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  • 1
    ISSN: 1432-1041
    Keywords: prednisolone ; hydrocortisone ; cushingoid syndrome ; pharmacokinetics ; renal transplant ; oral disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To establish if the appearance of cushingoid side effects in patients taking exogenous glucocorticoids is related to the disposition and metabolism of these steroids and endogenous hydrocortisone, 15 stable renal transplant patients and 12 patients treated with prednisone for oral mucocutaneous vesiculo-erosive diseases were investigated. All 27 patients were given their usual prednisone dose orally on one occasion, and 24 were given the same amount of prednisolone intravenously on another occasion. Following dosing, plasma samples were obtained for determination of the areas under the plasma concentration time curves of total prednisolone, prednisone and hydrocortisone by high performance liquid chromatography, and of unbound prednisolone by equilibrium dialysis. The bioavailability of prednisone, the interconversion of prednisone into prednisolone, the clearance of total and unbound prednisolone, the prednisolone binding capacity of albumin and transcortin, and the affinity of albumin for prednisolone did not differ between the 14 patients without cushingoid side effects and the 13 cushingoid patients. Compared to those who had cushingoid features, patients who developed no side effects had a higher affinity constant for prednisolone binding to transcortin − 2.04±0.27 × 107 L/M vs. 1.34±0.16×107 (X±SE;P〈0.05), more frequently exhibited peak hydrocortisone levels within the normal range (6/14 vs 1/13), more often had measurable (〉10ng/ml) hydrocortisone in the plasma samples collected during the kinetic studies (123/291 vs 74/325;P〈0.001) and had higher areas under the plasma concentration time curve of hydrocortisone (median, range), i.e. 8081 ng/ml · min (0–21 637 ng/ml · min) vs 386 ng/ml · min (0–16 329 ng/ml · min;P〈0.005). The data suggest that endogenous hydrocortisone production is not as suppressed in patients with visible cushingoid signs as in noncushingoid patients, and that there is no significant difference in the pharmacokinetics of exogenous glucocorticoids between patients with and without cushingoid side effects.
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  • 2
    ISSN: 1432-1041
    Keywords: prednisone ; prednisolone ; azathioprine ; 11 β-hydroxydehydrogenase ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Clinical and pharmacokinetic observations suggest that azathioprine may diminish the plasma level of prednisolone. To study the extent of this possible interaction, and to define the underlying mechanism, total and unbound prednisolone and total prednisone concentrations were assessed in 11 subjects following an oral dose of prednisone once with and once without concomitant oral administration of azathioprine. Azathioprine did not affect the area under the plasma concentration-time curve of total and unbound prednisolone; furthermore, the interconversion of prednisone into prednisolone was not influenced by azathioprine.
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  • 3
    ISSN: 1432-1041
    Keywords: prednisolone ; prednisone ; oral contraceptives ; 6β-hydroxylase ; transcortin ; protein-binding ; steroid metabolism ; pharmacokinetics ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The oestrogenic component of oral contraceptives affects the activity of liver enzymes and the concentrations of plasma proteins implicated in steroid metabolism and transport. The present study was designed to determine these effects on the kinetics of prednisone and prednisolone. After an oral dose of prednisone, women on oral contraceptive steroids (n=10) had higher mean (±SD) area under the plasma concentration versus time curves of total (428±67 µg/ml/min vs 188±28 µg/ml/min, p〈0.001) and unbound prednisolone (64±10 µg/ml/min vs 41±10 µg/ml/min, p〈0.001) than women not taking oral contraceptive steroids (n=10). The differences were attributable to a lower non-renal clearance of prednisolone and to a higher apparent systemic availability of the drug in contraceptive users than in the controls. The affinity of albumin and transcortin for prednisolone was lower in women on oral contraceptives than in controls (p〈0.001). Thus, altered kinetics and protein binding may account for the known increase in glucocorticoid efficacy by oestrogens.
