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Biomedical subjects

A R Fuchs

Publications and source records attributed to A R Fuchs.

At least 37 records · Page 2Linked to original sources

Serum prostaglandin F2 alpha (PGFM) and oxytocin levels correlate with sonographic changes in the cervix in patients with preterm labor.

This is a study on the correlation of maternal serum oxytocin and prostaglandin F2 alpha (PGFM) levels with sonographically measurable changes in the cervix and the internal cervical os in patients with preterm labor. Oxytocin levels significantly correlate (P = 0.03) with the width of the internal os and the PGFM values significantly correlate with the length of the cervix (P = 0.008). An increase in the oxytocin level resulted in a measurable widening of the internal os and an increase in the prostaglandin level resulted in a measurable shortening of the cervix.

Cervix Uteri↗

Effects of lumbar epidural analgesia on prostaglandin F2 alpha release and oxytocin secretion during labor.

The concentrations of plasma oxytocin and prostaglandin F2 alpha metabolite (PGFM) were measured in 10 parturients with and 10 without lumbar epidural analgesia. A blood sample was taken immediately before analgesia and another 60 min later. The control patients were matched for the stage of cervical dilatation at the time of the first blood sample; the second was drawn 60 min later. Plasma PGFM decreased significantly after lumbar epidural anesthesia and increased in controls resulting in a highly significant difference between the groups (P < 0.005). Plasma oxytocin concentrations levels also changed in opposite directions in the two groups but the difference did not reach statistical significance (P < 0.1). Uterine activity increased in the controls and decreased in the analgesia group resulting in a significant difference between the groups (P < 0.05). All subjects delivered vaginally. The total duration of labor was longer in the analgesia group (7.8 +/- 1.0 h vs. 4.7 +/- 0.6 h; P < 0.05) as was the duration after analgesia (5.1 +/- 0.9 h vs. 2.5 +/- 0.8 h; P < 0.05), whereas the duration of the second stage was not significantly different. We conclude that lumbar epidural anesthesia results in suppression of PGF2 alpha release which may be the cause of the diminished uterine activity and the prolonged duration of the first stage of labor.

Adult↗

Correlation of nocturnal increase in plasma oxytocin with a decrease in plasma estradiol/progesterone ratio in late pregnancy.

OBJECTIVES: Our purpose was to determine whether plasma oxytocin concentrations show a daily rhythm. STUDY DESIGN: Ten women between 37 and 39 weeks of gestation volunteered for the study. They were admitted 1 to 2 days before the experiment. Three blood samples were taken with 2-minute intervals each time, at 8 AM, 4 PM, and 12 midnight. Oxytocin, 17 beta-estradiol, progesterone, and cortisol were measured by radioimmunoassay with highly specific antibodies. Statistical analysis of variance by Friedman's test was followed by multiple range testing, and p < 0.05 was considered significant. RESULTS: Significant daily rhythm was found for plasma cortisol, progesterone, and oxytocin and for the estradiol/progesterone ratio. Oxytocin showed a nocturnal peak and a strong negative correlation with the estradiol/progesterone ratio. CONCLUSIONS: The daily rhythm in plasma oxytocin parallels the rhythm in uterine activity (shown by others), suggesting a causal relationship between the two. Both may in turn be related to the ratio of circulating estradiol and progesterone.

Circadian Rhythm↗

The metabolic effects of oxytocin are mediated by a uterine type of receptor and are inhibited by oxytocin antagonist and by arginine vasopressin in the dog.

