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Biomedical subjects

S Meuris

Publications and source records attributed to S Meuris.

At least 37 records · Page 2Linked to original sources

In-vivo and in-vitro assessment of the influence of ritodrine and oxytocin on the placental secretion of human chorionic gonadotrophin and placental lactogen.

The purpose of this study was to evaluate, in vivo and in vitro, the influence of ritodrine and oxytocin on the placental release of human chorionic gonadotrophin (HCG) and placental lactogen (HPL). The in-vivo study was performed on maternal sera collected before and 1 h after the onset of either ritodrine treatment (50 micrograms i.v./min; administered to 15 women at risk of premature labour) or oxytocin infusion (2 mU i.v./min; administered to 21 women for acceleration of slow labour). The in-vitro study was performed on human term placental explants incubated in the presence of 4-400 ng ritodrine/ml or 15-1500 microU oxytocin/ml. HCG and HPL were measured by radioimmunoassay on maternal sera and incubation media. Maternal circulating concentrations of HCG and HPL remained unaffected after 1 h of ritodrine or oxytocin treatment. The in-vitro release of HCG and HPL by placental explants was not modified when ritodrine or oxytocin was added to the incubation media. The lack of influence of ritodrine and oxytocin on the placental secretion of HCG and HPL suggests that beta 2-adrenergic and oxytocin receptors are not involved in the releasing process.

Adrenergic beta-Agonists↗

Total amount of circulating human chorionic gonadotrophin alpha and beta subunits in first trimester trisomies 21 and 18.

The aim of this study was to evaluate the variations in the balance between total (free and combined) circulating alpha and beta subunits of human chorionic gonadotrophin (hCG) in trisomy 21 and 18. Maternal serum samples were collected at 10 and 11 weeks of gestation from 22 singleton pregnancies with trisomy 21 (n = 17) and trisomy 18 (n = 5) and 66 chromosomally normal controls, matched for gestational age. The hCG and free alpha and beta subunits circulating levels were measured using specific immunoradiometric assays and converted in a common unit system obtained using calibration of the assays with intact and thermally dissociated purified hCG preparation. In trisomy 21, the only significant difference from controls was in the free beta hCG level which was increased. In trisomy 18, intact hCG, free beta hCG as well as total alpha hCG and total beta hCG levels were significantly lower whereas the free alpha hCG level was significantly higher than in controls. The decrease in total beta hCG was more pronounced than the decrease in total alpha hCG resulting in a significant increase in the total alpha- to beta hCG subunit ratio in trisomy 18. These findings suggest some modifications in the biosynthesis and/or release rates of the hCG subunits in these trisomies.

Chorionic Gonadotropin↗

Comparative evaluation of a high lipase pancreatic enzyme preparation and a standard pancreatic supplement for treating exocrine pancreatic insufficiency in chronic pancreatitis.

OBJECTIVE: To compare the efficacy and safety of two enzyme-containing preparations, Pancrease HL (Cilag) containing 25,000 units of lipase per capsule and Creon (Triosol) with 8000 units of lipase per capsule, in patients with chronic pancreatitis and exocrine insufficiency. DESIGN: The study is a monocentric open crossover prospective study including 25 patients entered from March 1993 to May 1994. PATIENTS: Chronic pancreatitis was alcohol-related in 23 patients, previous surgery was performed in 9, 16 had diabetes and all had steatorrhoea (fat balance > 10g/24h). METHODS: Patients were investigated during four periods of 2 weeks, each one corresponding to a new treatment regimen: Pancrease HL, 3 capsules/day or Creon, 9 capsules/day, with or without omeprazole 20 mg/day. Stools were collected on the last 3 days at the end of each period when the patients were on a standard diet with a fixed daily intake of 100 g fat/day. RESULTS: Faecal fat, protein and energy excretion did not differ when both preparations were compared at roughly pharmaceutically equivalent doses. No significant improvement in fat and protein absorption was observed when omeprazole was taken with the pancreatic enzymes. However, omeprazole treatment was associated with a marked decrease in the fat-protein content ratio, suggesting an improvement in the fat digestive process but a decrease in the efficiency of protein digestion. Drug safety was comparable in the four groups of treatment. CONCLUSION: Pancrease HL with high lipase activity provides effective pancreatic enzyme replacement therapy in patients with chronic pancreatitis at an appreciably lower number of capsules per day than with standard preparations.

