scholarly journals Pronounced between‐subject and circadian variability in thymidylate synthase and dihydropyrimidine dehydrogenase enzyme activity in human volunteers

2016 ◽  
Vol 82 (3) ◽  
pp. 706-716 ◽  
Author(s):  
Bart A. W. Jacobs ◽  
Maarten J. Deenen ◽  
Dick Pluim ◽  
J. G. Coen Hasselt ◽  
Martin D. Krähenbühl ◽  
...  
2021 ◽  
pp. 107815522110491
Author(s):  
Charlotte W Ockeloen ◽  
Aron Raaijmakers ◽  
Manon Hijmans-van der Vegt ◽  
Jörgen Bierau ◽  
Judith de Vos-Geelen ◽  
...  

Decreased dihydropyrimidine dehydrogenase enzyme activity is associated with severe fluoropyrimidine-associated toxicity. Four clinically relevant variants in the DPYD gene are associated with decreased dihydropyrimidine dehydrogenase activity. However, only ∼25% of DPYD variant carriers show a decreased dihydropyrimidine dehydrogenase activity in peripheral blood mononuclear cells. Objective To investigate if dihydropyrimidine dehydrogenase phenotyping has added value when combined with DPYD genotyping in predicting fluoropyrimidine-related toxicity. Methods Retrospective cohort study in which treatment and toxicity data were collected of 228 patients genotyped for four DPYD variants and phenotyped using an ex vivo peripheral blood mononuclear cell assay. Results Severe toxicity occurred in 25% of patients with a variant and normal dihydropyrimidine dehydrogenase activity, in 21% of patients without a variant and with decreased dihydropyrimidine dehydrogenase activity, and in 29% of patients without a variant and with normal dihydropyrimidine dehydrogenase activity (controls). The majority of patients with a variant or a decreased dihydropyrimidine dehydrogenase activity received an initial dose reduction (68% and 53% vs 19% in controls) and had a lower mean dose intensity (75% and 81% vs 91% in controls). Fifty percent of patients with a variant and decreased enzyme activity experienced severe toxicity, despite the lowest initial dose and whole treatment dose intensity. They also experienced more grade 4/5 toxicities. Conclusions Our results indicate that a combined genotype–phenotype approach could be useful to identify patients at increased risk for fluoropyrimidine-associated toxicity (e.g. patients with a variant and decreased dihydropyrimidine dehydrogenase activity). Because the group sizes are too small to demonstrate statistically significant differences, this warrants further research in a prospective study in a larger cohort.


1966 ◽  
Vol 52 (3) ◽  
pp. 455-464 ◽  
Author(s):  
Lakshmi Kumari ◽  
Joseph W. Goldzieher

ABSTRACT Eleven samples of normal human ovarian tissue from the various phases of the cycle were incubated with 7-3H progesterone and 4-14C-5-pregnenolone. Isolation, identification and quantitation of the metabolites showed clearly that pregnenolone is a far better substrate than progesterone for the production of C19 steroids. Under the conditions of these incubations, 3β-ol dehydrogenase enzyme activity converted the majority of the metabolites into androstenedione. The accumulation of radioactive androstenedione at the end of the incubation exceeded that of testosterone except in the later part of the luteal phase.


2020 ◽  
Vol 18 (3) ◽  
pp. 186
Author(s):  
Victoria Agatha Angela Sirait ◽  
Zulkifli Zulkifli ◽  
Tundjung Tripeni Handayani ◽  
Martha Lulus Lande

The purpose of this study was to find out how effective citric acid is against the nonenzymaticprocess of browning Yali Pear fruit juice (Pyrus bretschneideri Rehd. Theresearch was conducted in a complete randomized design consisting of 5 replications. Thenon-enzymatic browning inhibition process was tested with citric acid treatment as the mainfactor with five concentrations ie 0% w/v, 2,5% w/v, 5% w/v, 7,5% w/v and 10% w/v.Qualitative parameters were dehydrogenase enzyme activity and reducing sugar level.Quantitative parameters were browning index and total soluble carbohydrate content.Levene test, analysis of variance, and Tukey test were performed at 5% significant level. Theresults showed that decrease in dehydrogenase enzyme activity occurs along with increasingthe concentration of citric acid. The level of reducing sugar has increased along with theincrease of citric acid concentration. The 7,5% w/v citric acid concentration effectivelyinhibited non-enzymatic browning of Yali Pear juice with a 21% reduction in the browningindex. Total soluble carbohydrate content increased 7% at 7.5% w/v citric acidconcentration. From the results of the study it was concluded that citric acid at 7,5% w / vconcentration was the inhibitor of non-enzymatic browning and dehydrogenase enzymeactivity, but stimulator of total soluble carbohydrate and reducing sugar level.


Sign in / Sign up

Export Citation Format

Share Document