The effects of indomethacin on uterine activity and prostaglandin (PG) concentrations during labor induced by administering ACTH to fetal sheep.
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6-Ketoprostaglandin F1 alpha↗
Biomedical subjects
J E Patrick
Publications and source records attributed to J E Patrick.
The fetal membranes as a possible source of progesterone in the amniotic and allantoic fluids of pregnant sheep.
To assess the possible source of progesterone in the fetal fluids of pregnant sheep, we measured the changes in progesterone concentrations in amniotic fluid (AF) and allantoic fluid (ALF) during pregnancy and compared these values with those in the maternal and fetal circulations. In acute experiments, the concentration of progesterone in ALF was greater than that in AF, and in both compartments, progesterone rose progressively between day 50 of pregnancy and term (day 145). In contrast, in maternal peripheral and uterine venous blood as well as in umbilical cord blood the mean concentration of progesterone increased until day 130, but fell at term. Similar results were obtained in chronically catheterized sheep during late pregnancy. The pattern of progesterone change in the AF and ALF suggested that the steroid might originate from a different source than progesterone in the vascular compartments. By means of in vitro incubation studies, we showed that the chorioallantoic membrane and amnion from sheep at term pregnancy had the capacity to convert [3H]pregnenolone to [3H]progesterone. These results raise the possibility that there may be local changes in steroid hormone concentrations within the tissues and fluids of the pregnant uterus. These changes could be of importance in altering the intrauterine endocrine milieu at the time of birth.
Allantois↗
The development of fetal adrenal function.
The response profiles of fetal sheep adrenals to tropic stimulation have been examined ih vivo and in vitro. Isolated adrenal cells from sheep fetuses in early pregnancy (Day 50) reduced cortisol in response to ACTH, dibutyryl cyclic AMP and GTP. The response was minimal on Day 100, but reappeared near term. 17 alpha-Hydroxyprogesterone was converted to cortisol by adrenals of all ages, but pregnenolone and progesterone were converted to cortisol only in early and late, but not mid-pregnancy. These studies suggested that the mid-gestation loss of fetal adrenal responsiveness was associated with post-receptor/adenylate cyclase events and involved loss of 17 alpha-hydroxylase activity. Fetal adrenal function was activated by exogenous ACTH in vivo, and was reflected in an increase in the ratio of cortisol to corticosterone in fetal plasma and in augmented cortisol output in vitro from dispersed fetal adrenal cells. The results were consistent with an effect of ACTH administration on 17 alpha-hydroxylation. Fetal pituitary cells, prostaglandin E2, alpha-MSH and term placental extract are other potential (sources of) corticotropins, although further studies are required to delineate the nature and origin of the active substances, and/or their primary sites of action.
Adrenal Glands↗
Short-term fluctuations in the concentration of cortisol and progesterone in fetal plasma, maternal plasma, and amniotic and allantoic fluids from sheep during late pregnancy.
Fluctuations in the concentrations of cortisol and progesterone in fetal plasma, maternal plasma, and amniotic and allantoic fluids were measured in samples taken at 10-min intervals over a 90-min period from three groups of sheep sampled at different times during late pregnancy. During the last 30 days of gestation there was a significant rise in the mean concentration of cortisol in fetal plasma and amniotic fluid and a significant correlation between the cortisol concentration in these two fluids. The concentration of cortisol in allantoic fluid exceeded that in amniotic fluid. The concentration of cortisol in fetal plasma varied in a pulsatile manner, however the coefficient of variation (CV) within animals was greater (36%) on days -11 to -20, relative to the day of parturition (day 0), than on days -21 to -30 or days -5 to 0(15-19%). The CV values for cortisol in amniotic fluid and maternal plasma during the last 30 days of pregnancy were 20-50% and two at five times greater than the intraassay CV. The concentration of progesterone in amniotic fluid increased after day -20 but was not correlated with that in maternal plasma or fetal plasma. The concentrations of progesterone in paired samples of amniotic fluid and allantoic fluid were similar. The CV values for progesterone (18-34%) were similar in fetal and maternal plasma and amniotic fluid and did not change significantly during late pregnancy. Changes in the concentration of progesterone were unrelated to changes in cortisol. Interpretation of steroid profiles in fetal plasma and fluids through late pregnancy should take into account these short-term fluctuations in hormone concentrations.
Allantois↗
Fetal and maternal estrogen concentrations throughout pregnancy in the sheep.
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Amniotic Fluid↗
Uterine prostaglandin concentrations in sheep during late pregnancy and adrenocorticotropin-induced labor.
