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E Haug

Publications and source records attributed to E Haug.

At least 91 records · Page 5Linked to original sources

A comparison between two commercial methods for determining carbohydrate deficient transferrin (CDT).

The performance of CDTect (Kabi-Pharmacia, Uppsala, Sweden) and two versions of AXIS % CDT (AXIS Biochemicals, Oslo, Norway) for determining carbohydrate deficient transferrin (CDT) was examined in 502 consecutive patients admitted to the Department of Medicine, Aker University Hospital. The sensitivity for detecting an alcohol consumption > or = 50 g/day for the last 4 weeks was 69% for CDTect, 65% for AXIS % CDT, version 1 (AX CDT 1) and 50% for AXIS % CDT, version 2 (AX CDT 2). The specificity at the same level of alcohol consumption, markedly differed between the two methods: 92%, 76% and 90% for CDTect, AX CDT 1 and AX CDT 2, respectively. The variation coefficient (day-to-day) was 10%, 22% and 10% for CDTect, AX CDT 1 and AX CDT 2, respectively.

Adult↗

Androgen metabolism in the different lobes of the prostate gland of intact, gonadectomized or hypophysectomized rats with or without androgen substitution.

The effect of gonadectomy or hypophysectomy and the effect of substitution with testosterone, upon the reductive and oxidative metabolic transformations of testosterone, 4-androstene-3,17-dione, 17 beta-hydroxy-5 alpha-androstane-3-one, 5 alpha-androstane-3 alpha, 17 beta-diol and 5 alpha-androstane-3 beta, 17 beta-diol using NAD(H) and NADP(H) as added cofactors were examined in homogenates from the ventral (VP), lateral (LP) and dorsal prostate (DP), and coagulating gland (CG) of adult Wistar rats. The fall in serum testosterone induced by gonadectomy or hypophysectomy led to reduced activity of 5 alpha-reductase, NADP(H)-dependent 3 alpha-hydroxysteroid oxidoreductase (3 alpha-HSOR), NAD-dependent 3 alpha-HSOR, 3 beta-HSOR and 17 beta-HSOR, indicating that these enzymes are androgen dependent. The NADP dependent oxidation of 5 alpha-androstane-3 alpha, 17 beta-diol in LP increased upon hypophysectomy and gonadectomy. Testosterone substitution of gonadectomized or hypophysectomized rats generally maintained enzymatic activity at the level of the control group, except for the 5 alpha-reductase activity which fell in spite of this treatment. Hypophysectomy or gonadectomy had different effects on the activity of several androgen metabolizing enzymes; 5 alpha-reductase activity in DP and CG, NAD(H) dependent 3 alpha-HSOR in VP and NADPH dependent 3 beta-HSOR activity in LP, DP and CG. There were marked differences between the rat prostatic lobes, both concerning the activity of the androgen metabolizing enzymes and the responses to the different treatment modalities.

17-Hydroxysteroid Dehydrogenases↗

The estimated free concentration of calcidiol is higher in venous cord blood than in maternal blood.

The serum levels of calcidiol (25-hydroxy-vitamin D3), calcitriol (1,25-dihydroxy-vitamin D3), albumin and vitamin D-binding protein (DBP) were measured in venous cord blood and in maternal blood at delivery. These results were used to calculate the free concentrations of calcidiol and calcitriol in maternal and fetal blood. Fifty three women participated in the study. Seventeen of the participants were excluded from the calculations because their calcidiol levels were below the limit of detection (< 5 nmoll-1). The estimated free concentration of calcidiol was on average 26% higher in cord serum than in maternal serum, the mean difference being 1.1 pmoll-1 (p = 0.001). The estimated free concentration of calcitriol, however, was 21% lower on the fetal side (p < 0.001). The difference was small, the mean value being 0.07 pmoll-1. A strong positive association existed between the serum levels of free calcidiol (r = 0.82, p < 0.001) and free calcitriol (r = 0.83, p < 0.001) in maternal blood and cord blood.

Calcifediol↗

[Transgenic mice as animal model of Cushing's syndrome].

Transgenic mice were generated with the polyoma early region promoter linked to cDNA encoding polyoma large T antigen (PyLT). Light microscopic examination showed up to 5 mm large pituitary adenomas in clinically ill transgenic mice. The tumour cells showed positive ACTH immuno-reactivity. The adrenal glands of clinically ill mice showed an increase in weight and exhibited medullary hyperplasia. These findings were unexpected, and might have been caused by transgene expression in the neuroendocrine cells of the adrenal medulla. Plasma ACTH measurements showed significantly increased levels in clinically ill PyLT-1 transgenic mice.

