Elimination of 15N-thymidine after oral administration in human infants.
Elimination of 15N-thymidine after oral administration in human infants.
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DOI：
10.1371/journal.pone.0295651
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发表时间：
2024
期刊：
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
我们已经开发了一种新的临床研究方法，用于量化人类婴儿的细胞增殖，以解决有关组织更新和再生的未回答的问题。该方法包括口服15 N-胸苷给药以标记S期细胞，然后通过多同位素成像质谱法检测细胞核中掺入的标记。为了建立该方法，我们进行了一项观察性研究，以检查15 N-胸苷的摄取和消除。我们比较了法洛四联症（一种先天性心脏病）婴儿和心力衰竭婴儿的家庭标签给药与住院给药。我们检查了18名婴儿的尿样，他们连续5天口服15 N-胸苷（50 mg/kg体重）。我们使用同位素比质谱法来测定尿中15 N相对于14 N的富集（%）。15 N-胸苷给药导致尿液中15 N富集周期性升高。法洛四联症婴儿的平均峰值15 N富集比基线增加了3.2倍，心力衰竭婴儿的平均峰值15 N富集增加了4.3倍。两个患者人群之间的平均15 N富集无统计学差异（p = 0.103）。法洛四联症婴儿达到15 N富集峰值的时间为6.3 ± 1小时，心力衰竭婴儿为7.5 ± 2小时（平均值± SEM）。在法洛四联症和心力衰竭患者中，给药后15 N显著富集的持续时间分别为18.5 ± 1.7小时和18.2 ± 1.8小时（平均值± SEM）。达到峰值富集的时间和富集持续时间也无统计学差异（p = 0.617和p = 0.887）。所呈现的结果支持两个对未来应用有意义的结论：（1）证明15 N-胸苷标记物在家给药等同于在医院给药。(2)两种不同类型的心脏病在15 N-胸苷的吸收和消除方面没有差异。这使得不同类型的心脏病之间的细胞增殖的比较分析成为可能。
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. 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. 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). 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.
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