Development of a vaginal suppository suitable for single administration for interruption of second trimester pregnancy.
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Biomedical subjects
Publications and source records attributed to S Bergström.
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Scanning electron microscopy of zona-free blastocysts showed bulging trophoblast cells possessing slender microvilli and many small projections of various lengths. The trophoblast cells contained mitochondria in two shapes. One type consisted of spheroids with a few mitochondrial inner membranes. The other type had a more conventional appearance. Fibrous material varied in amount. The trophoblast cells from blastocysts cultured for 1 day had an appearance similar to that of trophoblast tissue fixed in vivo. However, the large, dense mitochondria with few cristae had diminished in number, and globular mitochondria occurred more frequently. Furthermore, the fibrous material was more sparsely distributed after culture. The experiments demonstrated that cultured hamster blastocysts have ultrastructural characteristics similar to those of in vivo blastocysts. Experiments are in progress to test whether the in vitro technique can determine the growth requirements of the hamster blastocyst.
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Escherichia coli K-12 ampicillin-resistant mutants hyperproducing chromosomal beta-lactamase arose spontaneously from strains carrying ampA1 ampC(+). Such mutants were found even in a recA background. Two Amp(r)-100 strains were analyzed genetically. The Amp(r)-100 resistance level of both strains could be transduced by direct selection for ampicillin resistance. Several classes of ampicillin-resistant transductants were found that differed from one another in the beta-lactamase activity and the ampicillin resistance mediated by an ampA1 ampC(+)-carrying strain. The data suggested that beta-lactamase hyperproduction was due to repetitions of the chromosomal amp genes. The size of the repeated region was calculated from cotransduction estimates, using the formula of Wu (Genetics 54:405-410, 1966), and was found to be about 1 min in one strain and 1.5 min in the other. Second-step Amp(r)-400 mutants were isolated from an Amp(r)-100 strain. The resistance of these mutants was apparently also due to repetitions, each mediating a resistance to about 10 mug/ml. Mutants of wild-type strains that were moderately resistant to ampicillin also gave rise to intermediate-resistance classes, suggesting repetitions of the wild-type amp alleles. F' factors hyperproducing chromosomal beta-lactamase by gene repetitions were constructed. They mediated levels of ampicillin resistance comparable to that of naturally occurring resistance plasmids. The expression of beta-lactamase hyperproduction was not affected by the presence of ampA and ampC alleles in trans and did not act in trans on the other alleles.
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Estrogen induces blastocyst implantation in diapausing female mice, increases uterine levels of adenyl cyclase and cyclic adenosine monphosphate (cylic AMP), and stimulates synthesis of ribonucleic acid and protein in both the uterus and blastocyst. Furthermore, the surface ultrastructure of trophoblast cells seen with scanning electron microscopy (SEM) changes with activation of the diapausing blastocyst by estrogen. Cyclic AMP-activated blastocysts were investigated with the use of SEM and compared to blastocysts activated by estrogen. Intraperitoneal administration of cyclic AMP was generally ineffective, whereas administration of cyclic AMP intraluminally in the uterus effectively mimicked the early estrogen activation. These findings are discussed in relation to other known activation changes in preimplantation blastocysts and with regard to similar findings after administration of various antiestrogens.
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15-methyl PGF2alpha methyl ester in a slow releasing vaginal device was administered to 30 women in the first and second trimester of gestation. Ten women were early pregnant (31-49 days following the last menstrual period) and the remaining 20 patients in the 10th to 20th week of gestation. The first group received either a device containing 10 mg 0.5% 15-methyl PGF2alpha methyl ester or a half of that device and the second group either a 0.5% or 1% device. The results were compared with those found following repeated vaginal administration of triglycerides suppositories, containing 15-methyl PGF2alpha methyl ester, to 50 early pregnant patients and 30 patients in the second trimester of gestation. The mean total dose of the compound given to these two groups was 3.9 and 7.8 mg respectively. All the 60 early pregnant patients aborted following treatment judged from clinical course and decreasing HCG values. Bleeding started as a rule three to six hours following the start of treatment and continued for 10 to 14 days. In two patients the abortion was incomplete. The side effects in the patients who received half the 0.5% device was comparable to those following the repeated vaginal suppositories while in the patients who obtained the whole 0.5% device, the frequency of side effects was increased indicating that an unnecessary high dose was given. In all the three groups of patients in the late first and second trimester of pregnancy, treatment resulted in abortion within 24 hours in 90% of the patients. In the 1% device an accumulation of side effects was found during the first hours following the start of treatment probably due to an initial, more rapid absorption of 15-methyl PGF2alpha methyl ester. With the repeated administration and with the 0.5% device, the side effects occurred mainly in the hours prior to abortion. However, in all three groups of patients the side effects were within acceptable levels. These preliminary results indicate that further development on the device may result in an effective one vaginal administration treatment for termination of both first and second trimester pregnancies.
Oestrogen administration to female mice with 'delayed' implantation induces changes in the uterus and blastocysts followed by implantation and normal gestation. The second messenger for oestrogen, adenosine 3' :5'-cyclic monophosphate (cAMP), was instilled into the uterine lumen of females with 'delayed implanting' blastocysts to determinewhether it also is able to induce implantation. Implantation of the blastocysts was induced by cAMP but the pregnancies were not maintained to tem. These results are discussed with respect to the changes in blastocysts induced by cAMP and with respect to the reported contraceptive effects of cAMP in normal mice.
Blastocysts that have been activated for implantation by an injection of oestrogen become separated from the uterine surface by a layer of secretion. By 8 hr after the injection, the trophoblast cytoplasm contains several glycogen granules, groups of ribosomes, and mitochondria of a condensed type. These ultrastructural changes are signs of the increased metabolic activity exhibited by the trophoblast at activation. It is suggested that the uterine epithelium keeps the trophoblast inactive by delivering only a minimal nutritive medium and that the epithelium activates the trophoblast by making more nutrients, probably some carbohydrate, available as a consequence of an oestrogen-induced increase in the secretory activity.
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The presence of paternal H-2 antigens on hybrid mouse blastocysts before and during implantation was investigated by means of the isotope anti-globulin technique. It was found that experimentally delayed blastocysts possess paternal H-2 antigens whereas these antigens can no longer be detected 14 hours after estradiol activation of delayed blastocysts.
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