Search PubMed⌕ Search

Biomedical subjects

M D Mitchell

Publications and source records attributed to M D Mitchell.

At least 361 records · Page 20Linked to original sources

Production of thromboxane B2 by the intra-uterine tissues from late pregnant Rhesus monkeys (Macaca mulatta) in vitro.

The rates of production of thromboxane B2 in vitro by intra-uterine tissues obtained from late pregnant monkeys by Caesarean section have been determined. The general quantitative order of rates of production was decidua basalis = decidua parietalis greater than placenta greater than chorion greater than amnion = myometrium. Myometrial production of thromboxane B2 was greater at term than during late pregnancy; no other tissue showed a significant trend with advancing gestation. These data demonstrate that the production of thromboxane B2 by intra-uterine tissues from late pregnant monkeys is both qualitatively and quantitatively different from the production of prostaglandins described previously. It is suggested that prostaglandins rather than thromboxanes are more intimately involved in the onset of labour in the rhesus monkey.

Amnion↗

Prostaglandins in the sheep fetus: implications for fetal function.

1. In chronically catheterized sheep fetuses, during normal pregnancy, the concentration of PGE in the fetal femoral arterial plasma is invariably greater than that of PGF, and increases during the 12 to 24 hr preceding delivery. The concentration of both PGE and PGF decreases repidly after birth. 2. These changes in fetal prostaglandin levels contrast with the marked increase in PGF, but negligible increase in PGE, in the maternal uteroovarian vein before parturition. 3. The changes in prostaglandin concentrations in fetal plasma at term are associated with only small changes in the concentrations of PGE and PGF in tracheal fluid. In amniotic fluid the concentrations of PGE and PGF increase during the last 4 days in utero. At birth the concentrations of PGE and PGF in fetal urine are similar to the concentrations in amniotic fluid. 4. The concentration of PGE in fetal plasma and in tracheal fluid is significantly elevated for up to 3 days after surgery. The concentration of PGF is significantly elevated in fetal plasma nad tracheal fluid for at least 24 hr after surgery. 5. Three fetuses which were chronically hypoxemic had elevated plasma PGE concentrations in utero. However, acute (1 hr) hypoxia or hypercapnia induced in the fetal lamb by making the ewe breathe appropriate gas mixtures did not produce consistent changes in fetal plasma prostaglandin concentrations. 6. During late pregnancy (day 128) exogenous PGE2 infused at about 1.6 microgram/min for 60 min into the fetal carotid artery achieved concentrations in the fetal femoral artery which were within the physiological range seen at term. At this infusion rate, there was no effect on fetal arterial Po2, Pco2, pH, or hematocrit, and no consistent effect on fetal blood pressure or heart rate. PGE2 infusion had no significant effect on the concentration of growth hormone or prolactin in fetal plasma. Within 30 min after beginning the infusion, however, there was a significant increase in the cortisol concentration in fetal plasma. This effect was seen even at times in pregnancy when the fetal adrenal gland responds only poorly to exogenous or endogenous ACTH.

Amniotic Fluid↗

Rapid increases in plasma prostaglandin concentrations after vaginal examination and amniotomy.

Peripheral plasma concentrations of 13,14-dihydro-15-keto prostaglandin F (PGFM) were measured in three groups of women after the 37th week of pregnancy. Samples were taken before and five minutes after (a) amniotomy, (b) vaginal examination with sweeping of the fetal membranes, or (c) vaginal examination without sweeping of the membranes. Each procedure significantly raised the circulating PGFM levels, although amniotomy and vaginal examination with membrane sweep were more potent stimuli than vaginal examination alone. These findings suggest that there is a considerable potential for rapid increases in prostaglandin production during late pregnancy and provide a possible explanation for the fact that amniotomy and vaginal examination with membrane sweep often initiate labour.

Amnion↗

Human parturition.

