A study of in vivo cell mediated immune status in patients of chronic myeloid leukaemia.
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Humans↗
Biomedical subjects
S K Saksena
Publications and source records attributed to S K Saksena.
Maintenance of pregnancy in rabbits treated with long-lasting progestins.
Fertilized eggs from rabbits 1 or 2.5 days after insemination were transferred to the oviduct or uterine horn of recipients that had received a single subcutaneous injection of 20 or 30 mg of one of seven long-acting progestins. The rabbits were observed daily, and the number of implantation sites was determined 10 or 11 days after egg transfer. No implantation sites were recorded in the recipient does treated with progesterone or ZK-5623 (Schering AG, Berlin, West Germany), a nor-steroid compound. Thirty-nine percent and 51% of the transferred eggs implanted in the recipient does treated with ZK-5410 (Schering AG) and chloromadinone acetate (Eli Lilly & Company, Indianapolis, IN), respectively. However, most of the pregnant animals aborted 14 to 20 days after egg transfer. The pregnancy was either maintained to term or was prolonged beyond the normal gestation length in the does treated with other compounds, ZK-53915, ZK-9349 (Schering AG) or Depo-Provera (Upjohn Company, Kalamazoo, MI). The young delivered after a subcutaneous injection of 17 beta-estradiol and oxytocin were found normal and active.
Animals↗
Effects of cadmium chloride on ovulation and on induction of sterility in the female golden hamster.
The effects of single subcutaneous injections of cadmium chloride (CdCl2) on ovulation, egg transport and early pregnancy in the golden hamster were studied. While a single dose of 1.25 or 2.5 mg/kg of CdCl2 imposed none to marginal effects, hamsters treated with 5 or 10 mg/kg CdCl2 experienced a period of sterility ranging from 11-69 (5 mg/kg) or 46-71 (10 mg/kg) days, followed by a normal pregnancy. Administration of CdCl2 also induced ovulation inhibition which was dose-and time-dependent. A minimum dose of 5 mg/kg CdCl2 was needed to inhibit ovulation. When CdCl2 was given closer to the time of the luteinizing hormone (LH) surge on the day of proestrus, a more pronounced effect on ovulation was recorded. The incidence of failure of ovulation was associated with decreased progesterone levels in serum and inflammation, hemorrhages and necrosis in the ovary. However, the ovarian lesions lasted less than 4 days. The results indicate that CdCl2 inhibits ovulation when administered close to the time of ovulation, whereas its influence on pregnancy is pronounced but temporary.
Animals↗
Cadmium: its effects on ovulation, egg transport and pregnancy in the rabbit.
The subcutaneous administration of cadmium chloride (CdCl2) 24 h before hCG-induced ovulation in rabbits sacrificed 14 h after induction of ovulation leads to a dose-dependent decrease in the number of oviductal eggs and the number of eggs shed. While a dose of 1.25 mg/kg CdCl2 imposed no effect, only 50-67% of the dogs treated with 2.5 or 5 mg/kg CdCl2 ovulated and of those ovulated eggs 35.6 and 45%, respectively, were found in the oviducts. At a dose of 7.5 mg/kg CdCl2, a higher proportion (57.1%) of the does failed to ovulate and only 16% of the eggs were recovered from the oviducts. Ligature of the uterotubal junction failed to increase the rate of eggs recovered from the oviducts. A sharp increase in serum progesterone (delta4 P) level within 2 h after induction of ovulation suggests that the reduction in the percentage of eggs recovered from the oviducts probably occurred due to altered fimbrial functions. On the other hand, in does treated with 5 mg/kg CdCl2 1 or 7 days before mating, pregnancy was interrupted in 60 and 75% of the does together with reduced delta4 P concentration and the conception rate (no. of implantations/CL) was significantly reduced. CdCl2 given 21 days before or 3 days after mating did not affect pregnancy and delta4 P concentration remained unaltered. Results suggest that the developing or mature follicles are sensitive to CdCl2 treatment. Once the CL is formed, the effect of CdCl is reduced. The receptivity of CdCl2-treated females indicates that probably the circulating estrogens were not affected and the ability to ovulate in response to hCG and mating reflects that, at least at the doses used, the hypothalamic-pituitary gonads functions are functional in the rabbit.