Adenoma↗

Surgically induced uremia in rats. I: Effect on bone strength and metabolism.

During the course of chronic renal failure (CRF) in man, renal osteodystrophy (osteitis fibrosa and/or osteomalacia) gradually develops. The present study aimed to establish a similar type of CRF leading to renal osteodystrophy in rats. During progressive CRF development over 225 days after 5/6 nephrectomy, the following serum variables were measured: creatinine, immunoreactive parathyroid hormone (iPTH), 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), a25-hydroxyvitamin D3, (25(OH)D3), alkaline phosphatase, albumin, phosphate, urea nitrogen, total calcium, and other blood electrolytes. Subsequent to sacrifice, mechanical properties of the rat femur, bone histomorphometry (osteoid and eroded surfaces) and bone contents of calcium, phosphate and hydroxyproline were also examined. Serum creatinine in rats with CRF gradually escalated by some 70%, while circulating 1,25(OH)2D3 was reduced beneath detection level. Total plasma calcium and phosphate concentrations were, however, almost unchanged indicating that PTH-induced bone remodeling due to moderate hyperparathyroidism sustained calcium homeostasis. Alkaline phosphatase levels were reduced by some 50%, which reflects chronically impeded bone formation. Bone histomorphometry assessment revealed substantial elevation of resorption with moderate accompanying fibrosis in about 70% of afflicted animals. Bone calcium, phosphate and hydroxypyrroline contents remained unaltered. However, hydroxyproline/calcium ratio was marginally reduced. These results, together with altered mechanical bending stress characteristics and diminished diaphysis cross section area, confirm development of mixed bone lesions in the uremic animals. Our results are compatible with the early development of CRF in man. The established rat model is therefore useful in elucidating the precipitation and early treatment of renal osteodystrophy in humans.

Alkaline Phosphatase↗

Calcitriol attenuates the thyrotropin-releasing hormone-stimulated inositol phosphate production in clonal rat pituitary (GH4C1) cells.

Three days pretreatment of the prolactin (PRL) secreting GH4C1 cells with 10 nM calcitriol attenuated both the basal and thyrotropin-releasing hormone (TRH)-stimulated (1 microM, 5 s) inositol trisphosphate (IP3) production by 30 and 26%, respectively. The effect was detectable at 10 nM (basal) and 1 pM (TRH-stimulated), and maximal at 1 microM (basal) and 10 nM (TRH), respectively. Calcitriol was at least 100 times more potent than calcidiol and 24-hydroxycalcidiol, and the effect was reversible upon cessation of pretreatment. Calcitriol pretreatment (1 microM, 5 days) also decreased the levels of phosphatidyl-inositol, phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate by 23, 55 and 32%, respectively. GTP gamma S-stimulated (100 microM, 30 s) IP3 production was decreased by 45% after calcitriol pretreatment (10 nM, 5 days). Pertussis toxin (1 nM, 4 h) attenuated both the basal and TRH-stimulated IP3 production, but this effect was omitted by calcitriol pretreatment. Thus, calcitriol specifically attenuates both the basal and TRH-stimulated inositol phosphate production in GH4C1 cells. The mechanism, at least partly, involves decreased availability of phosphoinositides for phospholipase C. Calcitriol regulation of a pertussis toxin-sensitive G-protein might also play some role.

24,25-Dihydroxyvitamin D 3↗

1,25-dihydroxyvitamin D3 attenuates TSH and 8-(4-chlorophenylthio)-cAMP-stimulated growth and iodide uptake by rat thyroid cells (FRTL-5).

The effects of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] on TSH and the 3',5'-cyclic adenosine monophosphate (cAMP) analogue 8-(4-chlorophenylthio)-cAMP-stimulated cell growth and iodide uptake were studied in a rat thyroid cell line (FRTL-5). 1,25-(OH)2D3 inhibited both TSH and 8-(4-chlorophenylthio)-cAMP-induced cell proliferation with the maximum effect at 100 nmol/L. The inhibitory effect of 1,25-(OH)2D3 (10 nmol/L) on TSH and 8-(4-chlorophenylthio)-cAMP-stimulated iodide uptake was observed after 2 days of incubation, and the effect was maximal after 4 days. The inhibition was dose-dependent and maximal at 100 nmol/L 1,25-(OH)2D3. 1,25-(OH)2D3 (10 nmol/L, 4 days) increased the median concentrations of TSH required to stimulate both cAMP production and iodide uptake half-maximally by 124 and 187%, respectively, whereas the median 8-(4-chlorophenylthio)-cAMP concentration was not changed. Lineweaver-Burke plots revealed that 1,25-(OH)2D3 reduced the Vmax of the sodium-driven iodide carriers to 30% of the control cells without effect on the Km. Iodide efflux was only slightly increased in the 1,25-(OH)2D3-treated cells. In conclusion, 1,25-(OH)2D3 potently inhibited the TSH-stimulated growth and iodide uptake by FRTL-5 cells both by reducing the TSH-stimulated cAMP production and by attenuating the stimulatory effects of cAMP.

