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Biomedical subjects

F Fuchs

Publications and source records attributed to F Fuchs.

At least 109 records · Page 6Linked to original sources

Oxytocin receptors and human parturition: a dual role for oxytocin in the initiation of labor.

The concentration of oxytocin receptors increased in the myometrium of pregnant women and reached maximum levels in early labor. Concentrations of oxytocin receptors were also high in the decidua and reached a maximum at parturition. In vitro, prostaglandin production by the decidua, but not by the myometrium, was increased by the addition of oxytocin. Oxytocin may therefore stimulate uterine contractions by acting both directly on the myometrium and indirectly on decidual prostaglandin production. Oxytocin receptors are probably crucial for the onset of human labor, and the stimulus for the increase in uterine prostaglandins may be oxytocin originating from the fetus.

Decidua↗

Parallel measurements of bound calcium and force in glycerinated rabbit psoas muscle fibers.

A simple double-isotope procedure has been developed for making simultaneous measurements of bound Ca2+ and relative force in glycerinated rabbit psoas bundles containing two fibers. With this preparation it is possible to study Ca2+-troponin interactions coincident with MgATP-induced force development. Over the free [Ca2+] range 6 . 10(-8)--1.2 . 10(-5) M the bound Ca2+ varied from 0.25 to 1.65 mumol/g protein. The free [Ca2+] at half-maximal Ca2+ saturation was 2 . 10(-7) M while that a half-maximal force was 5 . 10(-7) M. Half-maximal Ca2+ saturation was associated with 20% maximal force. The force-[Ca2+] saturation curve showed a steep rise in slope at greater than half saturation. The observed relationship was consistent with a model in which multiple occupancy of troponin Ca2+-binding sites is essential for initiation of cross-bridge cycling.

Animals↗

The origin of circulating 13,14-dihydro-15-keto-prostaglandin F2 alpha during delivery.

All uterine tissues as well as the fetal membranes and the placenta can form prostaglandins from endogenous precursors in vitro but it is not clear which of the tissues is the main site for the increase in PGF2 alpha production during human parturition. To examine this question, we measured plasma prostaglandin levels before and at intervals after expulsion of the fetus, placenta, and membranes. The concentration of PGFM at the beginning of the second stage of labor was significantly higher than before the onset of labor. Five minutes after the birth of the infant, the concentration had doubled. Thirty minutes after the expulsion of placenta and membranes, plasma PGFM had fallen to the levels at full dilatation; two hours postpartum it was still significantly raised over levels before labor. Since the halflife of PGFM in the circulation is about 7 minutes, these findings indicate that the uterine tissues are important sources of PGFM during labor. In contrast, endogenous oxytocin levels, which were significantly raised over control levels at the second stage of labor, did not change during the third stage, and declined postpartum to control levels. Oxytocin infusion did not influence PGFM levels at 5 and at 30 minutes postpartum, but raised them at 2 hours.

Adult↗

[Does fetal oxytocin initiate human labour? A hypothesis].

The concentration of specific oxytocin receptors increases during pregnancy and reaches a maximum at term after the onset of spontaneous labour. This constitutes a biochemical explanation for the well-known increase of oxytocin sensitivity during pregnancy. Oxytocin receptors were also found in human decidua and their concentration increased similarly. Based on these results the hypothesis was set up that oxytocin leads to an increase in prostaglandin production though specific receptors in decidua. Under specific incubation circumstances oxytocin indeed increased prostaglandin E and prostaglandin F synthesis of decidual tissue. In induction of labour with oxytocin PGF-levels in the maternal peripheral plasma increased significantly in all women in whom induction was successful. Since it is known that the fetus secretes considerable amounts of oxytocin in case of labour of spontaneous onset the hypothesis was set up that fetal oxytocin may initiate human labour by the mechanisms described above.

Decidua↗

Linear elimination kinetics but non-linear pharmacodynamics in theophylline intoxication in a child.

In an infant's acute theophylline intoxication following a medication error, plasma levels above 80 micrograms/ml were not associated with repetitive seizures, but also with heart rates above 200 bpm. The serum elimination kinetics were characterized by a first-order elimination process with a half-life of 15 h. Despite the exponential decay of plasma levels the heart rate remained at a high level during the first 20 h. This behavior is explained by a saturation phenomenon familiar in receptor and enzyme kinetics.

Female↗

Oxytocin and the initiation of human parturition. I. Prostaglandin release during induction of labor by oxytocin.

