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Biomedical subjects

Tore Henriksen

Publications and source records attributed to Tore Henriksen.

At least 19 recordsLinked to original sources

Increase in matrix metalloproteinases from endothelial cells exposed to umbilical cord plasma from high birth weight newborns.

Large for gestational age infants have increased risk of developing the metabolic syndrome and cardiovascular disease in child- and adulthood. The vascular endothelium is a target site in the pathogenesis of many cardiovascular disorders. The matrix metalloproteinases (MMP) are important modulators of the extracellular matrix and serve as markers of these disorders. Here, we asked whether umbilical cord plasma of high birth weight (HBW; >4 kg) infants could modulate functional properties of human umbilical vein endothelial cells (HUVEC) compared with plasma from normal birth weight (NBW; 3.1-3.6 kg) infants. To test this, HUVECs were exposed for 48 h to 20% venous cord plasma from HBW or NBW infants. The MMP activity in supernatants of HUVECs exposed to HBW plasma was nearly three times higher (P < 0.05) than that obtained with NBW plasma. MMP-9, but not MMP-2, protein concentration and mRNA expression were enhanced in HBW (P < 0.05). With specific blockers, MMP activity and mRNA-MMP-9 were inhibited by approximately 60-70%. Cord lipid and insulin concentrations were similar (P > 0.05) among the two groups. We could not detect any significant differences between the two groups in the concentrations of proinflammatory cytokines or specific tissue inhibitors of MMP in plasma or HUVEC supernatants. In conclusion, cord plasma from HBW infants induced more MMP-9 in HUVECs compared with cord plasma from NBW infants. Although not identified, cord plasma of HBW infants may contain factors that increase endothelial cell MMP. These findings may indicate an association between fetal nutritional conditions and endothelial cell functions.

Adult↗

Altered hemostatic balance and endothelial activation in pregnant women with familial hypercholesterolemia.

INTRODUCTION: Patients with familial hypercholesterolemia (FH) are prone to premature cardiovascular disease. During pregnancy plasma lipids reach higher absolute values in FH than in healthy women. Pregnancy is associated with activation of coagulation and possibly also of vascular endothelium, which might further increase the risk of cardiovascular disease in FH. However, whether hemostatic and endothelial activation markers are increased in pregnant FH women compared with non-FH pregnancies, is unknown. MATERIALS AND METHODS: Activation markers of hemostasis and endothelium were analyzed in blood samples collected prospectively from 22 heterozygous FH women during pregnancy and compared with those of a reference group of 149 healthy, pregnant women. RESULTS: A procoagulant pattern was detected in both groups, but was more evident among FH women at least partly due to their enhanced thrombin generation, and because tissue factor pathway inhibitor type 1 increased in the reference group only. Furthermore, plasminogen activator inhibitor type 2 antigen increased more in FH than in the reference group. Whereas C-reactive protein, intercellular adhesion marker-1 and E-selectin did not change appreciably, vascular endothelial cell adhesion molecule 1 rose markedly in FH. CONCLUSION: Increased lipid levels as well as a net procoagulant activity and an enhanced endothelial activation possibly confer additional risks of cardiovascular disease among pregnant FH women.

Adult↗

Effect of hyperglycemic condition on proteoglycan secretion in cultured human endothelial cells.

BACKGROUND: Proteoglycans (PGs) are important constituents of the plasma membrane and of the basement membrane supporting the endothelial cell layer. Changes in the amounts or the structures of PGs in the endothelium may affect important functions such as turnover of lipoproteins, filtration properties, and regulation of chemokines during inflammation, which are all relevant in diabetes. AIM OF THE STUDY: The purpose of this study was to investigate if hyperglycemic conditions would affect the biosynthesis and secretion of PGs in cultured primary human endothelial cells. METHODS: Primary human umbilical cord vein endothelial cells were established and cultured in vitro. The cells were cultured either in medium with low glucose (LG) (1 g/l) or high glucose (HG) (4.5 g/l). From day 3-4 cells were labeled with (35)S-sulfate for 24 h. (35)S-Labeled macromolecules (medium) were purified by gel chromatography, and isolated macromolecules were analyzed by gel chromatography after different types of treatment, electrophoresis, and immunoprecipitation. RESULTS: Lower levels of secreted PGs were found in human endothelial cells exposed to HG. The major part of the PGs released was of the heparan sulfate (HS) type, and immunoprecipitation experiments showed that one such PG was syndecan-1. However, there was no difference in the ratio between HS and chondroitin sulfate (CS) under the different experimental conditions. Further, the PGs expressed neither differ with regard to molecular size of the glycosaminoglycan (GAG) chains, nor were their polyanionic properties affected by the different experimental conditions. CONCLUSION: The results obtained suggest that treatment of primary human endothelial cells with hyperglycemia leads to a decrease in PG secretion in primary cultures of human endothelial cells.

