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  • 1
    Electronic Resource
    Electronic Resource
    s.l. ; Stafa-Zurich, Switzerland
    Solid state phenomena Vol. 135 (Feb. 2008), p. 65-68 
    ISSN: 1662-9779
    Source: Scientific.Net: Materials Science & Technology / Trans Tech Publications Archiv 1984-2008
    Topics: Physics
    Notes: Mechanical alloying (MA) process has been examined to synthesize ferritic stainlesssteel powder dispersed with nano-sized Y2O3 particles. A pilot-scale horizontal mill was fabricatedand compared with laboratory-scale ball mills and an attrition mill. Horizontal milling resulted in amuch better distribution of particle size and dispersoids than other milling methods. Althoughhorizontal milling is considered as a low-energy process requiring long times, processing time couldbe markedly reduced with increasing the diameter of horizontal mill with a proper control of millingparameters
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1157
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences
    Notes: Abstract Clay minerals of the surface sediments of Bransfield Strait, Antarctica, exhibit distinctive geographical distributions: kaolinite has the highest concentration near the shore of the South Shetland Islands in the northern strait (20%); chlorite, near Smith Island in the northwestern strait; illite, on the continental shelf off the Antarctic Peninsula in the southern strait (80%); and smectite, close to the Penguin and Bridgeman islands in the northeastern strait (25%). This distribution pattern, combined with hydrographic and climatic data for the strait, are used to infer clay mineral provenance and dispersal patterns.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1041
    Keywords: tolbutamide ; antipyrine ; selective inhibition ; metabolite formation ; pharmacokinetics ; drug interaction ; sulphaphenazole ; cimetidine ; primaquine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of sulphaphenazole, cimetidine and primaquine on the disposition of antipyrine and tolbutamide in healthy volunteers have been investigated. The model substrates were administered simultaneously in order more clearly to define any selective effects of the potential inhibitors. Sulphaphenazole produced a significant increase in the half-life of tolbutamide (7.10 to 21.50 h) and a correponding decrease in its clearance (0.260 to 0.084 ml·min−1·kg−1). Clearance to hydroxytolbutamide (OHTOL) and carboxytolbutamide (COOHTOL) was also significantly decreased. In contrast, sulphaphenazole had no effect on the disposition of antipyrine. Administration of cimetidine did not significantly alter the disposition of either model drug. However, a 1.6-times higher dose of cimetidine did increase the half lives both of tolbutamide and antipyrine (6.21 to 9.04 h and 14.2 to 19.2 h, respectively) and decrease their clearance (0.226 to 0.148 and 0.50 to 0.31 ml·min−1 kg−1, respectively). Clearance to OHTOL and hydroxymethylantipyrine (HMA) was reduced. A single dose of primaquine had no demonstrable effect on tolbutamide disposition whereas the half-life of antipyrine was increased (12.1 to 15.0 h) and its clearance decreased (0.63 to 0.38 ml·min−1·kg−1). The partial clearance to HMA, 4-hydroxyantipyrine (OHA) and norantipyrine (NORA) was also significantly reduced. The two main inferences are first, that tolbutamide and antipyrine are metabolished by different forms of cytochrome P-450, and second that a battery of model substrates is needed to investigate the inhibitory effects of a drug in man.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 36 (1989), S. 39-46 
    ISSN: 1432-1041
    Keywords: 6-beta-hydroxycortisol ; enzyme induction ; cytochrome P 450 ; urinary excretion ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of enzyme induction by antipyrine, phenobarbitone and rifampicin on the time-course of urinary 6β-hydroxycortisol (6β-OHC) excretion was investigated in healthy volunteers. The drugs were given chronically for either seven or 14 days. Significant increases in 6β-OHC excretion were observed after 4 days administration of antipyrine (1.2 g), 13 days administration of phenobarbitone (100 mg), and only 2 days administration of rifampicin (0.6 or 1.2 g). During 14 days rifampicin administration (1.2 g) 6β-OHC excretion, for individual subjects, reached a maximum on Days 11–14 when excretion was significantly greater than on day 7. On stopping rifampicin, in a 7-day study, excretion decreased over the next six days, but still remained significantly elevated compared to the original control values. These studies show that measurement of urinary 6β-hydroxycortisol provides a simple non-invasive method with which to monitor the time-course of enzyme induction by drugs in man. However, the method cannot be used to predict clinically important drug interactions until the cytochrome P-450 enzyme responsible for cortisol 6β-hydroxylation has been fully characterized.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 35 (1988), S. 241-247 
