Increase in urinary thromboxane excretion during pregnancy and labor

Urinary TXB2 excretion was measured during pregnancy and labor using high pressure liquid chromatography and radioimmunoassay. From the first trimester onwards TXB2 levels in urine of pregnant women (n = 60) were significantly (p less than 0.001) higher than in non-pregnant women (n = 12) and they increased, albeit not significantly, with advancing gestation. Labor was associated with a two-fold increase in urinary TXB2 excretion. Levels in established labor were significantly higher than at any other time in pregnancy (p less than 0.001), but the levels in incipient labor showed considerable overlap with these in late pregnancy. Thus urinary TXB2, while not necessarily originating from the pregnant uterus, appears to reflect the uterine activity of labor and may be the expression of a general stimulation of prostanoid production during parturition.     

Changes in urinary 6-keto-prostaglandin F1α excretion during pregnancy and labor

Urinary excretion of 6-keto-PGF_1α was measured by high pressure liquid chromatography and radioimmunoassay at various stages of pregnancy and labor. In the first trimester of pregnancy, urinary 6-keto-PGF_1α concentrations were nor different from those measured before pregnancy, but they showed a significant increase in the second trimester of pregnancy (p <0.001). The levels rose further in the third trimester, although this increase was not statistically significant when compared to levels obtained in the second trimester. There was no evidence for a significance change in 6-keto-PGF_1α excretion with the onset of labor. During well-established, progressive labor mean values of 6-keto-PGF_1α excretion were about twice as high as before the onset of labor, but the range of values during labor was so wide that there was no statistical difference with values obtained in the second half of pregnancy.It is concluded that the increase in the urinary excretion of 6-keto-PGF_1α occurs later in pregnancy than the increase in TXB₂ excretion and that labor at term is not associated with marked changes in 6-keto-PGF_1α excretion.     

Contribution of preterm delivery to perinatal mortality.

A detailed retrospective analysis was made of the records of 486 preterm infants, who accounted for 5-1% of all births during 1973 and 1974. Whereas preterm delivery did not contribute to perinatal mortality in terms of stillbirth, it outweighed all other causes in terms of early neonatal deaths. Preterm birth was responsible for 85% of the early neonatal deaths not due to lethal congenital deformities. Early neonatal mortality rates were closely linked both to gestational age and birth weight and to the reason for preterm birth. Early neonatal mortality was high (97 per 1000) when preterm labour was spontaneous, whether or not associated with material or fetal disease or with multiple pregnancy, but low (27 per 1000) when preterm delivery was elective. Preventing spontaneous preterm labour would considerably reduce neonatal mortality in our community.     

Human placental 15-hydroxy-prostaglandin dehydrogenase activity is under fetal genetic control

Placental 15-hydroxy-prostaglandin dehydrogenase (PGDH type I) was measured in 33 placentae obtained from 1 trizygotic, 7 dizygotic and 8 monozygotic pregnancies. PGDH activity ranged from 0.33 to 4.62 nmol PGF_2α metabolized per mg placental protein per min, which was within the range observed in singleton pregnancies. Expressing PGDH activity per mg DNA, offered no advantage over expressing it per mg total protein. PGDH activity differed significantly between the placentae of 6 of the 9 genetically non-identical placental pairs. The placentae of genetically identical twins, on the other hand, showed no difference in PGDH activity between the pairs. The data indicate that the genetic constitution of the fetus determines placental PGDH activity. They also provide us with the first evidence that the variation in prostaglandin catabolized capacity of the human placenta is not entirely dictated by the maternal endocrine environment, but is under fetal control.     

Secretory diarrhea in villous adenoma of rectum: Effect of treatment with somatostatin and indomethacin

The effects of treatment with the synthetic longacting somatostatin analogue SMS-201-995 were studied in a patient with a fluid and electrolyte secreting villous adenoma of the rectum. The effects of SMS-201-995 on rectal fluid volume and electrolyte loss, and local and general prostanoid production were compared with those of treatment with indomethacin.During treatment with the somatostatin analogue iso-osmolar rectal fluid production increased about 25%; the quantity of prostaglandin E₂ in the rectal fluid rose almost 20-fold. Prostaglandin F_2α, 6-keto-prostaglandin F_1α and 13,14-dihydro-15-keto-prostaglandin F_2α output showed similar, though less impressive increments during somatostatin treatment. The somatostatin analogue did not affect urinary prostanoid excretion except for levels of 2,3-dinor-thromboxane B₂, which doubled. With indomethacin treatment diurnal rectal fluid production dropped by about 50% and all prostanoids measured in urine and rectal fluid decreased below control values.It appears that the somatostatin analogue SMS-201-995 has a marked stimulatory effect on the in vivo prostanoid production by the villous adenoma. Perhaps this stimulation is not confined to the tumor only, but also affects thromboxane synthesis.     