Infusion of oxytocin (OT) into normal dogs, in doses which produced plasma levels of OT in the physiological range, has been shown to increase plasma levels of glucose, insulin and glucagon and increase rates of glucose production and uptake. This study sought to determine whether there was a correlation between these metabolic effects and the oxytocic potency of four less potent oxytocic analogues when infused into normal dogs. The rank order of oxytocic potency of all 4 correlated well with the rise in plasma glucose levels, and in 3 of the 4 with the rise in plasma insulin levels. An antagonist of the oxytocic effect of OT suppressed the usual OT-induced rise in plasma glucose, insulin and glucagon as well as the increased glucose production and uptake. Arginine vasopressin (AVP) infusion, which by itself did not produce any metabolic effects, blocked completely the effects of OT infusion to raise plasma glucose and insulin levels and increase glucose production and uptake. The data suggest that the metabolic effects of OT in the dog are mediated by OT receptors that are similar to those producing the oxytocic effects. Whether the inhibition by AVP of the metabolic and hormonal effects of OT occurs at the receptor or post receptor level or via other mechanisms remains to be determined.

Animals↗

[The significance of prostaglandin F2 alpha (PGFM)--and plasma oxytocin level in patients with premature labor].

In the present study, plasma oxytocin and prostaglandin F2 alpha metabolite (PGFM) concentrations were measured in 46 patients admitted for preterm labour. Gestational age ranged from 20-34 weeks. Samples were collected 12 hours before and after initiation of tocolysis. Patients with a premature rupture of the membranes and/or intra-amniotic infection were excluded in this study. There was a significant difference in the oxytocin (p = 0.05) and PGFM levels (p = 0.007, after 12 hours: p = 0.004) between a control group without preterm labour and women with preterm labour. No differences were seen between the successfully treated (delivery more than 5 days after start of tocolysis) and the failure group. There was no significantly different increase or decrease in PGFM and Oxytocin plasma levels between treatment failures and successfully treated patients.

Birth Weight↗

Oxytocin and bovine parturition: a steep rise in endometrial oxytocin receptors precedes onset of labor.

Oxytocin receptors were measured in myometrium and intercaruncular endometrium of cows during pregnancy and parturition. Concentrations of estradiol-17 beta, estrone, and progesterone in peripheral blood were also measured. Receptor concentrations in the endometrium rose almost 200-fold from Day 20 to term (p < 0.0001, ANOVA), from 40 +/- 11 to 7300 +/- 1430 fmol/mg protein. Myometrial receptor concentrations increased 10-fold from 180 +/- 36 fmol/mg on Day 20 to 1850 +/- 360 fmol/mg protein at term (p < 0.0001, ANOVA). During labor, endometrial receptors (6600 +/- 1300 fmol/mg) remained at prelabor values, whereas myometrial receptor concentrations had decreased to 1190 +/- 316 fmol/mg (not significant) and declined further postpartum. Plasma concentrations of progesterone declined from 4-5 ng/ml to about 2 ng/ml between Days 250 and 282 and dropped to < 0.2 ng/ml shortly before delivery. Plasma concentrations of estrone and estradiol-17 beta were below 10-20 pg/ml until Day 230. Estrone concentrations were significantly (p < 0.05) increased by Day 250 and estradiol-17 beta by Day 270, and then both rose rapidly. During labor, plasma estrone was 1135 +/- 245 pg/ml and plasma estradiol-17 beta was 226 +/- 131 pg/ml. The molar ratio of estrone and estradiol-17 beta to progesterone rose from less than 0.01 to 4.4 during labor, and was correlated with oxytocin receptor concentrations in endometrium (r = 0.5160, p < 0.001), but not those in myometrium (r = 0.0122). The regulation of oxytocin receptors by ovarian hormones in the two tissues may therefore differ.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Concentration of oxytocin receptors in the placenta and fetal membranes of cows during pregnancy and labour.

