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  • Author: Dagfinn Aarskog x
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Robert Bjerknes, Per Vesterhus and Dagfinn Aarskog

Abstract

Insulin-like growth factor-I (IGF-I) is a growth hormone-dependent peptide with growth and immunoregulatory properties, and in Laron syndrome growth hormone insensitivity induces impaired production of IGF-I. In the present study we have determined the neutrophil expression of IGF-I receptors (IGF-I-Rs), as well as the IGF-I-induced priming of neutrophil functional capacity, in two children with Laron syndrome treated with recombinant human IGF-I, and in age-matched controls. Before treatment, the patient neutrophil expression of IGF-I-Rs was significantly increased. However, with replacement therapy the neutrophil IGF-I-R expression was downregulated to levels similar to those of the controls within one month. In the patients, the phagocytic capacity and oxidative burst of unprimed neutrophils were normal and similar to controls before the start of treatment. Moreover, IGF-I efficiently primed both patient and control neutrophils to increase their phagocytic capacity and oxidative burst in vitro. However, before therapy, the priming response to IGF-I was significantly stronger in the neutrophils in the patients than in the controls. The present data support earlier studies by us and others demonstrating that IGF-I is a potent regulator of mature neutrophil function, but also suggest that these leukocytes may function normally in the presence of very low levels of IGF-I in vivo.

European Journal of Endocrinology 136 92–95

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Torleif Trydal, Johan R. Lillehaug, Lage Aksnes and Dagfinn Aarskog

Calcipotriol is a synthetic 1,25-(OH)2D3 analogue with high affinity for the 1,25-(OH)2D3 receptor, but with a lower affinity than 1,25-(OH)2D3 for vitamin D binding protein in serum. The inhibitory action of calcipotriol and 1,25-(OH)2D3 on proliferation of C3H/10T1/2 mouse embryo fibroblasts was examined in the non-transformed cell line CI 8 and in the two transformed, tumorigenic cell lines Cl 16 and TPA 482. Upon exposure to 10 nmol/l calcipotriol or 1,25-(OH)2D3, the proliferation of Cl 8 cell line was almost completely suppressed, whereas both hormones had no effect on the cell lines Cl 16 and TPA 482. Calcipotriol was at least as effective as 1,25-(OH)2D3 in inducing up-regulation of the 1,25-(OH)2D3 receptor. Displacement studies showed no difference between calcipotriol and 1,25-(OH)2D3 in the affinity for the receptor present in Cl 8 or Cl 16 cell extracts. Furthermore, the inhibition of cell growth in Cl 8 cells by calcipotriol was not accompanied by any consistent change in the steady-state expression of c-myc mRNA. In conclusion, calcipotriol had potent growth inhibitory effect on the non-transformed cell line similar to 1,25-(OH)2D3. In the transformed cell lines, calcipotriol did not inhibit proliferation despite potent up-regulation of the 1,25-(OH)2D3 receptor.

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Lage Aksnes, Ole Rødland, Ole R. Ødegaard, Kåre J. Bakke and Dagfinn Aarskog

Abstract.

The serum concentrations of 25-dihydroxyvitamin D, 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D, vitamin D-binding protein, PTH and calcitonin were measured in three groups of elderly Norwegian subjects (age 70–96 years): active elderly living at home, warded geriatric patients not supplemented with vitamin D, and warded geriatric patients supplemented with a daily dose of 400 IU vitamin D2. The results were compared with the concentrations of vitamin D metabolites found in a group of young and middle-aged adults (age 22–59 years). Decreased serum concentrations of 25-dihydroxyvitamin D3 were found in all groups of elderly compared with younger adults. Active elderly living at home had higher concentrations of 25-dihydroxyvitamin D3 than geriatric ward patients. Supplementation of geriatric ward patients with 400 IU vitamin D2 resulted in an increase in the median serum 25-dihydroxyvitamin D concentration by about 30 nmol/l. Decreased median concentration of 1,25-dihydroxyvitamin D was found in geriatric ward patients not supplemented with vitamin D, indicating that this group is at risk of vitamin D deficiency. The active elderly living at home and the warded geriatric patients receiving vitamin D supplementation had normal median concentrations of 1,25-dihydroxyvitamin D, indicating that nephrogenous synthesis of 1,25-dihydroxyvitamin D is not generally impaired in the elderly, and that a moderate vitamin D supplementation may correct low 1,25-dihydroxyvitamin D levels owing to vitamin D deficiency. However, the serum concentrations of 1,25-dihydroxyvitamin D showed great individual variations. No significant differences were observed for vitamin D-binding protein, 'free-1,25-dihydroxyvitamin D' or PTH between the groups. The median serum concentrations of 24,25-dihydroxyvitamin D were significantly lower in all three groups of elderly compared with the younger adults.

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Torleif Trydal, Jan Erik Varhaug, Andreas Myking, Lage Aksnes, Asbjørn Aakvaag and Dagfinn Aarskog

Vitamin D metabolites in serum and calcitriol receptor concentration in parathyroid tissue were examined in 52 patients operated on for primary hyperparathyroidism. The calcitriol receptor levels were not different in parathyroid adenomas (mean 224 fmol/mg of protein, range 29–509, N = 43), normal parathyroid tissue (mean 245, range 31–690, N = 20), and primary parathyroid hyperplasia (mean 172, range 46–477, N = 9). Preoperative serum levels of calcitriol concentration correlated inversely to the calcitriol receptor in normal parathyroid tissue in patients with adenoma (r= −0.57, N=17, p=0.017), but no such correlation was found in the corresponding adenomas (r=0.14, p = 0.59). In 31 patients in whom both pre- and post-operative vitamin D metabolite analyses were carried out, 23 had lower calcitriol postoperative concentrations compared to preoperative values (p = 0.012, sign test). No change was found in the other vitamin D metabolites postoperatively. By multiple regression analysis calcitriol concentration in serum was inversely correlated to the serum concentration of urea and phosphate (p = 0.003). We conclude that calcitriol may influence calcitriol receptor expression in normal parathyroid tissue, but not in adenomatous parathyroid gland. Furthermore, serum calcitriol was correlated to the renal function, and phosphate level, and in most patients the calcitriol concentration was lower after the operation.