15-keto-13-14-dihydroprostaglandin-f2alpha and Fetal-Death

We administered indomethacin orally for the treatment of premature labor in a prospective, randomized, double-blind fashion, and all infants were followed up. Indomethacin was significantly more effective than placebo in inhibition of premature labor during a 24-hour course of therapy, with treatment failure during therapy occurring in only one of 15 indomethacin-treated patients compared to nine of 15 placebo-treated patients (p less than 0.01). Mean plasma concentrations of indomethacin were approximately 0.8 micrograms/ml at both 4 and 12 hours after administration. Mean plasma levels of 15-oxo-13,14-dihydroprostaglandin F2 alpha (PGFM) were similar in the two groups before treatment, decreased markedly in the indomethacin group by 4 hours, and were not detected at 12 hours in all but the one indomethacin-treated patient who was delivered within 24 hours. Patients in the placebo group who were delivered prematurely had higher pretreatment PGFM levels (mean +/- SE, 83 +/- 18 pg/ml, n = 9) than the patients who responded to placebo (25 +/- 6 pg/ml, n = 6) (p less than 0.05). There was no difference between the indomethacin and placebo groups with respect to gestational age at delivery, birth weight, and neonatal morbidity and deaths. In particular, we found no evidence of premature closure of the ductus arteriosus, pulmonary hypertension, or increase in bleeding problems among the infants exposed to indomethacin in utero. Although no difference in neonatal outcome was observed in this small number of patients, it would seem prudent still to consider indomethacin as an experimental therapy.

Topics: Dinoprost; Double-Blind Method; Drug Evaluation; Estradiol; Female; Fetal Blood; Fetal Death; Humans; Indomethacin; Infant, Newborn; Infant, Newborn, Diseases; Male; Obstetric Labor, Premature; Pregnancy; Progesterone; Prospective Studies; Prostaglandins F; Random Allocation

The response to Claviceps purpurea sclerotia administration in pregnant goats was examined in terms of changes in the levels of plasma hormones, the development of pregnancy and kid production. Six treated goats were each given 15 mg milled sclerotia (i.e. 0.105 mg ergotamine) per kilogram live weight twice daily via a stomach tube from days 98 +/- 2 to 107 +/- 2 of gestation. Seven control goats were given water twice daily via a stomach tube during the same period of gestation. The goats were observed for clinical signs of disease, rectal temperatures and live weights were recorded and the condition of the foetuses was monitored by real-time ultrasonography. All control goats delivered live kids. In the treated group two goats aborted 33 and 47 days, respectively, after the start of the administration period, two goats each delivered one normal and one weak kid, and the two remaining goats delivered apparently normal kids. All six treated goats became depressed and had poor appetite during the period of sclerotia administration. Rectal temperatures were significantly increased and live weight changes significantly decreased in the animals in the treated group compared to the control group during the period of C. purpurea administration. Ultrasound examination revealed that foetal deaths occurred between 1 and 42 days before abortion or birth. The appearance of the aborted foetuses varied from fresh to mummified, depending on the number of days between foetal death and expulsion. Microbiological and serological investigations revealed no infectious causes of reproductive failure. The level of 15-ketodihydro-PGF2 alpha was high in goats that aborted following administration of C. purpurea compared with the level in control goats. The oestrone sulphate level did not increase before abortion in the treated goats as in the controls before parturition. There were also changes in these hormones in the four treated goats that delivered live kids, but the changes were considerably smaller. These findings indicate that the endocrine foetal-placental function was disturbed, probably due to injury caused by the C. purpurea toxin ergotamine in the placenta and foetus.

Topics: Abortion, Veterinary; Adrenergic alpha-Agonists; Animals; Body Weight; Claviceps; Dinoprost; Endocrine Glands; Enzyme-Linked Immunosorbent Assay; Ergotamine; Estrone; Female; Fetal Death; Goats; Heart Rate, Fetal; Placenta; Pregnancy; Pregnancy Outcome; Progesterone; Toxoplasma; Toxoplasmosis, Animal

