Effect of DL111-IT on progesterone biosynthesis and viability of rat luteal cells in vitro.
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AIM: To study the influence of DL111-IT on progesterone biosynthesis of cultured luteal cells (LC). METHODS: LC viability was assessed with trypan blue dye exclusion and progesterone concentration was measured with radioimmunoassay. RESULTS: DL111-IT decreased the viability of LC after 24-h incubation, its ED50 being 7.7 (95% confidence limits: 7.1-8.5) mg.L-1. DL111-IT inhibited basal secretion of progesterone in a concentration-dependent manner, and 3 mg.L-1 decreased progesterone concentration by 25% vs control. DL111-IT 3 mg.L-1 also inhibited the stimulatory effect of forskolin (cAMP activator) 10 mumol.L-1 and pregnenolone [converted to progesterone by 3 beta-hydroxysteroid dehydrogenase-isomerase complex (3 beta-HSD)] 10 mumol.L-1 on progesterone production in cultured LC, and their inhibitory rates were 43% and 155%, respectively. At the same concentration, DL111-IT did not influence hCG-induced progesterone production. CONCLUSION: DL111-IT inhibited progesterone synthesis by suppressing the conversion of pregnenolone to progesterone (inactivating 3 beta-HSD) and suppressed the activity of cAMP. DL111-IT 6-24 mg.L-1 decreased the viability of LC. (+info)
The effectiveness of non-surgical management of early interstitial pregnancy: a report of ten cases and review of the literature.
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OBJECTIVE: To assess the effectiveness of non-surgical management of interstitial pregnancy. DESIGN: A prospective interventional study. SUBJECTS: Eleven women with the ultrasound diagnosis of interstitial ectopic pregnancy. METHODS: Women with suspected early pregnancy complications were examined by transvaginal ultrasound. Those with the diagnosis of interstitial pregnancy were offered non-surgical treatment with methotrexate, which was administered systemically or by local injection. Follow-up with regular measurements of beta-human chorionic gonadotropin and ultrasound scans continued until the pregnancy had resolved completely. RESULTS: Ten women were managed non-surgically, and one woman opted for surgery. Five women received systemic and five local methotrexate. Local therapy was successful in all five cases (100%), whereas four out of five (80%) women receiving systemic methotrexate were cured. Significant side-effects were noted in two women following systemic therapy. In comparison, there were no side-effects in the group of women who received local therapy. There were no significant differences between the two treatment groups in the length of time taken for the pregnancy to resolve. CONCLUSIONS: Non-surgical treatment of interstitial pregnancy with methotrexate appears to be safe and effective. Local administration appears to be more successful and better tolerated by patients and may be used as the first-line therapy. (+info)
Once-a-month treatment with a combination of mifepristone and the prostaglandin analogue misoprostol.
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In this two centre study, the efficacy of 200 mg mifepristone orally followed 48 h later by 0.4 mg misoprostol orally for menstrual regulation was investigated. The dose of mifepristone was taken the day before the expected day of menstruation. Each volunteer was planned to participate for up to 6 months. A plasma beta human chorionic gonadotrophin (HCG) was measured on the day of mifepristone intake. The study was disrupted prematurely due to low efficacy. In 125 treatment cycles the overall pregnancy rate was 17.6% (22 pregnancies) and the rate of continuing pregnancies (failure) was 4.0%. Eight women discontinued the study due to bleeding irregularities which were seen in 15 cycles (12%). These effects on bleeding pattern made the timing of treatment day difficult. Late luteal phase treatment with a combination of mifepristone and misoprostol is not adequately effective for menstrual regulation. (+info)
Angiotensin II interacts with prostaglandin F2alpha and endothelin-1 as a local luteolytic factor in the bovine corpus luteum in vitro.