Concentrations of plasma prostaglandins E and F and the 15-keto-13,14 dihydrometabolite of PGF2 alpha (PGFM) were determined by radioimmunoassay in 15 women who underwent induction of labor with oxytocin. Plasma PGFM rose significantly during the oxytocin infusion in nine women who went on to deliver vaginally but did not change in six women in whom induction of labor failed. Plasma PGE and PGF levels also rose during the infusion in the nine women with successful induction of labor but the changes were not statistically significant. In comparison to the six women in whom induction failed, however, plasma PGE in the nine women with successful induction reached significantly higher levels. Oxytocin infusions elicited uterine contractions of similar frequency in both groups of women, but the cervix failed to dilate in the six women in whom induction failed. The oxytocin-induced rise in plasma PGFM is, therefore, not simply a consequence of uterine contractions. We suggest that oxytocin stimulates PGF production in the pregnant uterus when it is appropriately sensitized to oxytocin, causing a potentiation of the oxytocin-induced contractions which is necessary for the contractions to become efficient in dilating the cervix. We further suggest that the stimulation of PGF production by oxytocin is mediated by oxytocin receptors, probably in the decidua.

Dinoprost↗

Oxytocin and the initiation of human parturition. II. Stimulation of prostaglandin production in human decidua by oxytocin.

In the present study we have investigated the effect of oxytocin on the production of prostaglandins E and F (PGE and PGF) by human decidua, amnion, and myometrium in vitro. We found that oxytocin causes a significant increase in the production of both PGE and PGF in the decidua and in the production of PGE in the amnion. In the myometrium the stimulatory effect of oxytocin on PGF production was small and not statistically significant, and PGE production was not affected at all. On the basis of these results, we propose that oxytocin provides the stimulus for the accelerated prostaglandin production in decidua and fetal membranes at the onset of labor. Since oxytocin levels rise in the fetal circulation at this time, the oxytocin stimulus may be of fetal origin as well as of maternal origin.

Decidua↗

Prostaglandins in primary dysmenorrhea. Comparison of prophylactic and nonprophylactic treatment with ibuprofen and use of oral contraceptives.

Prostaglandin synthetase inhibitors have been used in clinical trials for the treatment of primary dysmenorrhea on the theory that the disorder may be caused by a high level of prostaglandins. However, a causal role of prostaglandin in dysmenorrhea has not been established, and there is only indirect evidence that the amelioration of dysmenorrhea by prostaglandin synthetase inhibitors is related to their inhibition of prostaglandin synthesis in the uterus. We, therefore, monitored menstrual prostaglandin release in 14 dysmenorrheic patients in a controlled, double-blind, cross-over trial of ibuprofen (Motrin) and in two dysmenorrheic subjects while they were receiving oral contraceptive therapy and while they were not. A total of 89 menstrual cycles were studied. We found that ibuprofen therapy reduced menstrual prostaglandin release and relieved dysmenorrhea but that placebo therapy did not. Oral contraceptives decreased menstrual flow, reduced prostaglandin release and also alleviated dysmenorrhea. We conclude that primary dysmenorrhea is related to a high level of menstrual prostaglandin release. Ibuprofen inhibits prostaglandin synthesis whereas oral contraceptives inhibit ovulation and cyclic endometrial development. Thus, the two drugs suppress endometrial prostaglandin through different mechanisms. Reduction of menstrual prostaglandin release leads to alleviation of dysmenorrhea.

Adult↗

Maternal and fetal oxytocin levels at parturition in a paraplegic woman.

Maternal and fetal oxytocin levels were measured by radioimmunoassay in a paraplegic woman with a spinal cord lesion at T-4/T-5 who went into spontaneous labor at 39 wk of pregnancy and delivered vaginally a male infant weighing 3220 g. She showed signs of autonomic hyperreflexia during labor. Maternal plasma oxytocin was 3-12 pg/ml in 3 blood samples and undetectable in another 4 taken during the first stage, with a surge of 38 pg/ml at delivery of the fetus. Oxytocin levels were 73 pg/ml in umbilical venous plasma, and 14 pg/ml in amniotic fluid. The findings indicate that the fetus was an important source of oxytocin to the maternal uterus.

Adult↗

Oxytocin release and plasma anterior pituitary and gonadal hormones in women during lactation.

