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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 45 (1993), S. 337-341 
    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
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  • 2
    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
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Environmental monitoring and assessment 19 (1991), S. 539-547 
    ISSN: 1573-2959
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract Pollution monitoring can provide an important aid in the choice of the strategy to control the level of some dangerous elements, whether in water or in the air. The difficulties of detecting polluting sources from experimental data are related not only to the adoption of systematic and suitable measuring procedure, but also to a correct management of the available information. From the theoretical point of view, the use of simplified models, coupled with classical regularization techniques, shows that, in general, the problem is badly posed and consequently, numerically ill-conditioned. Hence the possibility of using expert systems algorithms, introducing further qualitative information, improves the reliability of the solutions. In particular, this paper deals with the utilization of fuzzy optimization algorithms: fuzzy theory supplies a formal reasoning technique, which proposes solutions that are real consequences of the premises. An actual example of such a method is described, making reference to the computation of the distribution of polluting sources from ground concentration data. The inverse problem is first solved using traditional procedures, showing that the distributed sources are not recognized. Afterwards, different results obtained from various algorithms derived from the assumed a-priori knowledge are examined. In this case, it is possible to obtain a more realistic situation of the pollution sources, inside the boundaries of the controlled area.
    Type of Medium: Electronic Resource
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