Oxytocin in maternal circulation and amniotic fluid during pregnancy.

Oxytocin (OT) was measured by a specific and sensitive RIA in plasma and amniotic fluid throughout pregnancy. OT was detectable in 84.5% of 362 maternal plasma samples and showed a slow and fluctuating increase towards term with a significant sharp peak at 39 weeks of gestation. There was a highly significant correlation between mean plasma OT and the week of gestation (r = 0.5419, P less than 0.005). The minute to minute variability in plasma OT during pregnancy and labor in 7 subjects showed episodic release of OT with two or three spurts per 10 min, with the amplitude of the spurts being greater during labor. Serial maternal plasma OT throughout pregnancy in 10 patients revealed good concentrations of OT (greater than 10 pg/ml) in patients who subsequently had spontaneous labor and no intrapartum uterine dysfunction. Poor (less than 10 pg/ml) or undetectable OT levels were found in patients who subsequently developed intrapartum uterine dysfunction which necessitated cesarean section. OT was detectable in 89.7% or 87 amniotic fluid samples, with a mean +/- SE of 7.8 +/- 3.6 pg/ml at 14--15 weeks, 43.9 +/- 14.7 pg/ml at 40 weeks, and 30.8 +/- 10.5 pg/ml at 41--42 weeks. The significance of these findings is discussed in relation to the role and origin of OT in pregnancy and parturition.     

Relationships between glucose and mannose during late gestation in normal pregnancy and pregnancy complicated by diabetes mellitus: concurrent concentrations in maternal plasma and amniotic fluid

Enzymatic assays were modified to permit sensitive and highly reproducible simultaneous measurements of D-mannose and D-glucose in biological fluids during weeks 34-40 of human pregnancy. Plasma mannose and glucose averaged 9.8 +/- 0.4 (+/- SEM) and 790 +/- 16 micrograms/ml, respectively, after an overnight fast in pregnant women (n = 22) with normal carbohydrate metabolism. Significantly higher plasma mannose levels were found, despite only minor increases in plasma glucose, in pregnant women with relatively well controlled diabetes mellitus after an overnight fast (16.9 +/- 0.6 micrograms/ml mannose; 883 +/- 29 micrograms/ml glucose; n = 31) or 3-4 h after breakfast (15.7 +/- 1.2 micrograms/ml mannose; 1159 +/- 101 micrograms/ml glucose; n = 19). Plasma mannose correlated significantly with plasma glucose in the women with diabetes mellitus, particularly after an overnight fast. Samples of amniotic fluid were also obtained from the gravida with diabetes mellitus to provide some index of simultaneous relationships in utero. Amniotic fluid mannose and glucose averaged 5.9 +/- 0.4 and 302 +/- 24 micrograms/ml, respectively, after an overnight fast and 6.7 +/- 1.3 and 459 +/- 84 micrograms/ml 3-4 h after breakfast. In amniotic fluid, as in plasma, the concurrent levels of mannose and glucose conformed to relatively fixed relationships. Thus, both fetus and mother appear to be exposed to readily demonstrable amounts of mannose during late gestation and the absolute as well as relative abundance of mannose may be increased coincident with faulty maternal glucoregulation. However, since mannose did not exceed 3% of the concurrent concentration of glucose in any instance, it does not seem likely that endogenous levels of circulating mannose can modify glucose utilization appreciably by competing with glucose for phosphorylation via hexokinase and subsequent intracellular processing.     

The concentration of prostaglandin f2alpha in maternal plasma, foetal plasma and amniotic fluid during pregnancy in women.

The concentration of prostaglandin F2alpha has been determined in serial samples of peripheral venous plasma from women at defined times during labour, and studied in detail throughout two consecutive uterine contractions. In addition, the same compound has been measured in single samples of uterine venous plasma, cord venous plasma, and amniotic fluid in groups of patients during early and late pregnancy, labour and at delivery of the baby.     

Pro-EPIL forms are present in amniotic fluid and maternal serum during normal pregnancy.

