ZINC HOMEOSTASIS AND KINETICS IN CHILDREN WITH CYSTIC FIBROSIS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。锌对正常生长、发育和免疫功能是必不可少的。众所周知，胰腺功能不全会损害锌的吸收，而明显的锌缺乏(肠性肢端皮炎)在慢性萎缩性胰腺炎中有很好的描述。然而，由于缺乏良好的锌状况衡量标准，不太严重的锌缺乏症的重要性尚不清楚。最广泛使用的检测方法是血浆锌浓度，其特异性和敏感度较差，可能由于同时存在感染或低蛋白血症而在CF中被假性抑制。我们以前已经证明，锌动力学的变化(多室模型)可以在血浆锌浓度变得异常之前识别锌缺乏的适应性。本研究的具体目标是比较补锌和不补锌的CF儿童和年龄匹配的健康对照组儿童的锌吸收、内源性粪便锌排出、锌平衡和锌状况。24名患有慢性胰腺炎和胰腺功能不全的儿童，年龄8-14岁，将随机接受20 mg/d的锌作为醋酸锌或相同的安慰剂，为期2个月。在此之后，他们将住院6天，届时将口服和静脉注射锌稳定同位素，进行为期6天的完整尿液和粪便收集，并在注射同位素后采集多份血液样本。这些数据将被用来评估锌的吸收、内源性粪便锌的排泄、锌的平衡和锌的动力学(一种新的衡量锌状态的指标)。来自两组CF儿童的数据将与12名年龄匹配的对照组的数据进行比较，这些对照组的儿童摄入目前推荐的每日锌摄入量。我们假设，与对照组相比，服用安慰剂的CF儿童的锌吸收显著降低，内源性锌排泄增加，锌平衡更差，锌状况更差；而锌治疗的CF儿童将具有与对照组相似的锌平衡和锌状况。我们进一步假设，补锌不会导致铁状态(血红蛋白、铁蛋白、转铁蛋白受体)或铜状态(血清铜、铜蓝蛋白和铜锌超氧化物歧化酶)的任何不良影响。最后，我们假设脂肪吸收不良与内源性粪锌排泄呈正相关，与锌吸收和锌平衡呈负相关。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Zinc is essential for normal growth, developmental and immune function. Pancreatic insufficiency is known to impair zinc absorption and overt zinc deficiency (acrodermatitis enteropathica) is well described in CF. However the importance of less severe forms of zinc deficiency is unclear due to the lack of a good measure of zinc status. The most widely used test, plasma zinc concentration, has poor specificity and sensitivity, and may be falsely depressed in CF due to co-existing infection or hypoproteinemia. We have previously shown that changes in zinc kinetics (multi-compartmental models) can identify adaptation in zinc deficiency before the plasma zinc concentration becomes abnormal. The specific objectives of this study are to compare zinc absorption, endogenous fecal zinc excretion, zinc balance and zinc status in children with CF, with and without supplementary zinc, and healthy age-matched controls. Twenty-four children with CF and pancreatic insufficiency, aged 8-14y, will be randomized to receive 20 mg/d zinc as zinc acetate or an identical placebo for 2 months. After this they will be admitted for a 6-day in-patient stay when zinc stable isotopes will be administered orally and intravenously, a complete 6-day urine and fecal collection carried out, and multiple blood samples taken after isotope administration. This data will be used to assess zinc absorption, endogenous fecal zinc excretion, zinc balance and zinc kinetics (a novel measure of zinc status). Data from the two groups of CF children will be compared to data from 12 age-matched controls consuming the current recommended daily allowance for zinc. We hypothesize that the placebo-treated CF children will have significantly lower zinc absorption, higher endogenous fecal zinc excretion, poorer zinc balance, and worse zinc status than the controls; and that the zinc-treated CF children will have similar zinc balance and zinc status to the controls. We further hypothesize that zinc supplementation will not lead to any adverse effects of iron status (hemoglobin, ferritin, transferin receptors) or copper status (serum copper, ceruloplasmin and copper- zinc superoxide dismutase). Finally, we hypothesize that fat malabsorption will be positively correlated with endogenous fecal zinc excretion, and negatively correlated with zinc absorption and zinc balance.