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  • 1
    Electronic Resource
    Electronic Resource
    Minoxidil sulphation in human liver and platelets (1993)
    Springer
    European journal of clinical pharmacology 45 (1993), S. 337-341 
    Details
    ISSN: 1432-1041
    Keywords: Minoxidil ; sulphotransferase ; liver ; extrahepatic tissues ; platelets ; interindividual variability ; adults ; neonates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Minoxidil requires to be sulphated to exert its hypotensive effect. We report on interindividual variability in the rate of minoxidil sulphation in 118 specimens of human liver and in platelets obtained from 100 healthy subjects and 100 newborns. The frequency distribution histogram of the hepatic activity of minoxidil sulphotransferase was positively skewed; the mean was 631 pmol · min−1 · mg−1. After logarithmic transformation of the enzyme activity, the frequency distribution histogram became symmetrical and did not significantly deviate from normality. The rate of minoxidil sulphation was not different in platelets from adults (0.74 pmol · min−1 · mg−1) and newborns (1.16 pmol · min−1 · mg−1). The frequency distribution histograms were positively skewed and the results of normal equivalent deviation analysis was compatible with the presence of at least two subgroups of sulphotransferase in liver and platelets. Thus, two phenotypes of sulphotransferase exist in human liver and platelets, and the “extensive sulphator” phenotype contributes to skewing the frequency distribution. In platelets, the percentage of subjects that fall in the two subgroups is different at birth and in adulthood. This can explain the different shape of the frequency distribution in newborn and adult platelets and suggests that platelet minoxidil sulphotransferase undergoes modification after birth.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265951
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  • 2
    Electronic Resource
    Electronic Resource
    Stereoselective inhibition by chloroquine of histamine N-methyltransferase in the human liver and brain (1994)
    Springer
    European journal of clinical pharmacology 47 (1994), S. 345-349 
    Details
    ISSN: 1432-1041
    Keywords: Chloroquine ; Stereoselectivity ; Histamine ; methyltransferase ; liver ; brain ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract This study was designed to determine whether both enantiomers of chloroquine inhibit histamine N-methyltransferase. The mean estimates of IC50 for the d- and l-enantiomers of chloroquine were 4.9 and 17.8 μM (liver), respectively and 6.9 and 21.6 μM (brain), respectively. Ki estimates were significantly lower with d- than with l-chloroquine; hence, d-chloroquine interacts with the enzyme more effectively than l-chloroquine. If the adverse effects of chloroquine are due to the inhibition of histamine N-methyltransferase, therapy with the l-enantiomer might have lower toxicity. The residual activity of histamine N-methyltransferase should reflect both the degree of inhibition by chloroquine and the level of enzyme expression. The rate of histamine methylation was measured in 100 human liver samples and its range and fold of variation were 29% and threefold, respectively. Susceptibility to chloroquine should be greater in subjects with limited expression of histamine N-methyltransferase.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00191166
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  • 3
    Electronic Resource
    Electronic Resource
    Variability in the rate of 6-mercaptopurine methylation in the erythrocytes, liver and kidney in an Italian population (1996)
    Springer
    European journal of clinical pharmacology 51 (1996), S. 23-29 
    Details
    ISSN: 1432-1041
    Keywords: Key words 6-Mercaptopurine ; Thiopurine methyltransferase ; Polymorphism; erythrocytes ; liver ; kidney ; newborns ; adults
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective. The polymorphism of erythrocyte thiopurine methyltransferase (TPMT) is genetically regulated as an autosomal codominant trait, and so should be congenital. Results. We tested this hypothesis by measuring TPMT activity in erythrocyte preparations from adults and newborns and observed polymorphic distribution of TPMT activity in the adult and newborn erythrocytes. The activity of TPMT was higher in red cells from the newborns than adults. The frequency distribution of TPMT activity was also investigated in the liver and kidney. In the kidney, TPMT activity fell into two subgroups, whereas in the liver the distribution pattern was more complex. The activity of TPMT in erythrocytes and liver from the same subject was correlated, but the values of only half the cases fell within the 95% confidence limits, suggesting that the control of hepatic and/or erythrocyte TPMT is multifactorial.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050155
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