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  • 4
    ISSN: 1432-1041
    Keywords: haemodialysis ; protein binding ; prednisolone ; clearance ; renal transplant ; free clearance ; dialysate loss
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The impact of nonlinear plasma protein binding of a drug on its removal by haemodialysis has been quantified. Prednisolone 10–100 mg was given i.v. to 10 renal transplant patients on haemodialysis for acute tubular necrosis. Dialysate and afferent and efferent blood samples were collected simultaneously in 67 instances. Total and unbound prednisolone in plasma and its total concentration in blood and dialysate were assessed by high performance liquid chromatography and equilibrium dialysis. The amount of prednisolone lost, as measured directly in the dialysate (21.8±4.4 µg/min, $${{\bar x}}$$ ± SE), was predictable from the afferent-efferent blood concentration differences (20.1±4.8 µg/min), but not from measurements of total afferent-efferent prednisolone concentrations in plasma (13.1±3.0 µg/min). The amount of prednisolone lost in the dialysate increased linearly with unbound (r 2=0.96) and hyperbolically with the total prednisolone concentration in plasma. The latter hyperbolic relationship is adequately described by the equation for nonlinear plasma protein binding, using the affinity and capacity constants of albumin and transcortin for prednisolone (r 2=0.98). Thus, the haemodialysis clearance of total prednisolone is concentration-dependent, while the clearance of unbound prednisolone is constant (76 ml/min). Free clearance values or measurements of afferent-efferent blood concentrations are mandatory for a drug showing nonlinear plasma protein binding in order to predict the amount lost in the dialysate.
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  • 5
    ISSN: 1432-2242
    Keywords: Key words CpDNA polymorphism ; Heteroplasmy ; psbA gene ; Triazine resistance ; Senecio vulgaris
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  The weed Senecio vulgaris acquired high levels of resistance to triazine herbicides soon after the latter’s introduction. As in most weeds, triazine resistance is conferred by a point mutation in the chloroplast psbA gene that negatively affects the fitness of its carrier. To assess levels of triazine resistance in S. vulgaris field populations, we adopted a PCR-RFLP-based molecular diagnostic test recently developed for the triazine resistance-conferring region of the psbA gene of other weeds, including Brassica napus, Chenopodium spp. and Amaranthus spp., and compared these molecular results to the phenotypic response after triazine application. A highly significant linear correlation was found between phytotoxic symptoms and biomass reduction. Variability in phenotypic response was not only found between populations or inbred lines of S. vulgaris but also within replicates of the same inbred line. No clear relationship, however, was found between the DNA restriction pattern and the phenotypic response to triazine application, thereby throwing doubt on the use of such molecular diagnostic tests to track triazine resistance in S. vulgaris. Our results indicate that the chloroplast genome of S. vulgaris is polymorphic and that the level of polymorphism may be variable within single leaves of individual plants. We discuss the possible genetic basis of this polymorphism and its consequence for the acquisition and inheritance of chloroplast-based traits.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Protoplasma 39 (1950), S. 656-660 
    ISSN: 1615-6102
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Summary The cellulose ofTunicata (tunicin) consists of microfibrils with a diameter of about 250 Å, in much the same way as the cellulose of plants. In analogy to the bacterial cellulose ofBacterium xylinum, there is a tendency to forming ribbons by lateral aggregation. These ribbons allow of producing cellulose preparations of “higher” (three dimensional) orientation, which is impossible with the individualized microfibrils of plant fibres.
    Notes: Zusammenfassung Die Tunikatenzellulose (Tunicin) besteht wie die Pflanzenzellulose aus Mikrofibrillen von etwa 250 Å Durchmesser. Ähnlich den Mikrofibrillen der Bakterienzellulose haben diese das Bestreben, seitlich zu bandartigen Aggregaten zu verschmelzen. Solche Bänder gestatten eine dreidimensionale Orientierung des Zellulosekettengitters, während dies bei den Mikrofibrillen mit ihrem mehr isodiametrischen Querschnitt nicht möglich ist.
