Development of a compartmental model of human zinc metabolism: identifiability and multiple studies analyses

Miller, Leland V.; Krebs, Nancy F.; Hambidge, K. Michael

doi:10.1152/ajpregu.2000.279.5.r1671

Cited by 46 publications

(38 citation statements)

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“…An accurately weighed quantity of 67 Zn (≈1 mg) was administered intravenously over a ten-minute interval on day 10 at 9:00 am. The timing of the 67 Zn intravenous administration was optimized to ensure the accuracy of the dual tracer FAZ extrinsic determinations by means of a simulation of the tracer administration and sampling protocols using a compartmental model of human zinc metabolism [16]. The simulation was performed by using WinSAAM 3.0 software (University of Pennsylvania, Kennett Square, PA).…”

Section: Methodsmentioning

confidence: 99%

Measurement of Zinc Absorption From Meals: Comparison of Extrinsic Zinc Labeling and Independent Measurements of Dietary Zinc Absorption

Sheng

Hambidge

Miller

et al. 2009

International Journal for Vitamin and Nutrition Research

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Background Extrinsic labeling techniques are typically used to measure fractional absorption of zinc (FAZextrinsic) but none have been adequately evaluated. Objective To compare determination of the quantity of zinc absorbed (TAZextrinsic) using measurements of FAZextrinsic with results of simultaneous determinations of dietary zinc absorbed (TAZmetabolic) that are not dependent on labeling ingested food with an extrinsic tracer (modified metabolic balance technique). Design 70Zn was administered orally with all meals for 6 consecutive days to 21 healthy, free-living adult women consuming a constant diet. 68Zn and 67Zn were administered intravenously. FAZextrinsic was measured using a dual isotope tracer ratio technique and multiplied by dietary zinc to give TAZextrinsic TAZmetabolic was determined by addition of net absorption of zinc and endogenous fecal zinc, the latter determined by an isotope dilution technique. Results TAZextrinsic and TAZmetabolic were 3.0 ± 1.1mg/day and 3.1 ± 1.1 mg/day respectively, paired t-test p = 0.492. The correlation coefficient for TAZextrinsic and TAZmetabolic was 0.91, and for FAZextrinsic and FAZmetabolic was 0.95. A Bland Altman analysis indicated a bias of 0.07, and the limits of agreement of −0.86 to 1.01 for TAZextrinsic and TAZmatabolic Conclusion These results from two independent methods provide reasonable validation of our extrinsic labeling technique for a wide range of composite diets.

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Section: Methodsmentioning

confidence: 99%

Measurement of Zinc Absorption From Meals: Comparison of Extrinsic Zinc Labeling and Independent Measurements of Dietary Zinc Absorption

Sheng

Hambidge

Miller

et al. 2009

International Journal for Vitamin and Nutrition Research

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“…Detailed models have been published for zinc (Zn) metabolism in humans (3–5), rats (1,6), and piglets (7) but not for mice, even though their Zn kinetics have been studied extensively (8–11). Because mice are being used to study biological functions of proteins by knocking out or overexpressing genes, kinetic studies in genetically modified mice, combined with modeling, may provide insight into their functions in vivo.…”

Section: Introductionmentioning

confidence: 99%

Development of a Compartmental Model of Zinc Kinetics in Mice

Wastney

House

2008

The Journal of Nutrition

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To investigate zinc (Zn) kinetics in mice, tracer (65Zn) was administered orally to 9-wk-old female mice in the fed state and tracer and Zn concentration were measured in 21 tissues over the following 8 d. Data were analyzed by compartmental modeling using WinSAAM. A published model for Zn kinetics in rats was modified to fit the data from mice and to calculate transfer rates and pool sizes of Zn. Parallel studies were performed in mice lacking genes for metallothionein (MT), MT-I and MT-II (MT−/−), to quantify differences in Zn kinetics in the absence of these proteins in vivo. We confirmed that tracer time course in most tissues was similar in wild-type mice and those lacking MT, except for the pancreas of MT−/−, which retained less tracer. By fitting tissue and intestinal data simultaneously, we found that intestinal tracer could be explained by unabsorbed isotope and loss of Zn from pancreas went through plasma. Differences in pancreatic data in MT−/− were explained by Zn turning over twice as fast in this tissue (4 h) compared with wild type (9 h). These kinetic studies provide parameter values for normal, fed mice that can be used to assess Zn kinetics in abnormal conditions, as demonstrated by the higher turnover of Zn in the pancreas of MT knockout mice.

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“…Previously published essential element models for zinc 25,26 and copper 27,28 are based on a compartmental modeling approach. They captured the control of these essential elements under normal and deficient dietary conditions.…”

Section: Initial Developmentmentioning

confidence: 99%

Modeling Manganese Kinetics for Human Health Risk Assessment

Yoon¹,

Taylor²,

Clewell³

et al. 2014

Manganese in Health and Disease

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Manganese (Mn) is an essential element, present in significant concentrations in the central nervous system (CNS) and all other tissues. 1-4 Mn is required for normal immune function, regulation of blood sugar and cellular energy, lipid and carbohydrate metabolism, skeletal cartilage development, reproduction, and brain functions. It participates in metabolic pathways and a co-factor metal for Mn superoxide dismutase and glutamine synthetase. 5,6 The body's requirements for Mn are met through food and drinking water, with adult human consumption ranging from 1 to 10 mg Mn per day, of which about 1-5% is absorbed in the gut. 2,5,7 Homeostatic mechanisms controlling uptake, storage, and elimination of dietary Mn maintain tissue Mn concentrations at a relatively constant level despite widely varying dietary levels of Mn.

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Development of a compartmental model of human zinc metabolism: identifiability and multiple studies analyses

Cited by 46 publications

References 46 publications

Measurement of Zinc Absorption From Meals: Comparison of Extrinsic Zinc Labeling and Independent Measurements of Dietary Zinc Absorption

Measurement of Zinc Absorption From Meals: Comparison of Extrinsic Zinc Labeling and Independent Measurements of Dietary Zinc Absorption

Development of a Compartmental Model of Zinc Kinetics in Mice

Modeling Manganese Kinetics for Human Health Risk Assessment

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