Several forms of cytochrome P-450 (CYP) metabolize R,S-warfarin in a regio- and enantioselective manner, therefore R,S-warfarin can be recognized as a metabolic probe for a number of CYP isoforms. We have applied a warfarin model in vivo in order to estimate the inhibitory properties of 5- and 8-methoxypsoralens on the activity of rat CYP isoforms. The area under the serum concentration versus time curve (AUC) values from time zero to 5 h for R- and S-warfarin and their metabolites were calculated. R,S-Warfarin kinetics measurements were made three times on each rat: a week before the 7-days inhibitor treatment, 3 h after the last dose of inhibitor and 3-7 days after the inhibitor was withdrawn. The inhibitory effect of cimetidine on CYP 2C11 and CYP 2C6 activities was confirmed in this approach and can be recognized as a positive control in validation of the in vivo experiment. Both 5- and 8-methoxypsoralen inhibited CYP 2C6 activity as the respective AUC for metabolite/warfarin enantiomer ratio decreased significantly. The activity of CYP 2C6 in 5- and 8-methoxypsoralen-treated rats increased over control values after the inhibitor was withdrawn. It was also observed that cimetidine additionally inhibits the absorption of R,S-warfarin and a decrease in the sum of AUC for R- and S-enantiomers became evident in spite of inhibition of the activity of both CYPs. 5-Methoxypsoralen modified the serum R-warfarin/S-warfarin ratio and a selective increase in AUC(S-warfarin) was observed, the most pronounced being after the inhibitor was withdrawn. This effect is not likely to be mediated by P-glycoprotein (P-gp) because quinidine--, a P-gp inhibitor at a dose of 15 mg kg(-1) body wt.--did not influence the AUC for either enantiomer.
A multitude of factors considered necessary for an informed choice of the location of the vineyard can be overwhelming for the decision-maker. Is there still a place for knowledge valuable from the perspective of an experienced winegrower in the era of precise measurements? The informative use of so-called common knowledge is possible owing to fuzzy-based techniques, which allow for the representation of intuitive notions in terms of quantitative measures. The work uses tools based on fuzzy logic to cover the scope of common knowledge within the decision-making process. Owing to its flexibility and ability to deal with imprecise input data while maintaining the simple construction, the fuzzy logic solution filled the gap between GIS data and wine grower’s experience. Based on the data from the thematic literature, a set of rules was created to interpret the relationships between popular site selection criteria. The dynamics and manner of interaction between variables were determined using adequate membership functions. Pre-processing using GIS with remote sensing data was considered as a preliminary stage for the analysis. By using the graphical interface, the system operation facilitates the work of a potential user. The obtained results indicated the possibility of an alternative approach to classical analyses by replacing or extending the meaning of some variables using information based on feelings and perceptions. Research constitutes a premise for the further development of expert systems using widely understood domain knowledge.
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