Koletzko B, Demmelmair H, Hartl W, Kindermann A, Koletzko S, Sauerwald T, Szitanyi P
Kinderklinik nd Kinderpoliklinik, Klinikum Innenstadt, Ludwig-Maximilians University of Munich, Germany.
Early Hum Dev. 1998 Dec;53 Suppl:S77-97. doi: 10.1016/s0378-3782(98)00067-x.
Stable isotope methods are increasingly used in paediatrics for clinical diagnosis and research due to marked improvements in analytical technologies and better availability of suitable tracers. The safety of stable isotopes is of major importance for use in children. Large amounts of deuterium well above the doses applied under clinical conditions may induce adverse effects. In contrast, heavier stable isotopes such as 13C, 15N or 18O do not induce adverse effects even at the highest enrichments obtained, and they are safe. Breath tests with measurements of 13CO2 enrichment after oral application of a tracer can reliably evaluate helicobacter pylori infection and gastric emptying kinetics. Combined with an estimation of total CO2 production, 13CO2 breath tests allow estimation of the absorption and oxidation of 13C-labelled substrates, such as medium- and long-chain triglycerides, and demonstrates the beneficial effect of carnitine supplements on fat oxidation in primary carnitine deficiency. The study of metabolic processes may require the sampling of blood for isotopic analyses of metabolites of the applied tracer. Gas chromatography-isotope ratio mass spectrometry can detect tracer in individual components from small plasma samples. The high precision enabled us to utilize the small differences in natural 13C-enrichment between dietary fats to study fatty acid turnover in term infants, in whom the dietary fat source was switched to corn oil with a slightly higher 13C-content. With this approach we demonstrated active conversion of linoleic into arachidonic acid. We also applied biotechnologically produced, U-13C labelled linoleic and alpha-linolenic acids to infants and detected the conversion of these essential fatty acids to their longer chain polyunsaturated derivatives, with an apparent change of conversion activity with age. Moreover, it has become possible to measure tissue protein synthesis from small biopsy samples obtained in situ without surgery, such as forceps biopsies of rectal tumors. These few examples of recent developments demonstrate the great clinical and scientific potential of stable isotope methods in future paediatric applications.
由于分析技术的显著进步以及合适示踪剂的更易获取,稳定同位素方法在儿科学中越来越多地用于临床诊断和研究。稳定同位素的安全性对于儿童使用至关重要。大量远高于临床应用剂量的氘可能会引发不良反应。相比之下,较重的稳定同位素,如(^{13}C)、(^{15}N)或(^{18}O),即使在获得的最高富集度下也不会引发不良反应,它们是安全的。口服示踪剂后测量(^{13}CO_2)富集度的呼气试验能够可靠地评估幽门螺杆菌感染和胃排空动力学。结合总(CO_2)产生量的估计,(^{13}CO_2)呼气试验可以估计(^{13}C)标记底物(如中链和长链甘油三酯)的吸收和氧化,并证明肉碱补充剂对原发性肉碱缺乏症中脂肪氧化的有益作用。对代谢过程的研究可能需要采集血液以对所应用示踪剂的代谢物进行同位素分析。气相色谱 - 同位素比率质谱法可以从小血浆样本的各个成分中检测出示踪剂。高精度使我们能够利用膳食脂肪之间天然(^{13}C)富集的微小差异来研究足月儿的脂肪酸周转情况,这些足月儿的膳食脂肪来源换成了(^{13}C)含量略高的玉米油。通过这种方法,我们证明了亚油酸向花生四烯酸的活跃转化。我们还将生物技术生产的(U - ^{13}C)标记的亚油酸和α - 亚麻酸应用于婴儿,并检测了这些必需脂肪酸向其长链多不饱和衍生物的转化,且转化活性随年龄有明显变化。此外,现在已经能够从原位获取的小活检样本(如直肠肿瘤的钳取活检)中测量组织蛋白质合成。这些近期发展的少数例子证明了稳定同位素方法在未来儿科应用中的巨大临床和科学潜力。