Animals↗
The concentration of progesterone, 20 alpha-dihydroprogesterone, testosterone, oestrone and oestradiol-17 beta in serum, amniotic fluid and placental tissue of pregnant rabbits.
The concentrations of progesterone (delta 4P), 20 alpha-dihydroprogesterone (20 alpha-DHP), testosterone (T), oestrone (E1) and oestradiol-17 beta (E2 beta) in peripheral blood serum (PBS), amniotic fluid (AF) and placental tissue of rabbits during gestation were determined by radioimmunoassay. The placenta of the 10-day pregnant rabbit was fragile and composed mainly of maternal tissue. By the 12th day of pregnancy it was separable into maternal and foetal placentae. The mean concentration of delta 4P in PBS rose from 200 pg/ml (day 1 pregnancy) to 17--21 ng/ml (days 10--15) and decreased gradually to 1 ng/ml a few hours before parturition. The 20 alpha-DHP in PBS also showed an increase from 1.5 ng/mg (day 1) to 12 ng/ml (day 6) but fluctuated thereafter. The concentration of 20 alpha-DHP in the PBS tended to be lower than that of delta 4 P during pregnancy until the regression of the corpus luteum. An interesting observation was an increase of T on days 6--8 of pregnancy, the time when implantation occurs. The concentrations of E1 and E2 beta in PBS remained very low throughout pregnancy. delta 4P and 20 alpha-DHP in AF ranged between 25 pg to 1 ng/ml and in no case during the course of pregnancy were the levels of T, E1 and E2 beta in AF higher than in PBS. Where the maternal placental delta 4P content remained between 1--2 ng/placenta, the foetal placenta delta 4P rose to a level of 15 ng/placenta by day 31 of pregnancy. A similar trend was recorded for 20 alpha-DHP content. It is concluded that although a parallelism between PBS and myometrial steroid concentration was observed, no relationship could be drawn between the concentrations of steroid in PBS and those of the placental tissue and AF.
20-alpha-Dihydroprogesterone↗
The pituitary-ovarian complex in the aged anoestrous golden hamster.
Plasma and pituitary hormones of young (3--5 months of age) dioestrous hamsters with normal cycles and aged (13--17 months of age) anoestrous hamsters were compared. The anoestrous hamsters exhibited lower plasma values of progesterone (P less than 0.001), oestradiol-17 beta (P less than 0.005) and prolactin (P less than 0.001) and higher levels of plasma gonadotrophins (P less than 0.001) than did the dioestrous animals. Pituitary concentrations of LH were higher (P less than 0.005) in anoestrous hamsters, but pituitary FSH and prolactin values did not differ. In another series of experiments three groups of hamsters (3--5- and 13--17-month-old with normal cycles and 13--17-month-old in anoestrus) were ovariectomized. Blood samples were taken by cardiac puncture every 3--4 weeks after receiving s.c. injections of oestradiol-17 beta (1 or 10 micrograms/100 g body wt) for 2 or 9 consecutive days. The markedly lower levels of gonadotrophins in aged anoestrous hamsters indicated that the hypothalamic-hypophysial complex was incapable of responding to the same degree as it did in young and aged cyclic animals. Prolactin values were similarly depressed in all 3 groups. Oestradiol-17 beta treatment caused reduced gonadotrophin and increasing prolactin concentrations in all 3 groups. These results indicate that the ovaries of the senescent anoestrous hamster produce less steroids and suggest that age-related changes in the hypothalamic-hypophysial complex are largely responsible for the cessation of regular oestrous cycles.
Aging↗
Antifertility effects of gossypol in male hamsters.
In the male hamster, administration of 10 or 15 mg/kg/day of gossypol for 5 weeks did not alter the serum concentration of testosterone (T), prolactin (PRL), and luteinizing hormone (LH) or fertility. However, the total sperm population was significantly reduced in the males treated with 15 mg/kg/day of gossypol, and total sterility occurred within 8 weeks. On the other hand, males treated with 10 mg/kg/day of gossypol were sterile after 10 weeks of treatment. The T and total sperm population along the reproductive tract in these infertile males was significantly reduced. During the treatment period no change in body weight or weight of testes or seminal vesicles was observed. A full regaining of fertility, serum T level, and sperm population to the normal range were recorded within 8 nd 14 weeks (15 and 10 mg/kg/day, respectively) after the cessation of treatment.
