This is a pilot study with the objective of obtaining preliminary data which will be used to apply for federal extramural funding. We plan to collect information on the effects of dexamethasone (DEX) on protein and glucose metabolism in premature infants as well as to develop a model to characterize the specifics of these effects using the newborn piglet . DEX is now widely used in these infants, where it is very effective in the treatment of the lung disease of prematurity. However, one of its adverse affects is inhibiting short term growth (long term effects are unknown at the present time) by promoting a negative nitrogen balance and a resistance to the effects of insulin with resulting hyperglycemia. If we understand more about the mechanics of this process, then we will be able modify our use of DEX in ways to minimize its negative metabolic effects. This would include using smaller doses and shorter courses of the drug, altering the milieu of nutrients, and possibly using growth-like hormones to counter the effects of DEX. We plan to collect information from 20 Special Care Nursery infants on DEX as well as 10 control infants. We will also develop our piglet model to assess the affects of timing of the dose in relationship to the time of birth, the effects of methods of dosing DEX on protein and glucose metabolism, and finally, using amino acids labeled with radio isotopes, the time course of changes in amino acid oxidation and protein synthesis in response to DEX treatment. A secondary goal of this project, is to evaluate the negative effects of DEX on cardiac muscle in infants, and to evaluate the changes in cardiac muscle secondary to DEX in the piglets. Contrary to the effects on skeletal muscle (muscle breakdown) DEX causes hypertrophy of cardiac muscle in premature infants, resulting in an obstructive cardiomyopathy which is life threatening in some infants. Again, we hope to determine ways to minimize the negative effects of DEX on cardiac muscle.
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