Animals↗

Plasma oestrogens in postmenopausal women with endometrial cancer.

OBJECTIVE: To study plasma levels of estrogens and androgens, sex hormone-binding globulin (SHBG) and follicle stimulating hormone (FSH) in postmenopausal patients with endometrial cancer. DESIGN: Patients and controls were matched for age, body mass index, parity and years since menopause. SETTING: Department of Obstetrics and Gynaecology, Hvidovre Hospital, Denmark. SUBJECTS: Fifty postmenopausal patients with endometrial cancer and 54 matching controls. MEASUREMENTS: Plasma levels of SHBG, FSH, oestrone, oestradiol, oestrone-sulphate, dehydro-epiandrosterone sulphate, testosterone, and androstenedione were measured by radio-immunoassays. Free fractions of oestradiol and testosterone were calculated according to levels of SHBG and albumin. RESULTS: The levels of oestradiol, free oestradiol, and oestrone were elevated (P < 0.001) in patients compared with controls (oestradiol: 51 (45-59) vs 37 (34-41) pmol/l; free oestradiol: 0.69 (0.59-0.80) vs 0.48 (0.42-0.54) pmol/l; oestrone: 180 (159-204) vs 119 (107-133) pmol/l (mean values (95% CI) in patients vs controls)). Furthermore, an increased oestrone:androstenedione ratio (0.095 vs 0.072, P < 0.01) was found in patients. SHBG correlated negatively (P < 0.001) with body mass, while the free fractions of oestradiol and testosterone correlated positively (P < 0.01) with body mass, in both patients and controls. Multiple regression analysis showed that the differences in oestrogen levels between the two groups persisted when controlling for the effect of body mass, age, years since menopause, parity, and levels of SHBG and FSH. CONCLUSION: Patients with endometrial cancer exhibit increased plasma levels of oestradiol and oestrone. Speculatively, these oestrogens may result from an increased oestrone conversion from androstenedione, an increased ovarian and adrenal secretion of androstenedione, or alternative oestrogen production routes. The present findings support the hypothetical role for oestrogens in the aetiology of endometrial cancer.

Aged↗

Serum carbohydrate-deficient transferrin as a marker of alcohol consumption in patients with chronic liver diseases.

We measured serum levels of carbohydrate deficient transferrin (CDT) in 420 subjects: 100 healthy blood donors, 82 healthy employees, 70 abstaining patients with different chronic nonalcoholic liver disease, 16 abstaining patients with alcoholic fatty liver, 50 abstaining patients with alcoholic liver cirrhosis, 25 abusing patients with alcoholic fatty liver, 41 abusing patients with alcoholic liver cirrhosis, and 36 patients with alcohol dependence syndrome with a daily ethanol consumption of 173 +/- 120 g the last 4 weeks before blood was drawn. In controls the serum level of CDT was significantly higher in females compared with males (17.7 +/- 5.1 and 13.7 +/- 3.8 units/liter, respectively), and the upper normal limit was defined as 27 and 20 units/liter. Sixty-two of 102 (60.8%) abusing patients with alcoholic liver disease had increased levels of CDT compared with 1 of 66 abstaining (1.5%) patients with alcoholic liver disease, and 10 of 70 (14.3%) abstaining patients with nonalcoholic liver disease among them 3 with primary biliary cirrhosis and 2 with chronic autoimmune hepatitis. No correlation was found between serum CDT and gamma-glutamyltranspeptidase (GGT), AST, ALT, and mean red cell volume (MCV). The sensitivity and specificity for serum CDT was 61 and 92%, respectively, compared with 85 and 18% for GGT and 70 and 66% for MCV. No advantage was gained by using the CDT/transferrin ratio. Our study confirms that CDT is a specific marker for chronic alcohol abuse, except in few patients with other chronic liver diseases. Serum CDT seems to be a better indicator of abstention than GGT; AST and MCV in patients with alcoholic liver disease. However, in our hands CDT is not so sensitive for alcohol abuse in patients with liver disease as reported earlier in unselected alcoholics.