The roles of fetal adrenal hormones, of maternal oestrogen and progesterone concentrations, and of uterine prostaglandin synthesis are considered in relation to the onset of human labour. Evidence that the fetal adrenal may be involved in the onset of labour is discussed with particular reference to both cortisol and dehydroepiandrosterone sulphate. Towards the end of pregnancy circulating concentrations of both unconjugated and conjugated oestrogens increase, and evidence for the presence of arylsulphatase (EC 3.1.6.1) in various intrauterine tissues suggests that the conjugates are potentially active. The rise in oestrogens and a concomitant drop in progesterone during the last few weeks of pregnancy may play a facilitatory role in the onset of labour. The changes in steroid concentrations are considered in relation to the promotion of prostaglandin synthesis leading to labour. Concentrations of prostaglandins in amniotic fluid show only minor changes before the onset of labour compared to those found with the onset of and during labour. Evidence for a local control of prostaglandin synthesis within the uterus is presented.

Adrenal Cortex Hormones↗

Prostaglandin concentrations in intra-uterine tissues from late-pregnant sheep before and after labour.

Prostaglandin E (PGE), prostaglandin F (PGF) and 13,14-dihydro-15-keto-prostaglandin F (PGFM) have been measured in cotyledons and myometrium from sheep before and after labour. Fetal cotyledons contained more PGE than maternal cotyledons which in turn contained more than myometrium. The maternal cotyledon contained the highest concentrations of PGF, but the fetal cotyledon was the only tissue exhibiting a statistically significant rise in the concentration of PGF following labour. Concentrations of PGFM were closely correlated with (although usually lower than) those of PGF.

Animals↗

Prostaglandins in fetal tracheal and amniotic fluid from late pregnant sheep.

Concentrations of prostaglandin E (PGE), prostaglandin F (PGF) and 13,14-dihydro-15-keto-prostaglandin F (PGFM) have been measured in fetal tracheal and amniotic fluid from chronically catheterized sheep during late pregnancy. Amniotic fluid contained significantly greater concentrations of these prostaglandins than tracheal fluid (p less than 0.01); there was no correlation between the level of prostaglandins found in each fluid. In tracheal fluid concentrations of PGE and PGFM exceeded those of PGF (P less than 0.01) whereas no significant differences were found in amniotic fluid. The levels of prostaglandins in these fluids were similar in ewes bearing hypophysectomized fetuses.

Amniotic Fluid↗

Evidence for a local control of prostaglandins within the pregnant human uterus.

Prostaglandin F (PGF) and 13, 14-dihydro-15-keto-PGF (PGFM) have been measured in amniotic fluid in late human pregnancy. The method used to obtain amniotic fluid greatly influenced the levels of prostaglandins: fluid obtained by vaginal amniotomy contained significantly higher levels of both PGF and PGFM than samples taken at amniocentesis, reflecting an increase in synthesis and/or release of prostaglandin rather than a decrease in the rate of metabolism. After 36 weeks gestation there was no increase in levels of either PGF or PGFM if samples obtained by amniotomy and amniocentesis were considered separately, although if such samples were considered together a significant increase could be obtained. The apparently rapid change in prostaglandin concentrations in amniotic fluid in response to amniotomy strongly supports a local control of these compounds within the pregnant uterus.

Amniocentesis↗

Changes in prostaglandin F and 13,14-dihydro-15-keto-prostaglandin F concentrations in amniotic fluid at the onset of and during labour.

Concentrations of prostaglandin F (PGF) and its major circulating metabolite 13,14-dihydro-15-keto-PGF (PGFM) have been measured in amniotic fluid during spontaneous labour at term. Levels of both PGF and PGFM were significantly higher during early spontaneous labour, at a cervical dilatation of less than 4 cm, than before the onset of labour. Patients who started labour spontaneously but later required oxytocin therapy for failure to progress in first stage had lower levels of PGF and PGFM than patients who progressed adequately without oxytocin therapy. During spontaneous labour, concentrations of both PGF and PGFM increased significantly with advancing cervical dilatation. These indicate that the accumulation of prostaglandins in amniotic fluid during labour is not due to decreased metabolism. They furthermore provide the strongest evidence available so far for an increase in intrauterine prostaglandin synthesis during human parturition.

