Desensitization of oxytocin receptors in human myometrium.
(1/1238)
In the present study, we investigated the possible mechanisms by which oxytocin might regulate oxytocin receptor (OTR) density. Exposure of cultured myometrial cells to oxytocin for a prolonged period caused desensitization: the steady-state level of oxytocin binding was 210 x 10(3) binding sites/cell, but this was time-dependently reduced to 20.1 x 10(3) sites/cell by exposing the cells to oxytocin for up to 20 h. In contrast, Western blotting data showed that the total amount of OTR protein was not affected by oxytocin treatment for up to 24 h. Flow cytometry experiments demonstrated that OTRs were not internalized during this treatment. However, RNase protection assays and Northern analysis showed that in cultured myometrial cells OTR mRNA was reduced by oxytocin treatment to reach a new low steady-state concentration. Analysis of this mRNA in myometrial biopsies from 17 patients undergoing emergency Caesarean section showed how it decreased with advancing labour. Samples obtained after 12 h of labour contained approximately 50 times less OTR mRNA than samples obtained from patients in labour for less than 12 h. We speculate that this decrease in OTR mRNA represents in-vivo OTR desensitization. (+info)
Normal pregnancy is associated with enhanced endothelium-dependent flow-mediated vasodilation.
(2/1238)
Normal pregnancy is characterized by reduced systemic vascular resistance, which may be mediated by nitric oxide (NO). We compared endothelial vasomotor function in 71 normal pregnant women (13 in first, 29 in middle, and 29 in last trimester) to 37 healthy age-matched controls. With external ultrasound, brachial artery diameter was measured at rest, during reactive hyperemia [with increased flow causing endothelium-dependent dilation (FMD)], and after sublingual nitroglycerin (causing endothelium-independent dilation). Compared with controls, resting flow and brachial artery diameter were significantly higher during the middle and last trimesters. Reactive hyperemia was reduced in all pregnant groups. FMD increased from the first trimester (by 26%), reaching the highest value in the last trimester (to 47% above nonpregnant values). FMD was significantly correlated to pregnancy status (nonpregnant or pregnant) and to vessel size. Nitroglycerin-induced dilation was similar in pregnant and nonpregnant women. A longitudinal study of eight women evaluated in the first, middle, and last trimesters confirmed an increase in FMD throughout pregnancy. The study supports the idea that basal and stimulated NO activity is enhanced in normal pregnancy and may contribute to the decrease in peripheral resistance. (+info)
Fetal growth rate and adverse perinatal events.
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OBJECTIVE: To study fetal weight gain and its association with adverse perinatal events in a serially scanned high-risk population. SUBJECTS AND METHODS: A total of 200 pregnant women considered at increased risk of uteroplacental insufficiency had a total of 1140 scans in the third trimester, with a median of six scans in each pregnancy. The average fetal growth rate was retrospectively calculated for the last 6 weeks to birth, and expressed as daily weight gain in grams per day. Adverse pregnancy outcome was defined as operative delivery for fetal distress, acidotic umbilical artery pH (< 7.15), or admission to the neonatal intensive care unit (NICU). RESULTS: Fetuses with normal outcome in this high-risk pregnancy population had an average antenatal growth rate of 24.2 g/day. Compared to pregnancies with normal outcome, the growth rate was slower in those that required operative delivery for fetal distress (20.9 g/day, p < 0.05) and those that required admission to the NICU (20.3 g/day, p < 0.05). The growth rate in pregnancies resulting in acidotic umbilical artery pH also seemed lower, but this did not reach statistical significance. CONCLUSIONS: Impaired fetal weight gain prior to birth is associated with adverse perinatal events suggestive of growth failure. (+info)
Is normal pregnancy atherogenic?
