EFFECTS OF DEXAMETHASONE ON PROTEIN & GLUCOSE METABOLISM IN PREMATURE

这是一项试验性研究，目的是获得用于申请联邦校外资金的初步数据。我们计划收集有关地塞米松（DEX）对早产儿蛋白质和葡萄糖代谢影响的信息，并建立一个模型来表征这些影响的具体特征。DEX现在被广泛应用于这些婴儿，它对早产儿肺部疾病的治疗非常有效。然而，其不利影响之一是通过促进负氮平衡和抵抗胰岛素的作用而导致高血糖，从而抑制短期生长（长期影响目前尚不清楚）。如果我们对这一过程的机制有更多的了解，那么我们就可以调整DEX的使用方式，将其负面代谢影响降到最低。这将包括使用较小剂量和较短疗程的药物，改变营养环境，并可能使用生长样激素来抵消DEX的影响。我们计划收集20名特殊护理托儿所婴儿使用DEX的信息以及10名对照婴儿的信息。我们还将开发我们的仔猪模型，以评估给药时间与出生时间的关系，给药方法对蛋白质和葡萄糖代谢的影响，最后，使用放射性同位素标记的氨基酸，对DEX治疗后氨基酸氧化和蛋白质合成变化的时间过程进行评估。本项目的第二个目标是评估右美托咪唑对婴儿心肌的负面影响，并评估右美托咪唑对仔猪心肌的影响。与对骨骼肌（肌肉分解）的影响相反，DEX会导致早产儿心肌肥大，导致梗阻性心肌病，这对一些婴儿来说是危及生命的。再一次，我们希望找到最小化DEX对心肌的负面影响的方法。

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 %fill 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.