Basement Membrane↗

High glucose and Nepsilon-(carboxymethyl) lysine bovine serum albumin modulate release of matrix metalloproteinases in cultured human endothelial cells.

BACKGROUND: Hyperglycaemia may contribute to endothelial dysfunction. Disturbances in endothelial functions include changes in the extracellular matrix underneath the cells. This may result from altered biosynthesis of matrix molecules or from modified biosynthesis and secretion of enzymes involved in the turnover of extracellular matrix. One important class of such enzymes are the matrix metalloproteinases (MMPs). AIM OF THE STUDY: The aim of this study was to investigate whether the condition of high glucose concentration relevant both to diabetes type 1 and 2 and metabolic syndrome, would affect the synthesis and release of MMPs in human umbilical cord endothelial cells (HUVEC) in vitro. METHODS: The HUVEC were isolated and cultured in vitro. The cells were exposed to medium with either low glucose (LG, 1 g/l) or high glucose (HG, 4.5 g/l) or the advanced glycation end product (AGE) N(epsilon)-(carboxymethyl) lysine bovine serum albumin (CML-BSA), at a concentration of 10 microg/ml. The HUVEC-conditioned media were harvested and subjected to gelatin zymography and Western blotting. RESULTS: When HUVEC were incubated with HG or CML-BSA under serum free conditions a decreased secretion of pro MMP-2 was observed, both with gelatin zymography and Western blotting. The HUVEC also secreted MMP-9, but at lower levels, and effects of HG treatment were not significant. When HUVEC were stimulated with phorbol 12-myristate 13-acetate (PMA) secretion of pro MMP-2 was not increased, but the activation of pro MMP-2 into lower molecular forms increased, irrespective of culturing in LG, HG or CML-BSA. CONCLUSION: The HUVEC exposed to high glucose or AGE exhibit decreased secretion of MMP-2. These findings may be relevant in understanding the altered turnover of the endothelial extracellular matrix observed in the diabetic state.

Blotting, Western↗

Pregnancy complications by overweight and residential area. A prospective study of an urban Norwegian cohort.

BACKGROUND: Health varies in residential areas of different socioeconomic status in the capital of Norway. This study compares risks of pregnancy complications in Oslo according to prevalence of overweight and areas of residency. METHODS: Prospective cohort study of 3,677 pregnancies. Pregnancy outcomes were retrieved from medical records after delivery. Statistics were performed by logistic regression analyses. RESULTS: Pregnant women from areas of lower socioeconomic status (Oslo East) had higher prevalence of overweight than women from areas of higher status (Oslo West). Dose-response relationships were found between body mass index and increased risk of pregnancy complications (pre-eclampsia, gestational hypertension, gestational diabetes mellitus, macrosomia, cesarean deliveries, acute cesarean deliveries, transfer of the newborn to neonatal intensive care unit). Comparing Oslo East with Oslo West the relative risks of pregnancy complications were 1.8 for pre-eclampsia, 1.6 for gestational diabetes, 1.4 for acute cesarean deliveries, 1.6 for low birth weight (< or =2,500 g) and 1.5 for transfer to neonatal intensive care. Adjustment for body mass index did not change the increased risks of pre-eclampsia, acute cesarean deliveries, low birth weight, or transfer to neonatal intensive care among Oslo East women. Only the increased risk of gestational diabetes could partially be explained by higher body mass index. CONCLUSIONS: Residential areas of lower socioeconomic status had higher risk of pregnancy complications. Overweight was a strong independent predictor of pregnancy complications. The higher prevalence of overweight in Oslo East could, however, not explain the increased risk of pregnancy complications.

Adult↗

Eclampsia in Scandinavia: incidence, substandard care, and potentially preventable cases.

BACKGROUND: Description of incidence, clinical signs, symptoms, and consequences of eclampsia in Scandinavia, and assessment of substandard care and potential preventability. METHODS: A descriptive cohort study including all women giving birth in a 2-year period (mid-1998-mid-2000) in Scandinavia. Notifications of eclampsia cases were obtained from all obstetric units at 3-monthly intervals. All patient files were reviewed, and systematic audit was performed to identify potentially preventable cases by using predefined criteria. MAIN OUTCOME MEASURES: Signs and symptoms preceding the eclamptic seizure, the standard of medical care, maternal and perinatal morbidity, and mortality were all recorded. Potentially preventable cases through improved care and cases eligible for primary prophylactic magnesium sulfate (MgSO4) were estimated. RESULTS: The incidence of eclampsia was 5.0/10,000 maternities (CI = 4.3-5.7/10,000). Eighty-six percent had a diagnosis of pre-eclampsia before the seizure. Nine of 10 had at least one physical complaint before the first seizure, severe headache being the most common symptom, occurring in two-thirds. Most seizures (90%) occurred after admission to hospital. By audit, 89 cases (42%) were classified as having received substandard care. Prophylactic use of magnesium sulfate might have reduced the number of eclampsia cases by 35 (17%). CONCLUSIONS: Eclampsia occurred mainly in hospital and the majority of women had symptoms heralding the seizure. In retrospect, nearly half of the cases were found potentially preventable by timely intervention, improved medical care, and systematic use of prophylactic treatment with MgSO4.