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Serum cholesterol, triacylglycerols and low-density lipoprotein (LDL) subfractions were determined in 120 primagravid women during normal gestation (40 in each trimester) and in 20 non-pregnant age-matched controls. LDL subfractions were determined by PAGE, and an LDL score was calculated. The higher the score, the smaller the subfractions. The objective of the study was to determine the effects of the hyperlipidaemia, high oestrogen concentrations and insulin resistance known to exist in normal pregnancy on LDL subfraction formation. Pregnant women had an increased mean serum cholesterol concentration [5.78 (S.D. 1.09) mmol/l] in the first trimester compared with the non-pregnant controls [5.11 (0.77) mmol/l; P<0.01]. The serum cholesterol concentration increased progressively throughout gestation to a mean of 8.14 (1.39) mmol/l in the third trimester (P<0.001 compared with the second trimester). Triacylglycerol concentrations in the first trimester were similar to those of controls, and there was a non-significant increase by the second trimester to 1.32 (0.44) mmol/l. However, by the third trimester the mean triacylglycerol concentration had doubled [2.58 (0.98) mmol/l; P<0.001 compared with the first and second trimester]. During gestation the LDL score increased dramatically, from 1.17 (0.39) during the first trimester to 2.01 (0.37) in the second trimester (P<0.001) to 2.73 (0.48) in the third trimester (P<0.001 compared with the second trimester). Thus an atherogenic lipid profile develops during normal gestation. The significance of these changes remains unclear, but thay may have important implications for mother and foetus. (+info)
Characterization of human placental explants: morphological, biochemical and physiological studies using first and third trimester placenta.
(5/1238)
The primary objective of this study was to characterize an in-vitro model of the human placenta using morphological, biochemical and physiological parameters. Placental villi were obtained from normal first trimester and term pregnancies. The villi were incubated with Dulbecco's modified Eagle's medium: Ham's F12 nutrient mixture in a shaking water bath at 37 degrees C for up to 310 min. The viability was determined by the production of beta human chorionic gonadotrophin (HCG) and lactic dehydrogenase (LDH) and the incorporation of [3H]thymidine, [3H]L-leucine and L-[U14C]arginine, while ultrastructure was assessed by transmission electron microscopy. In the first and third trimester group, the release into the medium of the intracellular enzyme LDH remained unaltered throughout the experiment. By contrast, beta-HCG concentrations increased linearly and concentrations were higher in the first trimester than term villi (354.5 +/- 37.8 versus 107 +/- 8.1 IU/g villi protein; P < 0.001). Electron microscopy confirmed preservation of tissue viability for up to 4 h of incubation. The incorporation of thymidine (12.2 +/- 2.9 versus 5.2 +/- 0.5 nmol/g villi protein; P < 0.05), leucine (9.4 +/- 2.1 versus 1.9 +/- 0.4 nmol/g villi protein; P < 0.02) and arginine (17 +/- 4.4 versus 4.2 +/- 0.5 nmol/g villi protein; P < 0.05) were markedly higher in early than in term placenta. Furthermore, placental uptake of L-leucine by the first (9.4 +/- 2.1 versus 17 + 4.4 mol/g villi protein; P < 0.001) and third trimester placental villi (1.9 +/- 0.4 versus 4.2 + 0.5 mol/g villi protein; P < 0.001) was less than that of L-arginine. This study describes a simple technique using placental explants to determine relative rates of uptake of substrate amino acids throughout gestation. (+info)
Effect of insulin on fat metabolism during and after normal pregnancy.