Cross-Over Studies↗

Simultaneous measurement of 45Ca outflow and human placental lactogen release from placental explants.

Kinetics of 45Ca outflow and human placental lactogen (hPL) release were characterized in human placental explants. Measurements of the rate of 45Ca and [3H]-sucrose (extracellular space marker) outflow from preloaded explants showed that, after a 40 min washout period, the 45Ca effluent radioactivity presumably originated from an intracellular compartment. This view was further supported by the La3+ and temperature sensitivity of the 45Ca outflow. Moreover, the addition of ionomycin as well as an increase in the extracellular Ca2+ or Ba2+ concentration provoked a dose-dependent rise in both the 45Ca outflow and hPL release. There were no systematic temporal analogies between the pattern of 45Ca outflow and hPL release. Taken together, these observations suggest that the stimulation of 45Ca outflow reflects an increased rate of 40Ca entry. The present data also extend previous observations indicating that hPL release can be stimulated by Ca2+ entry. Lastly, the 'in vitro' method described herein allows one to compare rapid changes in hPL release with associated ionic events and can be used to further document the relationships between placental secretory responses and cell calcium metabolism.

Barium↗

Coelomic fluid chorionic gonadotrophin and protein concentrations in normal and complicated first trimester human pregnancies.

Coelomic fluid and maternal serum samples were collected from 43 normal pregnancies and 18 missed abortions between 7 and 12 weeks of gestation. The samples were analysed for the concentrations of intact human chorionic gonadotrophin (HCG), free alpha HCG, free beta HCG and total protein. The relationships between the biological findings and the ultrasound and pathological features were assessed by regression analysis. In normal pregnancies, intact HCG, free alpha HCG and free beta HCG concentrations were respectively 1.3, 185 and 33 times higher in coelomic fluid than in maternal serum. The coelomic concentrations of intact HCG and free alpha HCG decreased significantly with advancing gestation. No relationship was found between coelomic fluid and maternal serum concentrations of the different variables. These findings suggest that in normal pregnancies, the concentration of HCG in the coelomic fluid, as in maternal serum, is mainly influenced by cytotrophoblastic differentiation and that the metabolic clearance of HCG molecules is slower in the coelomic cavity than in maternal serum. In missed abortions, the serum concentrations of intact HCG, alpha HCG and free beta HCG and the coelomic concentration of total protein were significantly lower than in normal pregnancies. In three out of nine anembryonic pregnancies diagnosed by ultrasound, embryonic remnants were present at histological examination. The coelomic concentration of total protein was extremely low in all missed abortions with advanced trophoblastic necrosis whereas the HCG concentration was low when embryonic remnants were absent. These findings support the concept that embryonic and placental development are closely related in the first trimester of human pregnancy, placental biological functions persisting only for a limited period of time after embryonic demise.

Abortion, Missed↗

Temporal relationship between the human chorionic gonadotrophin peak and the establishment of intervillous blood flow in early pregnancy.

