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  • Genetic polymorphism  (2)
  • Trifolium repens  (2)
  • 24R,25-dihydroxy-26,27-dimethylvitamin D3  (1)
  • 1
    Electronic Resource
    Electronic Resource
    Calcium regulating activity of 26,27-dimethyl analog of 24R,25-dihydroxyvitamin D3 (1994)
    Springer
    Calcified tissue international 55 (1994), S. 190-197 
    Details
    ISSN: 1432-0827
    Keywords: Bone resorption ; Osteoclast-like cell formation ; Bone Ca mobilization ; Intestinal Ca transport ; 24R,25-dihydroxy-26,27-dimethylvitamin D3
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract To determine the possibility that methyl substitution in 26- and 27-positions of 24R,25-dihydroxyvitamin D3 [24,25(OH)2D3] alters activities of the original compound, the effects of 24,25(OH)2D3 on calcium (Ca) regulating activity were compared with those of its methyl analog [24,25(OH)2(CH3)2D3] in addition to 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3]. 24,25(OH)2D3 at 10-6 M and 24,25(OH)2(CH3)2D3 at 10-7 M and above significantly stimulated both bone resorption in neonatal mouse calvaria cultures and formation of osteoclast-like multinucleated cells (MNC) in mouse bone marrow cultures. A stimulative effect of 1,25(OH)2D3 on bone resorption and MNC formation was recognized in very low concentrations (10-11 M and above). Although a potency of 24,25(OH)2(CH3)2D3 in stimulating bone calcium (Ca) mobilization and intestinal Ca transport was higher than that of 24,25(OH)2D3, the potencies of both compounds were similar to that of 1,25(OH)2D3 unlike in vitro experiments. As 1,24R,25-trihydroxy-26,27-dimethylvitamin D3 showed almost the same effect as 24,25(OH)2(CH3)2D3, the dihydroxy form is suggested to be hydroxylated at 1α position and converted to trihydroxy form in vitamin D-deficient rats. From these results, methyl substitution in 26- and 27-position of 24,25(OH)2D3 was found to elevate Ca regulating activity of the original compound. In addition, it is suggested that the basis for a similarity in potency between 1,25(OH)2D3 and 24,25(OH)2D3 or its dimethyl analog in vitamin D-deficient rats is likely the result of 1 α-hydroxylation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00425874
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Lack of differences in diclofenac (a substrate for CYP2C9) pharmacokinetics in healthy volunteers with respect to the single CYP2C9 * 3 allele (2000)
    Springer
    European journal of clinical pharmacology 56 (2000), S. 65-68 
    Details
    ISSN: 1432-1041
    Keywords: Key words CYP2C9 ; Genetic polymorphism ; Diclofenac
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objectives: Evidence exists to suggest that diclofenac is metabolised by CYP2C9. The present study was undertaken in order to evaluate the effect of the single CYP2C9*3 variant on drug metabolism using diclofenac as a probe drug. Methods: A single dose of diclofenac was administered orally to 12 healthy subjects in whom the genotype of CYP2C9 had been determined previously. The disposition kinetics of diclofenac were compared between homozygotes for the wild type (CYP2C9*1/*1, n=6) and heterozygotes for the Leu359 variant (CYP2C9*1/*3, n=6). Results: For diclofenac, the following kinetic parameters were observed in the CYP2C9*1/*1 and CYP2C9*1/*3 subjects, respectively (mean ± SD): apparent oral clearance (ml/kg/h) 355.8 ± 56.9 and 484.4 ± 155.3; area under plasma concentration–time curve (μg h/ml) 2.7 ± 0.7 and 1.9 ± 0.6. The formation clearance of 4′-hydroxydiclofenac (ml/kg/h) was 63.6 ± 19.1 in the CYP2C9*1/*1 subjects compared with 75.9 ± 27.6 in the CYP2C9*1/*3 subjects. There were no significant differences in any of the kinetic parameters for either diclofenac disposition or formation clearance of 4′-hydroxydiclofenac between the two genotype groups. Conclusion: Since the disposition kinetics of diclofenac does not change in subjects with the single CYP2C9*3 mutant allele, it is suggested that the effects of CYP2C9 polymorphisms on the drug metabolism tend to be substrate specific.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050722
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  • 3
    Electronic Resource
    Electronic Resource
    CYP2C19 polymorphism effect on phenobarbitone (2000)
    Springer
    European journal of clinical pharmacology 55 (2000), S. 821-825 
    Details
    ISSN: 1432-1041
    Keywords: Key words Phenobarbitone ; CYP2C19 ; Genetic polymorphism ; Pharmacokinetics ; NONMEM
