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1.
The efficiency and acceptability of a single-dose, long-acting vaginal suppository containing 3.0 mg of 15-methyl PGF2α methyl ester was compared with intra-amniotic administration of 50 mg of PGF2α in 100 patients with a second trimester pregnancy termination. Within 24 hours, 78 per cent of the patients in the vaginal group and 92 per cent in the intra-amniotic group had aborted. The mean induction-abortion interval was 17.9 hours in the vaginal group and 15.8 hours in the intra-amniotic group.Gastrointestinal side-effects were more frequent, but the procedure was less painful, with vaginal 15-methyl PGF2α methyl ester than with intra-amniotic PGF2α.The vaginal route is technically simple for adaptation to large-scale use, but the high frequency of gastrointestinal side-effects still limits the acceptability of 15-methyl PGF2α methyl ester in vaginal administration. 相似文献
2.
Daniel L. Gawlak Sheila Stewart R.A. Edgren 《Prostaglandins & other lipid mediators》1974,8(6):539-544
When administered to hamsters twice daily on days 4, 5 and 6 of pregnancy, PGF2α is highly effective in terminating gestation. The response is all-or-none, pregnancies either being completely stopped or continuing with no change in status of the conceptus. The ED50 for termination of pregnancy is estimated at 1.75 μg (per each of the 6 injections). The method is a highly satisfactory assay for PG's, as judged by the effects of PGF2α.Single injections on days 5, 6 or 7 also terminate pregnancies. Although this approach has not been fully quantified, it may lend itself to a suitable assay procedure with some saving of compound and labor. 相似文献
3.
Two subcutaneous injections of Prostaglandin F2α THAM salt 24 hours apart terminated pregnancies in cats after the 40th day of gestation. Injections of 0.50 or 1.00 mg. PGF2α THAM salt/Kg. body weight were the most effective in terminating pregnancies. Parturition or abortion occurred within 24 hours after the initial injection in 9 cats and after the 2nd injection in 4 cats. 相似文献
4.
Midtrimester abortion was successfully induced in a series of 20 patient by intra-amniotic instillation of 15(S)-15-methyl-prostaglandin F2α with a mean abortion time of 17.78 hours. The patients in this study were divided into two groups, Groups I received on initial dose of 2.5 mg 15-ME-PGF2α and aborted in a mean time of 16.26 hours. The patients in Group II received 3.0 mg 15-ME-PGF2α and aborted in a mean time of 18.94 hours. There was no significant difference in the abortion time, occurrence of side effects or the initiation of uterine activity between Group I and Group II. Parous patients aborted somewhat faster than nulliparous patients but this difference was not significant. In this study 80% of the patients aborted in 24 hours or less, and the intra-amniotic instillation of 15-ME-PGF2α was an effective abortifacient technique from the 15th to the 23rd week of gestation. The uterine response to intra-amniotic instillation of 15-ME-PGF2α was characterized by the gradual appearance of low amplitude, high frequency contractions accompanied by a rise in baseline intrauterine tonus. Uterine activity developed gradually and peaked at 1:50 hours after intra-amniotic instillation of 15-ME-PGF2α. In this small series 15-ME-PGF2α administered via intra-amniotic instillation did not appear to have a distinct advantage over the naturally occurring PGF2α administered by the same method for the induction of midtrimester abortion; a larger series is indicated to define the advantages of either technique. 相似文献
5.
The use of prostaglandins E2 and F2α, administered by extra-amniotic instillation, for the induction of abortion was studied in 94 patients in the first and second trimesters of pregnancy. Abortion was successfully induced in 87% of patients within 36 hours and in 94% within 48 hours. The mean abortion time was 22·4 hours. In 60% of patients abortion was complete.Though the differences were not statistically significant, on average multigravid patients aborted more quickly than primigravidae, while the mean abortion time in PGE2-treated patients was less than in those receiving PGF2α.No serious complications occurred. Some side effects were observed. Occasional vomiting was the commonest symptom but the incidence of side effects was lower than with alternative routes of administration. A leucocytosis was often noted but there were no significant instances of infection.The method has proved a safe and effective means of terminating pregnancies in the second trimester. 相似文献
6.