Recent observations based on immunohistochemistry and RT-PCR demonstrate that early placenta insulin-like peptide (EPIL), encoded by the INSL4 gene, is present in the placenta during gestation. In the present study, we report on the development of a specific immunoassay, entirely based on two monoclonal anti-peptide antibodies (mAbs), and its use for the detection of pro-EPIL forms in biological fluids during pregnancy. One mAb directed against the C-connecting peptide was used to capture pro-EPIL forms and their binding was revealed by a radiolabeled anti-A chain mAb as the indicator. A composite synthetic peptide, encompassing the C- and A-domains, was utilized as the standard. Under these experimental conditions, the assay displays a sensitivity limit of 2 ng/mL. Pro-EPIL molecular forms were detected in both amniotic fluid and maternal serum of pregnant women. At 12 to 16 weeks of pregnancy, the pro-EPIL level was higher in amniotic fluid (246 +/- 50.8 ng/mL) than in maternal serum (5 +/- 2.0 ng/mL). As gestation advanced, so the concentration of pro-EPIL forms decreased in amniotic fluid while its level increased in maternal serum. Interestingly, in amniotic fluid, the pattern of pro-EPIL concentration during pregnancy is very similar to that observed for human chorionic gonadotropin (hCG) and its free subunits. The pattern of serum pro-EPIL concentration is similar to that of the free alpha-subunit. Together with our previous immunohistochemical observations, these results indicate that pro-EPIL is preferentially secreted by cytotrophoblasts in amniotic fluid and that the biosynthesis of hCG subunits and EPIL may be regulated by common pathways. Overall, our observations strongly suggest that EPIL may play a critical physiological role during embryonic and foetal development.     

The effect of morphine and naloxone administration on maternal oxytocin concentration in late pregnancy

OBJECTIVE Modification of the inhibitory control of oxytocin secretion by endogenous opiates in late pregnancy may be one of the factors involved in the onset of labour. The interrelationships between exogenously administered opioids and oxytocin may demonstrate activity of this control mechanism. This study was undertaken to investigate the effect of an opiate and an opiate antagonist on maternal oxytocin levels in late pregnancy. DESIGN Patients were randomized to receive either morphine (5 mg), naloxone (2.4 mg) or sterile water (1 ml) intravenously. PATIENTS Thirty women with singleton pregnancies greater than 36 weeks gestation who were not in labour were studied. MEASUREMENTS Blood for peripheral oxytocin levels was sampled every 2.5 minutes for 15 minutes before and 15 minutes after administration of the assigned substance. Oxytoxin was measured by radioimmunoassay. Peripheral β-endorphin levels were measured at the beginning and end of the study. RESULTS There was no significant change in the maternal oxytocin concentration after administration of either morphine, naloxone or sterile water compared to pretreatment levels. β-Endorphin levels did not change significantly, either from the beginning to the end of the study, or between groups. CONCLUSION In late pregnancy exogenous opiates and opiate antagonists have no effect on maternal peripheral oxytocin levels.     

Glucose tolerance in early pregnancy

The effect of pregnancy on oral glucose tolerance (50 g of glucose) and plasma insulin and glucagon responses to oral glucose was studied in weeks 10 and 32 of pregnancy and again 1 year post partum in 12 normal women. Already in week 10, fasting plasma glucose was decreased and the glucose-induced insulin secretion increased as compared with post partum. However, glucose tolerance was not affected at this time. In week 32, glucose tolerance had deteriorated, although the levels of both fasting and glucose-induced insulin were higher than those found in early pregnancy and post partum. At all investigations fasting plasma glucagon and the suppression of plasma glucagon after oral glucose were similar, indicating that glucagon is not implicated in the changes in glucose homeostasis seen in pregnancy. It is concluded that glucose tolerance is unaltered by pregnancy in week 10. Pregnancy has, however, at this very early stage already affected glucose homeostasis as seen by the decrease in fasting plasma glucose and the increase in the insulin response to glucose.     

