN: 1432-1440
    Keywords: Phentermine-resinate ; pulmonary arteries ; pharmacologically induced hypertrophy of the arterial wall ; Phentermin-Resinat ; Pulmonalarterien ; pharmakologisch induzierte Wandhypertrophie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung In zwei Versuchsserien wurde 60 Ratten (Wistar- bzw. SPF-Sprague-Dawley Stamm) beiderlei Geschlechts mit einem Ausgangsgewicht von 330 bzw. 180 g peroral über 30 Tage 12 bzw. 18 mg/kg Körpergewicht Phentermin-Resinat appliziert. Zur Kontrolle erhielten 40 Tiere p.o. physiologische Kochsalzlösung, während 40 Ratten unbehandelt blieben. Dabei konnten bei etwa 70% der älteren Phentermin-Resinat-behandelten Tiere Umbauprozesse der Pulmonalarterienäste beobachtet werden, die von einer mittelgradigen bis ausgeprägten Hypertrophie der Tunica media bis nahezu vollständiger Einengung des Lumens reichten.
    Notes: Summary Phentermine-resinate, 12 and 18 mg/kg body-weight, was applied in two test series for a period of 30 days to 60 rats (Wistar and SPF-Sprague-Dawley strain) of both sexes with a starting weight of 180 and 330 g, respectively. 40 control animals received physiological sodium chloride solution and 40 animals stayed untreated. 70% of the older phentermine-resinate treated rats displayed changes of the pulmonary arteries branches. The Tunica media in these cases showed a medium to considerably distinct hypertrophy with almost complete closure of the lumen.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Naturwissenschaften 59 (1972), S. 364-364 
    ISSN: 1432-1904
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General
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  • 10
    ISSN: 1432-1440
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Mit Hilfe der Neutronenaktivierungs-analyse wurde der Kupfergehalt im Leberpunktionsmaterial eines Patienten mit Morbus Wilson vor Behandlungsbeginn und nach mehrjähriger Penicillamin D-Medikation bestimmt. Die Ergebnisse werden mit den klinischen Befunden verglichen und zeigen, daß die Kupferbestimmung in der Leber genauere Aussagen zur Diagnose des Morbus Wilson und über den Therapieerfolg ermöglicht.
    Notes: Summary The copper contents of liver punctates from a patient with Morbus Wilson were determined by neutron activation analysis before and after treatment with Penicillamine-D for several years. The results were compared with clinical findings and show, that the determination of copper in liver permits more precise statements regarding both diagnosis and therapeutic success of Morbus Wilson.
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