Jerome M. Feldman James W. Plonk James C. Cornette 《Prostaglandins & other lipid mediators》1974,7(6):501-506
Using specific radioimmunoassay procedures we measured prostaglandin F2α (PGF2α) and 13, 14-dihydro-15-keto prostaglandin F2α (PGF2α metabolite) in 12 patients with carcinoid tumors. Although PGF2α and PGF2α metabolite were each modestly elevated in 17% of the patients the magnitude of the elevation did not correlate with the symptoms of the carcinoid syndrome. The 24 hour urinary 5-hydroxyindoleacetic acid excretion showed a good correlation with carcinoid symptoms while the serum serotonin concentration showed a fair correlation with carcinoid symptoms. We conclude that serum elevation of PGF2α is not a frequent occurrence in patients with the carcinoid syndrome. 相似文献
7.
Dilatation of the cervix with prostaglandin analogues prior to vaginal termination of pregnancy was attempted in 125 nulliparous women in the first trimester of pregnancy. The patients were divided into five groups (25 in each group) and given a single extra-amniotic dose of one of the following prostaglandin analogues 14–16 hours prior to the evacuation of the uterus by vacuum aspiration. (Group A) 15 (S) 15 methyl PGE2 (free acid); (Group B) 15 (S) 15 methyl PGE2 methyl ester; (Group C) 15 (S) 15 methyl PGF2α (free acid); (Group D) 15 (S) 15 methyl PGF2α methyl ester and(Group E) a mixture of 15 (S) 15 methyl PGE2 methyl ester and 15 (S) 15 methyl PGF2α methyl ester. Evacuation of the uterus without mechanical dilatation of the cervix was possible in 111 (90%) of the patients. In an additional 10 patients (8%) there was some degree of cervical dilatation and further mechanical dilatation could be performed easily. With the combination of 15 (S) 15 methyl PGE2 methyl ester and 15 (S) 15 methyl PGF2α methyl ester the incidence of gastrointestinal side effects and pyrexia were considerably reduced. 相似文献
8.
Four antiestrogens (anordiol, tamoxifen, RU 39411, ICI 182780) and the antiprogestin, mifepristone (RU 486), were administered to the following three animal models: (1) ovariectomized rats, (2) mated rats treated post-coitally; and (3) pregnant rats treated post-implantation. The antiestrogens were administered alone or in combination with mifepristone at doses effective in preventing and/or terminating pregnancy in rats. The objective of the study was to determine whether these drugs influenced uterine concentrations of prostaglandins (PGF2α and PGE2).Antiestrogens administered alone to ovariectomized rats did not effect uterine PGE2 or PGF2α concentrations; whereas the combination of anordiol/mifepristone increased uterine PGF2α concentration, resulting in an increase in the PGF2α/PGE2 ratio.Mated rats were treated post-coitally for three consecutive days with anordiol, tamoxifen, estradiol and mifepristone alone and with the combination of anordiol/mifepristone and tamoxifen/mifepristone. An increase in uterine PGF2α concentrations and in the PGF2α/PGE2 ratio occurred only in anordiol/mifepristone treated group. A decrease in uterine PGE2 concentrations occurred in animals treated with anordiol, tamoxifen and estradiol, resulting in an increase in the PGF2α/PGE2 ratio.Anordiol (5.0 mg/kg/day) and mifepristone (4.0 mg/kg/day) alone and the combination of anordiol/mifepristone (2.5/1.0 mg/kg/day) administered to pregnant rats on days 7, 8 and 9 of pregnancy induced an increase in PGF2α levels without affecting uterine PGE2 concentration. The changes in uterine PGF2α concentrations induced by anordiol and the combination of anordiol/mifepristone resulted in an increase in the PGF2α/PGE2 ratio.The antiestrogens tested except for ICI 182780 possessed agonist activity when assayed by measuring their capacity to increase the uterine weights in ovariectomized rats. Also, ICI 182789 was the only antiestrogen that did not influence uterine PG concentrations. It can be concluded that ICI 182780 is the only “pure” antiestrogen among those tested.The present results show that antiestrogens and the combination of mifepristone plus anordiol at doses preventing implantation and terminating pregnancy increase uterine PGF2α and/or decrease PGE2 concentrations, resulting in an alteration of PGF2α/PGE2 ratio. These findings suggest that there exists a critical balance of PGF2α to PGE2 concentrations in the uterus required for the normal passage of fertilized ova through the oviduct, initiating implantation of the blastocysts, development of embryos, and maintenance of pregnancy. 相似文献
9.
