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1.
John W. Wilks 《Prostaglandins & other lipid mediators》1982,24(6):837-842
Dose response relationships for pregnancy termination in hamsters following administration of prostaglandin F2α (PGF2α by three subcutaneous methods were determined in 526 hamsters. The median effective dose (ED50) for PGF2α given as a single subcutaneous injection in 500 μl of saline was 22.2 μg. Administration of the prostaglandin with an Alzet® osmotic minipump (subcutaneous insertion for 24 hours) required 1.35 times more PGF2α (ED50 = 30.0 μg). The least effective method of prenancy termination in the hamster involved administration of PGF2α by a single subcutaneous injection in 20.4 μl of saline (the same volume delivered by the minipump in 24 hours); the ED50 for this method of administration was 41.3 μg of PGF2α. 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.
Susan Kopia Sheila F. Stewart G. DiPasquale R.A. Edgren 《Prostaglandins & other lipid mediators》1974,8(6):531-537
Pseudopregnancy, induced in rats by sterile mating, lasted 13 days (median). The subcutaneous administration of PGF2α produced a significant shortening of this period (< 10 days), and PG administration on day 6 appears most suitable for assay purposes. A dose-response curve for PGF2α administered twice on day 6 is presented; the ED50 for termination of pseudopregnancy was estimated at 577 mcg/injection with 95% confidence limits at 463 and 723 mcg. PGE2 is also effective; 40% of rats returned to estrus at a dose of 1000 mcg twice on day 6, suggesting a potency of about
PGF2α. 相似文献
4.
M.D. S.D. Sharma M.D. R.W. Hale M.D. J.P. Muller 《Prostaglandins & other lipid mediators》1975,10(6):1019-1027
The efficacy of intravenous Prostaglandin F2α (PGF2α) infusion for induction of labor in two different dosage schedules was studied in 90 women between 36 and 43 weeks of gestation. The rate of PGF2α infusion was increased at four-hour intervals in 36 women in the low dosage group and every hour in 54 women in the high dosage group, never exceeding an infusion rate of 20 μg/min. in either group. Labor was successfully induced in approximately 90% of the patients in each group. There was no statistically significant difference in the mean induction-delivery interval between the two groups at the 5 percent level. Intravenous PGF2α was found to be effective and safe for both mother and infant in the dosage schedules used in this study for induction of labor. 相似文献
5.
Pregnancies in hamsters may be terminated with 10 μg PGF2α administered b.i.d. on days 4, 5 and 6 of gestation. Small (250 μg and above) daily injections of progesterone on the same days will reverse this PG effect; in contradistinction, 10 mg of progesterone per day failed to maintain normal pregnancies in hamsters spayed on day 5. Daily administration of 3 mg of progesterone and 1 μg of estrone essentially normalized the gestation; administration of PGF2α at 10 mg on days 5, 6 and 7 of pregnancy in steroid-maintained rats, resulted in pregnancy termination in all animals, while 1 mg was partly effective. These data demonstrate an extra-ovarian site of action of prostaglandin F2α on pregnancy in hamsters. 相似文献
6.
B.J. Broughton M.P.L. Caton E.C.J. Coffee D.J. Hambling M.N. Palfreyman M.T. Withnall K.R.H. Wooldridge 《Prostaglandins & other lipid mediators》1980,19(4):559-575
Some ω-chain phenyl- and 16-phenoxy- analogues of (±)-11-deoxyprostaglandin F1α have been synthesized and evaluated for anti-fertility activity in the hamster. 11-Deoxy-16-phenoxy-17,18,19,20-tetranor-PGF1α was the most active member of the series with an ED50 equal to that of PGF2α. 11-Deoxy-17-phenyl-18,19,20-trinor-PGF1α, which was one third as active as PGF2α, was more potent than the corresponding 16- and 18-phenyl compounds. Aryl ring substitution was found to lower activity, except that with the 16-phenyl compound, p-bromo and m-trifluoromethyl substitution increased the potency.The antifertility activity of the phenoxy compounds, which were poor substrates for 15-hydroxyprostaglandin dehydrogenase, was shown to correlate well with the binding affinity for the bovine corpus luteum PGF2α receptor. Some quantitative structure-activity data supporting this finding are presented. 相似文献
7.
