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Biomedical subjects

M D Mitchell

Publications and source records attributed to M D Mitchell.

At least 343 records · Page 19Linked to original sources

Specific production of prostaglandin E by human amnion in vitro.

Prostaglandin production by intra-uterine human tissues has been investigated using a method of tissue superfusion. Tissues were obtained at elective Caesarean section and after spontaneous vaginal delivery. It was found that all the tissues studied (amnion, chorion, decidua and placenta) produced more prostaglandin E (PGE) and 13,14-dihydro-15-keto-prostaglandin F (PGFM - the major circulating metabolite of prostaglandin F) than prostaglandin F (PGF). Amnion produced significantly more PGE (but not PGF or PGFM) than any other tissue. Prostaglandin production by each tissue was similar whether it was taken at elective Caesarean section or after spontaneous vaginal delivery.

Amnion↗

A sensitive radioimmunoassay for 6-keto-prostaglandin F1alpha: preliminary observations on circulating concentrations.

A radioimmunoassay for 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha) is reported. The mean least detectable mass of 6-keto-PGF1alpha is 1.45 pg and the mean mass of added 6-keto-PGF1alpha required to displace zero-point binding by 50% is 94.2 pg. Cross-reactivities of the antiserum with all the prostaglandins and related compounds tested are less than 0.1% except for PGE2 and PGF2alpha which are respectively 0.16% and 0.80%. The assay is both accurate and reproducible and measured levels are in good agreement following extraction of 0.25--4.0 ml of plasma. Mean circulating concentrations of 6-keto-PGF1alpha in five non-pregnant humans, rhesus monkeys and sheep were 115, 65 and 25 pg/ml respectively.

Animals↗

Selective elevation of circulating prostaglandin concentrations in hyaline membrane disease in pre-term infants.

The plasma concentrations of prostaglandins E and F (PGE, PGF) and 13, 14-dihydro-15-keto-PGF (PGFM) have been measured in pre-term neonates with hyaline membrane disease (HMD) and controls. The concentrations of PGF and PGFM were significantly higher in infants having HMD with a disproportionate increase in PGFM levels for the increase in PGF found. The vasoconstrictor nature of PGF may contribute to the morbidity associated with HMD and the possible therapeutic benefit from the use of prostaglandin synthetase inhibitors is discussed.

Humans↗

Blockade of the Ferguson reflex by lumbar epidural anaesthesia in the parturient sheep: effects on oxytocin secretion and uterine venous prostaglandin F levels.

The role of oxytocin in the increase in utero-ovarian venous prostaglandin F (PGF) level caused by vaginal distension was investigated by using lumbar epidural anaesthesia to block the oxytocin secretion reflex. Whereas vaginal distension raised jugular venous oxytocin and utero-ovarian venous PGF levels in untreated sheep, neither response occurred after lumbar anaesthesia. Lumbar anaesthesia had no effect on the rise in utero-ovarian venous PGF level caused by administered oxytocin. These findings support the suggestion that a reflex release of oxytocin is involved in the elevation of utero-ovarian venous PGF observed after vaginal distension in parturient sheep.

Anesthesia, Epidural↗

Prostaglandins in the human umbilical circulation at birth.

Prostaglandin E (PGE), prostaglandin F (PGF) and 13, 14-dihydro-15-keto-prostaglandin F (PGFM) have been measured in umbilical cord plasma obtained immediately after delivery of the baby before clampiing of the cord. In general the prostaglandin levels followed the pattern PGFM greater than PGE greater than PGF. A significant arterio-venous difference was demonstrated only for PGE with raised venous levels (P less than 0.01). In cord blood samples obtained from infants whose mothers had received epidural anaesthesia, no arterio-venous difference for PGE could be demonstrated although the mean levels were not significantly different from controls. The concentrations of prostaglandins in umbilical cord plasma proximal to the placenta were found to rise continuously from the time of delivery of the baby with no significant changes after cord clamping or placental delivery. The possible physiological significance of these findings is discussed.

Anesthesia, Epidural↗

Plasma steroid changes in pre-term labour in association with salbutamol infusion.

Serial measurements of peripheral plasma concentrations of progesterone and oestradiol-17beta were made in 23 women with singleton pregnancies who were given intravenous salbutamol in an attempt to inhibit pre-term labour. Mean levels of both hormones fell significantly during salbutamol infusion but returned to pre-treatment levels after therapy was stopped. Plasma human placental lactogen concentrations did not change during salbutamol infusion, suggesting that the fall in steroid hormone levels was unlikely to be an effect of altered uterine or placental blood flow.

Albuterol↗

Thromboxane B2 in amniotic fluid before and during labour.