    ISSN: 1432-1041
    Keywords: carbamazepine ; porphyria ; epilepsy ; haem biosynthesis ; enzyme induction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The anticonvulsant drug carbamazepine has been reported to produce a condition clinically and biochemically similar to acute intermittent porphyria (AIP). We have determined the effect of chronic carbamazepine treatment on the activities of the enzymes of haem biosynthesis in circulating blood cells and on the urinary excretion of porphyrins and their precursors in 53 epileptic patients receiving monotherapy and in 42 age- and sex-matched controls. In the patients the mean activity of leucocyte 5-aminolaevulinic acid (ALA) synthase, the rate-limiting enzyme of the pathway, was 218% of control values (p〈0.001) and ALA-dehydratase activity was reduced by 37% (p〈0.001). Circulating carbamazepine concentrations correlated negatively with ALA dehydratase (r s=−0.45;p〈0.01). Porphobilinogen deaminase and uroporphyrinogen decarboxylase appeared unaffected by carbamazepine treatment. Significant quantitative increases in the urinary excretion of porphobilinogen and total porphyrins (bothp〈0.05) accompanied the changes in enzyme activity. Similar dose-dependent effects on ALA synthase and ALA dehydratase were shown to occur in rats treated for 5 days with 3 different doses of carbamazepine. These findings further support the porphyrinogenicity of carbamazepine, but the pattern of enzyme alteration differs from that found in AIP.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1041
    Keywords: enzyme induction ; 6-beta-hydroxycortisol ; antipyrine ; phenobarbitone ; rifampicine ; urinary excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To assess the rate of drug metabolism in man, four different in vivo measurements of microsomal enzyme activity were compared before and after the administration of three drugs known to be enzyme inducers in man: antipyrine, phenobarbitone and rifampicin. 27 healthy volunteers, divided into four different groups, were given antipyrine 1000 mg or 1200 mg, phenobarbitone 100 mg and rifampicin 600 mg or 1200 mg daily for 14 days. Before and after each drug, estimates were made of total body clearance of antipyrine, γ-glutamyl-transpeptidase in plasma and d-glucaric acid, 6-β-hydroxycortisol and 17-hydroxycorticosteroid urinary excretion in 24 h, as parameters of hepatic microsomal enzyme activity. Following treatment with antipyrine, phenobarbitone or rifampicin 600 mg daily, the total body clearance of antipyrine increased by 44–60%, and after rifampicin 1200 mg there was an increase up to 125%. d-Glucaric acid excretion in urine showed a tendency to increase to the same extent in every group investigated, and γ-glutamyl-transpeptidase increased similarly following antipyrine and phenobarbitone, although it remained unchanged following rifampicin administration. Urinary excretion of 6-β-hydroxycortisol, corrected by the 17-hydroxycorticosteroids representing the percentage proportion of 6-β-hydroxycortisol of the total amount of 17-hydroxycorticosteroids excreted, increased from 4.6–5.2% up to 9.5–28.3% depending upon the drug given. Comparing all in vivo parameters of hepatic microsomal enzyme activity by means of linear regression, a significant correlation was found between total body clearance of antipyrine and urinary excretion of 6-β-hydroxycortisol, while none of the other parameters showed any significant correlation. In addition, a better seperation of the enzyme-inducing capacity of different drugs was seen using 6-β-hydroxycortisol as a parameter of microsomal enzyme activity. Therefore, measurement of 6-β-hydroxycortisol corrected by the 17-hydroxycorticosteroid excretion, combined with estimation of the total body clearance of antipyrine, gives a valuable index, suitable for use in further studies of induction in man.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1041