The purpose of this study was to investigate the temporal relationship between the early pregnancy peak of circulating human chorionic gonadotrophin (HCG) concentration and the establishment of maternal blood flow in the placental intervillous space. The presence of blood flow echoes within intervillous space was determined by colour Doppler imaging from 44 women with clinically uncomplicated pregnancy between 6 and 18 weeks gestation. Circulating HCG, free alpha- and beta HCG subunits, oestradiol and progesterone concentrations were immunoassayed in blood samples collected at the time of Doppler examination. A continuous intervillous blood flow was detected in all cases with a gestational age > or = 11.7 weeks (n = 18) but never before this time. Circulating concentrations of free alpha HCG, oestradiol and progesterone were linearly or exponentially correlated with gestational age (r = 0.860, 0.903 and 0.538 respectively, all with P < 0.001), indicating steady increase of these hormones with advancing gestation. However, the best fitted lines were found to be parabolic for HCG (r = 0.771, P < 0.001) and beta HCG (r = 0.695, P < 0.001), their highest points corresponding to 11.24 and 10.74 weeks gestational age respectively. The close temporal relationship between the Doppler advent of intervillous maternal blood flow and the HCG peak suggests that the establishment of the intervillous blood flow is associated with the decline in circulating HCG concentrations.

Chorionic Gonadotropin↗

Changes in the coelomic fluid composition following two different methods of cervical ripening.

We have evaluated the changes in maternal serum and coelomic fluid biochemical composition following two different methods of cervical ripening, i.e. mechanical and biochemical. Each study group included 20 women between 8 and 12 weeks of gestation who were requesting termination for psychosocial reasons. In the first group, a 3 mm hypan (synthetic hygroscopic dilator) was inserted into the cervix 12 h preoperatively. In the second group, two 1 mg pessaries of gemeprost (prostaglandin analogue) were inserted into the posterior fornix 6 and 2 h preoperatively. Coelomic fluid and maternal serum were obtained at the time of the surgical procedure and assayed for urea, total protein, potassium, sodium, human chorionic gonadotrophin (HCG) and alpha-fetoprotein (AFP). Significantly higher coelomic fluid sodium (t = 4.72; P = 0.029) and significantly higher maternal serum AFP (t = 13.21; P < 0.001) concentrations were observed after gemeprost than after hypan. There was no difference in the concentration of potassium, urea, total protein and HCG between the two groups. These findings indicate that prostaglandin analogues, when used for cervical ripening, provoke a breakdown of the placental barrier resulting in an increase in AFP molecules transferred from the fetal fluid compartments into the maternal circulation. The results also suggest that these drugs increase the placental permeability to sodium with a secondary accumulation of this ion in the coelomic fluid.

Abortion, Induced↗

Ca2+ entry through L-type voltage-sensitive Ca2+ channels stimulates the release of human chorionic gonadotrophin and placental lactogen by placental explants.

The release of human chorionic gonadotrophin (hCG) and placental lactogen (hPL) by human placental explants can be stimulated by Ca2+ entry. The aim of the present study was to characterize the modality of Ca2+ entry in the presence of high extracellular K+ concentration ([K+]o). A rise in [K+]o from 5 to > or = 50 mM induced a rapid and marked increase in the release of hCG and hPL from human term placental explants. The stimulatory effects of an excess [K+]o on the release of hCG and hPL were blocked in the absence of extracellular Ca2+ or in the presence of 0.5 mM Co2+. The presence of 50 microM methoxyverapamil, 20 microM nifedipine or 40 microM Cd2+ in the medium inhibited the stimulatory effects of [K+]o addition. Lastly, 40 microM Ni2+ failed to affect the increases in hCG and hPL releases elicited by [K+]o addition. Our data clearly show that a rise in [K+]o stimulates the release of hCG and hPL from placental explants. These secretory effects can be viewed as resulting from a Ca2+ entry through voltage-sensitive Ca2+ channels of the L-type.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Biochemical composition of the coelomic fluid in anembryonic pregnancy.