The concentrations of oxytocin receptors were measured in intercaruncular and caruncular endometrium, fetal cotyledons, chorioallantois and amnion during pregnancy and parturition in cows. Tissues were obtained on days 20 (endometrium only), 50, 100, 150, 200, 225, 250, 275, at term (days 280-284), during labour and within 24 h after calving. Receptor concentrations in intercaruncular endometrium were low on day 20 of pregnancy, 39 +/- 11 fmol mg-1 protein. By day 50, receptor concentrations had increased more than tenfold to 572 +/- 52 fmol and rose steadily until day 250 and then levelled off at about 4500 fmol mg-1. Shortly before parturition, on day 282 +/- 1, a further rise to 7300 +/- 1418 fmol mg-1 was observed, these concentrations were maintained throughout labour. By contrast, caruncular endometrial receptor concentrations remained low until term, mean 145 +/- 15 fmol mg-1, and then rose to 720 +/- 163 fmol mg-1 during labour (cervix 17 cm--fully dilated). Fetal cotyledons and membranes had very low oxytocin receptor concentrations during most of pregnancy, on average only 20 fmol mg-1 protein. At term and during labour, receptor concentrations were significantly increased in both tissues. Mean concentrations during labour were 163 +/- 36 fmol mg-1 for cotyledons, 270 +/- 61 fmol mg-1 for chorioallantois and 311 +/- 121 fmol mg-1 for amnion.(ABSTRACT TRUNCATED AT 250 WORDS)

Allantois↗

Role of insulin and glucagon in oxytocin effects on glucose metabolism.

Oxytocin (OT) infusion in normal dogs increases plasma insulin and glucagon levels and increases rates of glucose production and uptake. The purpose of this study was to determine whether the effects of OT on glucose metabolism were direct or indirect. The studies were carried out in normal, unanesthetized dogs in which OT infusion was superimposed on infusion of either somatostatin, which suppresses insulin and glucagon secretion, or clonidine, which suppresses insulin secretion only. Infusion of 0.2 microgram/kg/min of somatostatin suppressed basal levels of plasma insulin and glucagon and inhibited the OT-induced rise of these hormones by about 60-80% of that seen with OT alone. The rates of glucose production and uptake by tissues, measured with [6-3H] glucose, were significantly lower than those seen with OT alone, and the rise in glucose clearance was completely inhibited. Clonidine (30 micrograms/kg, sc), given along with an insulin infusion to replace basal levels of insulin, completely prevented the OT-induced rise in plasma insulin and markedly reduced the glucose uptake seen with OT alone, but did not reduce the usual increase in plasma glucose and glucagon levels or glucose production. To determine whether the OT-induced rise in plasma insulin was in response to the concomitant increase in plasma glucose, similar plasma glucose levels were established in normal dogs by a continuous infusion of glucose and an OT infusion was superimposed. OT did not raise plasma glucose levels further, but plasma insulin levels were increased, indicating that OT can stimulate insulin secretion independently of the plasma glucose changes. Studies by others have shown that the addition of OT to pancreatic islets or intact pancreas can stimulate insulin and glucagon secretion, indicating a direct effect. Our studies agree with that and suggest that in vivo, OT raises plasma insulin levels, at least in part, through a direct action on the pancreas. These studies also show that OT increases glucose production by increasing glucagon secretion and, in addition, a direct effect of OT on glucose production is likely. The OT-induced increase in glucose uptake is mediated largely by increased insulin secretion.

Analysis of Variance↗

Oxytocin secretion and human parturition: pulse frequency and duration increase during spontaneous labor in women.

The secretory pattern of oxytocin was determined in blood samples taken at 1-minute intervals for 30 minutes from 32 parturient women. The samples were collected in a manner that minimized degradation by plasma oxytocinase, and a highly specific antibody was used for the radioimmunoassay. The results indicated that oxytocin is secreted in discrete pulses of short duration. The frequency of the pulses was significantly higher during spontaneous labor than before the onset of labor. The mean pulse frequencies per 30 minutes were 1.2 +/- 0.54 before labor, 4.2 +/- 0.45 during the first stage, and 6.7 +/- 0.49 during the second and third stages of labor. The mean pulse durations in these three groups were 1.2 +/- 0.20, 1.9 +/- 0.28, and 2.0 +/- 0.26 minutes, respectively. The amplitude of the pulses was variable with no significant differences between the groups, the majority being around 1.0 microU/ml. The spontaneous pulses were of similar magnitude as those measured in 18 women after intravenous injections of 4 to 16 mU of oxytocin, which doses stimulated uterine contractions. We therefore conclude that the pulses of oxytocin observed at increasing frequency during spontaneous labor are of physiologic significance and provide evidence for the participation of oxytocin in the onset and maintenance of spontaneous labor.

