Search PubMed⌕ Search

Biomedical subjects

F A Van Assche

Publications and source records attributed to F A Van Assche.

At least 37 records · Page 2Linked to original sources

Cystic hygroma colli as the first echographic sign of the fetal akinesia sequence.

We report first trimester cystic hygroma colli with subsequent resolution and development of a fetal akinesia deformation sequence. Neuropathological examination of the brain showed intra- and extracellular white matter edema while spinal cord, peripheral nerves and muscles were normal. Hygroma colli as the first echographic sign of subsequent severe fetal akinesia sequence without muscular dystrophy as seen in the Lethal Multiple Pterygium syndrome has not been previously reported.

Abnormalities, Multiple↗

Growth characteristics of diabetic rat ectoplacental cones in vivo and in vitro.

AIMS/HYPOTHESIS: To investigate the outgrowth of the ectoplacental cone in diabetic rats in vivo and in vitro. METHODS: Female Wistar rats were injected intraperitoneally with streptozotocin (75 mg/kg body weight, n = 15), or with control buffer (n = 27) 3 days before mating. On day 9 (day 1 = copulation plug) decidual swellings were weighed and the volume and mitotic index of the embryo and ectoplacental cone were estimated. Also, ectoplacental cones were cultured either in the presence of decidual cells from pseudopregnant diabetic rats or in high glucose concentration media. Cultures were evaluated by the daily outgrowth and by the proportion of giant cells and proliferating cells on day 5. RESULTS: In diabetic rats on day 9, the weight of the decidual swellings and the mitotic index in the ectoplacental cone were lower compared with controls (p < 0.0001 and p < 0.05, respectively). In vitro, control ectoplacental cones in the presence of decidual cells from diabetic rats showed a slight reduction in outgrowth on day 3 and 5 of culture. Outgrowth of diabetic ectoplacental cones in high glucose concentration medium was impaired on day 1 (p < 0.0005) compared with control ectoplacental cones in control medium, and on day 1 and 2 (both p < 0.005) compared with control ectoplacental cones in high glucose concentration medium. In control medium, the outgrowth of diabetic ectoplacental cones was impaired on day 1 (p < 0.05), compared with control ectoplacental cones. Proliferation was stimulated in diabetic ectoplacental cone cultures. CONCLUSION/INTERPRETATION: These data suggest that the outgrowth of diabetic ectoplacental cones is impaired by high glucose concentrations.

Animals↗

Maternal serum levels of macrophage colony-stimulating factor are associated with adverse pregnancy outcome.

OBJECTIVE: The aim of this study was the measurement of maternal serum levels of M-CSF throughout pregnancy, in a low risk obstetrical population, to examine the relationship of M-CSF and pregnancy outcome. STUDY DESIGN: Maternal serum was obtained at various stages of pregnancy and post partum, M-CSF levels were measured by ELISA, pertinent clinical data tabulated, and pregnancy outcome was determined. RESULTS: In 564 pregnancies studied, 22% of 260 nulliparous pregnancies and 10% of 304 multiparous pregnancies were hypertensive. Preeclampsia occurred in 1.5% of nulliparous and in 1% of the multiparous women. In apparently normal pregnancies with good outcome, M-CSF levels rose throughout pregnancy. No cases of preeclampsia occurred if maternal serum M-CSF levels increased more than 100% throughout pregnancy. CONCLUSIONS: This study suggests that absolute levels and relative changes in maternal serum M-CSF levels during pregnancy are associated with adverse pregnancy outcomes.

Birth Weight↗

Increase of the isoprostane 8-isoprostaglandin f2alpha in maternal and fetal blood of rats with streptozotocin-induced diabetes: evidence of lipid peroxidation.