Cohort Studies↗

Serum adiponectin concentration prior to clinical onset of preeclampsia.

OBJECTIVE: This study assesses whether the adipokine adiponectin is a useful marker in pregnant women who subsequently develop preeclampsia (PE). METHODS: A retrospective case-control study was conducted to measure the total serum levels of adiponectin, measured by radioimmunoassay kit, in serum samples stored in serological biobanks. RESULTS: Total serum adiponectin concentrations between the groups were not significantly different (p = 0.22). There were no obvious clinical signs of the preeclamptic inflammatory process at the time when samples were drawn. CONCLUSION: Using this design, total adiponectin appeared not be a useful pre-clinical marker of PE.

Adiponectin↗

Nutrition and pregnancy outcome.

Nutrition in pregnancy has been recognized for millennia as being important, but the current nutritional practices of pregnant women often do not conform to what we already know to be optimum. Pregnant women are increasingly entering pregnancy overweight as the dietary habits of young women deteriorate in many societies. This increase in overweight was accompanied by a 5-fold increase in gestational diabetes within 15 years in Norway, together with an unprecedented increase in the prevalence of large babies. This is accompanied by increasing risks of fetal malformations, damage to mother and child during parturition, and an increased risk of both obesity and type 2 diabetes in mother and the adolescent child. The prevalence of overweight girls is therefore a public health challenge with intergenerational implications.

Diabetes Mellitus↗

[External cephalic version of breech presentation at term].

BACKGROUND: External cephalic version could be an alternative to either vaginal delivery or caesarean section in breech presentation at term. MATERIAL AND METHODS: A systematic literature review about external cephalic version in breech presentation. RESULTS: The numbers of breech presentation delivered by caesarean section could probably be reduced in Norway by offering version, but this would not affect perinatal mortality.

Breech Presentation↗

[Fetal nutrition and future health].

Fetal nutrition may permanently affect physiological properties of the new individual and hence the risk of future disease. Epidemiological studies indicate that fetal nutrition may significantly influence the risk of diabetes, cardiovascular disease, and cancer. Controlled animal studies show that even properties traditionally considered as exclusively genetic, like fur colour, may be modified by altered maternal nutrition. The expression "fetal programming" has been introduced to describe permanent effects of environmental conditions in fetal life. An important mechanism of fetal programming seems to be epigenetic regulation. One example of epigenetic regulation is methylation of the DNA base cytosine in promoter regions of some genes. DNA methylation will lead to decreased gene expression. Over the last two decades, marked changes in dietary habits and other life style features have taken place among young Norwegian women. This is particularly reflected in the increasing prevalence of obesity. Maternal weight and metabolic status is closely associated with the growth and development of the fetus. Thus, diet and physical activity become particularly important aspects of the health of young women.

Animals↗

Effect of a cholesterol-lowering diet on maternal, cord, and neonatal lipids, and pregnancy outcome: a randomized clinical trial.

OBJECTIVE: We assessed the effect of a cholesterol-lowering diet on maternal, cord, and neonatal plasma lipids and pregnancy outcome. STUDY DESIGN: Nonsmoking white women with singleton pregnancies (n = 290), aged 21 to 38 years, and with no previous pregnancy-related complications, were randomized to either continue their usual diet or to adopt a diet that promoted fish, low-fat meats and dairy products, oils, whole grains, fruits, vegetables, and legumes from gestational week 17 to 20 to birth. RESULTS: Maternal total and low-density lipoprotein cholesterol levels were lowered in the intervention compared with the control group (P < .01). Lipid levels in cord blood and in neonates born to mothers in the intervention versus the control groups did not differ. In the intention-to-treat cohort 1 (0.7%) of 141 women in the intervention group versus 11 (7.4%) of 149 women in the control group delivered before 37 weeks (RR 0.10; 95% CI 0.01-0.77). The incidence of other pregnancy complications and birth weight was similar in both groups. CONCLUSION: A cholesterol-lowering diet may modify maternal lipid levels but not cord and neonatal lipids. The marked observed effect of this diet on the reduction of preterm delivery in low-risk pregnancies should encourage future larger studies to clarify the role of such a diet in the prevention of preterm birth.

Adult↗

Complications of cesarean deliveries: rates and risk factors.