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Whereas development of resistance to the action of insulin on glucose metabolism during gestation has been recognized, it is presently not known whether there is also resistance to the action of insulin on lipid metabolism. We have, therefore, examined the effect of physiological hyperinsulinemia (during euglycemic-hyperinsulinemic clamping) on free fatty acid (FFA) turnover in seven nondiabetic overweight or obese women during and after pregnancy. Basal rates of FFA release, oxidation, and reesterification and basal plasma FFA concentrations were not significantly different from each other during the 2nd and 3rd trimester of pregnancy and postpartum. During euglycemic-hyperinsulinemic (approximately 500 pmol/l) clamping, however, lipolysis was significantly less inhibited during the 3rd trimester (from 7.0 +/- 0.9 to 4.9 +/- 0.9 micromol x kg(-1) x min(-1), -30%) than during the 2nd trimester (from 8.4 +/- 0.6 to 4.1 +/- 0.9 micromol x kg(-1) x min(-1), -51%) and postpartum (from 8.5 +/- 1.1 to 4.2 +/- 0.6 micromol x kg(-1) x min(-1), -51%). Similarly, fat oxidation was not inhibited at all (from 3.5 +/- 0.3 to 3.8 +/- 0.5 micromol x kg(-1) x min(-1)) during the 3rd trimester but was suppressed by 51% (from 3.9 +/- 0.2 to 1.9 +/- 0.3 micromol x kg(-1) x min(-1)) during the 2nd trimester and by 38% (from 2.6 +/- 0.7 to 1.6 +/- 0.5 micromol x kg(-1) x min(-1) postpartum. These data demonstrated that resistance to the action of insulin on lipolysis and on fat oxidation developed during late gestation and disappeared postpartum. (+info)
Multiple metabolic defects during late pregnancy in women at high risk for type 2 diabetes.
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Detailed metabolic studies were carried out to compare major regulatory steps in glucose metabolism in vivo between 25 normal pregnant Latino women without and 150 pregnant Latino women with gestational diabetes mellitus (GDM). The two groups were frequency-matched for age, BMI, and gestational age at testing in the third trimester. After an overnight fast, women with GDM had higher fasting plasma glucose (P = 0.0001) and immunoreactive insulin (P = 0.0003) concentrations and higher glucose production rates (P = 0.01) but lower glucose clearance rates (P = 0.001) compared with normal pregnant women. During steady-state hyperinsulinemia (approximately 600 pmol/l) and euglycemia (approximately 4.9 mmol/l), women with GDM had lower glucose clearance rates (P = 0.0001) but higher glucose production rates (P = 0.0001) and plasma free fatty acid (FFA) concentrations (P = 0.0002) than the normal women. These intergroup differences persisted when a subgroup of 116 women with GDM who were not diabetic < or = 6 months after pregnancy were used in the analysis. When all subjects were considered, there was a very close correlation between glucose production rates and plasma FFA concentrations throughout the glucose clamps in control (r = 0.996) and GDM (r = 0.995) groups. Slopes and intercepts of the relationships were nearly identical, suggesting that blunted suppression of FFA concentrations contributed to blunted suppression of glucose production in the GDM group. In addition to these defects in insulin action, women with GDM had a 67% impairment of pancreatic beta-cell compensation for insulin resistance compared with normal pregnant women. These results demonstrate that women with GDM have multiple defects in insulin action together with impaired compensation for insulin resistance. Our findings suggest that defects in the regulation of glucose clearance, glucose production, and plasma FFA concentrations, together with defects in pancreatic beta-cell function, precede the development of type 2 diabetes in these high-risk women. (+info)
Assessment of serum thyroxine binding capacity-dependent biases in free thyroxine assays.
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BACKGROUND: Free thyroxine (FT4) assays may exhibit biases that are related to serum T4 binding capacity (sBC). We describe two tests that can be used to assess the presence and magnitude of sBC-dependent biases in FT4 assays. METHODS: We used a direct equilibrium dialysis FT4 assay as the reference method and compared the results obtained with those of the FT4 assays under investigation, in patient sera having a wide range of sBC. We then compared the expected and observed FT4 results for sera diluted with an inert buffer. Because serum dilution causes a predictable decrease in sBC, an increasingly negative bias on progressive dilution is indicative of a sBC-dependent bias. RESULTS: The automated FT4 assay investigated (Vitros FT4) showed no demonstrable sBC-dependent bias by either test. CONCLUSION: These two tests can be used to screen for sBC-dependent biases in FT4 assays. (+info)