C.H. Spilman D.C. Beuving A.D. Forbes F.A. Kimball 《Prostaglandins & other lipid mediators》1977,14(3):477-488
The effects of prostaglandin (PG)F2α and PGF2α, 1–15 lactone were compared in luteal phase, non-pregnant and in early pregnant rhesus monkeys. Animals treated with either PG after pretreatment with human chorionic gonadotropin (hCG) had peripheral plasma progesterone concentrations that were not statistically different from those in animals treated with hCG and vehicle. However, menstrual cycle lengths in monkeys treated with PGF2α, 1–15 lactone were significantly (P <0.02) shorter than those in vehicle treated animals. In the absence of hCG pretreatment, plasma progesterone concentrations were significantly (P <0.008) lower by the second day after the initial treatment with either PGF2α or PGF2α, 1–15 lactone than in vehicle treated monkeys. Menstrual cycle lengths in monkeys treated with either PG were significantly (P <0.04) shorter than those in animals treated with vehicle. There were no changes in plasma progesterone concentrations in early pregnant monkeys treated with PGF2α, and pregnancy was not interrupted. In contrast, plasma progesterone declined and pregnancy was terminated in 5 of 6 early pregnant monkeys treated with PGF2α, 1–15 lactone. These data indicate that PGF2α, 1–15 lactone decreases menstrual cycle lengths in non-pregnant rhesus monkeys. More importantly, PGF2α, 1–15 lactone terminates early pregnancy in the monkey at a dose which is less than an ineffective dose of PGF2α. 相似文献
8.
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
9.
John R. G. Challis I. John Davies Kenneth J. Ryan Andrew G. Hendrickx 《Prostaglandins & other lipid mediators》1974,6(5):389-396
The concentration of prostaglandin F (PGF) has been measured in the peripheral plasma of normal rhesus monkeys (
) during the final third of gestation, and in monkeys treated with dexamethasone or PGF2α after day 145 of pregnancy. Daily administration of PGF2α (10–15 mg/day im) reliably induced abortion within 3–6 days. However, dexamethasone (8 mg/day im from day 145) had no effect on the length of gestation.The concentration of PGF in the femoral venous plasma of untreated or dexamethasone-treated monkeys was highly variable, both in serial samples taken from the same animal and in samples taken from different animals at the same time of gestation. There was no indication of an effect of dexamethasone treatment on the plasma PGF levels, nor did the concentration of PGF increase during late pregnancy before spontaneous parturition. These results show that the myometrium of the pregnant rhesus monkey is highly sensitive to exogenous PGF2α during late gestation. However, a significant increase in the peripheral plasma concentration of PGF prior to the onset of labor was not observed. 相似文献
10.
Intracerebroventricular administration of PGI2 or PGE2 reduced aconitine-induced cardiac arrhythmia in rats. PGF2α had no antiarrhythmic effect under the same conditions. The ED50 values of PGI2 and E2 were 0.25 μg/kg and 1.1 μg/kg, respectively. Central mechanisms may participate in the antiarrhythmic effect of these PGs. 相似文献
11.
U. Krishna A.C. Ganguli A.V. Mandlekar V.N. Purandare 《Prostaglandins & other lipid mediators》1978,15(4):685-693
Prostaglandin F2α and its methyl analogues were used for induction of abortion in 598 patients with gestational age from 9 to 20 weeks. Different routes of administration were studied and varous dosages given. The incidence of gastrointestinal side effects were within acceptable range for all methods. Both intra-amniotic injections of 50 mg PGF2α and 2.5 mg 15-methyl PGF2α as well as intramuscular and vaginal administration of 15-methyl PGF2α or its methyl ester, respectively, were highly effective in termination of pregnancy. The intramuscular route was, however, associated with the highest frequency of gastrointestinal side effects. If both efficacy and side effects were taken into consideration, the intra-amniotic and vaginal routes were superior. The ease of administration as well as the applicability over a wider range of gestation in termination of pregnancy may, however, in many situations speak in favour of the repeated vaginal administration of 15-methyl PGF2α methyl ester. 相似文献
12.
A. P. Lange N. J. Secher G. Thomsen Pedersen 《Prostaglandins & other lipid mediators》1974,6(2):149-157
PGF2α or hypertonic (20 per cent) saline followed by oxytocin was used to terminate pregnancy in 160 women between the 10th and 20th weeks of gestation.In the patients treated with PGF2α minor side-effects were reported in about 50 per cent of the cases, however, the method was superior to hypertonic saline with regard to the number of complications and the length of stay in hospital. 相似文献
13.