    Keywords: stanozolol ; porphyria ; aplastic anaemia ; anabolic steroids ; haem biosynthesis ; monooxygenases ; cytochrome P 450 ; vascular thrombosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Stanozolol is an anabolic steroid which is used in the treatment of aplastic anaemia and has been recently advocated for the prophylaxis of vascular thrombosis. Similar steroid substances stimulate the activity of δ-aminolaevulinic acid synthase (ALA S), the rate limiting enzyme of haem biosynthesis, in rat hepatocytes and chick embryo liver cell cultures and activate acute hepatic porphyria. In the present study stanozolol (10 mg daily for 14 days) has been shown to increase significantly leucocyte ALA S activity in 9 healthy male subjects. There was a concomitant rise in urinary ALA and total porphyrin excretion but no change in antipyrine kinetics or urinary 6 B hydroxycortisol excretion. In a complementary study in male Sprague Dawley rats, stanozolol administered intraperitoneally, produced a dose-dependent increase in hepatic ALA S activity without changing hepatic cytochrome P 450 content. Stanozolol has been clearly shown to elevate ALA S activity, probably directly, and, thereby, porphyrin production without affecting hepatic monooxygenase activity. This porphyrinogenic effect may be relevant to the successful treatment of aplastic anaemia with anabolic steroids. Leucocyte ALA S activity may provide a human system for the study of drug porphyrinogenicity in vivo.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 15 (1979), S. 193-197 
    ISSN: 1432-1041
    Keywords: norethisterone ; rifampicin ; enzyme induction ; antipyrine ; 6 beta-hydroxycortisol ; gamma-glutamyltranspeptidase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of norethisterone have been studied in 8 women during and one month after treatment with rifampicin (450–600 mg/day). Rifampicin caused a significant reduction in the A. U. C. of a single dose of 1 mg norethisterone from 37.8±13.1 to 21.9±5.9 ng/ml X h (p〈0.01). The plasma norethisterone half life (β-phase) was also reduced from 6.2±1.7 to 3.2±1.0 h (p〈0.0025). In one additional woman on long term oral contraceptive therapy the 12 hour plasma norethisterone concentration was reduced by rifampicin from 12.3 ng/ml to 2.3 ng/ml. Rifampicin caused a significant increase in antipyrine clearance, 6β-hydroxycortisol excretion and plasma gamma-glutamyltranspeptidase activity but there were no significant correlations between changes in these indices of liver microsomal enzyme induction. There was a significant correlation between the percentage increase in antipyrine clearance and the percentage decrease in norethisterone A. U. C. during rifampicin. The changes in norethisterone pharmacokinetics during rifampicin therapy are compatible with the known enzyme inducing effect of rifampicin.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 24 (1983), S. 247-250 
    ISSN: 1432-1041
    Keywords: antipyrine ; phenobarbitone ; rifampicin ; drug combinations ; enzyme induction ; antipyrine clearance ; 6-β-hydroxycortisol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of 2 different drug combinations on liver microsomal activity was investigated in healthy volunteers by administering antipyrine 1200 mg and phenobarbitone 100 mg, or the same dose of antipyrine with rifampicin 600 mg daily for 14 days. The effect of rifampicin 1200 mg given for only 8 days was also studied. Before and after each drug regimen, estimates were made of the total body clearance of antipyrine, γ-glutamyl-transferase (γ-GT) and urinary excretion of 6-β-hydroxycortisol as in vivo parameters of liver microsomal enzyme activity. Following combined antipyrine and phenobarbitone administration, the antipyrine clearance was increased by 80%, after antipyrine with rifampicin by 128%, and after rifampicin alone by 104%. 6-β-hydroxycortisol, corrected for 17-hydroxycorticosteroids, increased from 2.6% to 8% following antipyrine plus phenobarbitone, from 4.4% to 27.9% following antipyrine plus rifampicin, and from 5.4% to 29.7% after rifampicin given alone. Based on previous studies, antipyrine given with phenobarbitone produced slightly more induction than phenobarbitone given alone. Following antipyrine 1200 mg with rifampicin 600 mg for 14 days a significantly greater increase in antipyrine clearance and 6-β-hydroxycortisol excretion was observed than when either drug was given alone.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 33 (1987), S. 93-95 
    ISSN: 1432-1041
    Keywords: vitamin K1 ; anticonvulsants ; hepatic enzyme induction ; rifampicin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the effect of hepatic enzyme induction on vitamin K1 elimination in patients on long-term anticonvulsant therapy and in volunteers given rifampicin. Neither the anticonvulsants (phenytoin and phenobarbitone) nor rifampicin had any significant effect on vitamin K1 elimination half-life or AUC. The neonatal haemorrhage which occurs in babies born to mothers on long-term enzyme inducing drugs is unlikely to be related to an increased rate of vitamin K elimination in the mother.
    Type of Medium: Electronic Resource
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