Objective: Compared with healthy individuals, patients with chronic liver disease reportedly have lower L-[1-13C] phenylalanine breath test (PBT) values. However, there is no report detailing the relationship between the results of PBT and pathological data in liver disease patients. This study was designed to investigate the degree of histological changes in the liver that induce PBT changes and the time of measurement that reflects the histological change.
Materials And Methods: PBT was performed in 47 patients (10 with a normal liver, and 37 with chronic hepatitis C). After administering 10 mg/kg L-[1-13C] phenylalanine, 300 mL of expired air was collected over 90 min at 15-min intervals. The rate of hepatic phenylalanine oxidation (%13C dose h(-1)) at each time point was calculated from the amount of 13CO(2) in the exhaled air, assuming a CO(2) production rate of 300 mmol m(-2) body surface area per hour. Subsequently, we examined the relationship between the results of PBT and METAVIR pathological scoring.
Results: The highest correlation coefficients between the fibrosis score and %13C dose h(-1) and between the fibrosis score and %13C cumulative excretion were obtained at 45 min (r = -0.779, R(2) = 0.607; P < 0.0001) and 75 min (r = -0.768, R(2) = 0.590; P < 0.0001), respectively.
Conclusion: PBT is a useful adjunct for detecting histological changes in the liver. The %13C dose h(-1) value at 45 min and the %13C cumulative excretion value at 75 min of PBT are useful for detecting hepatic histological change.
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http://dx.doi.org/10.1016/s0022-4804(03)00278-6 | DOI Listing |
J Breath Res
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School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Rd, Qingdao, Shandong, 266003, CHINA.
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Department of Horticulture, Agriculture Faculty of Aburaihan, University of Tehran, P.O. Box 11365/4117, Tehran, Iran.
This research was conducted to determine the relationship between plant defense responses and the extent of treatment applied to either the aerial parts or roots of the plant. The experimental treatments included different methods of application (spraying versus soil drenching), varying treatment areas (one-sixth, one-third, half, or all of the plant's aerial parts and roots) with SA, and infecting the plants with root-knot nematodes. Evaluation of plant growth and nematode pathogenicity indices in the greenhouse section, HO accumulation rate, and phenylalanine ammonia lyase enzyme activity (in aerial parts and roots) were carried out in biochemical experiments.
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PTC Therapeutics, Warren, NJ, USA.
Sepiapterin is an exogenously synthesized new chemical entity that is structurally equivalent to endogenous sepiapterin, a biological precursor of tetrahydrobiopterin (BH), which is a cofactor for phenylalanine hydroxylase. Sepiapterin is being developed for the treatment of hyperphenylalaninemia in pediatric and adult patients with phenylketonuria (PKU). This study employed concentration-QT interval analysis to assess QT prolongation risk following sepiapterin treatment.
View Article and Find Full Text PDFAAPS J
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Moderna, Inc., Cambridge, Massachusetts, USA.
While the branched DNA (bDNA) assay is an established bioanalytical method for measurement of lipid nanoparticle (LNP)-encapsulated messenger RNA (mRNA) pharmacokinetic parameters, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) has been considered as an alternative platform. RT-qPCR and bDNA platforms were compared for sensitivity, specificity, correlation, and overall assay performance using serum and tissue samples from 2 nonclinical mouse studies of a therapeutic mRNA candidate, LNP-PAH-mRNA, which encodes for human phenylalanine hydroxylase enzyme. Pharmacokinetic parameter noncompartmental analysis was completed using Phoenix WinNonlin.
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