Ryo Kawata Yoshihiro Urade Masayoshi Tachibana Osamu Mizukoshi 《Prostaglandins & other lipid mediators》1988,35(2)
The exogenous and endogenous syntheses of prostaglandins (PG's) by the cochlea of adult mongolian gerbils were studied
. After incubation of the whole membraneous cochlea with [3H]-arachidonic acid (AA), syntheses of PGF2α, 6-keto PGF1α, PGE2, thromboxane (TX) B2 and PGD2 were evidenced in this order. The synthesis of radioactive PG's was almost completely inhibited by incubation with 10−5 M indomethacin. No significant amounts of those PG's were detected by radioimmunoassay (RIA) in the cochlea obtained from animals killed by microwave irradiation at 5.0 kw for 0.8 sec. However, when the homogenate of the whole membraneous cochlea obtained from animals without microwave irradiation was incubated at 37°C for 0–15 min, PGD2, PGE2, PGF2α and 6-keto PGF1α were found to be formed from endogenous AA in the cochlea by RIA. PG's were formed already at 0 time to considerable level (PGD2, PGF2α and 6-keto PGF1α, 90–120 pg/cochlea; PGE2, 370 pg/cochlea), reached to the maximum level (PGD2, PGF2α and 6-keto PGF1α, 170–200 pg/cochlea; PGE2, 500 pg/cochlea) at a 5-min incubation, and then gradually decreased. On the other hand, the amount of TXB2 was lower than the detection limit by RIA (<50 pg/cochlea) even after the incubation. The cochlea was dissected into three parts: organ of Corti + modiolus (OC + M), lateral wall (LW), and cochlear nerve (CN), and then PG's formed by these tissues were determined after a 5-min incubation of the homogenates. In the CN and OC + M, PGE2 was the major PG (100 and 160 pg/tissue, respectively), and the amounts of PGD2, PGF2α and 6-keto PGF1α were about
of those of PGE2. In the LW, the amounts of PGD2, PGE2, PGF2α and 6-keto PGF1α were about the same level (70–100 pg/LW). 相似文献
14.
In the female hamster, temporary sterility for a period of 10 or 15 days was induced by an intraperitoneal Silastic-PVP-tube containing 0.5 or 1.0 mg of PGF2α, respectively. All Silastic-PVP-PGF2α tube bearing animals regained fertility and delivered normal litters at various times after the placement of the tube. The release rate of 3H-PGF2α from the Silastic-PVP tube was described and their potential use as a drug delivery system discussed. 相似文献
15.
Roberto P. Rosenkranz 《Prostaglandins & other lipid mediators》1978,15(6):925-942
Intracerebroventricular administration of prostaglandins E1 or E2 was shown to block, while PGF2α increased the incidence of tonic convulsion due to electroshock in mice. The Prostaglandins were administered intracerebroventricularly (i.c.v.) to conscious mice by a modification of Haley and McCormick's method (1) prior to a transcorneal maximal electroshock (MES) or a transcorneal supra-maximal electroshock (SMES). PGE1 and PGE2 i.c.v. blocked the tonic hindlimb extension (THE) and protected the animals from death induced by MES with ED50's for PGE1 and PGE2 for inhibition of the THE of 6.6 (4.3–12.0) μg/mouse i.c.v. and 13.3 (8.9–22.4) μg/mouse i.c.v. respectively. When PGE2 was administered intraperitoneally (i.p.) in doses as high as 4.0 mg/kg it did not block the THE. However, the duration of the THE as well as the mortality were reduced by doses of 0.5–4.0 mg/kg PGE2 i.p.. Both PGE1 and PGE2 were shown to cause a dose related significant (p<.001) decrease in the duration of the THE with SMES in doses of 1–10 μg/mouse i.c.v. for PGE1 and 2–40 μg/mouse i.c.v. for PGE2. PGF2α, administered i.c.v. prior to a transcorneal electroshock equivalent to a current at the ED1 level, increased the incidence of the THE as well as the mortality in doses of 20–50 μg/mouse. 相似文献
16.