OBJECTIVE: Pregnancy complicated by diabetes is associated with maternal complications and fetal abnormalities. Animal models of diabetes suggest that heightened free radical production may be implicated in the pathogenesis of this condition. The purpose of this investigation was to evaluate oxidative stress in plasma from diabetic rats and their fetuses through measurement of concentrations of 8-isoprostaglandin F(2alpha), a stable marker of lipid peroxidation. STUDY DESIGN: Diabetes was induced in virgin and pregnant rats with streptozotocin. Blood samples were collected after 20 days of diabetes. Adult and fetal plasma 8-isoprostaglandin F(2alpha) concentrations were determined by gas chromatography-mass spectroscopy. RESULTS: Significantly higher plasma 8-isoprostaglandin F(2alpha) concentrations were observed in the virgin rats with diabetes and in both the pregnant dams with diabetes and their fetuses when compared with their respective control groups without diabetes (P <.001). CONCLUSION: Oxidative stress was induced in both mother and fetus in rodent pregnancy complicated by diabetes. This finding may have implications for fetal dysmorphogenesis and in fetal programming for adulthood disease.

Animals↗

Cytotoxic effects of tumour necrosis factor (TNF)-alpha and interferon-gamma on cultured human trophoblast are modulated by fibronectin.

Tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma, produced by maternal inflammatory cells, may compromise trophoblast survival at the trophoblast-maternal interface and notably in the placental bed which is invaded by trophoblast. Extracellular matrix components, e.g. fibronectin, may enhance trophoblast survival. A possible protective effect of fibronectin against toxic effects of TNF-alpha and IFN-gamma was investigated in cultured trophoblasts isolated from six human term placentas, grown on uncoated and fibronectin-coated plastics. IFN-gamma and increasing doses of TNF-alpha resulted in decreasing viability of trophoblast on uncoated as well as fibronectin-coated dishes, as shown by 3-[4, 5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assays, but for each TNF/IFN treatment condition viability on fibronectin was higher (P < 0.001). Epidermal growth factor (EGF), a growth factor reported to protect against TNF-alpha/IFN-gamma induced toxicity, resulted in further increased viability, but not if IFN-gamma was included in the treatment. EGF caused increased fibronectin secretion into the medium (P < 0.001), and double cytokeratin/fibronectin immunostaining confirmed the trophoblastic nature of fibronectin secreting cells. We conclude that fibronectin increases viability, but does not completely abolish the cytotoxic action of TNF-alpha and IFN-gamma on trophoblast. The protective effect of EGF may be related to stimulation of fibronectin secretion by trophoblast.

Cell Survival↗

PROLACTIN-deficiency in adult offspring of diabetic mothers.

Maternal diabetes induces fetal alterations, resulting in lasting consequences for the glucose tolerance of the offspring over several generations. In our experimental rat model, circulating prolactin, oestradiol, progesterone and corticosterone levels, known to influence insulin secretion and action, are determined in plasma of female adult offspring of mildly and severely diabetic mothers. Prolactin and progesterone levels are equally low in both groups as compared to controls, stressing the involvement of the CNS in the transgeneration effect; oestradiol and corticosterone levels are normal. No correlation is found between these hormonal alterations and the known differences in glucose tolerance.

Animals↗

Dietary calcium and phosphate restriction in guinea-pigs during pregnancy: fetal mineralization induces maternal hypocalcaemia despite increased 1 alpha,25-dihydroxycholecalciferol concentrations.

Guinea-pig fetuses at term are mineralized to a degree comparable with human fetuses, which makes the guinea-pig an attractive animal model to study maternal-fetal interactions with regard to Ca and phosphate (P) homeostasis. We studied non-pregnant and pregnant (day 57) vitamin D-replete guinea-pigs, fed either a normal guinea-pig chow with 9.6 g Ca/kg and 4.9 g P/kg or a study diet with 2 g Ca/kg and 1 g P/kg (low-Ca-P diet) for 7-8 weeks. Both pregnancy and the low-Ca-P diet decreased plasma concentrations of 25-hydroxycholecalciferol (25(OH)D3), but increased total and free 1 alpha,25-dihydroxycholecalciferol (1,25(OH)2D3), strongly suggesting an additive stimulation of 1 alpha-hydroxylase activity. Maternal and fetal 25(OH)D3 and 1,25(OH)2D3 levels were highly correlated (r 0.82 and 0.92 respectively, P < 0.001). Dual-energy absorption X-ray absorptiometry (DXA) showed that both pregnancy and the low-Ca-P diet decreased bone mineral density (BMD) of the maternal femur, particularly at the distal metaphysis. Despite higher 1,25(OH)2D3 concentrations and lower BMD, pregnant animals on the low-Ca-P diet were hypocalcaemic; blood Ca2+ levels were inversely correlated with the number of fetuses in this group (r -0.93, P < 0.001). Fetal growth as well as mineralization (assessed by whole-body and femoral DXA, bone histomorphometry and plasma-bone osteocalcin measurements) were unaltered in the low-Ca-P group. In conclusion, fetal mineralization proceeds normally but induces maternal hypocalcaemia in guinea-pigs with dietary restriction of Ca and P.