Severe maternal respiratory distress due to the amniotic fluid embolism syndrome in a twin pregnancy

A 28-year-old female with a twin pregnancy at 29 6/7 weeks who was having premature uterine contractions developed acute respiratory failure due to sudden pulmonary oedema requiring mechanical ventilation. No evidence for venous thromboembolism, pulmonary infection or myocardial infarction was found. Subsequently a mild coagulopathy and foetal distress developed. Ultrasonography revealed oligohydramnios of one of the foetuses. A Caesarean section was performed and postoperatively mother and babies had an uneventful clinical course. By exclusion of other causes, we diagnosed severe maternal acute respiratory distress due to the amniotic fluid embolism syndrome in a twin pregnancy.     

Pharmacokinetic profile in late pregnancy and cord blood concentration of tipranavir and enfuvirtide

The data on the use of tipranavir and enfuvirtide in pregnancy are very limited. We performed a pharmacokinetic profile in a pregnant woman with multidrug-resistant HIV-1 infection at 37 weeks gestation. Tipranavir levels were in the therapeutic range and the cord blood concentration at delivery was relatively high when compared with other protease inhibitors. No enfuvirtide was detected in the fetal compartment. Tipranavir and enfuvirtide were successfully used in pregnancy, but possible toxicities must be kept in mind.     

Pro-opiomelanocortin in human pregnancy: evolution of maternal plasma levels, concentrations in cord blood, amniotic fluid and at the feto-maternal interface

OBJECTIVE: The human placenta normally expresses the pro-opiomelanocortin (POMC) gene. The pattern and secretory kinetics of POMC and/or POMC-derived peptides by the placenta during gestation is still debated. We recently demonstrated that full length POMC was a normal product of the human placenta. The aim of our study was to establish its normal secretory kinetics and to explore its physiological relevance. DESIGN: In a prospective, longitudinal study, thirty normal pregnant women had monthly measurements of plasma POMC. In a cross-sectional study of 128 healthy pregnant women, plasma POMC and human chorionic gonadotrophin (hCG) were concomitantly measured to assess their correlation. Finally, POMC levels were assessed in venous and arterial cord blood samples, in amniotic fluid and in retroplacental blood. METHODS: Plasma POMC was measured by a specific IRMA in unextracted blood or biological fluid. RESULTS: Plasma POMC became detectable by the 8th week of pregnancy and reached its maximum at around the 20th week, remaining stable thereafter. The relationship between POMC and gestation time (weeks) best fitted with a third degree polynomia curve. A significant negative correlation (P=0.01) was observed between plasma levels of POMC and hCG after adjustment for gestation time to take into account the dependence of both hormones on this parameter. POMC was not secreted into the fetal circulation at term, but was present in very high levels in amniotic fluid. The highest levels of POMC were present in the retroplacental blood where the values were 35 times higher than in maternal blood; by comparison, corticotrophin releasing hormone and ACTH values in this compartment were twice or equal to those in the maternal blood. CONCLUSION: Placental POMC secretion increases during the first half of pregnancy and reaches a plateau from the 20th week to delivery. The inverse correlation between POMC and hCG plasma levels, and very high POMC levels at the feto-maternal interface suggest a physiological role for this precursor during pregnancy.     

Glucose concentration and insulin release in 5-thio-D-glucose-treated mice

Male albino mice were given a single dose of various concentrations (25, 50, and 100 mg/kg body weight) of 5-thio- -glucose or daily infusions (33 mg/kg body weight) of 5-thio- -glucose for 21 days. Elevated blood glucose and immunoreactive insulin (IRI) levels were observed in the mice treated with 5-thio- -glucose. Fasting glucose levels reached a maximum in 30 minutes and IRI levels reached a maximum in 60 to 90 minutes in the single-dose treated animals compared to preintubation levels. In the mice treated for 21 days, the fasting and fed glucose and IRI levels were significantly increased. Single dose of glucose (1 g/kg body weight) given to fasting and fed mice did not alter the glucose and IRI levels in the treated animals. However, a single dose of 5-thio- -glucose (33 mg/kg body weight) given to fasting and fed treated animals increased the IRI levels significantly but not the glucose concentration. These data show that both single-dose and 3-week treatment with 5-thio- -glucose produced a hyperinsulinemic diabetes in male albino mice.     