Concentrations of thromboxane B2 (TXB2) have been measured in amniotic fluid obtained during late pregnancy and labour. Samples taken at amniocentesis contained significantly lower levels of TXB2 than samples taken by amniotomy for the induction of labour which in turn contained significantly less than when the same procedure was performed during labour. In the latter group there was no correlation between the degree of cervical dilatation and the concentration of TXB2. There was no correlation between gestational age and the concentration of TXB2 in amniotic fluid obtained at amniocentesis whereas there was a significant correlation (P less than 0.025) between these parameters when fluid was taken by amniotomy before labour. It is suggested that the relative activities of the enzymes responsible for the conversion of prostaglandin endoperoxides to prostaglandins, thromboxane A2 and prostacyclin may be of great importance during parturition.

Amniotic Fluid↗

Melatonin in amniotic fluid during human parturition.

Concentrations of melatonin have been measured in amniotic fluid obtained during late pregnancy and labour. Samples obtained by amniotomy during labour contained higher concentrations of melatonin than samples taken at amniotomy for the induction of labour. Amniotic fluid obtained by amniocentesis in late pregnancy contained lower concentrations of melatonin than amniotic fluid obtained by amniotomy. The implications of these findings are discussed in relation to pineal influences on parturition.

Amniotic Fluid↗

Plasma concentrations of prostaglandins during late human pregnancy: influence of normal and preterm labor.

Highly sensitive and specific RIA procedures have been used to measure prostaglandin concentrations in the peripheral circulation of late pregnant and parturient women. The concentrations of prostaglandin E (PGE) and prostaglandin F (PGF) in plasma samples assayed within 4 weeks of collection were not significantly different among the groups studied, the levels (mean +/- SEM, picograms per ml) were: late pregnancy (n = 13): PGE, 4.8 +/- 1.0; PGF, 6.2 +/- 0.5; early term labor (n = 5): PGE, 6.8 +/- 1.5; PGF, 7.9 +/- 0.7; late term labor (n = 5): PGE, 5.4 +/- 2.2; PGF, 12.4 +/- 3.5; and preterm labor (n = 7): PGE, 4.4 +/- 0.4; PGF, 6.9 +/- 1.4. The concentration of 13,14-dihydro-15-keto-prostaglandin F (PGFM) in late pregnancy was 59.0 +/- 7.8 pg/ml. During spontaneous term labor, the concentration of PGFM was significantly elevated (P less than 0.01) to 142.8 +/- 32.3 pg/ml in early labor and 282.7 +/- 55.3 pg/ml in late labor. The concentration of PGFM in plasma from patients in preterm labor (62.7 +/- 17.4 pg/ml) was not significantly different from that found during late pregnancy, but was significantly lower than levels found at term during early labor (P less than 0.05). The concentration of PGE increased significantly in frozen plasma samples stored for more than 4 weeks in all groups studied; the concentration of PGF was significantly elevated after storage only in the late pregnancy group (P less than 0.01). The plasma concentration of PGFM in all groups studied was unaffected by storage. It is concluded that measurement of PGFM concentrations is the most reliable method available of monitoring prostaglandins in the peripheral circulation and that great care must be exercised in the assay and interpretation of prostaglandin levels in human plasma.

Female↗

In-vitro production of prostaglandins by intrauterine tissues from pregnant goats.

In the fetal cotyledons and membranes, PGE production (determined in a continuous superfusion system) was significantly greater than that of PGF (P less than 0.01 and P less than 0.02 respectively). The fetal cotyledon also produced more PGE than the maternal cotyledon (P less than 0.01) and more PGF after parturition than before (P less than 0.01).

Animals↗

Administration of extra-amniotic arachidonic acid and the suppression of uterine prostaglandin synthesis during pregnancy in the rhesus monkey.

After extra-amniotic treatment of pregnant rhesus monkeys premature parturition was induced in 4 given 2.5 mg PGE-2; none of the 4 monkeys given 100 mg arachidonic acid were affected. The concentrations of PGE, PGF, or 13,14-dihydro-15-oxo-PGF did not change after arachidonic acid treatment, but all increased after PGE-2. It is suggested that the availability of substrate, arachidonic acid, is not a major factor governing the control of PG synthesis but that the latter is suppressed during pregnancy.

Animals↗

Use of meclofenamic acid to investigate the role of prostaglandin biosynthesis during induced parturition in sheep.