Analysis of Variance↗

Plasma oxytocin but not prostaglandin F2 alpha metabolite levels at cerclage may predict preterm delivery.

Plasma oxytocin and prostaglandin F2 alpha metabolite (PGFM) concentrations were measured in 45 patients admitted for cerclage during the second trimester. Samples were collected before, 3 hours after, and 3 days after the Shirodkar procedure. Uterine activity was recorded by external tocography twice daily for 30 minutes. Twenty-eight women with uncomplicated pregnancy and commensurate gestational age served as controls. Cervical length, measured by ultrasonography, was significantly shorter before cerclage (36 +/- 2 mm) than after cerclage (43 +/- 2 mm) or compared with controls (48 +/- 1 mm). Bishop scores ranged from 3-6 (median 4) in the cerclage group and 0-1 (median 0) in controls. Fifteen cerclage patients and one control delivered preterm 5-22 weeks after the procedure. Initial plasma PGFM levels were significantly higher in cerclage patients than in controls. The cerclage procedure caused an immediate rise in plasma PGFM and a subsequent fall below initial levels to control values. Neither the initial levels of PGFM nor the increments 3 hours after cerclage correlated with the outcome of pregnancy. By contrast, plasma oxytocin levels before cerclage were significantly higher in patients who subsequently delivered preterm than in those who delivered at term. Cerclage resulted in a significant fall in plasma oxytocin at 3 hours in patients with preterm delivery, but after 3 days the oxytocin levels had returned to the precerclage values. Patients who had increased uterine contractions had significantly higher plasma oxytocin levels but lower PGFM levels than those without contractions.(ABSTRACT TRUNCATED AT 250 WORDS)

Dinoprost↗

Oxytocin and vasopressin binding sites in human and bovine ovaries.

Human ovarian tissue and bovine ovarian stroma and follicles bound tritiated oxytocin and tritiated arginine vasopressin with similar affinity, whereas bovine corpora lutea bound tritiated oxytocin only. Competition for the binding of tritiated oxytocin by various agonists and antagonists was suggestive of receptor function. The number of oxytocin binding sites varied cyclically in all tissues. In bovine ovarian stroma and corpora lutea the concentrations were lowest on day 14 and highest on days 17, 19, and 21 after ovulation, with a striking peak in the luteal concentration on day 19. In human ovarian tissues the concentrations also were highest in samples obtained in late luteal phase. In large follicles the concentration of oxytocin binding sites was highest on the day of estrus and lowest on day 7. In bovine ovary the number of arginine vasopressin binding sites was approximately 50% lower than oxytocin binding sites and the cyclic variations were not significant. Human ovarian tissue had similar numbers of oxytocin and arginine vasopressin binding sites. Because bovine ovaries produce oxytocin and arginine vasopressin the results suggest a paracrine or autocrine role for these neuropeptides in luteolysis and ovulation. Although their synthesis in human ovaries is still controversial the presence of binding sites suggests a physiologic role in the regulation of human ovarian function as well.

Analysis of Variance↗

Oxytocin and vasopressin receptors in bovine endometrium and myometrium during the estrous cycle and early pregnancy.

