The overall objective of the program is to establish a bonafide investigation in biochemical and pharmacological aspects of biomedical research. The proposed research program will encompass studies from subcellular to organism level, since any pharmacological response is caused by various biochemical and physiological contributing factors. The response might be due to an agent or to an environmental stress; thus one must monitor several interlocking aspects of the biochemical factors involved. The projects all are involved in directly monitoring the following factors: a) biochemical profile associated with the aging process, which would signal whenever aging develops prematurely; b) biochemical aspects of cyclopropanoid fatty acids and lipoxygenase toxicity in the mammalian organism; c) the neurosecretory elements will be examined with histochemicals and electron microscopy techniques to reveal detailed cytological characteristics; d) investigation of the role of biogenic amines in adrenal-ovarian interaction; e) studies of carbohydrate metabolism on the action of vasopressin and other agents from isolated hepatic parenchymal cells; f) cytological changes of various animal organs due to the deficiency of Vitamin B6 with respect to the role of pyridoxal phosphate and also several kinetic properties; g) studies of specific heat capacity as related to structural behavior of a phospholipid biological membrane; h) investigation delineating physiological and pharmacological conditions through corticosteroid metabolism which produces acidic metabolites and will be monitored by mass-fragmentographic technique; i) optimization of therapeutic index of cancer chemotherapeutic agents through cell kinetic and pharmacokinetic approaches. The last two projects in this program will involve synthesis of various ketodeoxyhexosyl uracils, substituted uracils and azouracils; and will establish analytical methods for monitoring cancer chemotherapeutic agents.