Absorptiometry, Photon↗

Cholesterol-independent endothelial dysfunction in virgin and pregnant rats fed a diet high in saturated fat.

1. Western diets high in saturated fat are associated with an increased incidence of cardiovascular diseases. In this study we have evaluated vascular endothelial function and oxidative stress in virgin rats fed a normal (VC) or high in saturated fat diet (VHF) (20 % lard and corn oil w/w) from weaning until adulthood, and throughout subsequent pregnancy (PC and PHF, respectively). 2. The saturated fat diet was associated with enhanced noradrenaline sensitivity in small mesenteric arteries from VHF rats (VHF vs. VC, P < 0.05) and blunted endothelium-dependent relaxation in VHF and PHF rats (VHF vs. VC, P < 0.001; PHF vs. PC, P < 0.05). Endothelial dysfunction was attributable to a reduced nitric oxide component of relaxation in VHF rats, and blunted prostacyclin and endothelium-derived hyperpolarizing factor components in PHF rats. 3. Other than plasma cholesterol, which was reduced in VHF and PHF rats, plasma lipids were normal. Fasting plasma insulin and glucose concentrations were raised in VHF rats (P < 0.05) and the plasma marker of oxidative stress, 8-iso PGF2alpha, was increased in PHF animals (P < 0.01). 4. These findings suggest that endothelial dysfunction induced by a saturated fat diet is cholesterol independent and likely to be of different mechanistic origin in virgin and pregnant rats.

Adipose Tissue↗

Streptozotocin diabetes in the pregnant rat induces cardiovascular dysfunction in adult offspring.

Severe diabetes in pregnant rats produces persistent metabolic consequences in adult offspring. This study investigated whether diabetes in pregnant rats could also lead to cardiovascular abnormalities in the adult offspring. Blood pressure, heart rate and in vitro vascular reactivity of small arteries were evaluated in female adult offspring of control rats and of rats rendered diabetic with streptozotocin. Rise in blood pressures were similar in both groups of offspring but heart rate was lower in the diabetic offspring (p < 0.05). The rise in blood pressure associated with infusion of a nitric oxide synthase inhibitor was similar in both groups, but the associated decrease in heart rate was more pronounced in diabetic offspring (p < 0.01). Small mesenteric arteries from this group showed enhanced sensitivity to noradrenaline (p < 0.05) and abnormal endothelium-dependent relaxation to acetylcholine (p < 0.01) and bradykinin (p < 0.05). Reduction in acetylcholine induced relaxation, reflected reduced synthesis of nitric oxide or a cyclooxygenase product and was not attributable to an endothelium-derived hyperpolarizing factor. Sensitivity to exogenous nitric oxide was normal. A subgroup of pups born to diabetic dams were suckled by control maternal dams and a subgroup of those born to controls by diabetic dams. Suckling was an important determinant of impaired growth; offspring of diabetic rats suckled by their own mother and those of control rats by diabetic dams showed impaired growth rates whereas growth of offspring of diabetic rats suckled by control dams paralleled those of control rats suckled by their own mother.

Acetylcholine↗

Misoprostol compared with methylergometrine for the prevention of postpartum haemorrhage: a double-blind randomised trial.

