Individual variability in relationship of human ketosteroid excretion to urine volume.
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Atypical puffing of polytene chromosomes of Chironomus plumosus (1 larvae, IV stage) from the Ivan lake in Chita region, southern part of Siberia, has been described. At the sites of ordinary localization of interdisks and puff-patterns typical of Ch. plumosus the puffs in our material displayed different levels of activity: from a light vacuolous spot to puffs of class 5. Most of these puffs were revealed in Ch. plumosus for the first time, namely, puffs IA10a-r, IB12v-y + 13a-d, IIC14p-z + 15a-z + 16a-e, IIC14p-z + 15a-h, IID14a-m + 13s-w, IID11-2a-d, IID1p-x + 2a-d, IIIE3g-a and IIIF13h-p + 14a-e. Some other puffs, such as IB16a-k, IB15m-r + 16a-m, IB21a-o, IIC20, IVG6 and IVG7, were described earlier (Maksimova, 1979, 1983). The majority of observed puffs turned out to be heterozygous. Only one puff-knob, IIIE3g-a of class 5 activity, was found in all cells of the studied salivary glands. Its origin may be due to the appearance of heterozygoous inversion pluE1.2. All other puffs were observed in some part of cells. It is supposed that the appearance of larvae with unusually high functional activity of chromosomes may be presumably induced by stress influence of certain environmental factors.
Acetohexamide, an oral antidiabetic agent, is metabolized by carbonyl reductase to hydroxyhexamide, which has a higher hypoglycemic potency than the parent compound. In the present study, interindividual variability of carbonyl reductase activity in erythrocyte was examined. Enzyme activity in 31 healthy subjects (23.9 plus minus 3.4 years, mean plus minus SD) was monitored by measuring formation of hydroxyhexamide using HPLC methods. Using 0.5 mM acetohexamide as substrate, reductase activity of 6.06 plus minus 0.06 nmol min(minus sign1) gHb(minus sign1) (range: 5.9--6.2) with a coefficient of variation of 15% was observed in erythrocytes. Acetohexamide-reducing activity in erythrocytes showed a normal distribution and the interindividual variability of the reductase activity was found to be small, implying that the large variability reported for the acetohexamide plasma half-life is not caused by the amount of reductase enzyme in erythrocytes.
Green tea and tea polyphenols have been studied extensively as cancer chemopreventive agents in recent years. The bioavailability and metabolic fate of tea polyphenols in humans, however, are not clearly understood. In this report, the pharmacokinetic parameters of (-)-epigallocatechin-3-gallate (EGCG), (-)-epigallocatechin (EGC), and (-)-epicatechin (EC) were analyzed after administration of a single oral dose of green tea or decaffeinated green tea (20 mg tea solids/kg) or EGCG (2 mg/kg) to eight subjects. The plasma and urine levels of total EGCG, EGC, and EC (free plus conjugated forms) were quantified by HPLC coupled to an electrochemical detector. The plasma concentration time curves of the catechins were fitted in a one-compartment model. The maximum plasma concentrations of EGCG, EGC, and EC in the three repeated experiments with green tea were 77.9 +/- 22.2, 223.4 +/- 35.2, and 124.03 +/- 7.86 ng/ml, respectively, and the corresponding AUC values were 508.2 +/- 227, 945.4 +/- 438.4, and 529.5 +/- 244.4 ng x h x ml(-1), respectively. The time needed to reach the peak concentrations was in the range of 1.3-1.6 h. The elimination half-lives were 3.4 +/- 0.3, 1.7 +/- 0.4, and 2.0 +/- 0.4 h, respectively. Considerable interindividual differences and variations between repeated experiments in the pharmacokinetic parameters were noted. Significant differences in these pharmacokinetic parameters were not observed when EGCG was given in decaffeinated green tea or in pure form. In the plasma, EGCG was mostly present in the free form, whereas EGC and EC were mostly in the conjugated form. Over 90% of the total urinary EGC and EC, almost all in the conjugated forms, were excreted between 0 and 8 h. Substantial amounts of 4'-O-methyl EGC, at levels higher than EGC, were detected in the urine and plasma. The plasma level of 4'-O-methyl EGC peaked at 1.7 +/- 0.5 h with a half life of 4.4 +/- 1.1 h. Two ring-fission metabolites, (-)-5-(3',4',5'-trihydroxyphenyl)-gamma-valerolactone (M4) and (-)-5-(3',4'-dihydroxyphenyl)-valerolactone (M6), appeared in significant amounts after 3 h and peaked at 8-15 h in the urine as well as in the plasma. These results may be useful for designing the dose and dose frequency in intervention studies with tea and for development of biomarkers of tea consumption.
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