The binding of [3H]oxytocin ([3H]-OT) and [3H]arginine vasopressin ([ 3H]-AVP) by bovine endometrial and myometrial membrane preparations obtained on days 0, 7, 14, 17, and 21 after estrus or mating was investigated. [3H]OT was bound with higher affinity than [3H]AVP by both tissues; the mean dissociation constants (KdS) were 0.95 x 10(-9) M and 1.56 x 10(-9) M for OT and AVP, respectively, P less than 0.0001, with no significant variations in the KdS during the cycle. The concentration of [3H]OT binding sites was on the average 50% higher than [3H]AVP across the cycle in both tissues. Endometrial receptor levels varied significantly during the cycle; it was lowest on days 7 and 14, rose significantly on day 17, and peaked on day 21. Myometrial receptor levels decreased from levels at estrus on days 7 and 14, but the changes were not significant. The ratio between endometrial and myometrial receptor concentrations changed from about 10 at estrus to less than 1 in the luteal phase. In early pregnancy, the receptor levels did not differ from nonpregnant levels on days 7 and 14, but on day 17 the endometrial receptor concentrations were significantly lower, and on day 21 those in both tissues were significantly lower. The endometrial OT and AVP receptor concentrations were inversely correlated with plasma progesterone levels (P = 0.005) with no correlation to plasma estradiol, whereas the myometrial receptor concentrations showed no correlation to plasma progesterone but an inverse correlation with plasma estradiol (P = 0.004). We conclude that the endometrial OT and AVP receptor concentrations are more tightly controlled by progesterone than myometrium, and that the bovine conceptus suppresses endometrial OT and AVP receptor concentrations in the preattachment stage either by a local action on the endometrium or indirectly via an antiluteolytic effect.

Animals↗

Vasopressin receptors in human pregnant myometrium and decidua: interactions with oxytocin and vasopressin agonists and antagonists.

Saturation analysis and competition experiments were performed to identify and characterize [3H]arginine vasopressin binding to human myometrium and decidua in late pregnancy. [3H]Arginine vasopressin bound with affinity similar to that of [3H]oxytocin to both tissues (dissociation constant 1 to 2 nmol/L). The concentration of [3H]arginine vasopressin binding sites was high, particularly in decidua, but in all instances was about 50% to 60% of [3H]oxytocin binding. Analogs with selective oxytocic potency (4-threonine oxytocin, isotocin) had high affinity to both [3H]arginine vasopressin and [3H]oxytocin binding sites, as did analogs with both oxytocic and vasopressor activity (vasotocin). Analogs with selective antidiuretic activity (1-deamino-8-D-arginine vasopressin) showed drastically reduced affinity to [3H]oxytocin binding sites and relatively low but significantly higher affinity to [3H]arginine vasopressin binding sites. A new oxytocin antagonist (RW22164 or [1-deamino-2D-tyrosine-(O-ethyl)-4-threonine-8-ornithine]oxytocin) competitively bound to both binding sites. Its affinity to [3H]oxytocin binding sites was greater than to [3H]arginine vasopressin binding sites whereas the relative affinities of a predominantly vasopressor antagonist [Manning compound) were reversed, suggesting the presence of distinct receptors for oxytocin and arginine vasopressin in pregnant human myometrium and decidua.

Animals↗

Prostaglandins E and F in cervical mucus of pregnant women.

Cervical mucus concentrations of prostaglandins E (PGE) and F (PGF) were measured by radioimmunoassay in samples collected from 30 pregnant women. The amount of mucus that could be aspirated did not vary significantly at various stages of gestation and was 67 mg on the average. Concentrations of both prostaglandins were lowest in the first trimester and increased significantly during the second trimester. No significant further increase was observed during the third trimester. Serial samples taken from five women at approximately weekly intervals from the 35th to the 36th week onward did not show any significant increase toward term, although several individual samples had very high concentrations, suggesting that the prostaglandins were secreted into the cervical lumen in pulses. During the first and second trimester, the concentrations of PGE and PGF were similar, but during the third trimester PGF levels were significantly higher. The mean concentrations of PGE and PGF in cervical mucus during the second half of gestation were 10 to 20 times higher than their reported levels in amniotic fluid at the same stage, and in the range reported by others to be effective in modulating cervical tissue responses in vitro. Two to 4 hours after intercourse, prostaglandin concentrations in the cervical mucus were found to be about 10- to 50-fold higher than normal. The prostaglandins in cervical mucus may well participate in the gradual changes in the extracellular matrix of the cervix that result in the extensive remodeling of the cervix during pregnancy.

Cervix Mucus↗

Pulsatile administration enhances the effect and reduces the dose of oxytocin required for induction of labor.