OBJECTIVE: Our purpose was to investigate the biochemical composition of the coelomic fluid in first-trimester anembryonic pregnancies. STUDY DESIGN: Coelomic and maternal serum were obtained from 17 anembryonic pregnancies and 17 apparently normal pregnancies between 7 and 12 weeks of gestation that were matched for gestational age. Electrolytes, total proteins, urea, creatinine, lactate, and human chorionic gonadotropin concentrations and pH were measured. RESULTS: Significantly higher pH (p < 0.005) and bicarbonate levels (p < 0.001) and significantly lower total protein (p < 0.05), phosphate (p < 0.005), and human chorionic gonadotropin (p < 0.001) levels were found in coelomic fluid from anembryonic pregnancies compared with normal pregnancies. No difference was found for chloride, sodium, potassium, urea, creatinine, and lactate between the study and control groups. CONCLUSIONS: The fluid collected in anembryonic pregnancies is of exocoelomic origin and its biochemical characteristics reflect a failure of most placental biological mechanisms such as metabolic function, transport function, and endocrine activity.

Bicarbonates↗

Immunolocalization and expression of insulin-like growth factor I (IGF-I) in the mammary gland during rat gestation and lactation.

We have studied the physiology and tissue expression of IGF-I and IGF-BP3 in pregnant and lactating rats. Specific assays (radioimmunoassays and a binding protein assay) were used to measure serum IGF-I, IGF-II, and IGF-BP levels. IGF-I and IGF-BP3 expression levels were determined in mammary gland and liver by slot-blotting. A sensitive and IGF-I-specific ribonuclease (RNAse) protection assay was further used to detect RNAs transcribed from the IGF-I gene. In the first half of pregnancy, the maternal serum IGF-I concentration rises while the IGF-BP level decreases. This may modify IGF-I availability, thus promoting rapid tissue growth and differentiation. In the second half of pregnancy, the mean serum IGF-I concentration falls sharply from 1140 +/- 150 ng/ml at seven days of pregnancy to 470 +/- 85 ng/ml at 20 days. Post-partum, serum IGF-I increases back to the level obtained in non-pregnant controls within 5 days. Serum levels of IGF-BP, during the same two periods, follow a similar pattern, decrease during pregnancy and increase after parturition. No IGF-II was detected at any time. From the onset of pregnancy to term, IGF-I gene expression in the mammary gland diminishes. In the liver, on the other hand, expression increases during very early pregnancy and diminishes thereafter, remaining below the level measured in non-pregnant animals from mid-pregnancy to term. The pattern of IGF-BP3 expression followed was similar in both organs, with a decrease during gestation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Origin and significance of the heterogeneity of protein hormones.

The heterogeneity of circulating protein hormone is the result of multiple steps including gene expression, mRNA maturation, post-translational processing and peripheral catabolism. As a consequence of these cumulative events, it seems difficult to evaluate the endocrine function by using specific radioimmunoassays for each circulating variant of a protein hormone. Moreover, the discovery of new molecular variants of protein hormones with unknown biological significance complicates the standardization and the clinical interpretation of immunoassays.

Blood Proteins↗

The release of human chorionic gonadotrophin and placental lactogen by placental explants can be stimulated by Ca2+ entry through a Na(+)-Ca2+ exchange process.

Isosmotical replacement of extracellular Na+ ([Na+]o) by K+, choline and to a lesser extent by saccharose stimulated the release of chorionic gonadotrophin and placental lactogen from human term placental explants. The effect of [Na+]o removal on the release of both hormones was concentration-dependent and was inhibited in the absence of extracellular Ca2+ or in the presence of 0.5 mM Co2+, a Ca2+ entry blocker. Blockers of the voltage-sensitive Ca2+ channels (20 microM nifedipine and 50 microM methoxyverapamil) or Na+ channels (5 microM tetrodotoxin) did not affect the stimulatory effects of [Na+]o omission. By contrast, Mg2+ and Sr2+ (10 mM) as well as amiloride (2 mM) and its analogue 2',4'-dimethylbenzamil (50 microns), all known to affect the Na(+)-Ca2+ exchange, markedly reduced the increase in hormone release elicited by [Na+]o removal. Lastly, the secretory responses to [Na+]o deprivation were increased in the presence of 2 mM ouabain, an inhibitor of the Na(+)-K+ ATPase. These results indicate for the first time that [Na+]o omission provokes a Ca(2+)-dependent stimulation of human chorionic gonadotrophin and placental lactogen releases. The pharmacological dissection of the secretory effects of [Na+]o removal supports the existence of a process of Na(+)-Ca2+ exchange in placental cells.