OBJECTIVE: The purpose of this study was to determine complication rates after cesarean delivery and to identify independent risk factors for complications. STUDY DESIGN: In a prospective population-based cohort study in Norway, rates of predefined types of complications from 2751 cesarean deliveries were determined. The complications that were studied were intraoperative complications, blood loss, wound infection, cystitis, endometritis, hematoma, and reoperation. Independent risk factors were identified by stratification and multiple logistic regression analysis. RESULTS: Altogether, 21.4% of the women had > or =1 complications. The degree of cervical dilation, general anesthesia, low gestational age, and fetal macrosomia were independent risk factors. For operations that were performed at 9 to 10 cm cervical dilation, the complication rate was 32.6% versus 16.8% at 0 cm (odds ratio, 2.39; 95% CI, 1.77-3.22; P<.001). CONCLUSION: Cesarean delivery was associated with a high complication rate. Increasing cervical dilation and, in particular, cervical dilation of 9 or 10 cm at the time of operation, general anesthesia, low gestational age, and fetal macrosomia were identified as independent risk factors.

Adolescent↗

Dietary supplementation with L-arginine or placebo in women with pre-eclampsia.

BACKGROUND: To investigate the effect of dietary intake of the NO-donor L-arginine on the diastolic blood pressure in women with pre-eclampsia. METHODS: A randomized double-blind study was designed to compare the effect of L-arginine and placebo in pre-eclamptic women with gestational length ranging from 28+0 to 36+0 weeks. The women received orally 12 g of L-arginine or placebo daily for up to 5 days. The primary end-point was to identify a difference in diastolic blood pressure alteration between the two groups after 2 days of intervention. Secondary end-points included the interval from study start to delivery, the proportion of women delivered after 2, 5 or 10 days from treatment start and mean birth weight. RESULTS: There was no statistically significant alteration in diastolic blood pressure in the L-arginine group compared with the placebo group after 2 days of treatment (p = 0.4). No differences in the proportions of women delivered by day 2, 5 or 10 after study start, in the mean interval from study start to delivery, or in mean birth weight percentile were observed between the two groups. CONCLUSIONS: Oral L-arginine supplementation did not reduce mean diastolic blood pressure after 2 days of treatment compared with placebo in pre-eclamptic patients with gestational length varying from 28 to 36 weeks. Whether L-arginine treatment could be clinically beneficial for the mother or the fetus if started earlier in the disease process than for the women in our study remains to be seen.

Adult↗

[Women and epilepsy].

Women with epilepsy have several gender-specific problems, first of all related to pregnancy and childbirth. They do, however, also meet with several other, less well-recognised specific problems. Many women have a marked change in seizure frequency in relation to their menstrual cycle, and menstrual disorders and polycystic ovaries induced by the use of antiepileptic drugs (AEDs), or by the condition itself, are more frequent in women with epilepsy. Cosmetic side effects of AEDs including weight gain, hair loss and skin problems can significantly reduce compliance in drug treatment and thus affect seizure frequency. Enzyme-inducing AEDs reduce the effectiveness of oral contraceptives and may lead to unplanned pregnancies. A higher incidence of sexual problems in women with epilepsy has also been reported. In menopause, the seizure frequency may change in parallel with the endocrine changes and some AEDs may facilitate the development of osteoporosis. Better understanding and awareness of these problems among patients and health care professionals can relieve many of the gender-specific problems in women. The goal is to tailor the treatment to the needs of the individual woman.

Anticonvulsants↗

[Pregnancy and birth in women with epilepsy].

More than 90 % of all women with epilepsy who take antiepileptic drugs (AEDs) will undergo normal pregnancies and give birth to children free of birth defects, though mothers on AEDs have two to three times higher incidence of malformations. Uncertainty exists regarding which AEDs are the most teratogenic. Valproate and carbamazepine have been associated with neural tube defects and phenytoin with cleft lip/palate and heart and urogenital defects. All women taking valproate and carbamazepine are advised to take 4 mg/day of folic acid at least one month before pregnancy and during the first trimester. Other women with epilepsy in fertile age are recommended to take 0.4 mg/day. Vitamin K 10 mg/day should be given the last 4 weeks to women on liver enzyme-inducing AEDs. During pregnancy, ultrasound should be performed around weeks 12 and 17. Amniocentesis for a-fetoprotein should be offered at week 15 to women using valproate and carbamazepine. Most women with epilepsy do not experience any change in seizure frequency during pregnancy and have normal vaginal deliveries. Use of monotherapy, lowest effective dose and retard formulations of AEDs, are advised during pregnancy. A seizure during labour is very rare, seen in 1-2 % of cases. Breast-feeding is encouraged for most AEDs, although barbiturates and benzodiazepines may have sedative effects on the infant. Pregnancy is generally safe in women with epilepsy, but preconception counselling and close collaboration during the pregnancy between the gynaecologist and the neurologist is warranted.

Abnormalities, Drug-Induced↗