Adult↗

Relationship between circulating vitamin D3 metabolites and prolactin or growth hormone levels in rat.

Previous studies (Haug & Gautvik 1985) have demonstrated specific receptors for 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in a clonal (GH3) strain of rat pituitary tumour cells. It was discovered that 1,25(OH)2D3 affected the production of prolactin and growth hormone in these cells in a calcium dependent manner. These findings were the basis for a hypothesis that vitamin D3 could be involved in the regulation of pituitary hormones in vivo. To further investigate this contention, female rats were given subcutaneous injections of 1,25(OH)2D3, 25-hydroxyvitamin D3 (25(OH)D3) or 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) three times a week for up to 12 weeks. Blood samples were withdrawn after 28, 56 and 84 days of treatment and analysed for vitamin D3 metabolites, prolactin and growth hormone, and serum ionized (free) and total calcium (Ca). Between treatment group comparisons of serum prolactin and growth hormone levels did not show significant vitamin D3 induced alterations. However, correlation matrix analyses on all variables revealed that serum level of growth hormone was significantly (P < 0.05) and inversely related to corresponding total Ca. Prolactin, on the other hand, may be subject to a complex regulation by 1,25(OH)2D3 and free Ca2+.

24,25-Dihydroxyvitamin D 3↗

Epidermal growth factor stimulates the prolactin synthesis and secretion in rat pituitary cells in culture (GH4C1 cells) by increasing the intracellular concentration of free calcium.

Epidermal growth factor (EGF) stimulated the prolactin (PRL) synthesis and release from the GH4C1 cells in a dose-dependent manner. The ED50 was between 10(-11) and 10(-10) mol/l. The maximal effect was obtained at 10(-9) mol/l EGF for the release, and 10(-8) mol/l EGF for the synthesis. EGF stimulated the release of PRL from cell perfusion columns after a lag period of about 30 s. The maximal secretion of PRL occurred about 60 s after the start of stimulation. The PRL secretion declined to basal levels within 2 min. The EGF-stimulated PRL release was additive to the secretion evoked by thyrotropin-releasing hormone (TRH) and vasoactive intestinal peptide (VIP). An instantaneous increase in the intracellular concentration of free calcium, [Ca2+]i, of the GH4C1 cells was observed after the administration of EGF. EGF modified neither the basal nor the TRH-stimulated inositoltrisphosphate production in the GH4C1 cells, and EGF did not show any effect on the cyclic adenosine monophosphate production of these cells.

Animals↗

Vitamin D deficiency amongst Pakistani women in Oslo.

To evaluate the vitamin D status in pregnant Pakistani women living in Oslo, we measured levels of serum calcidiol, calcitriol, vitamin D binding protein (DBP), osteocalcin, free calcium (Ca2+), phosphorous, alkaline phosphatase and intact parathyroid hormone (PTH). Thirty Pakistani and 23 Norwegian women who delivered vaginally after uncomplicated pregnancies were included. The serum levels of calcidiol were significantly lower in the Pakistani group (p < 0.0001) as compared with the Norwegians, the mean values being 15.1 nmol/l and 43.1 nmol/l, respectively. PTH levels were above 5.5 pmol/l in 13 of the Pakistanis, none of the Norwegians. There were no differences in calculated free calcitriol, free calcium and inorganic phosphorus between the groups. Alkaline phosphatase was high, while osteocalcin was low in both groups, but there were no significant differences between the groups. This study shows that there is a widespread vitamin D deficiency amongst pregnant Pakistani women living in Oslo, indicating the need for vitamin D supplementation to these women and their children.

Adult↗

Inhibitors of the arachidonic acid metabolism attenuate the thyroliberin (TRH) stimulated prolactin production without modifying the production of inositolphosphates in GH4C1 pituitary cells.

Some arachidonic acid metabolites might be among the intracellular signalling substances that regulate hormone release. We report that the phospholipase A2 and diacylglycerol lipase inhibitor quinacrine (1-10 mumol l-1) inhibited the thyroliberin stimulated prolactin (rPRL) production in a dose-dependent way in a rat pituitary tumour cell line (GH4Cl cells). The lipoxygenase inhibitor nafazatrom (5-50 mumol-1) also dose-dependently inhibited the thyroliberin stimulated rPRL production, while the cyclo-oxygenase inhibitor indomethacin had no such effect on rPRL production. The inhibitors of the arachidonic acid metabolism (quinacrine, ETYA and nafazatrom) had no effect on the accumulation of inositolpolyphosphates indicating that the arachidonic acid metabolites are not involved in the regulation of the phospholipase C activity.