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  • 7
    ISSN: 1573-8744
    Keywords: cyclosporine ; dark Agouti rat ; kidney ; liver ; hydroxylation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Since oxidation plays a key role in the metabolism of cyclosporine A (CsA), the pharmacokinetics and the toxicity of CsA was investigated in female dark Agouti rats exhibiting a deficiency for debrisoquine hydroxylation and for dextromethorphan demethylation. When compared with Wistar rats (n=10), dark Agouti rats (n=10) had a higher mean clearance (4.8 ml/min per kg vs. 3.3 ml/min per kg) and a lower mean residence time (606 min vs. 1361 min) after intravenous dosing of CsA. The systemic availability of subcutaneous CsA was close to 100%. The steady state CsA concentrations assessed by HPLC in whole blood after subcutaneous dosing of 20 mg/kg per day for 23 days (n=10) were about 1000 ng/ml in dark Agouti rats. When compared with dark Agouti rats treated with cremophore (n=10) or not treated at all (n=12, dark Agouti rats on chronic subcutaneous CsA plus cremophore for 23 days (n=10) had no difference in kidney histology but had slightly increased liver fatty changes. Rats on CsA and/or cremophore had a decreased uric acid clearance and evidence of hypoaldosteronism. The urinary ratio of debrisoquine/4-hydroxydebrisoquine decreased in rats on CsA, whereas the O-demethylation and N-demethylation of liver obtained from rats on cremophore was impaired. Thus, dark Agouti rats show no difference in the metabolism of CsA and when given CsA for 23 days show drug-induced functional but no relevant structural light microscopic changes in the kidney, and functional and slight structural changes in the liver.
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  • 8
    ISSN: 1573-0778
    Keywords: In vitro test system ; liver cell cultures ; sterol pathway ; TLC separation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Rat liver cells derived from male and female animals in primary monolayer cultures were investigated for suitability as a test system for xenobiotics affecting the cholesterol pathway. An appropriate mode of extraction and separation of newly formed cholesterol and precursors is described. This system can be widely applied. Rat liver cells from females in oestrus cycle had a higher synthesis rate of cholesterol than those from males. The disadvantages related to the cycle phases make male rats more appropriate donor animals for the test system developed. The altered in vitro cholesterol synthesis is relevant to that in vivo. The extraction of newly synthesized cholesterol and its precursors by means of columns packed with large-pore kieselgur is precise and time saving. The modified separation by thin-layer chromatography on silica gel layers impregnated with silver nitrate enables direct separation from the extract and is sufficient to recognize cholesterol and its precursors. The method in this form is suitable for processing a large number of specimens e.g. for screening.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Annales geophysicae 16 (1998), S. 1332-1342 
    ISSN: 0992-7689
    Keywords: Tomography ; Aurora ; EISCAT ; Ionosphere ; Conductivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract Tomographic reconstruction of the three-dimensional auroral are emission is used to obtain vertical and horizontal distributions of the optical auroral emission. Under the given experimental conditions with a very limited angular range and a small number of observers, algebraic reconstruction methods generally yield better results than transform techniques. Different algebraic reconstruction methods are tested with an auroral are model and the best results are obtained with an iterative least-square method adapted from emission-computed tomography. The observation geometry used during a campaign in Norway in 1995 is tested with the are model and root-mean-square errors, to be expected under the given geometrical conditions, are calculated. Although optimum geometry was not used, root-mean-square errors of less than 2% for the images and of the order of 30% for the distribution could be obtained. The method is applied to images from real observations. The correspondence of original pictures and projections of the reconstructed volume is discussed, and emission profiles along magnetic field lines through the three-dimensionally reconstructed arc are calibrated into electron density profiles with additional EISCAT measurements. Including a background profile and the temporal changes of the electron density due to recombination, good agreement can be obtained between measured profiles and the time-sequence of calculated profiles. These profiles are used to estimate the conductivity distribution in the vicinity of the EISCAT site. While the radar can only probe the ionosphere along the radar beam, the three-dimensional tomography enables conductivity estimates in a large area around the radar site.
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  • 10
    ISSN: 1618-2650
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
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