ZINC DEPRIVATION AND TERATOGENESIS

在这项研究计划的前六年， 全面定性和定量表征 边缘性缺锌对生长发育的影响 非人类灵长类动物的研究 我们现在可以集中精力 关于这些影响机制的假设。 将继续对怀孕和发育中的猴子进行研究， 针对这个问题的三个重要问题：（1） 确定最脆弱的发展时期;（2） 血浆金属硫蛋白（MT）作为一种快速、准确的 锌营养状况指标：（3）边缘锌的代谢相互作用 药物和补充剂的剥夺。 这些目标是 整合到两个实验中，在五年内完成 期 这些研究的结果是， 认识、预防和治疗这类疾病对健康的不良影响 将提供重要微量元素。 这项工作很重要 因为缺锌会对 怀孕和儿童发育。 然而， 所涉具体因素和机制的定义 锌对母婴健康的影响，包括 生长、发育、行为或免疫功能。 虽然 锌缺乏的母亲可以被认为是“营养上， 风险”的正常胎儿发育，目前还不清楚为什么有 个体差异以及锌与 其他因素也可能造成这一问题。 最后，血浆 锌仍然是锌营养状况的一个相对较差的指标， 更好的锌状态标志物，即，指数适用于快速 估计需要确定。 具体来说，我们将 妊娠期锌吸收和代谢特征 猴子和确定锌的相互作用，这可能有助于 “营养风险”;这包括详细的动力学和 锌和铁以及锌和丙戊酸的代谢相互作用。 我们将制备血浆mt的抗体并监测饲喂的动物 对照组和轻度缺锌组的MT日粮， 其他几种潜在的锌状态标志物，以确定 一个适当的和有效的标志物，用于快速估计锌的状态。 我们认为需要新的诊断工具来识别 自临床观察以来， 血浆锌水平在这方面已被证明是不足的。 我们 我相信，在这项研究完成后，我们将有 更好的概念，涉及锌的机制 相互作用，通过我们深入研究锌代谢， 体外和组织水平。

During the first six years of this research program, a comprehensive qualitative and quantitative characterization of the effects of marginal zinc deficiency on the developing nonhuman primate has been achieved. We are now able to focus on hypotheses concerning the mechanisms of these effects. Continuing work with pregnant and developing monkeys will be directed at three issues important to this problem: (1) identification of the most vulnerable developmental periods; (2) evaluation of plasma metallothionein (mt) as a rapid and accurate index of zinc status; (3) metabolic interactions of marginal zinc deprivation with drugs and supplements. These goals are integrated into two experiments to be completed, over a five year period. As a result of these studies, a strong scientific basis for recognizing, preventing and treating adverse health effects of this important trace element will be provided. This work is important because zinc deprivation can have significant effects during pregnancy and child development. However, there are few definitions of specific factors and mechanisms involved in the influences of zinc on maternal and child health, including aspects of growth, development, behavior or immune function. Although zinc deficient mothers may be considered to be "nutritionally-at- risk" for normal fetal development, it is unclear why there are individual differences and to what extent interactions of zinc with other factors might contribute to this problem. Finally, plasma zinc remains a reltively poor indicator of zinc nutriture and better markers for zinc status, i.e., indices suitable for rapid estimation need to be determined. Specifically, we will characterize zinc absorptiona and metabolism in pregnant monkeys and identify zinc interactions which might contribute to being "nutritionally-at-risk"; this includes detailed kinetic and metabolic interactions of zinc and iron and zinc and valproic acid. We will prepare antibodies to plasma mt and monitor animals fed control and marginally zinc deficient diets for mt as well as several other potential markers of zinc status to determine an appropriate and valid marker for a rapid estimation of zinc status. We believe that new diagnostic tools are needed to identify nutritionally-at-risk mothers since clinical observations and plasma zinc levels have proven inadequate in this regard. We believe, following completion of this study, that we will have much better concepts of the mechanisms involved in zinc interactions, through our intensive studies of zinc metabolism in vitro and at the tissue level.