Pulsatile administration of oxytocin was compared with continuous infusion of oxytocin for induction of labor in pregnant rats. The dosages consisted of intravenous injections of 0, 2.5, and 5 mU oxytocin every 10 minutes and intravenous infusion of 1 mU/minute of oxytocin in 0.9% sodium chloride. These doses are within the range of endogenously secreted pulses. All treatments began on day 22 at 2 p.m. and continued for 8 hours. Pulsatile administration resulted in a marked reduction in the dose of oxytocin required to induce labor. Using 5 mU pulses, birth was induced with 18.4%, and using 2.5 mU pulses, with 24% of the dose needed using continuous infusion. Parturition was advanced by 12 hours on the average by oxytocin treatment, but no significant differences were observed between the various oxytocin dosage regimens in this regard or in regard to gestation length, induction-delivery interval, duration of delivery, or the proportion of living or dead pups. Significantly more uterine activity was induced with each mU of oxytocin using pulsatile administration than using continuous infusion. There was no evidence for down-regulation of oxytocin receptors during a continuous infusion of oxytocin. We postulate that the greater efficacy of oxytocin pulses to induce uterine activity and delivery in comparison to continuous infusions is due to a more effective stimulation of prostaglandin F2 alpha release from the decidua. The amount of oxytocin needed for induction of labor with 2.5 mU pulses was similar to the decrease in neurohypophyseal oxytocin content during the first stage of spontaneous labor, and uterine activity elicited was also similar to that observed during spontaneous labor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Influence of premature rupture of membranes on induction of labor and plasma 13,14-dihydro-15-keto-prostaglandin F2 alpha and oxytocin levels in patients with unripe cervix.

Rupture of membranes at term, whether spontaneous or artificial, causes rapid and sustained increase in prostaglandin F2 alpha (PGF2 alpha) metabolite (PGFM) levels and is associated with augmentation of uterine contractions. To investigate why premature rupture of membranes (PROM) often fails to initiate uterine contractions, we measured plasma concentrations of PGFM and oxytocin (OT) in patients with PROM near term. Serial blood samples were taken before and after PROM as well as before and after local PGE2 gel application for cervical ripening. For comparison, patients with similar criteria with intact membranes were also studied, as were patients in spontaneous labor at term with and without spontaneous rupture of membranes. PROM was always associated with an initial, marked increase in plasma PGFM. Whether or not this increased PGF2 alpha production was maintained was related to the cervical status at the time of PROM. In patients with unripe cervix PGFM levels returned to initial levels within 2 hours and no contractions were elicited; when the cervix was 3 cm or more dilated, PGFM levels remained high and contractions began within 1 to 3 hours. PROM had no significant effect on plasma OT levels. When PGE2 gel was applied to ripen the cervix, PGFM levels increased moderately within 30 minutes in all patients regardless of the status of the membranes. In patients with intact membranes the concentration of PGFM in plasma declined to initial levels within 4 hours, whereas in patients with PROM, PGFM levels remained increased throughout the study period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Profile of an oxytocin antagonist, RWJ 22164 for treatment of preterm labor in laboratory models of uterine contractility.

An oxytocin antagonist, 1-deamino-[D-TYR(Oethyl)2,THR4,ORN8]oxytocin (RWJ 22164; dTVT), has recently been characterized in models of uterine contractility. Studies were undertaken to characterize the action of dTVT further on both oxytocin- and vasopressin-induced increases in uterine contractility both in vitro and in situ models and in a model of preterm labor. In these studies, dTVT was found to be a specific competitive inhibitor of both oxytocin- and vasopressin-induced contractions of both pregnant and nonpregnant guinea pig uterus in vitro. In situ, the intravenous administration of dTVT induced a dose-dependent inhibition of oxytocin- and vasopressin-induced contractions in a guinea pig model which measures uterine activity as changes in uterine perfusion pressure. Further studies demonstrated that the intravenous infusion of dTVT delays ongoing labor.

Animals↗