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Biomedical subjects

A B Anderson

Publications and source records attributed to A B Anderson.

At least 37 records · Page 2Linked to original sources

Inhibition of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activity in first- and second-trimester human pregnancy and the luteal phase using Epostane.

The effects of a competitive inhibitor of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) (Epostane, Sterling Winthrop, Guildford, England) on serum progesterone (P), estradiol (E2), and cortisol have been studied in three groups of pregnant women awaiting termination of pregnancy (5 to 8 weeks, 8 to 12 weeks, and 12 to 18 weeks of pregnancy) and 15 women in the luteal phase of the menstrual cycle. A single-dose randomized double-blind study was performed, each woman receiving a placebo, 50 mg of Epostane, or 100 mg of Epostane. In the pregnant group, there was a significant decline in the serum P concentration after both 50 mg and 100 mg of Epostane. The percentage fall increased with both drug dosage and advancing gestation. A similar fall in serum E2 was observed. Both of these effects were temporary. In the luteal phase group, a significant decline in serum P was observed after 100 mg of Epostane, but the serum E2 was not significantly different from the pretreatment concentration. Serum cortisol did not differ significantly from control values. These findings suggest that Epostane is an effective inhibitor of placental and ovarian 3 beta-HSD, which may have a role as an interceptive agent.

3-Hydroxysteroid Dehydrogenases↗

The influence of spontaneous and induced labour on the rise in prostaglandins at amniotomy.

Maternal peripheral plasma levels of 13,14-dihydro-15-keto-prostaglandin F (PGFM) were measured immediately before and 5 min after amniotomy. Three groups of women were studied: women in late pregnancy; women in spontaneous labour; and women who had received intravaginal prostaglandin E2 (PGE2) pessary. There was no significant difference in the magnitude of the rise in PGFM after amniotomy in late pregnancy or during spontaneous labour suggesting that labour has no influence on the release of prostaglandin F2 alpha (PGF2 alpha) induced by artificial rupture of the fetal membranes. However, local administration of PGE2 before amniotomy caused a greater rise in PGFM suggesting that PGE2 can influence the release and/or metabolism of PGF2 alpha.

Adult↗

Quantitative uterine histology during the menstrual cycle in relation to measured menstrual blood loss.

Endometrium and myometrium were collected at hysterectomy from 42 women with measured menstrual blood loss (range 4-840 ml). The specimens, obtained throughout the menstrual cycle, showed no evidence of organic disease on histological examination. The volume fraction occupied by arteries at the myometrial-endometrial junction, and by glandular tissue throughout the endometrium was estimated with a point counting technique. The index of volume-to-surface ratio of endometrial glandular tissue was examined by a combination of point counting and linear intercept methods. No correlation was found between menstrual blood loss and endometrial and myometrial arterial density, endometrial glandular density and volume-to-surface ratio. Consequently, menorrhagia, occurring in the absence of obvious pathology, does not appear to result from an excessive number of arteries of from abnormal glandular distribution.

Adult↗

A functional study of platelets in menstrual fluid.

Platelets were isolated from menstrual and peripheral venous blood samples taken from nine women during the first 2 days of menstruation. The washed platelets were tested for their ability to aggregate in response to arachidonic acid, ADP, and collagen, and to metabolize arachidonic acid. Menstrual platelets differed from venous platelets in (1) failing to aggregate when challenged with aggregatory stimuli and (2) producing no appreciable cyclo-oxygenase products from arachidonic acid as reflected in thromboxane B2 release. However, incubation of peripheral venous platelets with menstrual serum obtained from the same patients induced aggregation. The responses of menstrual and peripheral venous platelets were the same irrespective of the patients' total menstrual blood loss. Uterine venous platelets collected during menstruation from two patients at hysterectomy aggregated normally and produced thromboxane B2.

Adenosine Diphosphate↗

Prostaglandins in menstrual fluid in menorrhagia and dysmenorrhoea.

Menstrual fluid was collected in vaginal cups inserted for 2 h during the first 2 days of menstruation and menstrual serum concentrations of prostaglandins PGF2 alpha and PGE2 were measured by radioimmunoassay. In 16 women from whom menstrual fluid was collected on both days, PGF2 alpha and PGE2 concentrations were significantly higher on day 1 than on day 2. The highest concentrations of PGF2 alpha and PGE2 were found in dysmenorrhoeic women on day 1. In non-dysmenorrhoeic women, the amount of PGF2 alpha and PGE2 collected in 2 h correlated directly with total menstrual blood loss. There was no statistically significant difference in the amount of prostaglandins collected in 2 h in pain-free menorrhagic women and dysmenorrhoeic women with normal loss. There was also no significant 9-ketoreductase or 9-hydroxydehydrogenase activity present in menstrual fluid which could suggest PGE2 to PGF2 alpha interconversion.

