S.R. Chowdhury

Studies with sub-toxic doses of α-chlorohydrin in the male monkey (Macaca Mulatta)

Subtoxic doses of alpha-chlorohydrin (3-chloro-12 -propanediol or U-5897) 20 mg per kg twice daily were fed to 5 adult male rhesus monkeys and 30 mg per kg for 15 days to 4 others in an attempt to produce functional sterility. 4 out of the first 5 died of unknown cause in 7 15 and 32 days; all appeared anorexic and sedated. The remaining monkeys were killed after 6 weeks (group 1) or 15 days (group 2) and were examined for genital tract and pituitary weight and histology; pituitary gonadotropin (mouse bioassay); sperm counts sperm zinc and oxygen uptake (Warburg technique); epididymal alkaline phosphatase; lactic acid total lipids phospholipids phosphoryl glyceryl choline sodium and potassium; seminal vessicle fructose; and prostate acid phosphatase. The only significant changes were increased zinc-65 uptake (6500 and 9100 counts per 100 seconds per 100 million sperm in 2 controls and 10300 and 16700 in 2 treated monkeys); and oxygen consumption (mean 270.4 mcl per hour per 100 million sperm in 3 controls and mean 577.6 in 2 treated monkeys) by vasal spermatozoa.

A PRIMATE MODEL OF ANXIETY

Pentylenetetrazol (PTZ; 30 mg/kg, i.m.) produced an acute anxiogenic effect on the behaviour of a social colony of rhesus monkeys acclimatized to laboratory conditions. The animals exhibited hypervigilance, aggressiveness, tachypnea, piloerection and frequent change of posture and also had raised plasma cortisol levels. These effects of PTZ were antagonized by benzodiazepines (diazepam; 1 mg/kg, i.v. and alprazolam; 0.05 mg/kg, p.o.). Non-benzodiazepine anxiolytic drug (buspirone; 10 mg/kg, p.o.) blocked the behavioural effects but not the rise in plasma cortisol concentration. On the other hand, pretreatment with hypnosedative (promethazine; 5 mg/kg, i.m.) or anticonvulsant (sodium valproate; 40 mg/kg, p.o.) agents did not attenuate the effects of PTZ indicating the specificity of its anxiogenic response. The model, thus, seems suitable for evaluation of potential anxiolytic agents.

Antigestagenic activity of Ixora finlaysoniana in rat

Oral administration of crude ethanolic extract of the serial parts of Ixora finlaysoniana Wall. ex G. Don to adult female rats at 250 mg/kg dose on days 1-5 or 1-7 post-coitum prevented pregnancy in 100% rats. The extract was also effective when administered on days 1 or 1-3 post-coitum, but the minimum effective dose increased with decreased duration of administration and was 1000 mg/kg and 500 mg/kg, respectively, in the two schedules. At lower doses, a significant reduction in implantation number and increased post-implantation resorption rate were observed in all the schedules. Almost complete resorption of all implantations was observed after administration of 1000 mg/kg dose of the extract during the peri-implantation period. A slight acceleration in tubal transport rate of embryos and delay in blastocyst formation were observed in rats treated postcoitally with the single anti-implantation dose of the extract. Significantly fewer embryos were recovered after their entry into the uterus. Except in one rat receiving 250 mg/kg dose of the extract on days 1-5, in which one apparently normal zona-free blastocyst was recovered from the uterus, uterine flushings of none of the nonpregnant animals contained any unimplanted embryos by day 10 post-coitum. In immature rat bioassay, the extract was found to possess estrogenic activity as evidenced by dose-dependent increase in uterine weight and cornification of the vaginal epithelium at doses ranging from 50-1000 mg/kg. At the 500 and 1000 mg/kg doses, it also induced premature opening of the vagina. Taking 100% increase in uterine weight as the parameter, the extract was found to be about 1.6X10(5) times less estrogenic than ethinylestradiol. The extent and duration of estrogenic responses exerted by single contraceptive dose of the extract were also markedly lower than that induced by ethinylestradiol. The extract was devoid of any estrogen antagonistic or synergistic activity and did not affect ovarian prenidatory estrogen or progesterone synthesis. The findings indicate that the extract at its contraceptive dose a) exerts a differential estrogenic response at the fallopian tube and the uterine levels, b) does not appear embryocidal, but causes slight asynchrony in development and tubal transport rate of pre-implantation embryos, which together with their loss through vagina after entry into the uterus, due to estrogenic action of the extract, might contribute to its anti-implantation action, and c) its anti-implantation and post-implantation resorptive actions are not mediated via altered ovarian function.

Functional sterility in male rats after micro-dose estrogen treatment.

