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Biomedical subjects

J R Challis

Publications and source records attributed to J R Challis.

At least 235 records · Page 13Linked to original sources

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↗

Plasma cortisol concentrations during Caesarean section.

The effects of extradural and general anaesthesia on the adrenocortical response to elective or emergency Caesarean section were studied in 72 patients. Maternal plasma concentrations of cortisol were measured before surgery, at delivery, and 30 and 60 min after skin incision. Umbilical vein and artery plasma cortisol concentrations at delivery were determined also. Maternal plasma cortisol concentrations in patients receiving extradural anaesthesia did not change significantly from control at any of the time intervals. In the general anaesthesia group concentrations were significantly increased from control, at 30 and 60 min after skin incision for elective Caesarean sections, and at 60 min after skin incision during emergency surgery. There were no significant differences between the mean umbilical vein and artery plasma cortisol concentrations compared within or between extradural or general anaesthesia groups. Extradural anaesthesia, in contrast to general anaesthesia, decreases the adrenocortical response to Caesarean section surgery by blocking afferent neurogenic pathways from the surgical site. The method of anaesthesia does not influence the fetal cortisol response.

Anesthesia, Epidural↗

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↗

Metabolism of [3H]oestrone sulphate by fetal membranes, placenta and uterine tissues from pregnant rabbits.

The distribution of radioactivity within the fetal membranes and uterine tissues from pregnant rabbits after an intra-amniotic injection of [3H]oestrone sulphate was determined, and the conversion to oestrone and oestradiol-17 beta during in-vitro incubation of these tissues with [3H]oestrone sulphate was measured. After intra-amniotic injection, radioactive oestrone and oestradiol-17 beta were recovered from amniotic fluid, amnion, placenta, decidua and myometrium of the injected fetus, and, in some experiments, from tissues of an adjacent fetus. During incubation, extensive metabolism of oestrone sulphate occurred in placenta and chorion, and oestrone sulphatase and 17-oxidoreductase activities were found in these tissues as well as in amnion, decidua and myometrium. We suggest that oestrone sulphate, present in amniotic fluid, may be accessible for metabolism to unconjugated oestrogen by several intrauterine tissues of the pregnant rabbit.

Animals↗

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↗

Diurnal variations in maternal and fetal steroids in pregnant rhesus monkeys.

To examine diurnal changes in maternal and fetal steroids in chronically catheterized pregnant rhesus monkeys, we have measured cortisol (F), progesterone (P4), estone, and estradiol in maternal blood and F, P4, and dehydroepiandrosterone sulphate (DHAS) in simultaneous samples of fetal blood taken in the morning (0700--1000 h) and in the evening (1700--2100 h). In the mother, the concentrations of F, estradiol, and estrone were higher in the morning than in the evening. In contrast, progesterone was higher in evening than in morning samples. In fetal blood, there was no significant morning-evening difference for F; however, the concentrations of P4 and DHAS were higher in the evening than in the morning samples. In three individual monkeys, the concentrations of P4 and DHAS in serial samples of fetal blood were correlated. We conclude 1) that there are marked diurnal changes in the concentration of several steroids in samples of maternal and fetal blood and 2) that the concentration of F in maternal blood shows the opposite pattern to that of possible fetal adrenal steroids in fetal blood.

Animals↗

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↗

Ultrastructural basis for maintenance and termination of pregnancy.

Myometrial tissues from guinea pigs, sheep, and human subjects at various stages of gestation and postpartum were quantitatively examined in the electron microscope for the presence of gap junctions between muscle cells. Gap junctions were found in tissues from guinea pigs and sheep which were being delivered or ready to be delivered and in tissues taken immediately post partum. Gap junctions were also present in 19 tissues obtained from 69 women undergoing elective or emergency cesarean section for a variety of reasons. The frequency of their occurrence varies in relation to the presence or absence of labor and other conditions. We propose that gap junctions are required for effective muscle contractions leading to termination of pregnancy in all animals, including human beings. The absence of gap junctions throughout gestation may be necessary for maintenance of pregnancy and the premature appearance of the cell contacts may lead to premature labor.

Animals↗

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↗