Effect of an oxytocin antagonist on plasma oxytocin levels during nocturnal uterine contractions in the pregnant baboon.

TT-235 is a potent oxytocin (OT) antagonist that blocks the action of OT at the receptor level. Previous studies have shown that pregnant baboons demonstrate nocturnal uterine contractions induced by OT as they near delivery. The purpose of this study was to evaluate the changes in plasma OT levels following uterine contraction blockage with TT-235. A tethered pregnant baboon model in its last trimester of pregnancy was used. Three blocks of arterial blood samples, immediately before, plus 1 h and plus 2 h following an OT antagonist injection, were collected once nocturnal uterine contractions were detected. Each block consisted of a continuous 10 min withdrawal with 10 samples per block (1 ml/min). A TT-235 dosage of 300 micrograms/kg and saline for control were utilized. Uterine activities were monitored as pressure changes in the amniotic fluid, and the frequency and mean amplitude of contractile activity per 10 min intervals were expressed as contractile force. Plasma OCT levels were determined by a radioimmunoassay following plasma extraction with petroleum ether. The contractile force was decreased by 77% (p < 0.05) within 2 h after TT-235 administration while it increased 23% following saline infusion. Plasma OT levels were unchanged following saline infusion while they increased 82% (p < 0.05) 2 h after the administration of TT-235. If a positive feedback existed between uterine contractions and OT release, one would expect plasma OT levels to be decreased with contractile activity following TT-235 infusion. Since this is not the case in the present study, the data suggest that there is either a negative feedback or an independent relationship between nocturnal uterine contractions and OT release.

Diurnal changes in plasma prolactin during the last one third of pregnancy in the baboon.

Previous studies in our laboratory revealed that daily plasma prolactin (Prl) levels were higher in the evening than in the morning in the pregnant baboon suggesting a diurnal variation. The goal of this study was to examine in more detail the diurnal alterations in plasma Prl levels. A tethered pregnant baboon model was utilized for these studies. Hourly venous blood samples were taken from 0700 to 2400 hr (n=10) or until 0700 hr the following day (n=5). The studies were performed at various days of pregnancy from day 135 until delivery. Plasma samples were analyzed for Prl by radioimmunoassay. A surge in plasma Prl was detected, starting around 1500 to 1600 hr and lasting for 3 to 5 hr. The surge occurred before the lights went off in the colony (1800 hr). Baseline Prl levels were higher in animals < 15 days before delivery compared to those > 15 days before delivery (P < 0.05). In contrast, no differences were found in the average peak Prl values between these two groups of animals. In summary, in the pregnant baboon during the last one-third of pregnancy plasma Prl surges, beginning around 1500 to 1600 hr and lasting for 3 to 5 hr. Less than 15 days before delivery the mean baseline Prl levels are higher compared to animals greater than 15 days before delivery.

Effect of pregnancy on the metabolic clearance rate and the volume of distribution of oxytocin in the baboon.

Pharmacokinetic parameters of oxytocin (OT) metabolism were determined during the last third of pregnancy and again 4-8 wk after delivery in the baboon. Animals were placed on a tether system with venous and arterial access and a continuous monitoring of uterine contractions during gestation. Two methods of determining OT pharmacokinetics were utilized (bolus injection vs. continuous infusion). The metabolic clearance rate of OT as determined during the bolus trials (n = 7) was 22.2 +/- 1.5 ml.min-1.kg-1 in pregnancy and 16.3 +/- 1.4 ml.min-1.kg-1 postpartum (P < 0.05), respectively, and 23.7 +/- 2.8 vs. 16.9 +/- 3.7 ml.min-1.kg-1 (P < 0.05), respectively, as determined during the 1-h infusion trials (n = 4). The initial dilution volume and the volume of distribution at steady state of OT after administration did not differ between pregnant and postpartum animals (P > 0.05). The mean residence time (MRT) of OT was shorter during pregnancy, 7.7 +/- 0.8 vs. 10.8 +/- 1.2 min postpartum (P < 0.05). In summary, OT metabolism during pregnancy in the baboon is characterized by 1) increased clearance rate (1.4-fold), 2) accelerated turnover due to the shorter MRT, and 3) unaltered distribution.

Strategies to decrease costs associated with GBS prophylaxis in preterm gestations.

Objective: 1) To evaluate the costs associated with a practice of routinely culturing women for Group B beta-Streptococcus (GBS) who are at risk for preterm delivery. 2) To evaluate the charges associated with a policy of empiric antibiotic therapy in women suspected of imminent delivery prior to 37 weeks gestation.Methods: In our hospital, women who present with preterm contractions (PTC), preterm labor (defined as uterine contractions resulting in cervical change, PTL), and preterm rupture of the membranes (PROM) were cultured for GBS. Women with PTL and PROM received parenteral antibiotic therapy pending availability of culture results (48 hours). We reviewed the records of women who participated in a study to determine the sensitivity and specificity of a rapid test for GBS (Am J Obstet Gynecol 1997;176:S35). Results of the Lim broth culture, our gold standard, were used for this analysis. The charges for performing cultures ($32/culture) and administering intravenous ampicillin ($54/dose) were calculated.Results: There were 118 women with PTC, 52 women with PTL, and 64 with PROM. Thirty-four (14.5%) of the cultures were positive. The results are presented below.In women with PTC, the incidence of GBS was 12.7%. The culture results were available and guided care in only the 6 women who delivered between 2 and 7 days. In women with PTL the incidence of positive cultures was 11.5%. All of the women received antibiotics pending results of cultures. The majority of the women had delivery delayed 48 hours until results were available. Care was modified in the 7 women who delivered between 2 and 7 days. In women with PROM the incidence of GBS was 20.3%. The culture results were available and guided therapy in 11 women.Conclusions: Our findings suggest that GBS cultures have limited clinical value in women with PTC. Only 6 women, 5.5%, had their care modified as a result of the cultures, at a cost of $3776. In women with PTL, we over-treated the majority of women with antibiotics, most of whom delivered after culture results were available. Cultures had minimal impact on management. Antibiotics should be reserved for women whose labor is progressing on tocolysis. In women with PROM, most delivered prior to availability of culture results. We would have saved $2048 had no cultures been obtained. These results are probably irrelevant, if routine antibiotic administration is utilized in PROM to prolong latency intervals regardless of GBS status.

Thyroid stimulating hormone inhibits rat granulosa cell steroidogenesis in primary culture.

It is not known why hypothyroidism predisposes the ovary to develop cystic follicles in hCG-treated rats. This study examined the effect of TSH on steroidogenesis in cultured granulosa cells. Granulosa cells were isolated from the ovaries of hCG-treated Long-Evans rats. Cells were cultured in medium with either 0 or 100NM: testosterone or 25(OH)cholesterol and treated with 0, 2.5, 10 or 20 ng/ml of TSH. TSH reduced 3ß-HSDI activity in these cells to 12% of control. Progesterone secretion decreased by 72% and estradiol secretion was non-detectable during the second day of treatment with 20 ng/ml of TSH. We conclude that TSH is capable of regulating the secretion of progesterone and estradiol by cultured granulosa cells.