Terephthalamidine: past and future.

Terephthalamidine (NSC 57155) is one of 800 terephthalanilides and related compounds which were synthesized and tested preclinically in the late 1950's and early 1960's. Based upon their activity against murine leukemias, some of these agents were tested briefly in clinical trials at that time. Despite the observation of responses, the compounds were dropped because of severe and unusual neurotoxicity. More recently, terephthalamidine has been screened for antitumor activity and chosen for further clinical investigation by the NCI's Project for the Review of Old Drugs (P.R.O.D.) because of its novel structure and spectrum of preclinical activity. The current availability of a plasma assay for the drug permits further study of its clinical pharmacokinetics and pharmacodynamics and, perhaps, the development of improved scheduling strategies.

Breeding laboratory cats during artificially induced estrus.

Mature female cats of known reproductive history were randomly divided into groups for natural breeding or mating following hormonal induction of estrus. Treatment with a single injection of 100 international units of pregnant mares' serum followed in 7 days by 50 international units of human chorionic gonadotropin produced results comparable to natural breeding. Daily injections of pregnant mares' serum (300-500 international units total) resulted in fewer successful pregnancies and adversely affected the ability of kittens to survive to weaning.

Hormone-mediated oviductal influence on mouse embryo development.

This study presents evidence that estradiol, mediated through oviduct fluid, may adversely affect the development of early embryos. Two-cell mouse embryos were cultured in Whitten-Biggers medium with or without 0.2 to 20 microgram/ml of estradiol or progesterone or in mouse oviduct fluid from donors treated with estradiol or estradiol and progesterone. Embryos cultured in fluid from estrogen-dominated donors were significantly less able to develop to morula (65%) or blastocyst (14%) than were those cultured in either Whitten-Biggers medium (91% and 41%) or progesterone-dominated fluid (87% and 36%). Transfer of cultured morulae and blastocysts to uteri of pseudopregnant recipients resulted in 2/3, 4/6, and 0/7 recipients' becoming pregnant for control, progesterone-dominated, and estrogen-dominated, respectively. When estradiol or progesterone was added directly to the control medium, no inhibitory effects were observed at levels higher than those found physiologically in plasma. Protein concentration and osmolalities for representative samples of oviduct fluid were 5.2 mg/ml and 329 mOsM for estrogen-dominated fluid and 1.6 mg/ml and 339 mOsM for progesterone-dominated fluid.