Amniotic Fluid↗

Increase of the prostaglandin precursor, arachidonic acid, in amniotic fluid during spontaneous labour.

Concentrations of free arachidonic acid have been measured by gas liquid chromatography in amniotic fluid obtained during spontaneous labour at term. Levels of arachidonic acid ranged from 0.14 to 2.9 microgram/ml and increased significantly (P less than 0.01) with advancing cervical dilatation. Concentrations of arachidonic acid showed no significant relation to concentrations of either prostaglandin F or 13,14-dihydro-15-keto-prostaglandin F. These findings are discussed with respect to the role of arachidonic acid in the control of prostaglandin biosynthesis during human parturition.

Amniotic Fluid↗

Increasing uterine response to vaginal distension during late pregnancy in sheep.

Intrauterine pressure changes were monitored in 5 pregnant ewes and uterine venous prostaglandin (PG) F concentrations were determined after distension of the vagina. Uterine contractility and utero-ovarian PGF concentrations were elevated by vaginal distension and the magnitude of both effects increased as parturition approached.

Animals↗

Changes in myometrial and placental 15-hydroxyprostaglandin dehydrogenase with ovine parturition: production of prostaglandin metabolites in vitro and in vivo.

15-Hydroxyprostaglandin dehydrogenase (PGDH) was measured in vitro in myometrium and maternal cotyledons from 6 sheep and in fetal cotyledons from 3 sheep before and after parturition. Maternal cotyledons contained more PGDH than fetal cotyledons or myometrium. At parturition, PGDH activity decreased in myometrium but increased in fetal and maternal placental tissue. The enzymatic activity observed in vitro did not result in a large, consistent release of prostaglandin F metabolites into the utero-ovarian vein in vivo, and such activity may have a strictly localized effect in ovine parturition.

Animals↗

Steroid and prostaglandin concentrations in the plasma of pregnant ewes during infusion of adrenocorticotrophin or dexamethasone to intact or hypophysectomized foetuses.

Catheters were implanted into 16 ewes and their foetuses between days 110 and 124 of gestation. Hypophysectomy was attempted in eight of these foetuses. Continuous infusion of synthetic ACTH (10 microgram/h) or dexamethasone (1mg/24 h) into the foetus, starting between days 124 and 129, induced premature parturition. The concentration of progesterone in the maternal peripheral plasma decreased before parturition in all animals while the level of oestradiol increased in ewes with intact foetuses or in those in which hypophysectomy was incomplete. When hypophysectomy was complete, no increase in the maternal level of oestradiol occurred before delivery. The concentration of 13,14-dihydro-15-oxo-prostaglandin F2alpha increased in the peripheral plasma of ewes with intact or hypophysectomized foetuses infused with ACTH. It is suggested that an intact foetal pituitary gland is required for the rise in the level of oestrogen prepartum, but that this rise is not essential for increased prostaglandin production of parturition.

Adrenocorticotropic Hormone↗

Plasma concentrations of 13,14-dihydro-15-keto-prostaglandin F during pregnancy in sheep.

A specific and sensitive radioimmunoassay is decribed for 13,14-dihydro-15-keto-prostaglandin F in ovine plasma. Using this assay it has been shown that, in sheep, jugular venous 13,14-dihydro-15-keto-prostaglandin F concentrations increase at parturition and correlate well with concentrations of prostaglandin F in the utero-ovarian vein. It is suggested that uterine prostaglandin F production under these conditions may be assessed by measuring peripheral venous 13,14-dihydro-15-keto-prostaglandin F, thereby avoiding the need for chronic utero-ovarian venous catheters.

Animals↗