Detection of Toxoplasma gondii DNA by PCR in mother's blood, amniotic fluid and child's blood in selected cases of pathological pregnancy

Prenatal screening of Toxoplasma gondii infection is controversial. The diagnosis is based on serological tests detecting IgM and IgG antibodies against T. gondii, but interpretation of these tests results is often confusing. It is commonly made retrospectively when serological screening indicates a possibility of recent infection. Most women have antibodies against T. gondii and serial testing is required only in monitoring of pregnancies where initial screening is negative. The introduction of Polymerase Chain Reaction (PCR) assay for detection of Toxoplasma gondii DNA in selected cases of pathologic pregnancies has permitted a more accurate and faster diagnosis of congenital toxoplasmosis infections.     

Detection of house-dust-mite allergen in amniotic fluid and umbilical-cord blood

Mononuclear cells in umbilical-cord blood display allergen-specific reactivity, but how allergen exposure occurs in utero is unknown. We investigated the presence of a common inhalant allergen (Der p 1), to which mothers are exposed throughout pregnancy, by ELISA in matched maternal blood and amniotic fluid samples at 16-17 weeks of gestation, and in matched maternal and umbilical-cord blood at term (> or =37 weeks of gestation). Der p 1 was detectable in 24 of 43 amniotic fluid samples where it was also present in maternal blood, and in 15 of 24 cord-plasma samples at significantly higher concentrations than in the maternal plasma (p=0.022). The detection of Der p 1 in the amniotic fluid and the fetal circulation provides direct evidence of transamniotic and transplacental allergen exposure.     

Study of concentration of amniotic fluid Alpha-fetal protein in thalassemia fetus

Objective:To test the hypothesis that concentration of amniotic fluid alpha-fetal protein(AFAFP) is increased in thalassemia fetus.Methods:A total of 135 cases of amniocentesis admitted from July 2013 to December 2014 were included in this study.Among them 98 cases of normal fetuses were assigned into control group and 37 cases of thalassemia fetus were included as thalassemia fetus group.Alpha-fetoprotein levels detected by enzyme linked immunosorbent assay and the alpha-fetoprotein concentration were compared between the two groups.There is no significant difference in gestrational age between the two groups.Results:1.AFP concentration in thalassemia fetus group was significantly higher than that of normal control group [(1541.65±734.78) μg/mL vs.(2728.84± 1539.97) μg/mL ],and amniotic fluid AFP concentration was related to fetal thalassemia.2.AFAFP concentration in pureα-thalassemia fetus was higher than that of β thalassemia fetus or mixed αand was not significant.Conclusions:Concentration of a β thalassemia fetus,but the difference mniotic fluid alpha-fetal protein is increased in thalassemia fetus.AFP concentration inα-thalassemia fetus was higher than that of β thalassemia or mixed αand lore β thalassemia fetus but difference was not significance.Further studies are needed to exp the possible correlation between Down syndrome and biochemical markers of Thalassemia.     

Correlation of maternal serum fetuin/alpha2-HS-glycoprotein concentration with maternal insulin resistance and anthropometric parameters of neonates in normal pregnancy and gestational diabetes

