Elimination of 15N-thymidine after oral administration in human infants.

Autor: Ammanamanchi N; Division of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America., Yester J; Division of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America., Bargaje AP; Division of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America., Thomas D; Division of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America., Little KC; Division of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.; Clinical Research Support Services (CRSS), Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America., Janzef S; Division of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America., Francis K; Division of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America., Weinberg J; Division of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America., Johnson J; Division of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America., Seery T; Division of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America., Harris TH; Division of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America., Funari BJ; Division of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America., Rose-Felker K; Division of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America., Zinn M; Division of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America., Miller SA; Division of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America., West SC; Division of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America., Feingold B; Division of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America., Zhou H; Division of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America., Steinhauser ML; UPMC Heart and Vascular Institute, UPMC Presbyterian, Pittsburgh, PA, United States of America.; Aging Institute, University of Pittsburgh, Pittsburgh, PA, United States of America., Csernica T; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, United States of America., Michener R; Department of Biology, Boston University Stable Isotope Laboratory, Boston, MA, United States of America., Kühn B; Division of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.; McGowan Institute of Regenerative Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Jan 25; Vol. 19 (1), pp. e0295651. Date of Electronic Publication: 2024 Jan 25 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0295651
Abstrakt: Background: We have developed a new clinical research approach for the quantification of cellular proliferation in human infants to address unanswered questions about tissue renewal and regeneration. The approach consists of oral 15N-thymidine administration to label cells in S-phase, followed by Multi-isotope Imaging Mass Spectrometry for detection of the incorporated label in cell nuclei. To establish the approach, we performed an observational study to examine uptake and elimination of 15N-thymidine. We compared at-home label administration with in-hospital administration in infants with tetralogy of Fallot, a form of congenital heart disease, and infants with heart failure.
Methods: We examined urine samples from 18 infants who received 15N-thymidine (50 mg/kg body weight) by mouth for five consecutive days. We used Isotope Ratio Mass Spectrometry to determine enrichment of 15N relative to 14N (%) in urine.
Results/findings: 15N-thymidine dose administration produced periodic rises of 15N enrichment in urine. Infants with tetralogy of Fallot had a 3.2-fold increase and infants with heart failure had a 4.3-fold increase in mean peak 15N enrichment over baseline. The mean 15N enrichment was not statistically different between the two patient populations (p = 0.103). The time to peak 15N enrichment in tetralogy of Fallot infants was 6.3 ± 1 hr and in infants with heart failure 7.5 ± 2 hr (mean ± SEM). The duration of significant 15N enrichment after a dose was 18.5 ± 1.7 hr in tetralogy of Fallot and in heart failure 18.2 ± 1.8 hr (mean ± SEM). The time to peak enrichment and duration of enrichment were also not statistically different (p = 0.617 and p = 0.887).
Conclusions: The presented results support two conclusions of significance for future applications: (1) Demonstration that 15N-thymidine label administration at home is equivalent to in-hospital administration. (2) Two different types of heart disease show no differences in 15N-thymidine absorption and elimination. This enables the comparative analysis of cellular proliferation between different types of heart disease.
Competing Interests: The authors declare that they have no competing interests.
(Copyright: © 2024 Ammanamanchi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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