Calcium↗

Total amounts of circulating human chorionic gonadotrophin alpha and beta subunits can be assessed throughout human pregnancy using immunoradiometric assays calibrated with the unaltered and thermally dissociated heterodimer.

The aim of the present study was to determine the variations in the balance between total (free plus combined) circulating alpha and beta subunits of human chorionic gonadotrophin (hCG) throughout human pregnancy. The equivalence between the International Units (IU) of hCG (IRP 75/537) and those assigned to the alpha (IRP 75/569) and beta (IRP 75/551) free subunits was experimentally determined by using intact and thermally dissociated hCG. Heat exposure (2 min at 100 degrees C) of hCG preparations resulted in a complete dissociation of hCG into free, soluble and intact alpha and beta subunits. The hCG and alpha and beta subunit contents of unaltered and heated hCG preparations were assessed by specific immunoradiometric assays. The amount of immunoreactive subunits dissociated by heat from hCG could then be evaluated on a molar basis. Circulating hCG and its free alpha and beta subunits were immunoassayed in 836 blood samples collected from healthy pregnant women at different gestational ages. After conversion of hCG and its subunits into a common IU system, the gestational profiles of the total amounts (free plus combined) of alpha- and beta hCG subunits increased together and peaked at 9-10 weeks of gestation. Thereafter, total alpha and beta subunits decreased and subsequently remained stable until term. The decline in total alpha hCG subunit was less marked than that of total beta hCG subunit. The alpha- to beta hCG ratio was equimolar until 10 weeks of gestation when it increased almost fourfold until term (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Chorionic Gonadotropin↗

Placental production of human chorionic gonadotrophin alpha and beta subunits in early pregnancy as evidenced in fluid from the exocoelomic cavity.

Levels of human chorionic gonadotrophin (hCG) and of its free alpha and beta subunits were measured using specific immunoradiometric assays in exocoelomic fluid (ECF) and maternal serum (MS) collected from five pregnant women at 6.6-8 weeks of gestation. Mean levels of hCG and its free subunits were significantly (P < 0.001) higher in ECF than in MS: 3.5-fold for hCG, 600-fold for free alpha hCG and 38-fold for beta hCG. There was no correlation between either hCG levels or levels of its free subunits in ECF and MS. On a molar basis, the quantity of free alpha hCG subunit expressed as a percentage of the total (free+combined) amount was 83% in ECF and 2.7% in MS (P < 0.001). The amount of free beta hCG subunit as a percentage of the total was 22% in ECF and 3.5% in MS (P < 0.001). The ratio of the total amounts of alpha- and beta hCG subunits amounted to 4.6 in ECF and 0.99 in MS (P < 0.001). The heterogeneity of hCG was further investigated by polyacrylamide gel electrophoresis followed by immunoblotting. Several bands with molecular mass ranging from 42 to 57 kDa, corresponding to hCG dimers, were immunodetected in ECF and MS with anti-alpha hCG and anti-beta hCG monoclonal antibodies. A free 35 kDa beta hCG immunoreactive band was found in ECF and MS. A free alpha hCG immunoreactive band was observed at 23 kDa in ECF and at 21 kDa in MS. These findings suggest that the exocoelomic cavity is a reservoir where hCG and its subunits produced by trophoblast accumulate directly.(ABSTRACT TRUNCATED AT 250 WORDS)

Chorionic Gonadotropin↗

The role of relaxin in the development of the uteroplacental circulation in early pregnancy.