Concentrations of prostaglandin E (PGE), PGF, and 6-oxo-PGF1 alpha (the hydrolysis product of PGI2) were measured by RIA in different areas of myometrium, endometrium, cotyledons, amnion, and chorioallantoic membrane taken from chronically catheterized sheep. The animals were 130 days pregnant and had been treated for 70 h with continuous intrafetal infusions of either ACTH-(1-24) or saline. Maternal and fetal plasma samples were collected at 8-h intervals beginning 48 h before the start of infusion, and maternal plasma progesterone, estrone, and estradiol and fetal plasma cortisol concentrations were estimated by RIAs. As suggested by a significant fall in maternal plasma progesterone and rises in maternal plasma estrone and fetal plasma cortisol concentrations, sheep receiving intrafetal ACTH were in early labor at the time tissue samples were taken for PG determinations. For myometrium, analysis of variance indicated a significant effect of uterine area on PG concentrations. Concentrations of 6-oxo-PGF1 alpha were elevated toward the cervical end of the myometrium in ACTH-treated animals. PGF and PGE concentrations were higher at the tubal and cervical ends of the myometrium in both groups of animals. In the endometrium of treated animals, concentrations of PGE, but not PGF or 6-oxo-PGF1 alpha, were elevated significantly. For cotyledons and chorioallantois, concentrations of PGF and 6-oxo-PGF1 alpha, but not PGE, were elevated significantly in ACTH-treated animals. PG concentrations were not elevated in amnion taken from ACTH-treated animals. For both groups, the areas of highest PG concentrations were cotyledons and chorioallantois, suggesting that these may be major sites of synthesis.
6-Ketoprostaglandin F1 alpha↗
Diurnal changes in the concentration of progesterone in the plasma of women at 34-35 weeks of gestation.
The concentration of progesterone has been measured in ten women at 34-35 weeks of gestation in blood samples taken at 30 or 60 min intervals during a 24 h study period. Plasma progesterone concentrations showed a distinct diurnal rhythm. Most values determined between 04.00 and 11.00 h were significantly lower than the peak concentrations measured between 13.00 and 01.00 h. The relation of these changes in plasma progesterone to those in plasma cortisol and oestrogens is discussed.
Circadian Rhythm↗
The role and regulation of prostaglandins in late pregnancy and parturition in sheep.
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Adrenal Glands↗
Diurnal changes in maternal plasma oestrone and oestradiol at 30 to 31, 34 to 35 and 38 to 39 weeks gestational age.
Diurnal changes in the concentrations of oestrone (E1) and oestradiol (E2) in maternal peripheral plasma have been measured in samples of blood taken at one hour intervals from women at 30 to 31, 34 to 35 and 38 to 39 weeks of pregnancy. There was a significant effect of time of sampling on the plasma concentration of E1 at all stages of gestation, and circadian changes in the levels of E1 were apparent at 34 to 35 and 38 to 39 weeks. Peak values were measured around 0830 to 0930 hours, and troughs occurred between 0130 and 0530 hours. Significant effects of time of sampling on the plasma concentration of E2 were found at 34 to 35 and 38 to 39 weeks of pregnancy; night-time concentrations were lower than the peak values at 0730 to 0830 hours. The relation of these changes to the circadian rhythms in the concentrations of cortisol and oestriol in maternal plasma are discussed.
Circadian Rhythm↗
Increase in the response to adrenocorticotrophin of isolated maternal adrenal cells from sheep in late pregnancy.
Adrenal cells were prepared from non-pregnant (anoestrous) sheep, from ewes at days 50, 100 and 130 of pregnancy and at term, and from animals at 1-5 days post partum. The ability of the cells to respond to adrenocorticotrophin (ACTH1-24), alpha-melanocyte-stimulating hormone (alpha-MSH), or combinations of these peptides has been examined in vitro. There was a progressive rise in the basal output of cortisol during pregnancy and in the absence of adrenocorticotrophin the cortisol output from adrenal cells of late pregnant and post-partum sheep the amount of ACTH required to produce half the maximum output of steroid (ED50) was 8 pg/ml. The ED50 increased in early pregnancy to 112 pg/ml and then fell to < 5 pg/ml between day 100 and term. At term both the stimulation ratio and the absolute increment in cortisol output elicited by a maximal concentration of ACTH were greater than at any other time tested in pregnant or non-pregnant sheep. Cortisol output during pregnancy was not increased by alpha-MSH, although at term the stimulatory effect of ACTH1-24 was partially antagonized by alpha-MSH. These results suggest that there may be an increase in the responsiveness of the maternal adrenal during pregnancy, although the factor(s) responsible remains unknown.
Adrenal Glands↗
The production of prostaglandins and thromboxanes in the feto-placental unit and their effects on the developing fetus.
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Aging↗
The disposition of [3H]cortisol after intra-amniotic administration to sheep late in pregnancy.
The disposition of [3H]cortisol was determined after an intraamniotic injection into chronically catheterized sheep between days 120 and 146 of pregnancy. [3H]Cortisol disappeared from amniotic fluid with a half-life of 55.6 +/- 10.8 (SEM) min. Radioactivity, identified as [3H] cortisol appeared in allantoic fluid, fetal blood and tracheal fluid. The concentration of [3H]cortisol in allantoic fluid rose such that it approached that found in amniotic fluid at 60 min after injection. The highest concentration of [3H]cortisol in fetal blood was found 15 min after injection. The time-course for appearance of [3H]cortisol into tracheal fluid was variable, but in individual experiments peak values were found 45-150 min after injection. We conclude that during late gestation, cortisol in amniotic fluid is readily accessible to the allantoic fluid and to the fetus.
