ZINC HOMEOSTASIS AND KINETICS IN CHILDREN WITH CYSTIC FIBROSIS

囊性纤维化儿童的锌稳态和动力学

• 批准号: 7605871
• 负责人: IAN J GRIFFIN
• 金额: $ 0.94万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-15 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7605871
• 关键词: Adverse effects; Affect; Age; Blood specimen; Ceruloplasmin; Child; Collection; Computer Retrieval of Information on Scientific Projects Database; Copper; Cystic Fibrosis; Data; Depressed mood; Development; Equilibrium; Ethnic Origin; Excretory function; Exocrine pancreatic insufficiency; Fatty acid glycerol esters; Ferritin; Fibrocystic Disease of Pancreas; Funding; Gender; Grant; Growth; Hemoglobin; Homeostasis; Hypoproteinemia; Infection; Institution; Intervention; Iron; Isotopes; Kinetics; Lead; Malabsorption Syndromes; Measures; Modeling; Patients; Personal Satisfaction; Placebos; Plasma; Randomized; Recommended Daily Allowances; Research; Research Personnel; Resources; Sensitivity and Specificity; Serum; Source; Supplementation; Techniques; Testing; United States National Institutes of Health; Urine; Zinc; Zinc Acetate; Zinc deficiency; absorption; abstracting; acrodermatitis enteropathica; aged; base; children with cystic fibrosis; copper zinc superoxide dismutase; day; healthy aging; immune function; novel; receptor; stable isotope; urinary

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. ABSTRACT 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. HYPOTHESES We hypothesize that, 1. Children with CF will have worse zinc status, lower fractional zinc absorption, increased endogenous fecal zinc excretion, and poorer zinc balance, than age-matched controls. 2. After two months of zinc supplementation with 20 mg/d zinc as zinc acetate children with CF will have similar zinc status, fractional zinc absorption, endogenous fecal zinc excretion, and zinc balance to age-matched controls. 3. Two months of zinc supplementation will not affect iron status (Hemoglobin, serum ferritin, serum transferin receptors) or copper status (serum copper, ceruloplasmin, copper/ zinc superoxide dismutase). 4. Zinc absorption, endogenous fecal zinc excretion and zinc balance will be positively correlated with the degree of fat malabsorption. SPECIFIC AIMS The aims of this study are to use stable isotope-based multicompartmental modeling techniques to evaluate zinc balance, zinc status, zinc absorption, endogenous fecal zinc excretion and urinary zinc excretion in children with cystic fibrosis (CF,) with or without additional zinc supplementation and compared them to healthy age-matched controls. Specifically, we will randomize 24 children with CF and pancreatic insufficiency to receive 2 months of zinc supplementation (20 mg/d) or placebo. At the end of the intervention we will use stable isotope techniques to assess zinc absorption, endogenous fecal zinc excretion, zinc balance, and zinc kinetics (using a multi-compartmental model). We will also assess the effect of zinc supplementation (or placebo) on iron and copper status. Comparisons will be made between the two randomized groups of CF children and 12 healthy age- gender- and ethnicity-matched controls.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 抽象的 锌对于正常生长、发育和免疫功能至关重要。众所周知，胰腺功能不全会损害锌的吸收，而明显的锌缺乏（肠病性肢端皮炎）在 CF 中有详细描述。然而，由于缺乏良好的锌状态测量方法，不太严重的锌缺乏症的重要性尚不清楚。最广泛使用的测试是血浆锌浓度，其特异性和敏感性较差，并且可能由于合并感染或低蛋白血症而在 CF 中出现错误的降低。我们之前已经表明，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。本研究的具体目标是比较患有 CF 的儿童（补充或不补充锌）和健康年龄匹配对照的锌吸收、内源性粪便锌排泄、锌平衡和锌状态。 24 名 8-14 岁患有 CF 和胰腺功能不全的儿童将随机接受 20 毫克/天的醋酸锌锌或相同的安慰剂，为期 2 个月。此后，他们将入院接受为期 6 天的住院治疗，期间将口服和静脉注射锌稳定同位素，进行完整的 6 天尿液和粪便收集，并在同位素给药后采集多个血液样本。该数据将用于评估锌吸收、内源性粪便锌排泄、锌平衡和锌动力学（一种新的锌状态测量方法）。两组 CF 儿童的数据将与 12 名摄入当前建议每日锌摄入量的年龄匹配的对照组的数据进行比较。我们假设，与对照组相比，接受安慰剂治疗的 CF 儿童的锌吸收量显着较低，内源性粪便锌排泄量较高，锌平衡较差，锌状态较差；并且接受锌治疗的 CF 儿童将具有与对照组相似的锌平衡和锌状态。我们进一步假设补充锌不会导致铁状态（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）的任何不利影响。最后，我们假设脂肪吸收不良与内源性粪便锌排泄呈正相关，与锌吸收和锌平衡呈负相关。 假设 我们假设， 1. 与年龄匹配的对照组相比，CF 儿童的锌状况较差，锌吸收分数较低，内源性粪便锌排泄增加，锌平衡较差。 2. 服用 20 mg/d 锌（醋酸锌）两个月后，CF 儿童的锌状态、锌吸收分数、内源性粪便锌排泄和锌平衡将与年龄匹配的对照相似。 3. 补锌两个月不会影响铁状态（血红蛋白、血清铁蛋白、血清转铁蛋白受体）或铜状态（血清铜、铜蓝蛋白、铜/锌超氧化物歧化酶）。 4.锌的吸收、内源性粪锌排泄和锌平衡会与脂肪吸收不良的程度呈正相关。 具体目标 本研究的目的是使用基于稳定同位素的多室建模技术来评估囊性纤维化（CF）儿童的锌平衡、锌状态、锌吸收、内源性粪便锌排泄和尿锌排泄，无论是否额外补充锌，以及将他们与健康年龄匹配的对照进行比较。 具体来说，我们将随机 24 名患有 CF 和胰腺功能不全的儿童接受为期 2 个月的锌补充剂（20 毫克/天）或安慰剂。在干预结束时，我们将使用稳定同位素技术来评估锌吸收、内源性粪便锌排泄、锌平衡和锌动力学（使用多室模型）。我们还将评估补锌（或安慰剂）对铁和铜状态的影响。 将在两组随机化的 CF 儿童和 12 名年龄、性别和种族匹配的健康对照之间进行比较。