Serial plasma oxytocin (OT), PRL, TSH, FSH, LH, estrone, estradiol, and progesterone were measured by RIA in 12 women before and during a 30-min breast-feeding period on the third or fifth postpartum day. Plasma OT increased significantly from 10.8 +/- 3.4 to 22.4 +/- 3.5 pg/ml (mean +/- SE) within 2 min of suckling (P = less than 0.05) to reach the mean peak level of 53.2 pg/ml at 10 min. The increase in plasma OT was bimodal. Plasma PRL and TSH also increased significantly from baseline levels of 192 +/- 39 ng/ml and 16.9 +/- 5.6 microU/ml, respectively, to reach maximum levels of 427 +/- 91 ng PRL/ml at 10 min (P = less than 0.025) and 281.5 +/- 56.6 microU TSH/ml at 25 min (P = less than 0.005). Plasma FSH-beta (range of means, 3.5-4.6 ng/ml), LH (range of means, 1.7-2.6 mIU/ml), and estradiol (range of means, 29.8-38.2 pg/ml) were low and remained unchanged throughout breast feeding. Plasma progesterone was 6.0 +/- 0.4 ng/ml before breast feeding and did not alter significantly during breast feeding. The significance of these findings is discussed in relation to the milk let-down reflex and the relationship of TSH to PRL.

Estradiol↗

Plasma oxytocin levels and disappearance rate after buccal Pitocin.

Plasma concentrations of oxytocin (OT) were determined by a highly specific and sensitive radioimmunoassay in (1) nine pregnant women near or at term who were given 400 units of buccal OT every 20 minutes to induce labor or to augment uterine contractions; (2) four adult males who were given 200 units and 400 units of buccal OT every 20 minutes in two separate experiments each lasting 2 hours; and (3) three adult males at regular intervals up to 45 minutes after discontinuation of buccal OT. Plasma concentrations of OT increased in all the women studied, and exceeded 50 picograms per milliliter in six of nine patients after buccal OT was given. However, the net increase in OT was less than 50 pg/ml in six of nine patients. In males, 90% of the plasma samples collected when 400 units of OT was given had detectable levels of OT, with mean levels of 24 to 32 pg/ml; when 200 units was used, only 53% of the plasma samples had detectable OT, and mean levels were consistently below 10 pg/ml. Plasma OT decreased to one third but not to baseline levels in the course of 45 minutes after OT was discontinued. The findings indicate that with 400 units of buccal OT every 20 minutes, plasma OT concentrations attained were similar to those found during the first stage of labor, and that the disappearance of OT from the plasma after discontinuation was slow.

Administration, Oral↗

Infants of mothers treated with ethanol for premature labor.

Presented is a retrospective study of the newborn infants of mothers who were treated with ethanol in order to arrest premature labor, in comparison with matched control infants. In regard to neonatal mortality, there was no statistical difference between the study and the control infants. However, infants born within 12 hours after administration of ethanol had a significantly lower 1-minute Apgar score and a higher incidence of respiratory distress syndrome. This indicates that treatment with ethanol should be discontinued as soon as it becomes evident that labor cannot be arrested.

Apgar Score↗

The effect of magnesium ions on the binding of calcium ions to glycerinated rabbit psoas muscle fibers.

The effect of Mg2+ on Ca2+ bound to glycerinated rabbit psoas muscle was studied by means of a double-isotope technique. The troponin-C content of the fibers was analyzed by quantitative sodium dodecyl sulfate polyacrylamide gel electrophoresis and found to be 0.5 mumol/g fiber protein. In the absence of Mg2+ the fibers bound a maximum of 3.5 mumol Ca2+/g protein. This value could be readily accounted for in terms of the four Ca2+-binding sites of troponin-C and the two divalent cation-binding sites of myosin. In the presence of 1 mM Mg2+ the entire Ca2+ titration curve was shifted downward with a maximum bound Ca2+ of slightly more than 2 mumol/g, or 4 mol Ca2+/mol troponin-C. Further increase in Mg2+ concentration to 10 mM had little effect on Ca2+ binding when the free Ca2+ concentration was in the upper part of the physiological range (5 . 10(-7)-5 . 10(-6) M) but caused a marked reduction when the Ca2+ concentration was low. The results are consistent with biochemical data showing two groups of (Mg2+/Ca2+)-binding sites. One group, located in myosin, has a high affinity for Mg2+ while the other group, located on troponin-C, has a low affinity for Mg2+. If the free Mg2+ concentration in muscle is in the range of 2--5 mM, as suggested by recent data, it can be inferred that the binding sites on myosin will never be occupied by Ca2+ under physiological conditions.

Animals↗