OBJECTIVE: To compare the efficacy and side effects of misoprostol, compared with methylergometrine, for the prevention of postpartum haemorrhage. DESIGN: A double-blind, randomised clinical trial of 200 women with apparently normal pregnancies. SETTING: University teaching hospital. PARTICIPANTS: Two hundred women with apparently normal pregnancies. METHODS: After the baby had been born, all women received two capsules by mouth and the contents of an ampule by intravenous injection. Each woman only received one active product. The capsules contained either a total of 600 microg misoprostol or placebo, and the ampule 200 microg of methylergometrine or placebo. MAIN OUTCOME MEASURES: Need for further oxytocic drugs, blood pressure, the presence of side effects, mean haemoglobin and haematocrit three days after delivery. RESULTS: Two hundred women completed the study (100 received methylergometrine and 100 misoprostol). Postpartum haemorrhage occurred in 4.3% of the methylergometrine group and 8.3% of the misoprostol group (P = 0.57). The need for further oxytocic drugs was 4.4% and 12.8% after methylergometrine and misoprostol, respectively (P = 0.065). One hour after the birth of the baby there was no difference in the mean systolic blood pressure (117 +/- 12 mmHg versus 115 +/- 11 mmHg) (P = 0.26) or the mean diastolic blood pressure (72 +/- 10 mmHg versus 71 +/- 11 mmHg for the groups receiving methylergometrine or misoprostol, respectively) (P = 0.97). The mean temperature in the misoprostol group rose to 37.4 degrees C, compared with 37 degrees C in the methylergometrine group (P < 0.0001). In the misoprostol group 34% developed fever (> 38 degrees C) compared with 3% in the methylergometrine group (P < 0.0001). Shivering (visual analogue score > or = 8) also occurred more often after misoprostol (42%) than after methylergometrine (8.5%) (P < 0.0001). The haemoglobin level (g/dL) on the third postpartum day was similar for both groups ( 11.0 and 11.2 for methylergometrine and misoprostol, respectively) (P = 0.39). CONCLUSIONS: This study suggests that although protection from postpartum haemorrhage using parenteral methylergometrine and oral misoprostol is nearly equal, misoprostol is associated with more side effects.

Administration, Oral↗

Rupture of membranes before 26 weeks of gestation: outcome of 148 consecutive cases.

AIMS: To assess the outcome of preterm prelabor rupture of the membranes (PPROM) before 26 weeks of gestation and to develop a prediction model for survival. METHODS: 148 consecutive cases of PPROM before 26 weeks of gestation, collected between 1988 and 1996, were retrospectively analyzed. A multivariate analysis (generalized estimating equations) of 21 process and 5 short and long term outcome variables was performed. RESULTS: 40 out of 148 children (27%) died before or during birth, 57 (38.5%) of the children survived more than 28 days, from which still 5 died after one month. Amongst the 52 survivors (35.1%), the Bayley Mental Development Index and Psychomotor Development Index at a corrected age of 7 months was normal in respectively 85.7% and 75.5% of the cases. At 6-7 years of age, 24 out of 33 children (73%) performed adequately at school. Sex, gestational age at PPROM, birth weight, the administration of steroids and interactions of steroid administration with sex and with gestational age at the time of PPROM largely determined the chances of survival. CONCLUSIONS: Overall fetal survival after PPROM before 26 weeks of gestation was 35.1%. Survival can be predicted with an accuracy of 75%, a sensitivity of 85% and a specificity of 60%. More than 70% of the survivors behaved and performed adequately at school age, but 27% require special long-term attention and care.

Birth Weight↗

Maternal food restriction in the second half of pregnancy affects vascular function but not blood pressure of rat female offspring.

Food restriction during pregnancy in rats induces intrauterine growth retardation with consequences persisting into adulthood. In the present study we have investigated the hypothesis that malnutrition in pregnant rats may lead to altered cardiovascular function in adult female offspring. Perinatal growth retardation was induced by a 50% reduction of normal dietary intake in rats during the second half of pregnancy. Systolic and diastolic blood pressure values and heart rate were recorded in conscious female offspring (100 d old) using a femoral artery probe. No significant differences in heart rate, or in systolic and diastolic blood pressures were recorded between control offspring and offspring of nutritionally deprived rats. In order to ascertain whether cardiovascular variables in the offspring were influenced by lactation, subgroups of offspring from food-restricted dams were fostered with lactating dams fed on a normal diet. Blood pressure and heart rate were also found to be normal in these offspring. The rise in blood pressure associated with NO inhibition was similar in all groups. Isolated resistance artery function was assessed in vitro in offspring (100-120 d old) of a second group of semi-starved dams. Small mesenteric arteries from these animals showed reduced endothelium-dependent relaxation (to acetylcholine and bradykinin), but enhanced sensitivity to exogenous NO (sodium nitroprusside). We conclude that food restriction during the second half of pregnancy and/or lactation does not induce hypertension in adult offspring, but may effect subtle changes in vascular function.