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Recent findings suggest that the ovarian renin-angiotensin system may regulate ovarian function through the paracrine/autocrine actions of angiotensin II (Ang II). In this study, we have examined and characterized the local effects of Ang II as a luteolytic factor and its interaction with prostaglandin F2alpha (PGF2alpha) and endothelin-1 (ET-1) in the bovine corpus luteum (CL) of the mid-luteal phase, by using an in vitro microdialysis system (MDS). Ang II was detected in the MDS perfusate (4 pg/ml), and infusion of PGF2alpha (10(-6) M) for 2 h increased the Ang II release by 50-100% during the following experimental period, in addition to its stimulation of ET-1 release. Two 2-h infusions of Ang II (10(-7)-10(-5) M) separated by a 2-h interval induced a dose- and time-dependent decrease of progesterone (P4) release by 41-66%. When the luteal explants were pre-perfused with PGF2alpha (10(-6) M) for 2 h, two consecutive perfusions of Ang II (10(-6) M) at a 2-h interval rapidly reduced the P4 release (by 50%). This reduction occurred 6 h earlier than those of infusions of PGF2alpha or Ang II alone. The simultaneous infusion of either 1) Ang II (10(-6) M) with PGF2alpha (10(-6) M), 2) ET-1 (10(-7) M) with PGF2alpha, or 3) Ang II + ET-1 with PGF2alpha (10(-6) M) for 2 h also induced a rapid and pronounced (60%) decrease in P4 release. Perfusion with the Ang II antagonist blocked the P4-suppressing activity of Ang II alone or PGF2alpha + Ang II infusion. Ang II stimulated the release of ET-1 and oxytocin during infusion but inhibited them after infusion. These results show that Ang II is released in the bovine midcycle CL in vitro, and this peptide, either alone or together with PGF2alpha, can suppress the release of P4. As PGF2alpha directly stimulated Ang II release, Ang II may influence the critical period for starting the cascade of functional luteolysis in vivo and might lead to structural luteolysis with ET-1 as a major vasoconstrictor. The overall results suggest that Ang II may have an important role at luteolysis in the bovine CL. (+info)
Does an acidic medium enhance the efficacy of vaginal misoprostol for pre-abortion cervical priming?
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Absorption pharmacokinetics reveal a relationship between plasma concentrations of misoprostol and its therapeutic effect. To achieve a constant plasma profile and optimal efficacy, it is important to develop a medium that ensures complete dissolution of vaginal misoprostol tablets. Vaginal misoprostol is said to liquefy better in an acidic medium; thus, the aim of this study was to determine whether a 200 microg misoprostol tablet dissolved in acetic acid would be more efficacious than 200 microg misoprostol dissolved in water for pre-abortion cervical priming. A total of 120 healthy nulliparous women requesting legal termination of pregnancy between 6-12 weeks gestation were allocated randomly to either of the study groups. Vacuum aspiration was performed 3-4 h after insertion of the misoprostol tablet. Using Hegar's dilator, the degree of cervical dilatation before operation was measured. Of 60 women, 14 (23%) achieved a cervical dilatation of >/=8 mm when the misoprostol dose was dissolved in acetic acid; 12 (20%) achieved a similar cervical dilatation when the dose was dissolved in water. The mean cervical dilatation for the acid and water media used was 6.3 mm and 6.2 mm respectively; these differences were not statistically significant, neither were pre-operative and intra-operative blood losses statistically different between the two groups. Twenty-four (40%) and four (7%) respectively of women in whom a water medium was used experienced vaginal bleeding and abdominal pain; 20 (33%) and 0 women respectively among those in whom an acetic acid medium was used experienced vaginal bleeding and abdominal pain. These differences in side effects were not statistically significant. Our study shows that the use of acetic acid to dissolve vaginal misoprostol does not improve the efficacy in achieving successful cervical dilatation for pre-abortion cervical priming. (+info)
The use of misoprostol for pre-operative cervical dilatation prior to vacuum aspiration: a randomized trial.
