Efficacy of HCG and ovarian steroids in the maintenance/interruption of pregnancy in-albino rats.

We investigated the efficacy of human chorionic gonadotrophin (HCG) and ovarian steroids in the maintenance/interruption of pregnancy in normal pregnant rats. Holtzman's strain rats were laparotomized to observe the number of implantations. In this study, continuous administration of HCG (5 IU) to normal pregnant rats, from day 8 through days 14 or 19, interrupted gestation, resulting in fetal resorption with many placentomas and placental scars. By contrast, a single injection of HCG (5 IU or 1 IU) on day 8 had no deleterious effect on pregnancy, except that the percent fetal survival was slightly reduced, attributable to a slight hyperstimulation of the ovaries of the pregnant rats. One possibility is that prolonged treatment with HCG might have caused progesterone/luteal hormone deficiency with a concomitant increase in estrogen secretion, resulting in the interruption of pregnancy. Hence, here we tested whether progesterone (5 mg) or estradiol-17beta (1 microg) administered to HCG treated rats could compensate this deficiency and maintain pregnancy. The results indicate that these steroids cannot prevent the interruption of pregnancy induced by the continuous administration of HCG, possibly due to an overstimulation of the ovaries by gonadotrophin.

Maintenance or interruption of pregnancy by human chorionic gonadotrophin in adrenalectomized albino rats.

In the present study, we investigated the efficacy of human chorionic gonadotrophin (HCG) in the maintenance of pregnancy in adrenalectomized rats. Holtzman's strain albino rats were adrenalectomized on day 8 of pregnancy and at the same time were laparotomized to observe the number of implantations. Adrenalectomy on day 8 caused abortions or fetal resorption in almost all rats. Administration of 5 or 50 IU HCG in adrenalectomized rats, from day 8 through 14 or 19, was not able to maintain gestation, resulting in fetal resorption with many placentomas and placental scars. However, a single injection of 5 IU or 1 IU HCG administered on day 8 only maintained the pregnancy to full term in adrenalectomized rats. Hence, the present experiment indicates that replacement therapy of a single dose of 5 IU or 1 IU HCG might be sufficient for maintaining pregnancy in adrenalectomized rats.

Antitumor activity of 4-amino and 8-methyl-4-(3diethylamino propylamino)pyrimido[4',5':4,5]thieno (2,3-b) quinolines.

The interaction of 4-aminopyrimido [4',5':4,5] thieno (2,3-b) quinoline and 8-methyl-4-(3-diethylaminopropylamino) pyrimido [4',5':4,5] thieno (2,3-b) quinoline with DNA was studied by UV-Vis and fluorescence spectrophotometry as well as by hydrodynamic methods. On binding to DNA, the absorption spectra underwent bathochromic and hypochromic shifts and the fluorescence was quenched. These compounds are able to bind to DNA with an affinity of about 10(6) M(-1) for calf thymus DNA at ionic strength 0.01 M and their intercalating characteristic (lengthening of the DNA) depends upon the length of the chain. Binding to the GC-rich DNA of Micrococcus lysodeikticus was stronger than the binding to calf thymus DNA at ionic strength 0.01 M. The cytotoxicities of these compounds on leukemia HL-60, melanoma B16F10 and neuro 2a cells are quite similar and inhibition (IC50) is in the range of 0.992-3.968 microM. The anticancer efficacy against B16 melanoma, has provided evidence of major antitumor activity for 8-methyl-4-(3diethylaminopropylamino) pyrimido [4',5':4,5] thieno(2,3-b)quinoline. Single or multiple intraperitonial (i.p) doses of drug proved high level activity against the subcutaneous (s.c) grafted B16 melanoma, significantly increasing survival (p<0.001) and inhibiting tumor growth (T/C of 4%). This study offers a new intercalation functional group to DNA-targeted drug design.

Development of the adrenal gland in the tropical lizard Calotes versicolor.

The development of the adrenal gland in the lizard Calotes versicolor was studied histologically and histochemically from the day of oviposition (stage 27) to 60 days after hatching. At stage 27, the adrenocortical cells are found in association with the genital ridge (primordial gonad). The separation of adrenocortical cells from the gonad takes place at stage 31. Organization of adrenocortical cells into cords takes place at stage 34. The catecholamine-secreting chromaffin cells can be seen distinctly on the dorsal region of the adrenal at stage 36, indicating the presence of biologically active catecholamines; the noradrenaline-secreting chromaffin cells appear first at stage 36 and the adrenaline-secreting cells appear later at stage 41. The cortico-medullary ratio of 6:1 during early embryonic development decreases with the increase in age and is 3:1 in posthatching lizards. The histochemical localization of Delta(5)-3beta-hydroxysteroid dehydrogenase (3beta-HSD) and glucose-6-phosphate dehydrogenase in the adrenocortical cells as early as at stage 27 (prior to the gonadal differentiation) indicates the capability of these cells to synthesize steroids. The intensity of the enzyme activity is maximum on the day of hatching and remains more or less the same in the posthatching lizards. The localization of 17beta-HSD enzyme activity observed in the adrenocortical cells at stage 34 is suggestive of their ability to synthesize sex steroids during embryonic life. The intense 3beta-HSD activity on the day of hatching in C. versicolor suggests high production of steroids which may be corticoids. The results of the present work also suggest that the onset of steroid secretion occurs prior to catecholamine secretion during embryogenesis of the adrenal gland in C. versicolor. In addition, there is a significant relationship between ontogenic steroidogenesis of the adrenal gland and sexual differentiation of the gonad.