W.F. Williams G.S. Lewis W.W. Thatcher C.S. Underwood 《Prostaglandins & other lipid mediators》1983,25(6):891-899
On day 17 postestrus or postmating, heifers were given intrauterine injections of saline (2 pregnant, 2 non-pregnant) or 200 μg PGF2α (7 pregnant, 6 nonpregnant) through cannulae installed surgically into the uterine horn ipsilateral to the corpus luteum bearing ovary. Jugular blood samples were collected prior to the laparotomy at which the cannulae were installed during surgery, and for 90 min following the intrauterine injection. Plasma was assayed for progesterone and 13,14-dihyro-15-keto-PGF2α )PGFM). Laparotomies were reopened to confirm proper cannula placement and to determine if blastocysts were present in mated heifers. Concentrations of PGFM were higher in pregnant compared to nonpregnant heifers during the presurgery (68
26
24
26 pg/ml; P < 0.25) and surgery (186
47
65
17 pg/ml; P < .05) periods. Pregnancy status did not alter the mean concentrations of PGFM (pregnant, 554
70 pg/ml; nonpregnant, 422
81 pg/ml) or the half-life of its decline in concentration (18 min) following intrauterine injection of PGF2α. Pregnancy at 17 days in cattle does not appear to influence PGF2α transport from the uterine lumen or its metabolism in the uterus or elsewhere in response to an acute intrauterine injection. 相似文献
10.
Prostaglandin F2α (PGF2α) at 14, 30 or 50 μg/hamster/day from Days 3–5 of pseudopregnancy (PSP) shortens PSP from a mean length of 9.1 to 5.6–7.9 days, depending on the dose of PGF2α administered. Bilateral intrauterine device (BIUD) bearing hamsters exhibit a mean length of PSP of 9.2 days, which is comparable to that in normal saline controls. Combination of PGF2α (14 μg/day on Days 3–5 of PSP) and BIUD also resulted in shortening of PSP although the mean length of PSP resulted from the combined treatment was not significantly different from those PSP animals treated with 14 μg/day of PGF2α alone. It is concluded that the antifertility effect of intrauterine device possibly is attributed to a small and continuous release of PGF which interferes with the normal implantation processes but does not curtail PSP. 相似文献
11.
Pregnant hamsters were administered (SC) prostaglandin or vehicle on the morning of the 4th day of pregnancy. Serum progesterone was significantly depressed (p<.01) at 0.5, 2, and 6 hours after treatment with 100 μg PGF2α. Serum progesterone levels were unchanged 2 hours and 6 hours after treatment with 100 μg PGF2β and 2 hours after treatment with 1 mg PGF2β. Progesterone levels were depressed to less than 1 ng/ml 6 hours after treatment with 1 mg PGF2β. The specific uptake of 3H-PGF2α in whole hamster corpora lutea was significantly depressed 2 hours and 6 hours following 100 μg PGF2α treatment. A 15% depression in specific uptake occurred 0.5 hour post-treatment. Treatment with 100 μg PGF2β resulted in no change. Administration of 1 mg PGF2β resulted in depressed 3H-PGF2α uptake at both 2 and 6 hours post-treatment.Prostacyclin (PGI2) treatment resulted in no change in either 3H-PGF2α specific uptake or serum progesterone 2 hours after 100 μg treatment SC. These parameters were both reduced approximately 30% 6 hours post-treatment. Treatment with 6-keto-PGF1α resulted in a complete lack of measurable 3H-PGF2α uptake and serum progesterone levels less than 1 ng/ml at both 2 and 6 hours after treatment with 1 mg SC. 相似文献
12.