Adult↗

Endometrial and myometrial prostaglandin release during the menstrual cycle in relation to menstrual blood loss.

Endometria and myometria were collected at hysterectomy from 42 women with measured menstrual blood loss. Specimens were obtained throughout the menstrual cycle [menstrual (n = 11), follicular (n = 9), early luteal (n = 6), midluteal (n = 9), and late luteal (n = 7)]. In vitro endometrial and myometrial release of prostaglandin F2 alpha (PGF2 alpha), PGE2, and 6-keto-PGF1 alpha were examined using a superfusion technique. In the endometrium, the principal PG produced was PGF2 alpha, while in the myometrium, it was 6-keto-PGF1 alpha. Cyclical changes in PG release were found only in the endometrium, with an increase toward the end of the menstrual cycle and during menstruation. No significant correlation was found between menstrual blood loss (range, 4-840 ml) and PGF2 alpha, PGE2, or 6-keto-PGF1 alpha release in either endometrium or myometrium. Furthermore, there was no correlation between either the PGF2 alpha to PGE2 or the PGF2 alpha to 6-keto-PGF1 alpha ratios and menstrual blood loss.

Adult↗

Raised prostaglandin levels in the third stage of labor.

Serial measurements of maternal peripheral plasma concentrations of 13,14-dihydro-15-keto-prostaglandin F (PGFM) and oxytocin were made during the three stages of labor and in the immediate puerperium. PGFM levels increased a labor progressed, and reached maximal levels before placental separation had occurred. The mean value in the second stage of labor was significantly higher than that in the first stage (p less than 0.01); similarly, the value 5 minutes after delivery, before expulsion of the placenta, was significantly greater than that in the second stage of labor (p less than 0.01). There was no significant difference between the mean PGFM concentration at placental separation and the level 5 minutes after delivery or in the second stage of labor. Two hours after delivery of the placenta, PGFM levels were not significantly different from values observed in the first stage of labor. Peripheral plasma concentrations of oxytocin did not change significantly at any stage of labor or 2 hours post partum. These results suggest that prostaglandins have a role in the third stage of labor, and this finding may have important clinical implications.

Female↗

Oxytocin in the fetal and maternal circulations during induced and spontaneous parturition in sheep.

Oxytocin has been measured in fetal and maternal plasma samples obtained serially from 6 sheep during late pregnancy, spontaneous labor and labor induced by intrafetal infusion of Synacthen (ACTH1-24). Fetal plasma contained significantly (P less than 0.001) greater concentrations of oxytocin than maternal plasma. Concentrations of oxytocin rose in maternal plasma during the later stages of spontaneous and induced labor, whereas concentrations in fetal plasma did not exhibit a consistent trend.

Animals↗

Immunohistochemical localisation of cyclooxygenase in the human uterus.

The distribution in the human uterus of the enzyme cyclooxygenase,, involved in prostaglandin synthesis, was studied using the peroxidase-antiperoxidase immunohistochemical technique. Specific staining was observe only during the luteal phase of the menstrual cycle It was found that cyclooxygenase was localised in the surface and glandular epithelium of the endometrium but could not be demonstrated in the endometrial stroma, myometrium or blood vessels The location of specific staining for cyclooxygenase and its variation during the menstrual cycle was the same regardless of the amount of menstrual blood loss. Tissue samples obtained from early pregnant and postmenopausal patients failed to exhibit any specific staining.

Female↗

Glucocorticoid binding by human fetal membranes at term.

Cytosol preparations in Tris-buffer of human term amnion, choriodecidua, and decidua were incubated with [3H]dexamethasone for up to 24 h at 0 C. Under these conditions the specific binding of [3H]dexamethasone was low, ranging from 3-13 fmol/mg protein. Furthermore, when samples of whole choriodecidual homogenate were incubated with [3H]dexamethasone for 1 h at 37 C, there was no significant nuclear translocation of the steroid. In contrast to these findings, when cytosol preparations of sheep fetal lung were incubated with [3H]dexamethasone at 0 C, there was a rapid uptake of the steroid, reaching specific binding values of 399 +/- 81 fmol/mg protein. The inclusion of sodium molybdate in the homogenization buffer led to an increased uptake of [3H]dexamethasone by amnion and choriodecidua; the specific binding ranged from 9-25 fmol/mg protein for cytosol and was 8 fmol/mg protein for nuclear preparations. Scatchard plot analysis of the data showed that both amnion and choriodecidua possess high affinity (Kd = 5-10 nM), low capacity (50-170 pM) binding sites for [3H]dexamethasone. These findings suggest that the human fetal membranes at term contain specific glucocorticoid receptors, although in low concentrations compared to other glucocorticoid target tissues.