Animals↗
Effect of RMI-12,936 on fertilization and egg transport in the rabbit.
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20-alpha-Dihydroprogesterone↗
Effects of Colprone on in vitro release of androgens from the reproductive organs of the male rat.
Effects of medrogestone (6,17 alpha-dimethyl-4-,6-pregnadiene-3, 20-dione; Colprone) on the release of testosterone (T) and 5 alpha-dehydrotestosterone (5 alpha-DHT) in the reproductive organs of the male rat were tested in vitro. The minced testes released twice as much T into the medium when incubated in the presence of 50 mIU/ml of hCG. The release of T was inhibited significantly when 10 or 50 micrometers Colprone was added to the incubation medium. More 5 alpha-DHT was released into the medium from the testes mince in the presence of hCG, while the addition of 10 or 50 micrometers of Colprone inhibited 5 alpha-DHT release as compared to hCG controls. On the other hand, hCG failed to stimulate the release of T and 5 alpha-DHT from the minced caput and cauda epididymis and ventral prostate. The addition of Colprone (10--50 micrometers/ml) to the medium containing caput epididymis or ventral prostate resulted in a significant inhibition of T and 5 alpha-DHT. However, no significant change in the rate of T or 5 alpha-DHT release was recorded in medium containing cauda epididymis. In spite of its anti-androgenic effects reported by several investigators, Colprone in the present study has shown differential effects on T and 5 alpha-DHT release from different reproductive tissues of the male rat.
Animals↗
Effects of Gossypol on the fertility of male rats, hamsters and rabbits.
Oral administration of Gossypol acetic acid induced sterility in male hamsters and rats when given at a dose level of 5 or 10 mg/kg daily for 12 weeks. This was shown by the appearance of dead and abnormal sperm in the male tract and the failure of pregnancy or decrease in implantation sites in the females mated to the Gossypol-treated males. Similar treatment of male rabbits at dose levels varying from 1.25 to 10 mg/kg and given for 5 to 14 weeks did not affect the average number of sperm per ejaculate, although the motility of sperm was poor during treatment in some bucks. The pregnancy rates and the proportion of implantation sites were also not affected by insemination of female rabbits with sperm from males during treatment with Gossypol.
Animals↗
Further studies on the trichosanthin-induced termination of pregnancy.
Trichosanthin (TCS), a protein from the root extract of Trichosanthis kirilowii, terminated pregnancy when injected once in 15-day pregnant rabbits (2 mg/doe) but failed to interrupt pregnancy in 12-day pregnant rabbits even at higher doses. In vitro release of progesterone (delta 4P) from the maternal or fetal placental tissue into the incubation medium was not affected by TCS. When the distribution of 125I-TCS was traced in 12-day pregnant mice, persistently higher concentration of 125I-radioactivity was detected in the kidney. By contrast, in other organs, including the reproductive organs, blood serum and amniotic fluid 125I-radioactivity declined between 12-48 h after treatment. The low 125I-radioactivity in both the reproductive organs and amniotic fluid suggests a possible barrier between the embryo and maternal blood. It is suggested that TCS might be acting directly on the placental unit, causing fetal death and dislodging of the placenta. Administration of TCS to PD-19 mice or PD-28 rabbits resulted in premature delivery. This effect of TCS in pregnant mice was comparable to the administration of PGF2 alpha.
Abortion, Spontaneous↗
Temporal relationship between progestin and luteinizing hormone concentrations in pseudopregnant rats treated with prostaglandin-F2 alpha.
The temporal changes in progesterone (delta 4P), 20 alpha-dihydroprogesterone (20 alpha-DHP) and luteinizing hormone (LH) concentrations in pseudopregnant (PSP) rats after treatment with a single subcutaneous Silastic-PVP tube containing 600 micrograms PGF2 alpha were correlated. Progesterone levels fell and LH levels rose significantly 2h after initiation of treatment, while 20 alpha-DHP levels were found to increase significantly 12h after treatment. Since the changes in delta 4P and LH concentrations occurred concurrently, it seems that the increase in LH levels could have been due to a direct effect of PGF2 alpha on the ovary causing a reduction in delta 4P and thus a negative feedback effect on LH release. Alternatively, PGF2 alpha might exert a direct effect on LH secretion at the hypothalamic-pituitary level.
