Development of 13C-retinol isotope dilution techniques

描述（由申请人提供）：需要改进的，简化的方法来确定维生素A状态，以准确评估维生素A缺乏或毒性风险的个人和人群。在不发达国家和美国，社会经济地位较低的妇女和儿童的维生素A状况受到损害。造成这种状况的多种原因包括饮食摄入量低、孕期和哺乳期需求增加以及反复感染。13c -视黄醇同位素稀释（13C-RID）测试首先在啮齿类动物模型中使用13c4 -视黄醇乙酸酯和气相色谱-燃烧-同位素比值质谱（GCCIRMS）建立，具有灵敏和准确的特点。该项目的主要目标是验证13C-RID测试在人群中的应用，以评估维生素A的全身储备，并确定年轻人对维生素A的需求。该项目的成功将为研究人员提供一种敏感的工具，以利用最小的样本量来评估个人和人群的维生素a状况。该测试可直接用于确定旨在改善维生素A状态的干预策略的结果，并确定人类和动物在其整个生命周期中对维生素A的需求。拟议的研究将首次：(1)验证13C-RID测试以评估亚毒性维生素a在非人灵长类动物中的状态；(2)验证13C-RID试验评价断奶仔猪亚临床维生素A缺乏症；(3)通过研究不同的剂量水平和血液采样次数，改进13C-RID测试以供人类使用；(4)调查13C-RID测试在一项人为干预研究中的应用，该研究旨在研究年轻人对维生素a的需求。

DESCRIPTION (provided by applicant): Improved, simplified methods to determine vitamin A status are needed to accurately assess both individuals and populations at risk of either vitamin A deficiency or toxicity. The vitamin A statuses of women and children in lower socioeconomic groups in both the underdeveloped world and the United States are compromised. Multiple reasons for this compromised status include low dietary intakes, increased demands during pregnancy and lactation and recurrent infections. The 13C-retinol isotope dilution (13C-RID) test, first developed in the rodent model using 13C4-retinyl acetate and gas chromatography-combustion-isotope ratio mass spectrometry (GCCIRMS), is sensitive and accurate. The major goals of this project are to validate the 13C-RID test for use in human population groups to assess total body reserves of vitamin A and determine vitamin A requirements of young adults. The success of this project will provide a sensitive tool for investigators to evaluate the vitamin A status of individuals and population groups using minimal sample sizes. The test has direct application to determining the outcome of intervention strategies aimed at improving vitamin A status and in determining vitamin A needs of humans and animals throughout their life cycles. The proposed studies will for the first time: (1) validate the 13C-RID test to assess a sub-toxic vitamin A status in non-human primates; (2) validate the 13C-RID test to assess sub-clinical vitamin A deficiency in the weanling pig; (3) refine the 13C-RID test for use in humans by looking at different dose levels and blood sampling times; and (4) investigate the use of the 13C-RID test in a human intervention study designed to look at vitamin A requirements in young adults.