The broad objective of this proposal is to determine if and in what manner selected dietary, intestinal liminal and mucosal factors affect zinc metabolism, homeostasis and nutritional status.
Specific aims are to determine the effects of postconceptional age, type of feed (including own mother's milk) and Zn on total absorption (TA), fractional absorption (FA) and net absorption (NA) of Zn and the fecal excretion of endogenous zinc (FEEZ) in premature infants; to assess the Zn status of premature infants with broncho pulmonary dysplasia and the effects of Zn supplement on growth, motor and cognitive function, T cell function, IGFI and circulating metalothionein (MT); to quantitate the effects of iron fortification and iron supplements on Zn absorption by formula fed infants; to determine FA, TA, NA of Zn and FEEZ, to assess Zn status and calculate Zn requirements in breast fed infants; to investigate the cause of Zn deficiency in young children with non-organic failure to thrive who have a growth response to Zn supplementation; to measure the effects of steatorrhea on FA, TA, NA of Zn and on FEEZ in Cystic Fibrosis and to determine the effects of exocrine pancreatic enzyme replacement; to determine FA, TA, NA of Zn and FEEZ and to complete a detailed evaluation of Zn nutritional status and Zn metabolism in regional enteritis with active ileocecal disease; to determine the effects of high dose folate supplements on Zn absorption and Zn nutritional status. A core feature of this proposal is the application of Zn stable isotope techniques to investigations of Zn absorption, endogenous Zn losses and Zn metabolism and to assist in the assessment of Zn nutritional status. These techniques, based on the fast atom bombardment/mass spectrometry will be further refined as part of this proposal. Extensive evaluation of their application will be undertaken in normal adults who will also provide essential control data. Whenever feasible, measurements of absorption and endogenous losses will be supplemented with plasma and erythrocyte kinetic studies. Experimental indices of Zn """"""""status"""""""" will include half-life of the Zn pool that readily exchanges with plasma Zn (EP), size of EP, circulating MT levels and post-prandial net afflux of Zn from the plasma compartment. Zn supplementation studies will be undertaken to further assess Zn status in selected populations and will include determination of the effects on cognitive and motor development, taste perception, T cell function, and somatomedin (IGFI).
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