Acetylcholine↗

Interaction of interstitial trophoblast with placental bed capillaries and venules of normotensive and pre-eclamptic pregnancies.

While endovascular trophoblast invasion of the human placental bed spiral arteries has been studied extensively, no information is available on the interaction between interstitially invading trophoblast and uterine capillaries and venules. Placental bed biopsies of eight normotensive and 15 pre-eclamptic patients were double-immunostained for cytokeratin and the endothelial marker CD31, providing satisfactory staining results in six and 10 biopsies, respectively. Interstitial trophoblast tissue density did not differ between the two series of biopsies, implying that this pathway of invasion is not impaired in pre-eclampsia. Both groups showed a similar incidence of approach of non-arterial vascular structures by perivascular trophoblast. Differences in CD31 staining intensity were noticed in different vascular cross-sections. Lower staining intensity was related to the presence of perivascular trophoblast. Because of the identity of CD31 with the platelet-endothelial cell adhesion molecule (PECAM)-1, the trophoblast-dependent downregulation of CD31 may play a role in the control of leukocytic traffic within the placental bed. The phenomena described in this paper did not show any difference between the normotensive and pre-eclamptic patients, implying that interaction of interstitial trophoblast with venous and capillary structures is not related to the pathogenesis of pre-eclampsia.

Adult↗

Immunolocalization of tumour necrosis factor-alpha (TNF-alpha) in the placental bed of normotensive and hypertensive human pregnancies.

To identify tumour necrosis factor (TNF)-alpha immunopositive cells, third trimester human placental bed biopsies were selected from nine normotensive control women, 16 severely pre-eclamptic patients and seven patients with pre-existing hypertension with superimposed pre-eclampsia. In addition, five first and early second trimester specimens were included in the study. Immunostaining was performed with a mouse IgG1 monoclonal antibody (J1D9) reactive specifically with human TNF-alpha (1:300 ascitic fluid), using a biotin-streptavidin-peroxidase technique. Variable staining of stromal cells was noted in all biopsies. Specimens of early pregnancy showed marked immunostaining for TNF-alpha on proliferating tips of anchoring villi, invasive interstitial cytotrophoblast (but not the multinuclear giant cells), and endovascular trophoblast invading the spiral arteries. At term, weak staining was found in trophoblast incorporated within spiral artery walls. In biopsies from pre-eclamptic patients, spiral arteries without physiological change showed very little staining except in atherotic vessels where the infiltrated lipophages often showed intense immunolabelling. The marked presence of TNF-alpha in extravillous cytotrophoblast of young specimens is suggestive of a role in early invasion. Immunostaining of foam cells in non-invaded spiral arteries in pre-eclampsia at or near-term indicates a potential role of this cytokine in the development of atherotic lesions.

Animals↗

Ultrastructural evaluation of B-cell recruitment in virgin and pregnant offspring of diabetic mothers.

Adult offspring of diabetic rat mothers display a disturbed glucose tolerance and gestational diabetes. The amount of endocrine pancreas and of B-cells is largely sufficient in these non-pregnant and pregnant youngsters. The present work aims a morphometric evaluation of B-cell activity in adult youngsters from control, mildly and severely diabetic mothers, in basal condition and in their adaptation to pregnancy. B-cells are divided, on basis of the ultrastructural morphology of their organelles, in dark non-activated B-cells and pale activated B-cells. These data are related to the concepts of functional B-cell heterogeneity and dose-dependent recruitment of pancreatic B-cells on stimulation. The recruitment of B-cells in each of the groups is evaluated from the proportion pale/dark B-cells. In control animals this is about 50/50, in both experimental groups there is a marked predominance of pale B-cells. During normal pregnancy, a shift occurs towards a majority of pale B-cells. In the offspring of diabetic mothers, the ratio does not further change during gestation. It can be concluded that the disturbance in B-cell stimulation and the development of gestational diabetes in offspring of diabetic mothers is associated with a maximal recruitment of the B-cells already in basal non-pregnant condition.