An experiment was performed to determine the effect of elevated prostaglandin F2 alpha (PGF2 alpha) on pregnancy rates of progestogen-treated bred cows in the presence or absence of luteal tissue. Ninety-one beef cows were bred (Day 0) and assigned randomly to receive either 3 mL saline (CON), 15 mg PGF2 alpha, or 15 mg PGF2 alpha + lutectomy (P + L) administered intramuscularly (i.m.) at 8 h intervals on either Days 5-8, 10-13, or 15-18 postbreeding. Lutectomies were performed by transrectal digital pressure before initiation of treatment on Day 5, 10, or 15 for the respective treatment groups. All cows were fed 4 mg/day of melengesterol acetate from two days prior to initiation of treatment until Day 30 postbreeding. Mean concentrations of 13,14-dihydro-15-keto-PGF2 alpha (PGFM) were increased in cows administered PGF2 alpha and P + L treatments (398 +/- 23 and 413 +/- 22 pg/ml, respectively; p < 0.01) compared to the CON group (80 +/- 29 pg/ml) regardless of treatment group. Mean concentrations of oxytocin (OT) were increased in cows given PGF2 alpha on Day 10 and 15 (p < or = 0.0001) and tended to be increased on d 5 when compared to CON and P + L treatment groups on Day 5. Pregnancy rates were reduced (p < or = 0.03) in the PGF2 alpha treatment group (23%) and by Day 5-8 compared to CON (72%). Lutectomy tended to improve pregnancy rate in P + L (5-8; 55%) compared to PGF2 alpha (5-8; p = 0.1). Pregnancy rates tended (p < or = 0.07) to increase in the PGF2 alpha treatment groups on Days 5-8 treatment (23%, 50%, and 60% for Days 5-8, 10-13, and 15-18, respectively). The later the treatments were initiated pregnancy rates did not differ between treatments given on Days 10-13 and 15-18. In conclusion, the most susceptible period of embryonic growth to the negative effects of PGF2 alpha was during morula to blastocyst development. Removal of luteal tissue diminishes the negative effects of PGF2 alpha through interruption of the luteal oxytocin-uterine PGF2 alpha feedback loop.

Topics: Abortion, Veterinary; Animals; Cattle; Corpus Luteum; Dinoprost; Drug Administration Schedule; Estradiol; Female; Fetal Death; Oxytocin; Pregnancy; Pregnancy, Animal; Progesterone; Progestins; Time Factors

Guinea-pigs treated by gavage with a total dose of 100 mg polychlorinated biphenyls (PCB: Clophen A50) during Days 17-61 of gestation had higher plasma concentrations of 15-keto-13,14-dihydroprostaglandin F-2 alpha, oestrone sulphate and oestradiol-17 beta during the later stages of gestation than did vehicle-treated guinea-pigs. No changes were observed in plasma progesterone concentrations. Our results provide no support for the hypothesis that an enzyme-induced decrease in progesterone concentrations is the main cause of the fetal death observed in PCB-treated guinea-pigs.

Topics: Animals; Dinoprost; Environmental Pollutants; Estradiol; Estrogens; Estrogens, Conjugated (USP); Estrone; Female; Fetal Death; Guinea Pigs; Polychlorinated Biphenyls; Pregnancy; Progesterone

The infusion of Salmonella typhimurium endotoxin into pregnant mares resulted in a biphasic release pattern of PGF-2 alpha as determined by 15-keto-13,14-dihydro-PGF-2 alpha concentrations. The initial phase of 1 h duration was followed by accentuated release by 2 h after infusion; concentrations reached basal levels by 6 h. In 7 mares at 23, 26, 29, 33, 36, 53 and 55 days of gestation, fetal death occurred between 36 and 120 h after infusion; 12 mares at 46, 51, 56, 59, 65, 71, 73, 85, 103, 138, 283 and 318 days of gestation did not abort after endotoxin infusion. Luteal activity was compromised in all mares by 9 h after infusion. Progesterone concentrations were consistently lower in mares that aborted (1-2 ng/ml) than in those that did not abort. Mares therefore appear to be vulnerable to fetal loss by a clinical syndrome induced by Salmonella typhimurium endotoxin until about 50-60 days of gestation.

Topics: Animals; Dinoprost; Endotoxins; Female; Fetal Death; Horse Diseases; Horses; Lipopolysaccharides; Pregnancy; Progesterone; Prostaglandins F; Salmonella typhimurium

Pregnancy was terminated in 4 cows by manual rupture of the amniotic vesicle on day 41 (n = 1) and day 46 (n = 3) after insemination. Each cow was necropsied 36 days after vesicle rupture, by which time only one cow had come into estrus. Luteal activity, monitored daily by plasma progesterone assay, was still evident in 2 cows 35 days after fetal death; in the remaining 2 cows, regression of the corpus luteum (CL) was achieved at 28 and 32 days, respectively. Uterine release of prostaglandin F2 alpha (PGF2 alpha), measured as the 15-keto metabolite (PGFM) PGF2 alpha, was monitored by a plasma sampling schedule; specimens were obtained every 4 hours. There were no appreciable releases of PGF2 alpha associated with fetal death. The first appreciable PGF2 alpha release in episodic form was seen only in conjunction with CL regression. In all cows, a palpable membrane slip was evident for 18 days after rupture of the amniotic vesicle, although at that time, uterine resilience was diminished in the 2 cows in which the CL subsequently regressed. After 18 days, the uterus was noticeably edematous and fluid-filled in all cows; in 1 of the cows with a regressed CL, the uterus had returned to prepregnancy size and tone by day 33.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Cattle; Cattle Diseases; Corpus Luteum; Dinoprost; Estrus; Female; Fetal Death; Pregnancy; Pregnancy Tests; Progesterone; Prostaglandins F; Uterus