China
Africa
Explore chapters and articles related to this topic
Dihydropyrimidine Dehydrogenase Deficiency and Fluoropyrimidine-Toxicity
Published in Sherry X. Yang, Janet E. Dancey, Handbook of Therapeutic Biomarkers in Cancer, 2021
André B. P. van Kuilenburga, Eva Gross
Several phenotyping procedures have been developed to screen patients for a DPD deficiency, such as measurement of the uracil/dihydrouracil (U/UH2) ratio, assessment of the DPD activity in peripheral blood mononuclear cells, and loading studies with uracil [72]. Furthermore, a clinical benefit for DPD deficient patients was achieved when the DPD phenotypic status was determined prior to treatment and subsequent dose-tailoring of 5FU [73]. In a study assessing the ability of different approaches to detect patients with a DPD deficiency, it was shown that the combination of a phenotyping and genotyping was more accurate than genotyping alone [74]. Furthermore, the analysis of the DPD enzyme activity has been proposed to be the most reliable method to identify patients at risk [75].
Mass Spectrometric Analysis
Published in Adorjan Aszalos, Modern Analysis of Antibiotics, 2020
Considerable work has been reported in the characterization of tunicamycin and streptovirudin, two similar nucleoside antibiotic complexes that inhibit the transfer of N-acetylglucosamine from UDP-GlcNAc to intermediates used in the synthesis of complex lipids. Previously reported were four major components and several decomposition products [212—214]. More recently, improved chromatography has enabled the separation and identification of six additional components [215]. The identifications were aided by EI mass spectra that provided molecular ions and characteristic fragments. The tunicamycin components contain uracil; the streptovirudins contain uracil and dihydrouracil. Molecular weights and elemental compositions of the streptovirudins were obtained by FD [216]. Sensitive GC-MS methods using EI were used to detect uracil and dihydrouracil, as well as determine the fatty acid components after acid hydrolysis [217]. Some of the streptovirudins are identical to tunicamycin components. Another uracil antibiotic, nikko-mycin, was identified from the EI spectra of the derivatized nucleoside and hydrolysis products [218].
Introduction to the disorders of purine and pyrimidine metabolism
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
Two patients who excreted large amounts of uracil, dihydrouracil, and β-ureidopropionate were found to have ornithine transcarbamylase deficiency (Chapter 26). In nine patients treated with Vigabatrine, β-alanine was markedly elevated. This drug inhibits γ-aminobutyrate (GABA) transaminase and so interferes with the catabolism of β-alanine.
Dihydropyrimidine dehydrogenase (DPD) genotype and phenotype among Danish cancer patients: prevalence and correlation between DPYD-genotype variants and P-uracil concentrations
Published in Acta Oncologica, 2022
Niels Herluf Paulsen, Camilla Qvortrup, Fie Juhl Vojdeman, Peter Plomgaard, Stig Ejdrup Andersen, Anne Ramlov, Birgitte Bertelsen, Maria Rossing, Claus Gyrup Nielsen, Elke Hoffmann-Lücke, Eva Greibe, Hanne Spangsberg Holm, Heidi Hvid Nielsen, Ihab Bishara Yousef Lolas, Jonna Skov Madsen, Marianne Lerbaek Bergmann, Morten Mørk, Palle B. Nielsen Fruekilde, Pernille Bøttger, Peter Clausager Petersen, Peter Henrik Nissen, Søren Feddersen, Troels K. Bergmann, Per Pfeiffer, Per Damkier
The DPD-phenotype can be measured using different methods, including dihydrouracil/uracil ratio, uracil measurements in saliva, or uracil in plasma. The latter method was implemented into clinical practice in Denmark because it is commonly used in Europe and is recommended by the EMA [6,7,9,12]. The physiological role of the DPD-enzyme is to metabolize the two endogenous pyrimidines, thymine, and uracil, leading to an elevated plasma-uracil concentration ([U]) in patients with DPD-deficiency. [U] is affected by food intake and circadian rhythm [13,14] and is significantly increased in patients with end-stage renal disease [15]. The [U] concentration may also be affected in patients with tumor lysis syndrome, where a pronounced increase in [U] has been reported [16]. Furthermore, [U] is not stable in whole blood, so plasma must be isolated immediately after blood sampling and stored at −20 °C or analyzed. Incorrect or prolonged handling of samples could lead to falsely elevated [U] values [17]. Recently, De With et al. found significant between-center variance in pretreatment [U], underlining that measurement of [U] can be susceptible to preanalytical errors as well as the difference between unstandardized methods [18]. Patients with [U] ≥ 16 ng/mL and >150 ng/mL are categorized as having partial DPD deficiency and complete DPD deficiency, respectively [19].
An in vitro approach to simulate the process of 5-fluorouracil degradation with dihydropyrimidine dehydrogenase: the process in accordance to the first-order kinetic reaction
Published in Xenobiotica, 2021
Wei Qin, Xiaoxue Wang, Wenqian Chen, Wenwen Du, Dan Zhang, Xianglin Zhang, Pengmei Li
Multiple tests have been conducted for assessing DPD enzyme activity in different tissues including blood cells. DPD activity test in peripheral blood mononuclear cells (PBMCs), Uracil breath test, uracil oral loading dose test, endogenous uracil/dihydrouracil (U/DHU) or dihydrouracil/uracil (DHU/U) ratio test, 5-FU therapeutic drug monitoring, and DPYD genetic variants assessment are currently used to evaluate DPD enzyme activity (Kristensen et al., 2010; Neto et al., 2018; Pluim et al., 2015; van Kuilenburg et al., 1999; van Staveren et al., 2013). However, the current tests for identifying DPD-deficient patients have limitations in routine clinical usage. Measurement of DPD activity in PBMCs is labor intensive and therefore expensive. Uracil breath test and uracil oral loading dose test need to take extra medication. 5-FU therapeutic drug monitoring is conducted after first dose of 5-FU. Determination of endogenous DHU/U ratio may not always correctly reflect 5-FU levels (Kristensen et al., 2010; van Staveren et al., 2013). Genetic variants assessment varied along with different races (Amstutz et al., 2018).
Effects of a synbiotic on the fecal microbiome and metabolomic profiles of healthy research cats administered clindamycin: a randomized, controlled trial
Published in Gut Microbes, 2019
Jacqueline C. Whittemore, Jennifer E. Stokes, Joshua M. Price, Jan S. Suchodolski
Treatment group by time and treatment group differences were identified for 10 and 5 metabolites (Figure 5a–c, Supplementary Table 2), respectively. Significant group by time interactions were present for 2-deoxytetronic acid, 5,6-dihydrouracil major, dihydrocholesterol, fumaric acid, malic acid, malonic acid, myristic acid, N-acetylaspartic acid, palmitoleic acid, and threitol. In addition to having significant group by time interactions, profiles for six metabolites differed significantly by time (2-deoxytetronic acid, malic acid, malonic acid, myristic acid, N-acetylaspartic acid, and palmitoleic acid) and one (dihydrocholesterol) by treatment group. Significant associations between metabolite profile and treatment group alone were found for 2-hydroxybutanoic acid, myo-inositol, octadecanol, and squalene (though post hoc analysis did not clarify the group association for squalene).