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The aim of this study was to clarify the effect of genetic polymorphisms of CYP2C19 on the pharmacokinetics of phenobarbitone (PB) using a nonlinear mixed-effects model (NONMEM) analysis in Japanese adults with epilepsy. Methods: A total of 144 serum PB concentrations were obtained from 74 subjects treated with both PB and phenytoin but without valproic acid. All patients were classified into three groups by CYP2C19 genotyping: G1, G2 and G3 were homozygous for the wild type of CYP2C19 (*1/*1), heterozygous extensive metabolizers (EMs), (*1/*2 or *1/*3), and poor metabolizers (PMs), (*2/*2, *2/*3), respectively. All data were analyzed using NONMEM to estimate pharmacokinetic parameters of PB with respect to the CYP2C19 genotype. Results: Thirty-three patients belonged to G1 (44.6%), 35 to G2 (47.3%), and 6 to G3 (8.1%). The total clearance (CL) of PB significantly decreased by 18.8% in PMs (G3) relative to EMs (G1 and G2). The CL tended to be lower in G2 than in G1. Conclusion: In this study, we first demonstrated the effect of the CYP2C19 polymorphism on pharmacokinetics of PB by genotyping. The contribution of other metabolic enzymes in the metabolism of PB in humans remains to be elucidated; however, it appears that the disposition of PB is mediated in part by this enzyme. The estimated population clearance values in the three genotype groups can be used to predict the PB dose required to achieve an appropriate serum concentration in an individual patient.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050703
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  • 4
    Electronic Resource
    Electronic Resource
    Cultivar variation for seed development in white clover (Trifolium repens L.) (1992)
    Springer
    Euphytica 65 (1992), S. 211-217 
    Details
    ISSN: 1573-5060
    Keywords: ovule number ; ovule sterility ; seed abortion ; seed set ; Trifolium repens ; white clover
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary A controlled environment study was undertaken to clarify the factors responsible for poor seed set and to study seed development, ovule degeneration and seed abortion, both morphologically and cytologically, in three Japanese cultivars of white clover. Although the mean number of ovules per floret was 4.2–5.1, the average number of seeds per floret was found to be only 2.3–2.7. Microscopic examination of carpels from 0 to 28 days following floret maturity and pollination showed that 26–33% and 8–17% of the total seeds lost occurred within the first three days and the third through fifth day following pollination, respectively. Beyond this period occasional seed abortion was observed at all stages of seed development, but this represented a very small proportion (2–7%) of the total seeds lost. A stain clearing technique was used to examine the cytoplasmic state of the embryo sac in intact, unfertilized, mature ovules and embryos of the ovules at 3 and 5-day periods following pollination. It was found that 20–22% of unfertilized and matured ovules were sterile, suggesting that ovule degeneration before fertilization was the major cause for the high percentage of seeds lost within a 0 to 3-day period following pollination. Cytological observations revealed that abortion of developing seed was due to a sudden arrest in embryo growth and that the early development of the embryo of such aborting seed was normal. Either nutrient shortage or meiotic irregularities may be the cause for high ovule sterility or post-fertilization abortion of developing seeds.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00023085
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  • 5
    Electronic Resource
    Electronic Resource
    Plant regeneration of meristematic callus of white clover (Trifolium repens L.) cooled to −196°C by vitrification (1993)
    Springer
    Euphytica 70 (1993), S. 197-203 
    Details
    ISSN: 1573-5060
    Keywords: cryopreservation ; meristemoid ; Trifolium repens ; vitrification ; white clover
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary A callus line of white clover capable of forming numerous meristemoids (meristematic cell masses) has been selected and subcultured on agar B5 medium containing 0.5 mg/l 2,4-D and 0.5 mg/l kinetin for three years. The meristematic callus was successfully cryopreserved by vitrification and subsequently regenerated plants. Preculturing callus in liquid B5 medium containing 0.6 M sorbitol at 25°C for 16 hr was essential to the process. Precultured samples (50 mg) were transferred to a 1.8 ml plastic cryotube and then 1 ml of a highly concentrated cryoprotective solution (designated PVS2) was added and mixed. After treatment with PVS2 at 25°C for 7 min or 0°C for 20 min, the sample was directly plunged into LN. After rapid warming, PVS2 was drained from the cryotubes and replaced twice with liquid B5 medium containing 1.2 M sucrose. Samples were transferred onto filter disc over agar B5 medium. Some surviving cells in the cryopreserved meristematic callus proliferated and produced new meristemoids. After 30 days the meristematic callus was transferred onto hormone-free MS agar medium. The meristemoids developed directly into shoots and spontaneously formed roots. Plant regeneration efficiency expressed as a percent of control amounted to about 90%. This vitrification method appears promising as a routine method for cryopreserving meristematic callus of white clover.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00023760
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