5,8,11,14-Eicosatetraynoic Acid↗

[Familial hypocalciuric hypercalcemia].

Familial hypocalcuric hypercalcemia is a condition that is often incorrectly diagnosed and treated. We studied a family with seven members who had familial hypocalcuric hypercalcemia. In four of the family members it was difficult to make the diagnosis. A correct diagnosis was made in the other three on the basis of known family history. Subtotal parathyroidectomi was carried out on three of the family. After operation, two of these experienced a relapse, and one became permanently hypocalcemic.

Adult↗

Short-term effects of treatment with simvastatin on testicular function in patients with heterozygous familial hypercholesterolaemia.

The effects of simvastatin 40 mg per day for 14 weeks on the pituitary-testis axis of 19 men with familial hypercholesterolaemia have been examined in a single-blind study. Simvastatin significantly reduced serum low density lipoprotein (LDL) cholesterol and triglycerides by 45% and 30%, respectively, and significantly increased high density lipoprotein (HDL) cholesterol by 15%. The alterations, which were stable 4 weeks after the start of treatment, were not associated with any significant change in sperm quality, the seminal plasma concentrations of various sex gland products (prostate-specific acid phosphatase, polyamines, citrate, fructose, alpha-glucosidase), or the serum concentrations of cortisol, testosterone, LH, FSH, or prolactin. It is concluded that a short-term reduction in circulating LDL-cholesterol has no marked effect on testicular function or sperm quality.

Adult↗

Primary hyperparathyroidism or hypercalcaemia of malignancy?

The introduction of two-site immunometric assays measuring intact parathyroid hormone (PTH) and radioimmunoassays measuring PTH-related peptide (PTH-RP) have simplified the evaluation of patients with hypercalcaemia. We present a 63-year-old man with recurrent hypercalcaemia after surgical treatment for primary hyperparathyroidism 3 years previously. PTH measured with a mid-region radioimmunoassay gave normal values, at the same level as during his primary hyperparathyroidism. Intact PTH was, however, clearly suppressed, and he had a highly elevated level of PTH-RP. This suggested that he had humoral hypercalcaemia of malignancy. The patient died after 2 months, and at autopsy an adenocarcinoma of the pancreas with no skeletal metastases was found.

Adenocarcinoma↗

Polycystic ovary syndrome: low-dose follicle stimulating hormone administration is a safe stimulation regimen even in previous hyper-responsive patients.

We studied 23 women with polycystic ovarian syndrome (PCOS), resistant to clomiphene citrate, who had a previous history of multifollicular ovarian development on gonadotrophin stimulation. Each woman had one cycle of gonadotrophin-stimulating hormone agonist/human menopausal gonadotrophin (GnRHa/HMG) stimulation and then one cycle of low-dose follicle stimulating hormone (FSH) stimulation. All GnRHa/HMG cycles were multifollicular. On the low-dose FSH protocol, 10 cycles were unifollicular, while two to three follicles were observed in nine cycles, and four cycles were multifollicular. The ovarian hyperstimulation syndrome ensued in one of the FSH cycles versus 13 of the GnRHa/HMG cycles. Despite decreasing luteinizing hormone (LH) levels and increasing FSH levels, androgen levels increased during stimulation on both protocols. There was one pregnancy in the GnRHa/HMG cycles versus six pregnancies following the FSH cycles. In conclusion, low-dose FSH administration seems a safe stimulation regimen with a satisfactory conception rate even in PCOS women with a previous record of multifollicular ovarian development.

Estradiol↗

Serum levels of intact parathyroid hormone in elderly patients with hip fracture living at home.

The serum levels of intact parathyroid hormone and cholecalciferol metabolites have been measured in patients with hip fracture above 70 years of age admitted to hospital from home-living conditions and compared with serum levels in age- and sex-matched home-living control subjects. It was found that patients with hip fracture had significantly lower levels of calcidiol (29.7 +/- 15.9 vs 46.0 +/- 27.8 nmol/l) and calcitriol (63.6 +/- 25.0 vs 91.1 +/- 39.5 pmol/l) with no difference in serum levels of intact parathyroid hormone (4.7 +/- 2.1 vs 5.3 +/- 3.3 pmol/l). The data suggest that secondary hyperparathyroidism is not an important risk factor in our population of patients with hip fracture.

Aged↗