The effect of prostaglandin F2α(PGF2α) on endocrine and ovarian function during the early luteal phase of the domestic cat was investigated. Queens were induced to ovulate and then injected subcutaneously with 0.5–5.0 mg PGF2α/kg body weight. The greatest dose was found to approach toxicity. Concentrations of progesterone were similar in cats following treatment with PGF2α compared to values of controls. Development and regression of corpora lutea as determined by serial laparoscopy were similar in all groups. These data indicate that PGF2α at the tested dosages, given during the early luteal phase is not luteolytic in this species and suggest that these regimens would be ineffective for the premature termination of pseudopregnancy. 相似文献
17.
J. N. Stellflug T. M. Louis H. D. Hafs B. E. Seguin 《Prostaglandins & other lipid mediators》1975,9(4):609-615
During diestrus in three consecutive estrous cycles, each of six heifers was given (im) 30 mg, 15 mg (twice at 6-hr intervals) and 60 mg prostaglandin F2α (PGF2α) tham salt. Neither the decline in blood progesterone, the increase in blood estradiol, the duration or the peak of the LH surge, the interval to onset of estrus, nor the interval to ovulation was affected significantly by dose of PGF2α. Thus, relative to that after 30 mg PGF2α im, two injections of 15 mg at 6-hr intervals or 60 mg PGF2α did not hasten luteolysis. Thirty mg was an ample im dose of PGF2α to cause luteolysis. Regardless of im dose of PGF2α, blood PGF peaked at about 6.0 ng/ml within 10 minutes and returned to basal values (<1.0 ng/ml) within 90 minutes. In another trial, after a single iv injection of 5 mg PGF2α, blood PGF peaked (25 ng/ml) within 5 minutes and returned to basal values within 15 minutes. During a 30-minute infusion (0.5 mg/minute) of PGF2α, blood PGF plateaued at 29.5 ng/ml with a metabolic clearance rate of 17.0 liters per minute. 相似文献
18.
C.F. Rosenkrans Jr. B.C. Paria D.L. Davis G. Milliken 《Prostaglandins & other lipid mediators》1992,43(4)
Two experiments were conducted to determine the effects of 2-hydroxy-estradiol-17β (2---OH---E2; 0, 50 and 100 μM) and estradiol-17β (E2; 0, 25 and 50 μM) on prostaglandin (PG) E and PGF2α synthesis by day-10 pig blastocysts (day 0 is first day of estrus). Blastocysts were incubated in a modified Krebs-Ringer bicarbonate medium, supplemented with bovine serum albumin (4 mg/ml) and the vitamins and amino acids (essential and nonessential) in Minimum Essential Medium (without phenol red or antibiotics). The incubations were conducted at 39°C for three 2-h periods; the second and third periods included an E2 or catechol estrogen treatment. Release of PGF2α into the culture medium decreased (p<0.001) linearly with increasing concentrations of 2---H---E2 in both periods. Release of PGE was not affected by 2---OH---E2, therefore 2---OH---E2 increased (p<0.06) the PGE:PGF2α. When E2 was added to the medium, release of PGE was decreased (p<0.01) during the second and third periods. Release of PGF2α also was decreased (p<0.05) by E2 during period 2, but E2 did not alter the PGE:PGF2α. Content of PGs in blastocysts at recovery was less than 10% of the PGs released in vitro. Therefore, these studies demonstrate effects of both the primary and catechol forms of E2 on the synthesis of PGE and PGF2α. Catechol estrogens and E2 may inhibit PG synthesis and modify the PGE:PGF2α during the establishment of pregnancy in pigs. 相似文献
19.
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
20.
D. Favara U. Guzzi R. Ciabatti F. Battaglia A. Depaoli L. Gallico G. Galliani 《Prostaglandins & other lipid mediators》1983,25(3)
Some 13-aza-14-oxo prostaglandin analogues of PGF2α, PGE2 and PGA2, have been synthetized in optically active form, starting from Corey's intermediate and evaluated for antifertility activity in the hamster. The C-15 absolute configuration was established and found critical for the biological activity, but unexpectedly the highest potency was always associated with the 15 epi derivatives.Among the PGF2α analogues the 15 epi derivatives was about one tenth as potent as PGF2α.The preparation of a few 16-phenoxy 17,18,19,20 tetranor-derivatives led to more potent compounds with the p-fluorophenoxy analogue having the same potency as PGF2α. 相似文献