Elimination of 15N-thymidine after oral administration in human infants.
<h4>Background</h4>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-ph...
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Public Library of Science (PLoS)
2024-01-01
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| author | Niyatie Ammanamanchi Jessie Yester Anita P Bargaje Dawn Thomas Kathryn C Little Shannon Janzef Kimberly Francis Jacqueline Weinberg Jennifer Johnson Thomas Seery Tyler Hutchinson Harris Bryan J Funari Kirsten Rose-Felker Matthew Zinn Susan A Miller Shawn C West Brian Feingold Hairu Zhou Matthew L Steinhauser Timothy Csernica Robert Michener Bernhard Kühn |
| author_facet | Niyatie Ammanamanchi Jessie Yester Anita P Bargaje Dawn Thomas Kathryn C Little Shannon Janzef Kimberly Francis Jacqueline Weinberg Jennifer Johnson Thomas Seery Tyler Hutchinson Harris Bryan J Funari Kirsten Rose-Felker Matthew Zinn Susan A Miller Shawn C West Brian Feingold Hairu Zhou Matthew L Steinhauser Timothy Csernica Robert Michener Bernhard Kühn |
| author_sort | Niyatie Ammanamanchi |
| collection | DOAJ |
| description | <h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results/findings</h4>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).<h4>Conclusions</h4>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. |
| format | Article |
| id | doaj-art-fa25fa000f8e469180c21b9ff6df5486 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj-art-fa25fa000f8e469180c21b9ff6df54862025-08-20T02:10:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-01191e029565110.1371/journal.pone.0295651Elimination of 15N-thymidine after oral administration in human infants.Niyatie AmmanamanchiJessie YesterAnita P BargajeDawn ThomasKathryn C LittleShannon JanzefKimberly FrancisJacqueline WeinbergJennifer JohnsonThomas SeeryTyler Hutchinson HarrisBryan J FunariKirsten Rose-FelkerMatthew ZinnSusan A MillerShawn C WestBrian FeingoldHairu ZhouMatthew L SteinhauserTimothy CsernicaRobert MichenerBernhard Kühn<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results/findings</h4>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).<h4>Conclusions</h4>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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0295651&type=printable |
| spellingShingle | Niyatie Ammanamanchi Jessie Yester Anita P Bargaje Dawn Thomas Kathryn C Little Shannon Janzef Kimberly Francis Jacqueline Weinberg Jennifer Johnson Thomas Seery Tyler Hutchinson Harris Bryan J Funari Kirsten Rose-Felker Matthew Zinn Susan A Miller Shawn C West Brian Feingold Hairu Zhou Matthew L Steinhauser Timothy Csernica Robert Michener Bernhard Kühn Elimination of 15N-thymidine after oral administration in human infants. PLoS ONE |
| title | Elimination of 15N-thymidine after oral administration in human infants. |
| title_full | Elimination of 15N-thymidine after oral administration in human infants. |
| title_fullStr | Elimination of 15N-thymidine after oral administration in human infants. |
| title_full_unstemmed | Elimination of 15N-thymidine after oral administration in human infants. |
| title_short | Elimination of 15N-thymidine after oral administration in human infants. |
| title_sort | elimination of 15n thymidine after oral administration in human infants |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0295651&type=printable |
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