OBJECTIVE: To evaluate the relation between the development of the uteroplacental circulation as assessed by Doppler velocimetry and the maternal blood relaxin concentration. METHODS: Transvaginal color Doppler investigation of the uteroplacental circulation was performed in 42 healthy women at 6-15 weeks' gestation before termination of pregnancy for psychosocial reasons. The resistance index (RI), pulsatility index (PI), and maximum peak velocity were recorded at the level of the main uterine artery, and the presence of intervillous flow was noted. Relaxin, hCG, 17 beta-estradiol (E2), and progesterone levels were measured in maternal venous blood. RESULTS: Limited intervillous flow was noted from 10 weeks' gestation and continuous intervillous flow from 12 weeks. An inverse relation was observed between the circulating levels of both E2 and progesterone and uterine artery RI and PI, whereas the relaxin level correlated positively with uterine RI and PI. Estradiol and progesterone levels also correlated positively with uterine peak systolic velocity and intervillous blood flow. Multiple linear regression analysis indicated that both hormones contributed to the decrease in downstream resistance to uterine blood flow with advancing gestational age, as assessed by uterine RI. In addition, relaxin contributed to the uterine RI and PI and to the intervillous blood flow. CONCLUSION: These data suggest that relaxin, E2, and progesterone may influence the changes in uterine blood flow that occur in early pregnancy. The role played by E2 and progesterone in the development of the uteroplacental circulation may be modulated by relaxin, constituting a novel function for this ovarian peptide.

Blood Flow Velocity↗

Deficient activity of FAD-linked glycerophosphate dehydrogenase in islets of GK rats.

In pancreatic islet extracts of rats with hereditary non-insulin-dependent diabetes mellitus (GK rats), the activity of the mitochondrial FAD-linked glycerophosphate dehydrogenase, as measured by either a radioisotopic or colorimetric procedure, only represented 30 to 40% of that found in control rats. This decrease in enzymic activity was not attributable to any sizeable change in either islet DNA content or the relative contribution of insulin-producing beta cells to total islet mass. It contrasted with a normal activity of other mitochondrial dehydrogenases and hexokinase isoenzymes. It coincided, however, with an increased activity of glutamate-pyruvate transaminase, as already observed in adult rats injected with streptozotocin during the neonatal period. The decreased activity of islet FAD-linked glycerophosphate dehydrogenase also contrasted with an increased activity of the same enzyme in the liver of GK, as compared to control rats. In the light of these findings and recent metabolic data collected in intact islets of GK rats, it is proposed that a deficiency of beta-cell FAD-linked glycerophosphate dehydrogenase, the key enzyme of the glycerol phosphate shuttle, may represent a cause of inherited non-insulin-dependent diabetes.

Alanine Transaminase↗

Serum levels of intact human chorionic gonadotropin (HCG) and its free alpha and beta subunits, in relation to maternal thyroid stimulation during normal pregnancy.

The main objective of the present study was to present additional evidence of the potentially important thyrotropic role of hCG to regulate the maternal thyroid gland during normal pregnancy. Sequential determinations (first and last trimesters) of intact hCG, free alpha and beta-hCG subunits concentrations (using monoclonal IRMAs), and assessment of parameters of thyroid function and thyroid volume were carried out in 62 pregnant women who exhibited during the first trimester of gestation low TSH levels (< or = 0.20 mU/L), and compared to 276 pregnant women with normal TSH levels. The prevalence of having low serum TSH represented 18% of all pregnancies, with almost one half of cases who transiently had undetectable TSH levels. Lowering of TSH was associated with high hCG levels, and occurred primarily during the first trimester. About 10% of women with low TSH presented transient gestational thyrotoxicosis, frequently associated with vomiting. In comparison to control subjects, women with a suppressed serum TSH had significantly and markedly higher intact hCG and free beta-hCG subunit concentrations. The results suggest that TSH reduction may result from a relative oversecretion of both intact hCG and free beta-hCG subunits, compatible with three hypotheses: a) transient overexpression of the beta-hCG gene, leading to enhanced production of hCG heterodimer; b) increased glycosylation of circulating hCG, with in turn a prolonged half life; c) larger syncytiotrophoblast mass with increased hCG production.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