20-alpha-Dihydroprogesterone↗
Effects of prostaglandin F2 alpha and an antiprogestational steroid, RMI 12,936, on rat pregnancy.
The abortifacient efficacy of RMI 12,936 (17 beta-hydroxy-7 alpha-methyl androst-5-en-3-one), a synthetic steroid, alone or in combination with prostaglandin-f2 alpha (PGF2 alpha), was studied in the rat. Administration on day-8 of pregnancy (PD-8) of 0.25 mg RMI 12,936/rat neither altered the progesterone (delta 4P) levels, the relative ovarian weight (ROW) nor terminated pregnancy. Doses of 2.0, 1.0 or 0.5 mg RMI 12,936/rat, when given on PD-8, terminated pregnancy in 100% of the animals. Highly significant increases in ROW and serum alpha 4P level were recorded on PD-14. However, delta 4P/20 alpha-dihydroprogesterone ratio remained unaltered. These results suggest that RMI 12,936 increased luteal activity which contributed to the enhanced serum delta 4P levels and ROW. Bilateral insertion of Silastic-PVP tubes containing 75 micrograms PGF2 alpha/tube into each uterine horn on PD-10 did not disturb pregnancy, whereas similar tubes given on PD-10 to rats treated with 1.0 mg RMI 12,936 on PD-8 expelled the embryos and placental tissue on PD-11. This phenomenon was attributed to a decreased serum delta 4P caused by PGF2 alpha, allowing the expulsion of uterine contents. A time lapse of 17--35 days was needed for the rats to regain fertility in terms of normal gestation period and offsprings. Although expulsion of conceptus was facilitated by PGF2 alpha in the RMI 12,936 treated rats, PGF2 alpha treatment did not alter the time lapse between RMI 12,936 treatment and subsequent conception. It is concluded that RMI 12,936 is feto-toxic; it possesses high contraceptive activity and its abortifacient efficacy can be improved by PGF2 alpha.
Abortion, Induced↗
Effects of prostaglandin-F2 alpha and a plant protein "Trichosanthin", on 10-day pregnant rabbits.
The effect of Trichosanthin (TCS), a protein obtained from the roots of Trichosanthis kirilowii, alone or in combination with prostaglandin-F2 alpha (PGF2 alpha; Tromethamine salt) on the termination of pregnancy in rabbits was investigated. Intraperitoneal injection of 1 or 2 mg TCS/10-day pregnant rabbits neither altered the serum progesterone (delta 4P) level nor interrupted pregnancy. Doses of 0.5 or 0.25 mg PGF2 alpha incorporated in a Silastic-PVP tube and inserted intravaginally, terminated pregnancy within 72 h of treatment in 75 and 16% of the treated does, respectively. By contrast, does treated on day-10 of pregnancy with a combination of a non-effective dose of TCS (1 mg) and a sub-effective dose of PGF2 alpha (0.25 mg) terminated pregnancy in all the treated animals as no live embryos were found within 3 days of treatment. Pregnancy interruption was associated with a significant reduction of serum delta 4P and delta 4P/20 alpha-dihydroprogesterone (20 alpha-DHP) ratio. The present study indicates that TCS and PGF2 alpha act synergistically, rendering the termination of 10-day pregnancy possible in the rabbit. It was also noted that pregnancy cannot be maintained when the serum delta 4 P level drops below 4 ng/ml and delta 4P/20 alpha-DHP falls lower than 0.6 in the 10-day pregnant rabbit.
Abortifacient Agents↗
Effects of RMI 12,936 on some reproductive processes in the female golden hamster.
A single subcutaneous injection of 2 mg RMI 12,936 (17 beta-hydroxy-7 alpha-methylandrost-5-en-3-one) given a day after estrus disrupted estrous cycle for over 30 days and inhibited ovulation in 100 percent of treated Golden hamsters. Administration of RMI 12,936 (2 mg) on Day 6 of pregnancy caused termination of pregnancy within 4 days of treatment. In association with the termination of pregnancy was a significant reduction in the concentrations of progesterone and estradiol-17 beta together with an elevated testosterone level. After termination of pregnancy by RMI 12,936, the hamsters remained sexually receptive for 4 weeks but failed to conceive. It is concluded that RMI 12,936 causes termination of pregnancy due to an induction of functional luteolysis.