The maternal administration of meclofenamic acid (a prostaglandin synthetase inhibitor) to pregnant sheep prevented the dexamethasone-induced delivery of live lambs and delayed delivery after foetal death in utero. Administration of meclofenamic acid had no effect on the changes in the levels of progesterone and oestrogen in the plasma which occur before lambing in response to foetal glucocorticoid. Despite normal maternal endocrine changes, increased uterine activity did not occur at the expected time, although it could be elicited by vaginal distension or by administration of oxytocin. The rates of cervical ripening and dilatation were reduced by meclofenamic acid and lambing was frequently associated with some degree of cervical dystocia. Withdrawal of meclofenamic acid did not immediately result in an increase in the level of prostaglandin F in the plasma despite the appearance of co-ordinated uterine contractions; the concentration of prostaglandin in the plasma was not raised until vaginal passage of the lambs. It is concluded that the synthesis or release of prostaglandins mediates the effects of changes in the levels of steroids in the maternal plasma on uterine contractility in sheep.

Animals↗

Prostaglandin production by intra-uterine tissues from periparturient sheep: use of a superfusion technique.

A technique for the continuous superfusion of small tissue samples in vitro has been applied to the study of prostaglandin production by ovine intra-uterine tissues. Basal and oxytocin-stimulated production of prostaglandins was studied at 120-125 days of pregnancy and after dexamethasone-induced delivery. In general, the relative rate of prostaglandin production by tissues was: foetal cotyledon = maternal cotyledon greater than myometrium and in quantitative order the prostaglandins produced were prostaglandin E (PGE) greater than prostaglandin F (PGF) = 13,14-dihydro-15-oxo-prostaglandin F (PGFM). Considerable variations was found between the rates of prostaglandin production in individual sheep. Oxytocin had no effect on the production of prostaglandins by tissues obtained before labour but myometrium and maternal cotyledon obtained at delivery exhibited a significant increase in production of PGE and PGF (though not PGFM) in response to oxytocin. Administration of arachidonic acid increased the production of PGE and PGF by the foetal cotyledon.

Animals↗

Foetal and maternal plasma concentrations of 13, 14-dihydro-15-oxo-prostaglandin F in the mare during late pregnancy and at parturition.

The concentrations of 13, 14-dihydro-15-oxo-prostaglandin F(PGFM), the stable metabolite of prostaglandin F, were measured in the plasma of catheterized mares and foetuses and non-catheterized thoroughbred mares and ponies during the last months of gestation. The plasma concentration of PGFM increased gradually towards term in all groups of animals. During the operation for insertion of catheters, maternal and foetal concentrations of PGFM were high, but the values fell to basal levels 24--48 h after the operation. It was found the preoperative starvation (24 h) led to a rise in the concentration of PGFM in the maternal plasma. The raised concentrations of PGFM during the operation were associated with low progestogen and high oestrogen concentrations in umbilical venous plasma. The subsequent survival period of the catheterized foal was inversely related to the maximum concentration of PGFM were studied during normal parturition in thoroughbred mares, during oxytocin-induced delivery in non-catheterized ponies and during premature delivery or abortion in the catheterized animals. The greatest increase in the concentration of PGFM was seen in the thoroughbred animals during second-stage labour; oxytocin also resulted in a very rapid rise in the level of PGFM, which remained high until delivery. In the catheterized animals, the birth of live foetuses was associated with a rise in the concentration of PGFM in both foetal and maternal plasma during the last 2 h before delivery. Less consistent changes were found during abortion.

Adrenal Cortex Hormones↗

Specific change in the direction of prostaglandin synthesis by intra-uterine tissues of the rhesus monkey (Macaca mulatta) during late pregnancy.

The rates of production of prostaglandin E (PGE), prostaglandin F (PGF) and 13, 14-dihydro-15-oxo-prostaglandin F (PGFM) by intra-uterine tissues from pregnant monkeys in vitro have been determined using a method of tissue superfusion. The amnion, chorion, placenta, decidua basalis, decidua parietalis and myometrium were obtained at Caesarean section during late pregnancy. Production of PGE by all tissues was significantly lower at term than during late pregnancy, whereas production of PGF by the amnion, chorion, decidua parietalis and myometrium was significantly greater. All tissues produced significantly more PGE than PGF and also, excepting the decidua basalis and decidua parietalis, more PGFM than PGF. Close to parturition the amnion was quantitatively (per unit weight) the major source of prostaglandins. It is suggested that a specific change in the direction of prostaglandin synthesis by intra-uterine tissues occurs near parturition in the rhesus monkey.

Animals↗

Thromboxane B2 and human parturition: concentrations in the plasma and production in vitro.

The concentration of thromboxane B2 has been measured in the plasma of women during late pregnancy, during term and pre-term labour, in women with pre-eclampsia and in umbilical cord arterial and venous plasma. In addition, the rates of production of thromboxane B2 in vitro were determined for placental tissues obtained after spontaneous vaginal delivery or elective Caesarean section. The results obtained indicate significant differences during parturition between the sources and controlling mechanisms of thromboxane and prostaglandin production.

Female↗