OBJECTIVE: Human fetuin/alpha(2)-HS-glycoprotein (AHSG) is a 49 kDa serum and tissue protein which is a natural inhibitor of insulin receptor signaling. We investigated serum AHSG levels during pregnancy and whether the protein is involved in insulin resistance observed in healthy pregnant women and patients with gestational diabetes. DESIGN: One hundred and four healthy pregnant women and 23 of their neonates, 30 patients with gestational diabetes and their neonates and 30 healthy age-matched non-pregnant females as a control group were investigated in a case-control cross-sectional study. METHODS: Serum AHSG was determined by radial immunodiffusion. RESULTS: We observed an increase of serum AHSG concentration in the second and third trimesters. Gestational diabetes patients had significantly higher AHSG levels than healthy pregnant women and non-pregnant controls. There was a highly significant positive correlation between serum AHSG concentration and indirect parameters of insulin resistance, i.e. tumor necrosis factor-alpha (TNF-alpha), leptin, C-peptide and C-peptide/blood glucose ratio. There was also a negative correlation between maternal AHSG, TNF-alpha, leptin levels and head circumference, body length and body weight of newborns. CONCLUSION: AHSG, TNF-alpha and leptin may contribute to insulin resistance during normal pregnancy and gestational diabetes. AHSG along with these cytokines may also negatively regulate neonatal skeletal development.     

Decrease in the insulin of rabbit pancreas in late pregnancy

Summary Plasma insulin levels and extractable insulin of the pancreas of normal and pregnant rabbits have been studied. — The mean plasma insulin of non-pregnant controls was 25U/ml (range 18 to 33); extractable pancreas insulin was 3.56g/100 mg tissue (3.33 to 3.76). — The insulin level in the blood increases during late pregnancy to 56U/ml (range 37 to 81) and the extractable pancreatic insulin decreases to 1.17g/100 mg tissue (0.65 to 1.73). — The fine structure of B and A-cells has been studied in pregnancy: insulin stored in B granules decreases and the A-cells show definite signs of increased activity. — The above findings might be interpreted as suggesting that in late pregnancy an increased synthesis and secretion of glucagon augment the insulin secretory activity of the pancreas.

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Abnahme des Pancreas-Insulins beim Kaninchen während der fortgeschrittenen Schwangerschaft

Zusammenfassung Bei normalen und graviden Kaninchen wurden die Plasma-Insulinspiegel und das aus dem Pancreas extrahierbare Insulin gemessen. — Die mittleren Insulinspiegel der normalen Kontrolltiere lagen bei 25E/ml (zwischen 18–33), das Pankreasinsulin bei 3.56g/100 mg Gewebe (3.33–3.76). Die Seruminsulin-spiegel steigen während der späten Schwangerschafts-stadien auf 56E/ml (37–81) an und das extrahierbare Pancreas-Insulin nimmt auf 1.17G/100 mg Gewebe (0.65–1.73) ab. — Wir untersuchten die Feinstruktur der Alpha- und Beta-Zellen während der Schwangerschaft: Dabei nahm das in den Beta-Granula gespeicherte Insulin ab und die Alpha-Zellen zeigten eindeutige Zeichen gesteigerter Aktivität. Die oben skizzierten Befunde könnten daraufhin deuten, daß während der späten Schwanger-schaftsstadien eine gesteigerte Glucagon-Synthese und Sekretion die insulinsekretorische Aktivität der Bauchspeicheldrüse erhöht.

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Diminution de l'insuline dans le pancréas du lapin pendant la gestation avancée.

Résumé Le contenu en insuline du plasma de lapins normaux et en gestation a été étudié par rapport à la quantité d'insuline qui pouvait être extraite de leurs pancréas. — Le contenu plasmatique moyen en insuline des lapins normaux, utilisés comme témoins, était de 25U/ml (entre 18 et 33) et l'insuline extraite de leurs pancréas était de 3.56g/100 mg de tissu (entre 3.33 et 3.76). — Lorsque la gestation était à un stade avancé, le contenu en insuline dans le sang s'élevait à 56U/ml (entre 37 et 81), alors que l'insuline extraite du pancréas tombait à 1.17g/100 mg de tissu (entre 0.65 et 1.73). — L'ultrastructure des cellules A et B pendant la gestation a également été étudiée. La teneur des granules B en insuline diminue et les cellules A présentent des signes évidents d'une haute activité. — Les observations précédentes suggéreraient que lors de la gestation avancée, une synthèse et une sécrétion de glucagon accrues augmentent l'activité sécrétrice du pancréas en insuline.