Burkhard Scherer Jürgen Schnermann Mike Sofroniev Peter C. Weber 《Prostaglandins & other lipid mediators》1978,15(2):255-266
Thw radioimmunological (RIA) determination of prostaglandin (PG) E2 and of PGF2α in urine humans and rats is described in detail. After extraction and chromatography PGE2 was determined by using a PGE specific antibody or by using either PGB or PGF2α specific antibodies after the respective conversion procedures. The three different RIA procedures were compared to each other. PGF2α was determined by a specific antibody to PGF2α. Basal excretion of PGE2 and of PGF2α in healthy women on free diet was 9.3 ng/hour ± 0.96 and 18.3 ng/hour ± 2.5 respectively. Furosemide increased the excretion of PGE2 and of PGF2α in humans significantly, while PG-excretion rates decreased on indomethacin. In rat urine PGE2 and PGE2α increased markedly from 46.2 pg/min ± 9.3 and 27 ± 3.4 to 253.8 ± 43.3 and 108 ± 12.6 pg/min (per one kidney) in the anesthetized-laparotomized animal. This increase was abolished after giving two different PG synthetase inhibitors. 相似文献
13.
Castracane V. D. Saksena S. K. Shaikh A. A. 《Prostaglandins & other lipid mediators》1974,6(5):397-404
The presence of an intrauterine device in the pseudopregnant (PSP) rat suppressed decidual cell reaction (DCR). Treatment with PGF2α or PGE2 also suppressed DCR, but had no effect on IUD horn. Treatment with PGF2α from days 1–4 before trauma in ovariectomized rats treated with estradiol and progesterone did not have a significant effect on DCR. However, when PGF2α was given for 4 days after trauma there was significant inhibition of DCR indicating a direct endometrial effect of PGF2α. Inhibition of DCR was also recorded when indomethacin was administered to intact PSP or to ovariectomized rats maintained on estradiol and progesterone. This indicated that prostaglandins probably are necessary for normal DCR. 相似文献
14.
A group of 10 patients, with pregnancies of varying gestational age, complicated by missed abortion, intra-uterine death, anencephaly and chromosomal anomaly, underwent induction of labor by intra-amniotic prostaglandin F2α infusion. Induction of labor was successful in all cases and the side-effects were mild. The induction-delivery interval did not differ significantly from that recorded when labor in such cases has been induced by intravenous PGF2α.The induction-delivery interval showed no apparent relation to the state of the fetus (living or dead) suggesting that no significantly active role is mediated by the fetus in PGF2α-induced labor. 相似文献
15.
Shiro Ohki Katsuhiro Imaki Fumio Hirata Toshio Hanyu Nobuhiko Nakazawa 《Prostaglandins & other lipid mediators》1974,6(2)
Radioimmunoassays for measuring prostaglandin F2α (PGF2α) and 5α, 7α-dihydroxy-11-keto tetranorprosta-1,16-dioic acid, PGF2α-main urinary metabolite (PGF2α-MUM), with 125I-tyrosine methylester amide (TMA) of PGF2α and PGF2α-MUM were developed.Antibody to PGF2α was produced in rabbits immunized with conjugates of PGF2α coupled to bovine serum albumine. Antibody to PGF2α-MUM was also produced in rabbits immunized with conjugates of PGF2α-MUM coupled to bovine serum albumin.PGF2α-125I-TMA had an affinity to antiserum to PGF2α. PGF2α-MUM-125I-TMA also responded to antiserum to PGF2α-MUM. 相似文献
16.
Hiroshi Yamamoto Toshiaki Endo Tamotsu Kiya Taeko Goto Satoru Sagae Eiki Ito Hiroshi Watanabe Ryuichi Kudo 《Prostaglandins & other lipid mediators》1995,50(4)
In rat luteal cells labeled with (3H]oleic acid, PGF2α-stimulated phospholipase D (PLD) activation was investigated. The PLD activity was detected by measuring the accumulation of [3H]phosphatidylethanol (PtdEt) in the presence of ethanol. PGF2α stimulated PtdEt accumulation at concentrations of more than 100 nM in the presence of ethanol. However, PtdEt accumulation did not change in the absence of ethanol. PGF2α (1 μM) increased PtdEt accumulation after 1 min, and the accumulation reached a plateau by 2–3 min. These results indicate that PGF2α activates PLD in rat luteal cells. U-73122, a phospholipase C (PLC) inhibitor, and staurosporine, a protein kinase C (PKC) inhibitor, did not inhibit PGF2α-stimulated [3H]PtdEt accumulation. These results suggest that PGF2α-induced PLD activation is different from PLC-PKC systems. We reported previously that PGF2α stimulated the release of arachidonic acid. The effects of indomethacin, nordihydroguaiaretic acid (NDGA), and 5,8,11,14-eicosatetraynoic acid (ETYA), inhibitors of arachidonic acid metabolism, on PGF2α-stimulated PtdEt accumulation were examined. Pretreatment with indomethacin enhanced PGF2α-induced PtdEt accumulation. In contrast, pretreatment with NDGA and ETYA inhibited PGF2α-induced PtdEt accumulation. It is suggested that PGF2α-stimulated PLD activation is mediated via lipoxygenase products. 相似文献
17.