Animals↗

Cortisol:cortisone interconversion by human decidua in relation to parturition: effect of tissue manipulation on 11 beta-hydroxysteroid dehydrogenase activity.

Cortisol:cortisone interconversion was studied in human decidua obtained from three groups of patients at term (37-42 weeks): before the onset of labour (at elective Caesarean section), after labour of spontaneous onset, and after labour of induced onset. When intact tissue was incubated with [3H]cortisol or [3H]cortisone in phosphate buffer without added substrate or cofactors, cortisone to cortisol was the dominant conversion. However, when damaged cells or tissue homogenates were used in the same conditions, the dominant direction of the reaction was reversed, with a large increase in oxidative (cortisol to cortisone) activity. Cortisol:cortisone interconversion was similar in the three groups of samples using either intact tissue or homogenates, as was the total 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) activity measured in tissue homogenates in the presence of added substrate (cortisol or cortisone) and cofactors (NADP+ or NADPH). Endogenous cortisol concentrations in decidua were higher than those of cortisone, and the ratio of cortisol to cortisone was similar in the three groups. These findings suggest that there are no changes in human decidual 11 beta-HSD activity in relation to parturition. Specific activity of 11 beta-HSD decreased at high protein concentrations, suggesting the presence of some enzyme inhibitor(s) in homogenized decidual tissue.

11-beta-Hydroxysteroid Dehydrogenases↗

Plasma oxytocin concentrations during the menstrual cycle.

Concentrations of oxytocin have been measured in plasma samples obtained daily from 6 women throughout complete menstrual cycles. Measurements of menstrual blood loss and plasma levels of luteinizing hormone (LH), progesterone and 17beta-oestradiol suggested that normal ovulatory cycles were studied. A significant elevation in the circulating concentration of oxytocin was found in association with peak levels of LH. It is suggested that oxytocin may have a role in the process of ovulation in the human female.

Adult↗

A comparison of plasma prostaglandin levels in term and preterm labour.

Peripheral plasma levels of 13,14-dihydro-15-keto-prostaglandin F (PGFM) were determined in women during pregnancy and in term and preterm labour. The PGFM concentrations at term were not significantly different from the levels between 26 and 34 weeks gestation. In both term and preterm labour there was a rise in PGFM levels with increasing cervical dilatation although the mean values tended to be lower during preterm labour. These findings may provide an explanation for the effectiveness of prostaglandin synthetase inhibitors in suppressing myometrial activity in preterm labour.

Cervix Uteri↗

The relation between the release of prostaglandins at amniotomy and the subsequent onset of labour.

Maternal peripheral plasma levels of 13,14-dihydro-15-keto-prostaglandin F (PGFM) were measured in 16 women following amniotomy performed for the induction of labour at term. After 5 1/2 hours, seven patients were in established labour (Group I) but the remaining nine patients required an intravenous infusion of oxytocin (Group II). An initial rapid rise in PGFM concentrations within five minutes of amniotomy occurred in all women and, therefore, the onset of labour does not appear to be a direct consequence of this initial increase. In Group I there was a significant increase in PGFM concentrations between five and 30 minutes after amniotomy and from 30 minutes to the time at which the last sample was collected; these later rises were associated with the onset and progress of labour in these women. These increases in PGFM concentrations did not occur in patients in Group II. The reason for this difference in response to amniotomy is as yet unclear.

Dinoprost↗

Is oxytocin involved in parturition?

Peripheral plasma levels of oxytocin were determined in women during pregnancy and labour. There was a significant increase in maternal plasma oxytocin with advancing gestation but no significant change in levels at any stage of labour. Oxytocin concentrations in umbilical cord plasma were measured after spontaneous vaginal delivery and at elective caesarean section. A significant arteriovenous difference, with higher arterial levels, was found in both groups and the values after labour were significantly higher tha at elective caesarean section. These findings suggest that the fetus is able to produce oxytocin which may play a role in human parturition.

Female↗