Allantois↗
High-performance liquid chromatographic assay for the antiprotozoal agent, tinidazole, in human plasma.
A rapid and specific high-performance liquid chromatographic (HPLC) assay for the quantitative determination of tinidazole in human plasma is described. After a simple extraction procedure, the compound is analyzed by HPLC using a reversed-phase column and a UV detector. Quantitation is accomplished using an external standard, and peak areas are determined with an integrating computer. The average recovery of tinidazole over a concentration range of 0.20-20.0 microgram/ml was 86.9 +/- 2.8% SD. The maximum sensitivity of the assay is approximately 0.10 microgram/ml; it is suitable for use in pharmacokinetic studies following administration of therapeutic levels of tinidazole to humans.
Chromatography, High Pressure Liquid↗
High-performance liquid chromatographic assay for the anthelmintic agent mebendazole in human plasma.
A rapid and specific high-performance liquid chromatographic (HPLC) assay for quantitative plasma mebendazole determination is described. After a simple extraction, the compound was analyzed by HPLC using a reversed-phase column and a UV detector (313 nm). Quantitation was accomplished using an internal standard; peak area ratios were determined with an integrating computer. The average mebendazole recovery over a concentration range of 0.01-0.20 microgram/ml was 75.9 +/- 3.8% SD, and the maximum assay sensitivity was approximately 10 ng/ml.
Benzimidazoles↗
Short in vitro half-life of thymopoietin32--36 pentapeptide in human plasma.
Thymopoietin32--36 (TP5) is a synthetic pentapeptide that has the biological activity of its parent molecule, the 49 amino acid thymic hormone thymopoietin. Tritiated thymopoietin32--36 (3 /-TP5) was prepared by reductive tritiation of dibromotyrosyl-TP5. The stability of 3 H-TP5 in human plasma was studied by analyzing samples by thin-layer chromatography at different time points and quantitating the radioactivity associated with TP5 (Arg-Lys-Asp-Val-Tyr) and its tyrosyl-containing breakdown products (Lys-Asp-Val-Tyr, Asp-Val-Tyr, Val-Tyr, Tyr). In plasma (but not in saline) the pentapeptide was rapidly degraded (apparent t1/2 approximately 30 seconds) with the corresponding appearance of radioactivity associated with the other tyrosyl-containing reference compounds. These data imply that the pentapeptide, which is active in vivo, may rapidly trigger changes in responsive cells; sustained circulating levels may not be required for activity.
Adult↗
Calcium regulation in the myometrium of pregnant sheep.
Fractionation of pregnant sheep myometrium has been carried out and the fractions obtained analysed for their marker enzyme content and Ca2+ transporting properties. A fairly pure mitochondrial fraction and a very pure plasma membrane fraction were obtained. Both fractions could accumulate Ca2+ in the presence of ATP but the mechanisms were different, mitochondrial uptake had a high capacity and was inhibited by azide. Plasma membrane uptake was of low capacity and unaffected by azide. The effect of oxalate on plasma membrane suggests that there is an outwardly directed Ca2+ pump in the myometrial cell membrane. Both mitochondria and plasma membrane may be important in the Cas2+ accumulation of relaxation in this muscle.
Animals↗
Evaluation of fetal monitoring by telemetry.
A radiotelemetry system for the direct monitoring of fetal heart rate and intrauterine pressure during labor has been evaluated at 5 different institutions. A conventional fetal scalp electrode and a special intrauterine pressure sensor are connected to a radio transmitter placed on the patient's thigh. The receiver can be located up to 50 feet away from the transmitter and is either a self-contained monitor or a unit that converts a conventional fetal monitor to a telemetric one. The telemetry recordings are of similar quality to those obtained from conventional monitors. Telemetry allows for greater patient comfort and mobility as well as greater convenience to the clinical staff. Continuous data can be obtained from patients while they are ambulatory or sitting in a chair as well as while they are in bed.
Electrodes↗
High-performance liquid chromatographic assay for suprofen, a potent new analgesic, in plasma.
A simple, rapid, high-performance liquid chromatographic (HPLC) determination of therapeutic levels of suprofen, a potent new analgesic, in human plasma is described. After a simple extraction, the compound is analyzed by HPLC using a reversed-phase column and a UV detector. Quantitation is accomplished using an external standard; peak areas are determined by computer. An average recovery of 80.0 +/- 8.5% SD of the drug was obtained over the 0.2-20.0-microgram/ml range. Maximum sensitivity is approximately 0.1 microgram/ml. No interference is encountered from any known metabolite of suprofen.
Chromatography, High Pressure Liquid↗