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Misoprostol is effective for cervical priming prior to vacuum aspiration for first trimester termination of pregnancy. Previous studies showed that the oral route was more acceptable to patients but there were higher incidences of side-effects when compared with the vaginal route. This study is to determine the optimal dosage and route of administration of misoprostol for pre-operative cervical dilatation. A double-blind, randomized trial was undertaken for 225 nulliparous women with 8-12 weeks amenorrhoea. They were randomly assigned to groups given 0 (placebo), 200 or 400 microg oral or vaginal misoprostol 3 h prior to vacuum aspiration. In misoprostol-treated groups the baseline cervical dilatation was significantly increased when compared with the placebo group; the effect was dose-related in the oral but not in the vaginal group. The cumulative force and blood loss was significantly decreased in the misoprostol-treated groups. The incidences of side-effects were more frequent in misoprostol groups but were not related to the route and dosage of medication. The duration of procedure, incidences of post-operative complications, the duration of post-operative bleeding and the interval to the first period were similar in the five treatment groups. We conclude that a 3 h pre-treatment interval is effective for both oral and vaginal routes. When given orally, 400 microg is more effective than 200 microg. The efficacy was otherwise similar when compared with the vaginal route. We recommend 400 microg oral misoprostol 3 h prior to vacuum aspiration for cervical dilatation. (+info)
Induction of parturition in bitches with minimal side effects by two injections of a low dose of fenprostalene, a prostaglandin F2alpha analogue, and pretreatment with prifinium bromide.
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An experiment using 16 Beagle bitches (aged 11 months to 6 years and 2 months) in their 56th to 58th day of pregnancy was carried out to investigate the effects of two injections of a low dose of fenprostalene, a long-acting prostaglandin F2alpha analogue, and pretreatment with prifinium bromide, a parasympathetic nerve blocking agent, on the induction of parturition and severity of side effects. The bitches were divided into three treatment groups: one injection of 5 microg/kg of fenprostalene (group I, n=5); one injection of 7.5 mg/head of prifinium bromide followed by one injection of 5 microg/kg of fenprostalene at 5 min after prifinium bromide injection (group II, n=6); and one injection of 7.5 mg/head of prifinium bromide followed by two injections of 2.5 microg/kg of fenprostalene, one injection at 5 min after prifinium bromide injection and the next at 1 hr after the fenprostalene first injection (group III, n=5). Following the injection of fenprostalene, side effects such as salivation, vomiting, colic symptoms, and watery diarrhea occurred most frequently (80-100% of cases) in group I bitches. Apart from colic symptoms, no side effects were observed in group III bitches. Group III bitches also showed the smallest increase in plasma cortisol concentration. No significant difference in the time to initiation of parturition was found between the three groups. The one-week survival rate of newborn puppies was highest in group III. The results showed that pretreatment with prifinium bromide and two injections of 2.5 microg/kg of fenprostalene can alleviate side effects following fenprostalene administration and have no adverse effect on the survival of newborn puppies, indicating that this method is a reliable and safe way of inducing parturition in bitches. (+info)
A comparison of two regimens of intravaginal misoprostol for termination of second trimester pregnancy: a randomized comparative trial.
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A prospective randomized trial was conducted in 148 women to compare the efficacy of two regimens of vaginal misoprostol for termination of second trimester pregnancy. Women aged 16-40 years requesting termination of second trimester pregnancy were randomized into two groups. Women in group 1 were given vaginal misoprostol 400 microg every 3 h for a maximum of five doses in 24 h. Women in group 2 were given vaginal misoprostol 400 microg every 6 h for a maximum of three doses in 24 h. If women did not abort in 24 h, the same regimen was repeated. The median induction-abortion interval in group 1 (15.2 h) was significantly shorter (P < 0.01) than that in the group 2 (19.0 h). The percentage of women who achieved successful abortion within 48 h in group 1 (90.5%) was also significantly higher (P < 0.02) than that in group 2 (75.7%). The incidence of fever was more common in group 1 (P = 0.01). It is concluded that the regimen of vaginal misoprostol 400 microg every 3 h with maximum of five doses in 24 h was more effective than the regimen of misoprostol every 6 h in termination of second trimester pregnancy. (+info)