This application describes our continuing use of stable, non-radioactive isotopes in non-invasive studies of protected populations. Specifically, we propose: 1. To develop new techniques for quantitative metabolic studies in neonatal, pediatric, pregnant and lactating subjects based on a) administration of 13C labeled compounds, b) automated measurement of 13C abundance in respiratory CO2 using high precision gas isotope ratio mass spectrometry and c) multiexponential and compartmental analysis of 13CO2 production curves. 2. To strengthen the basis of carbon isotopic tracer studies by quantitative documentation of HCO3/CO2 kinetic parameters and CO2 production rates in these subject categories as a function of physiological and nutritional status. 3. To develop advanced scoring methods for 13C breath tests that enable resolution of abnormal from normal intestinal and liver function. 4. To develop 13C-labeled forms of substrates of greater biological complexity than presently available, such as UL-13C-protein and UL-13C-fiber for use in studies of small and large bowel function. Such information will provide characterization of normal processes of absorption, transport, utilization and excretion of lipids, carbohydrates and amino acids in those human subjects protected from radioisotopic tracer usage. Comparison of the parameters in normal subjects with those values obtained in longitudinal studies of development or in specific disease states will provide numerical values for the change of physiological processes during growth, development and disease. These include studies of the development of lactase in the newborn, the absorption of amino acids and peptides by the damaged intestinal mucosa, liver function in children receiving total parenteral nutrition, and the mobilization of lysine by the lactating woman for milk protein synthesis.
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