Changes in plasma levels of PGF2 alpha and PGI2 metabolites at and after delivery at term

Plasma levels of 6-keto-PGF1 alpha and 13,14-dihydro-15-keto-PGF2 alpha (PGFM) were measured by high pressure liquid chromatography and radioimmunoassay during and up to 48 hours after term labor. PGFM levels increased during labor to reach values which at full dilatation, at delivery of the fetal head and at placental separation were each time higher than levels obtained earlier. In all women (n = 10) PGFM levels reached their maximum and started to decline within 10 min. after placental separation. Levels decreased to prelabor values within 2 to 3 hours after delivery and no temporary increases were observed within the first 2 days. Levels of 6-keto-PGF1 alpha on the other hand, showed no consistent trends throughout labor and the early puerperium. The observed changes are believed to be of relevance for ensuring adequate hemostasis after birth.     

Gas chromatographic determination of E prostaglandins in human amniotic fluid

A simple procedure is described for the extraction and purification of prostaglandins from amniotic fluid. Combined with gas chromatography with electron-capture detection, this provides a rapid and specific method for the determination of PGE in human amniotic fluid.     

Increase in placental 15-hydroxy-prostaglandin dehydrogenase in the first half of human pregnancy

NAD-dependent 15-hydroxy-prostaglandin dehydrogenase (PGDH) activity was measured in homogenates of 25 human placentae obtained between 7 and 17 weeks of gestation. PGDH activity, expressed in nanomoles PGF_2α metabolized per min, ranged from 0.2 to 5.4 nmoles per mg placental protein and from 1.5 to 80 nmoles per g wet weight. PGDH activity per mg protein and per g weight increased significantly in function of gestational age (p<0.001). Between 7–8 weeks' gestation and 15–16 weeks mean values increased tenfold from 0.4 to 3.0 nmoles per mg protein and from 2.7 to 36.6 nmoles per g wet weight. Per unit of weight these early placentae contained less PGDH activity than term controls, but this related mainly to their high water content. Per mg placental protein PGDH activities already equalled values found at term before the end of the first trimester. The data indicate that the development of terminal villi and the migration of trophoblast into the maternal spiral arteries is associated with a substantial increase in the placental capacity for prostaglandin metabolism.     

Not prostacyclin synthase but prostaglandin endoperoxide synthase increases with human placental development

Prostaglandin endoperoxide synthase (i.e. cyclooxygenase; PGH sythase) and prostacyclin synthase (PGI synthase were quantitated with specific immunoradimetric assays in microsomes from human placentae (n=20) obtained from 7 up to 17 weeks of gestation. Over that period, wherein trophoblastic invasion of the uterine spiral arteries occurs, the placetae showed a significant increase in concentrations of PGH synthase (r=0.73, p<0.001; n=20), but not in those of PGI synthase. While the variation between individual placentae was much larger for PGI synthase than for PGH synthase concentrations, there was no evidence for a large excess of PGI synthase over that of PGH synthase in any of these early placentae. The data indicate, first, that the developing placenta contains PGI synthase, but in amount which are relatively small and do not appear to increase with advancing gestation. Second, they seem to indicate that the capacity for bioconversion of arachidonic acid into prostaglandin endoperoxides increases markedly with placental development.     

Increase in concentrations of prostaglandin endoperoxide synthase and prostacyclin synthase in human myometrium in late pregnancy

Concentrations of prostaglandin endoperoxide synthase (i.e. cyclooxygenase; PGH synthase) and prostacyclin synthase (PGI synthase) were quantified with specific radioimmunometric assays inhuman myometrium during the last trimester of pregnancy (n=23) and in non-pregnant controls (n=8). Pregnant myometrium contained 3 times more PGH synthase per mg microsomal protein than non-pregnant myometrium (p < 0.01) but there was no increase with increasing gestational age in the third trimester nor with the onset of labor. In pregnancy, as compared to the non-pregnant state, there was no significant change in the PGI synthase content of myometrial microsomes, but significantly more PGI synthase was recovered in other subcellular fractions (p < 0.01). This suggests that pregnancy affects preferential changes in the subcellular distribution of PGI synthase in myometrial cells.Relative to its PGI synthase content pregnant myometrium contained twice as much PGH synthase as non-pregnant myometrium (p < 0.01). This may offer further evidence that PGH synthase rather than PGI synthase itself is the rate limiting factor in myometrial PGI₂ production. On the other hand, the much larger increase in PGH synthase than in PGI synthase in pregnant as compared to non-pregnant myometrium, may serve to promote preferential synthesis of prostaglandins that are potent myometrial stimulants and of critical importance in human parturition.