Abortion, Spontaneous↗
RMI 12,936 and pseudopregnancy in rats.
RMI 12,936, when injected subcutaneously at a dose of 2 mg, either on Day 6 of psuedopregnancy (PSP-6) or on PSP-6,7 and 8, shortened the duration of PSP from 12.3 +/- 0.3 (control) to 8.3 +/- 0.1 or 8.7 +/- 0.2 days, respectively. During PSP, plasma progesterone (delta 4P) levels in the peripheral plasma showed a trend of decrease by PSP-9 (52.0 +/- 4.6 on PSP-8 to 42.3 +/- 3.1 ng/ml on PSP-9). Administration of RMI 12,936 on PSP-6 resulted in a significant decrease in delta 4P and pregnenolone (delta 5P) within 24 hr after treatment but caused no apparent changes in 20 alpha-dihydroprogesterone (20 alpha-DHP) levels. However, a significant decrease of delta 4P/20 alpha DHP ratio was encountered 24 hr after RMI 12,936 treatment. The persistent occurrence of proestrous smear after PSP termination, but absence of estrous vaginal cytology, might be attributed to the slight estrogenicity of RMI 12,936. After the premature termination of pseudopregnancy induced by RMI 12,936, the female rats were sexually receptive for at least 3 weeks but failed to conceive, suggesting that this compound has a prolonged contraceptive effect.
Androstenols↗
Termination of pregnancy in the rat by RMI 12,936.
Administration of a steroid RMI 12,936 (2 MG) ON DAY 8 OF PREGNANCY RESULted in an interruption of gestation within 5 days. No significant changes in progesterone (delta 4P), 20 alpha-dihydroprogesterone (20 alpha-DHP) and pregnenolone (delta 5P) were recorded during the course of termination of pregnancy by RMI 12,936. However, a significant rise in serum delta 4P and hypertropic corpora lutea were evident on day 13 of pregnancy when all treated females showed dead conceptus. The placental tissue was still present at the time of pregnancy termination. On the other hand, serum LH levels was significantly suppressed 24 hr after the treatment and maintained at a very low level. The reduction of LH might be due to a lowered hypophyseal sensitivity towards LH-RH. The occurrence of in utero dead fetus without interference of delta 4P production suggests that in the rat RMI 12,936-induced termination of pregnancy is due to its embryotoxic rather than luteolytic effect. Although the treated females did not return to normal estrous cycles for a period of 2 weeks after pregnancy termination, they were sexually receptive. Successful mating resulted in normal pregnancy which occurred 30-35 days after RMI 12,936 treatment.
Abortifacient Agents↗
Termination of pseudopregnancy in rats by silastic-PVP-PGF2 alpha tube.
The efficacy of a one-end or both-end open Silastic-polyvinyl-pyrrolidone (Silastic-PVP) tube containing 600 microgram prostaglandin-F2 alpha (PGF2 alpha) and placed subcutaneously on day-6 of pseudopregnancy (PSP) in the induction of premature termination of PSP was compared. A both-end open Silastic-PVP-PGF2 alpha tube was more efficacious in inducing an early termination of PSP with a mean duration of 7.8 days. By contrast, PSP females receiving a one-end open Silastic-PVP-PGF2 alpha tube showed a mean duration of PSP of 9.9 days. The shortened duration of PSP in both these treatment groups was significantly different from the control value of 13.1 days. The significant drop in progesterone (delta 4P) but rise in 20 alpha-dihydroprogesterone (20 alpha-DHP) occurred 24 hr after treatment in PSP rats treated with both-end open Silastic-PVP-PGF2 alpha tube, whereas similar changes in delta 4P and 20 alpha-DHP took place 48-72 hr after the deposition of a one-end open Silastic-PVP PGF2 alpha tube. It is concluded than an initial larger amount of circulating PGF2 alpha is needed to induce an early premature termination of PSP. The exposure of corpus luteum to a more sustained but lower level of PGF2 alpha leads to a slower response.
20-alpha-Dihydroprogesterone↗