Animals↗

Fetal growth and long-term consequences in animal models of growth retardation.

Perturbations of the maternal environment involve an abnormal intrauterine milieu for the developing fetus. The altered fuel supply (depends on substrate availability, placental transport of nutrients and uteroplacental blood flow) from mother to fetus induces alterations in the development of the fetal endocrine pancreas and adaptations of the fetal metabolism to the altered intrauterine environment, resulting in intrauterine growth retardation. The alterations induced by maternal diabetes or maternal malnutrition (protein-calorie or protein deprivation) have consequences for the offspring, persisting into adulthood and into the next generation.

Animals↗

Renin-like immunoreactivity in uterus and placenta from normotensive and hypertensive pregnancies.

OBJECTIVES: (1) To identify the distribution of renin-like immunoreactivity in placental bed, placenta-free uterine wall, placenta, fetal membranes, and intertwin membranes obtained from normal pregnancies and (2) to compare the findings in normal pregnancies with those in pregnancies complicated by various hypertensive disorders. STUDY DESIGN: Biopsies were taken from 31 normotensive pregnant women, eight of whom had twin pregnancies, and from 28 women with various hypertensive disorders of pregnancy. The anti-human renal renin monoclonal antibody, F37.1A1, was used for immunostaining. Histological structures were identified with standard H&E and PAS techniques, supplemented with immunostaining using the specific cell markers CD68 and cytokeratin. RESULTS: Renin-like immunoreactivity was found in cytokeratin immunolabelled placental syncytiotrophoblast, amnionic and glandular epithelium, but most consistently in CD68 immunolabelled maternal and fetal macrophages. The distribution of renin-like immunoreactivity throughout the pregnant uterus roughly parallelled reported renin concentrations in the various tissues, while its localization conforms also with that of cathepsin D. There were no obvious differences in renin-like immunolabelling between normotensive or hypertensive women. Renin-like immunoreactivity was particularly common in the atherotic lesions that are observed more often in pregnancies complicated with hypertensive disorders of pregnancy and/or intra-uterine growth restriction. CONCLUSIONS: The data complement earlier findings showing that only two of four anti-renal renin monoclonal antibodies, both of which cross-react with cathepsin D, give a positive immunostaining in placental tissue. They question whether classical concepts on renin localisation in uteroplacental tissues all relate to one and the same enzyme. The demonstration of renin-like enzymes in different cell types, including macrophages, may explain the diversity of functions that has been attributed to uterine renin. There were no differences between tissues obtained from normotensive and hypertensive pregnancies, except for the consistent presence of renin-like immunoreactivity in atherotic lesions.

Antigens, CD↗

Lymphocytes and dendritic cells in the normal uterine cervix. An immunohistochemical study.

OBJECTIVE: Assessment of the appearance, distribution and numerical density of immune cell populations in the normal human uterine cervix. STUDY DESIGN SETTING: University Hospital Gasthuisberg. SUBJECTS: 29 healthy women undergoing total hysterectomy for non-cervical benign uterine disease. ANALYSIS: Immunohistochemistry and morphometrical analysis on histological sections containing ectocervix, transformation zone and endocervix, using antibodies against the following antigens: HLA-DR, CD4, CD22, CD1a and CD8. STATISTICAL ANALYSIS: Wilcoxon rank sum test. RESULTS: Lymphocytes in the epithelial and stromal compartments are predominantly T-lymphocytes. Intraepithelial T-lymphocyte and Langerhans' cell densities and their distribution are not influenced by the menstrual cycle and are the same in both ectocervix and transformation zone. CONCLUSION: The wide variation of T lymphocyte subpopulations and Langerhans' cell densities in the normal epithelium of the uterine cervix is stressed. We are the first to present a large and well-defined control series, which is indispensable to study the effect of smoking and other factors on the cervical immune system.

Adult↗