Abstract Adult male rats were injected with estradiol dipropionate at the rate of 0.1, 1.0, 5.0, 50.0 and 100.0 μg daily for 15 or 30 days. Doses lower than 5 μg had no effect on spermatogenesis and fertility, but higher doses caused spermatogenic arrest and inhibition of libido. The minimum effective dose was found to be 5 μg/15 days which caused 100% reduction in fertility without disturbing spermatogenesis or libido. However, when the treatment period was extended for 30 days varying degrees of spermatogenic interruption and loss of libido were recorded. The mechanism of antifertility action is discussed.

Quantitative analysis of spermatogenesis in rats made azoospermic with compound CDRI 84/35

Abstract Compound CDRI 84/35 (1-formyl-4-dichloroacetamidopiperazine) was reported to exert its effect on seminiferous epithelium without affecting Leydig cells and accessory sex organs. Adult rats administered CDRI 84/35 (100 mg/kg body weight for 15 days followed by 25 mg/kg) showed a significant atrophy of testis indicating 21.8 ± 4.4, 79.6 ± 5.3, 94.8 ± 2.1 and 79.5 ± 2.1% abnormal tubules at 22, 41, 54, and 64 days following treatment at the time of autopsy). The Sertoli cell-germ cell ratio showed a significant reduction in number of primary spermatocytes and spermatids during the treatment. Marked decrease in pachytene spermatocytes and in stages of spermatogenesis was observed on day 54. In contrast, the testes in estradiol benzoate (EB; 5 g/rat/day) treated rats showed 64.6% ± 21.85% abnormal tubules at day 22 and almost all affected tubules on from day 41 onwards, exhibiting a significant decline in number of spermatocytes and spermatids, while spermatogonia were affected only at 64 days of treatment. Reversibility studies showed 76.5% ± 2.1% normal tubules with significant inhibition in spermatogenesis following 60 days cessation of CDRI 84/35. At 120 days recovery, 74.7% ± 18.8% testicular tubules revealed quantitatively normal spermatogenesis, whereas 25.3% ± 18.8% tubules showed incomplete recovery of spermatogenesis until 120 days. The present study revealed a marked inhibition of spermatogenesis at the pachytene spermatocyte stage by CDRI 84/35 compared to EB in the seminiferous epithelium of rat. Its antispermatogenic effect was found to be irreversible up to 120 days.

Biochemical composition of human vas deferens

Abstract The biochemical composition (protein, non-protein nitrogen, urea, alkaline phosphatase, acid phosphatase, sialic acid, glycogen, fructose, lactic acid, phospholipids, glycerylphosphorylcholine, sodium, potassium and chloride) of human vas deferens was determined. Glycerylphosphorylcholine was present only in the luminal washings of the vas. The possibility of vas deferera having both secretory and resorptive functions is discussed.

Early abortifacient action of RU 486 by continuous intravenous infusion in rat

RU 486 administered through constant intravenous infusion at 20 mg/kg dose on day 8 of pregnancy induced frank vaginal bleeding and resorption of all implantations in 100% rats. This was associated with an almost 4-fold reduction in progesterone secretion rate by the dispersed luteal cells ex-vivo. At 12 mg/kg dose, an incomplete resorption of implantations was observed in all treated animals. Results indicate that slow and continuous intravenous infusion of this antiprogestin was highly effective in terminating pregnancy shortly after implantation in the rat and this could, at least partially, be related to its luteolytic action in this species.

Effect of long-term Centchroman treatment on plasma steroid and peptide hormones in female rhesus monkeys (Macaca mulatta)

Effect of weekly oral administration of Centchroman (3,4-trans-2, 2-dimethyl-3-phenyl-4-(p-(beta-pyrrolidinoethoxy)-phenyl)-7-met hoxychroman) at 1 and 2.5 mg/kg for 12 months on plasma estradiol, progesterone, luteinizing hormone and follicle stimulating hormone of female rhesus monkeys was studied. Centchroman administration at both doses did not disturb the menstrual pattern of rhesus monkeys except for a prolongation of the first treatment cycle. The subsequent cycles were of normal duration. The general pattern of plasma estradiol, progesterone, luteinizing hormone and follicle stimulating hormone was not affected by Centchroman treatment. The basal and peak levels were similar in pretreatment, control and treatment cycles. The results clearly indicate that Centchroman treatment up to 1 year does not affect the hypothalamo-pituitary-ovarian axis in female rhesus monkeys.

The nature and kinetics of biochemical response of the genital organs of ovariectomized female rhesus monkeys to sex hormones

Abstract The kinetics of action and interactions of estradiol dipropionate and progesterone (100 μg and 20 mg, respectively, by a single intramuscular injection) with respect to some biochemical constituents of the uterus and the fallopian tube of ovariectomized rhesus monkeys ( Macaca mulatta ) have been investigated. The concentration of these constituents (protein and non-protein nitrogen, nucleic acids, glycogen, lactic acid and phospholipid) records an increase under the influence of the hormones (with the exception of non-protein nitrogen). However, when injected concurrently their stimulatory action is generally diminished. The implications of these findings are discussed.