Purification and characterization of trichosanthin. Homology to the ricin A chain and implications as to mechanism of abortifacient activity.
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Trichosanthin, a protein from the Chinese medicinal herb Trichosanthes kirilowii, was purified in two essentially quantitative steps involving CM-Sephadex chromatography and reverse-phase high performance liquid chromatography. The protein was found to have a molecular mass of 25-26 kDa, to contain no cysteine, and to contain no glycosidic linkages. Pure trichosanthin was found to have potent abortifacient activity in pregnant mice. In order to understand the molecular basis of this unique biological activity, we have examined the amino acid sequence of the protein. As purified, trichosanthin was found to contain two amino-terminal sequences which differed only in the absence or presence of a tyrosine at residue 1. Sequence analysis of trichosanthin has allowed for determination of the NH2-terminal 38-amino acid residues. Comparison of this sequence to those present in a data base revealed homology with the ricin A-chain. Consistent with this structural homology, we have found that trichosanthin is a potent inhibitor of protein synthesis in a reticulocyte lysate system. (+info)
Inhibition of egg development and implantation in rats after post-coital administration of the progesterone antagonist RU 486.
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RU 486 was administered to rats on Day 1 or Days 1 + 2 of pregnancy. Endometrial sensitivity (i.e. decidualization in response to oil instillation) was delayed by 2.5 mg/kg injected s.c. on Day 1, and almost half of the animals also exhibited a delay in implantation of 1-2 days. Higher doses (5 or 10 mg/kg) administered on Days 1 + 2 reduced the number of implantations to zero in all animals. Apparently normal morulae were found up to the evening of Day 4 in the oviduct and/or the uterus of most animals. However, on the morning of Day 5, ova were detected in only 25% of the animals and all were in the uterus: none was at the blastocyst stage and they appeared to be degenerated or compacted morulae. Egg survival and rate of egg recovery from the uterus was not improved by early ovariectomy, showing that this antiprogestagen acts on these events independently of the presence of circulating oestrogens. (+info)
Breed differences in return to estrus after PGF2 alpha-induced abortions in swine.
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Fifty-seven Duroc, 41 Landrace and 38 Yorkshire purebred sows in d 10 to 53 of pregnancy were aborted to synchronize estrus by using prostaglandin F2 alpha (PGF2 alpha). Breed differences in time between injection of two 10-mg doses of PGF2 alpha and return to estrus were observed in these three breeds of pregnant sows during two breeding seasons. Duroc sows returned to estrus .9 d faster (P less than .01) than Yorkshire and 1.3 d faster (P less than .01) than Landrace sows. Seasonal differences were also observed. The mean days from injection to estrus were 1.8 d fewer (P less than .01) for the spring season than in the fall season. All sows expressed estrus 5 to 11 d after injection. Normal gestation, parturition and piglet survival were observed in the sows after the treatment. Genetic differences in response to induced abortion and return to estrus could have implications in planned breeding and farrowing systems. (+info)
Use of intra-amniotic urea as a second trimester abortifacient.(60/75)
Comparison of natural and synthetic prostaglandin E2 tablets in labour induction.
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A multicentre, randomized, double-blind trial compared the efficacy and safety of and tolerance to natural and synthetically produced prostaglandin E2 tablets in the induction of labour in 202 women. The compounds were similarly effective, inducing labour in approximately 66% of patients. The total dose required and the interval between induction and delivery were similar in the two groups, as were the Apgar scores at 1 and 5 minutes and the incidence of maternal and fetal side effects. (+info)
A bacterial mutagenicity study of rivanol, an acridine derivative used as an abortifacient.
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We have used the forward mutation to resistance to 6 azauracil to test the mutagenicity of rivanol (6,9 diamino 2-ethoxy acridine) on Escherichia coli. Rivanol has been used to induce therapeutic abortions in midpregnancy and is considered safe and effective for this purpose. The findings reported here that rivanol, like other acridines, is a mutagen, at least in procaryotes, suggests that such use of rivanol be reconsidered in light of its possible genetic toxicity. (+info)
Effects of alpha-trichosanthin and alpha-momorcharin on the development of peri-implantation mouse embryos.
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alpha-Trichosanthin (0.3 mg/25 g) and alpha-momorcharin (0.2 mg/25 g) given intraperitoneally to mice on Days 4 and 6 of pregnancy led to an inhibition of implantation. In-vitro study of the effects of these proteins on developing mouse embryos showed that these proteins did not affect the transformation of morulae to blastocysts but further development was impaired: many blastocysts failed to hatch from the zona, the incidence of successful attachment to a plastic substrate decreased and the extent of trophoblastic outgrowth diminished. Inner cell mass development was less affected than was the trophoblast. The in-vivo inhibition of implantation may therefore be a consequence of the deleterious effect of these proteins on the trophoblast. (+info)
Interruption of early pregnancy in the monkey with mestranol and 5-oxa-17-phenyl-18,19,20-trinor prostaglandin F1 alpha methyl ester.
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Prior work has shown that 5-oxa-17-phenyl-18,19,20- trinor prostaglandin F1 alpha methyl ester (PGF-analog) inhibits luteal progesterone secretion, but does not shorten menstrual cycles in human chorionic gonadotropin (hCG)-treated, nonpregnant monkeys. This report demonstrates that a combination treatment of PGF-analog and mestranol not only reduces blood progesterone concentrations in the hCG-treated monkey, but also results in a significant shortening of menstrual cycles. The corpus luteum-inhibiting activity of PGF-analog in hCG-treated, nonpregnant monkeys was not enhanced by simultaneous administration of nonestrogenic steroids (norethisterone, oxymetholone, azastene , 17 alpha-allyl-3-methoxy-1,3,5(10)- estratrien-17 beta-ol). Most importantly, pregnancy was interrupted in 11 or 12 monkeys when PGF-analog and mestranol were administered on Day 28 of fertile menstrual cycles; this abortifacient activity of the prostaglandin-estrogen treatment was not prevented by concomitant administration of progesterone. Administration of PGF-analog and mestranol in the third trimester terminated pregnancy in only 1 of 3 monkeys. The data indicate that a combination treatment of PGF-analog and mestranol is highly effective for the termination of early pregnancy in the monkey. Although PGF-analog and mestranol clearly inhibit the monkey corpus luteum, it is unlikely that this activity is essential for the abortifacient activity of the prostaglandin-estrogen treatment. (+info)