O. Ylikorkala P. Kirkinen P. Jouppila P.A. Jrvinen 《Prostaglandins & other lipid mediators》1975,10(2):333-341
15-me-PGF2α was administered as single intrauterine injection for interruption of very early pregnancy in 30 out-patients. After 2 weeks, abortion was complete in 60 % induced with 125 or 200 μg and 80 % induced with 300 μg. After 3 weeks, abortion was complete in 90 % induced with 125 μg, in 70 % induced with 200 μg and in 100 % induced with 300 μg. One failure occurred in patients treated with 200 μg and 2 curettages were performed because of incompleteness of abortion. No serious complications occurred. Compared with our previous results it appears that 15-me-PGF2α is as effective as natural PGF2α in inducing abortions during very early pregnancy but causes somewhat fewer side-effects. 相似文献
18.
John W. Wilks 《Prostaglandins & other lipid mediators》1977,13(1):161-170
The naturally-occurring metabolite of prostaglandin F2α, 15-keto prostaglandin F2α (15-keto PGF2α), elicited rapid and sustained declines in serum progesterone concentrations when administered to rhesus monkeys beginning on day 22 of normal menstrual cycles. Evidence for luteolysis of a more convincing nature was obtained in studies where a single dose of 15-keto PGF2α was given on day 20 of ovulatory menstrual cycles in which intramuscular injections of hCG were also given on days 18–20; serum progesterone concentrations fell precipitously in monkeys within 24 hours following intramuscular administration of 15-keto PGF2α. However, corpus luteum function was impaired in only 4 of 11 early pregnant monkeys when 15-keto PGF2α was administered on days 30 and 31 from the last menses, a time when the ovary is essential for the maintenance of pregnancy. Gestation failed in 2 additional monkeys 32 and 60 days after treatment with 15-keto PGF2α, but progressed in an apparently normal manner in the remaining 5 animals. Two pregnant monkeys treated with 15-keto PGF2α on day 42 from the last menstrual period, a time when the ovary is no longer required for gestation, continued their pregnancies uneventfully. Corpus luteum function was not impaired in 9 control monkeys which received injections of vehicle or hCG at appropriate times during the menstrual cycle or pregnancy. 相似文献
19.
Several hours following administration of long acting vaginal suppositories containing 3.0 mg of 15-methyl-PGF2α for interruption of second trimester pregnancies there is an up to 10-fold increase in endogenous production of PGE2 and PGF2α before abortion as reflected by gas chromatographic-mass spectrometric determination of the major plasma metabolites of PGE2 and PGF2α. The data suggest that this increased formation of endogenous prostaglandins contributes to the induced uterine activity during the latter part of the abortion process. 相似文献
20.
Ray V. Haning Jr. Leslie Choi Amber J. Kiggens Donna L. Kuzma John W. Summerville 《Prostaglandins & other lipid mediators》1982,23(1):29-40
Explants from term human placentas were maintained in culture with daily changes of medium. Daily output of PGF2α and PGFM1 decreased during the course of the incubation. Addition of 4 μg/ml DHEAS or 67 μg/ml LDL cholesterol had no effect on output of PGF2α or PGFM. Addition of 1.6, 3.2, or 6.4 μg/ml of LHRH to the culture plates had no effect on output of PGFM or PGF2α, but LHRH increased hCG output. Dibutyryl cAMP (1mM, 2mM, and 4mM) increased output of PGF2α, PGFM, and hCG. Aromatase inhibitor decreased hCG output, but it was without effect on output of PGF2α, or PGFM. Significant correlations were demonstrated between progesterone, PGFM, PGF2α, and hCG, suggesting that PGF2α originates in the syncytiotrophoblast cell. The ability of LHRH to stimulate output of hCG but not PGF2α while dbcAMP stimulated both suggests that either PGF2α and hCG arise in different cells or that LHRH does not act through cAMP. 相似文献