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Biomedical subjects

O Tørring

Publications and source records attributed to O Tørring.

At least 19 recordsLinked to original sources

Calcium and vitamin D3 supplements in calcium and vitamin D3 sufficient early postmenopausal healthy women.

OBJECTIVE: To study the calcium homeostasis in healthy, calcium and vitamin D replete early postmenopausal women during oral supplementation with calcium and vitamin D3. DESIGN: A prospective, placebo-controlled, randomised, double-single-blind, 3-week study. SETTING: Outpatient clinic at Copenhagen University Hospital, Denmark. SUBJECTS: In all, 17 started, one was excluded. Totally, 16 healthy women, 45-61 y of age (mean 57.3 y) who were at least 4 y after menopause (mean 6.7 y) completed. INTERVENTIONS: All underwent three consecutive 7-day study periods. Each began with 4 days of normal diet followed by 3 days treatment of either C: one tablet of 1.250 mg calcium carbonate (ie 500 mg Ca2+ per tablet) twice daily (breakfast and dinner), or CD3: as in C but plus 400 IU vitamin D3 b.i.d., or P (only) placebo tablets b.i.d. RESULTS: At baseline plasma 25-hydroxycholecalciferol was normal (66+/-22 nmol/l) and the calcium intake without supplements 850 mg/day. In group C, the 24-h urinary calcium increased by 35% (6.9+/-2.0 mmol), vs the placebo group P (5.1+/-1.6 mmol) (P < 0.05). Addition of 800 IU vitamin D3 daily (CD3) did not increase calcium excretion further (6.6+/-2.1 mmol) but decreased plasma 1,25-(OH)2-vitamin D3 by 21% (P < 0.05). CONCLUSIONS: In this carefully controlled study calcium plus vitamin D3 supplements only had minor influences of uncertain significance on the calcium balance in healthy, calcium and vitamin D sufficient early postmenopausal women.

Administration, Oral↗

Effect of acute endurance and strength exercise on circulating calcium-regulating hormones and bone markers in young healthy males.

Physical activity plays a role in the maintenance of the skeleton but the mechanical, metabolic and hormonal mechanisms involved are largely unknown. The influence of acute endurance and strength exercise on circulating levels of calcitonin, parathyroid hormone (PTH), PTH-related peptide (PTHrP), osteocalcin, carboxyterminal cross-linked telopeptide of type I collagen (ICTP) and ionized calcium (Ca2+) was therefore evaluated. Eight healthy young males performed three exercise bouts on separate occasions: endurance exercise, i.e. cycling on a cycle ergometer for 45 min at 55% of Vo2max (E55%) and 15 min at 85% of Vo2max (E85%) and strength exercise at 85% of three repetitions maximum using a leg-press device (STR). Control experiments included the same subjects with the same time schedule but without exercise. Blood samples were taken before, immediately after exercise and during the recovery period. Hormones and bone markers were measured by use of various immunoassays. There was no obvious influence on calcitonin and PTHrP levels, whereas PTH was increased after strength exercise. ICTP and osteocalcin levels correlated positively at all times and showed regular variations. In comparison with the controls, ICTP levels showed a more pronounced decrease following physical activity whereas osteocalcin followed the same pattern as the controls except for after prolonged endurance exercise when a decrease was abolished. In conclusion, an increase in PTH after strength exercise and a pronounced decrease in ICTP after all exercise together with a relative increase in osteocalcin after prolonged endurance exercise might reflect some mechanisms involved in the positive effect of physical activity on bone mass.

Adult↗

Circulating monomer-like calcitonin in osteoporotic patients.

Physiological concentrations of monomeric calcitonin can inhibit osteoclastic bone resorption in vitro. We therefore investigated the circulating molecular forms, including monomer-like calcitonin, and their concentrations in 9 men and 9 women with established osteoporosis. Calcitonin was immunoextracted from serum by the use of rabbit calcitonin antibodies coupled to Sepharose 4B. The lyophilized extracts were incubated with 6 M urea overnight and gel chromatographed in a fast protein liquid chromatography (FPLC) system; calcitonin was measured by radioimmunoassay in the fractions. FPLC disclosed immunoreactive calcitonin of three different molecular sizes in the patients. The two largest forms were approximately 30 and 10 kDa and one eluted at the same position as monomeric calcitonin (3.4 kDa). After extraction and FPLC we found slightly higher calcitonin concentrations in osteoporotic women than previously reported levels in age-matched healthy women. Male patients had higher levels than female patients. None of the osteoporotic patients lacked monomer-like calcitonin. There was no significant correlation between the extracted total or monomer-like calcitonin and bone mineral density of the femoral neck. It is concluded that the circulating calcitonin in both male and female patients comprises three different molecular forms and that there is no deficiency of the monomer-like form. The calcitonin levels in the female patients were slightly higher than in a previous control group.

Aged↗

Serum calcitonin forms and concentrations in young and elderly healthy females.

To further investigate the role of calcitonin (CT) in normal physiology we studied circulating forms and the secretion after "calcium clamp" in young and elderly healthy females. Heterogeneity of CT in serum was disclosed after immunoextraction, fast protein liquid chromatography, and radioimmunoassay in young (27 +/- 3 years; mean +/- SD, n = 6) and elderly females (69 +/- 6 years, n = 11). Three distinct molecular forms appeared with approximate mol wt of 30, 10, and 3-4 kDa. All young women studied had considerable amounts of circulating monomer-like CT whereas several elderly had undetectable or low levels. The influence of age on basal and calcium stimulated, immunoextracted CT in serum was also studied in young (26 +/- 4 years; mean +/- SD, n = 13) and elderly (63 +/- 6 years; n = 12) healthy females. The calcium stimulation was carried out by means of the standardized calcium clamp method, where calcium was kept on a presettled level at 1.45 mmol/liter (+/- 2%) for 60 minutes. CT was immunoextracted from serum in all series of experiments with a polyclonal antiserum directed against the mid- and carboxyterminal region of the CT molecule, and the amount of extracted CT was determined by radioimmunoassay using another polyclonal antiserum against the carboxyterminal portion. After calcium infusion, the increase in CT was significantly higher in young women than in elderly (P < 0.05). At basal conditions, the CT levels were not significantly different but slightly higher in young than in elderly females. In conclusion, several elderly women lack monomer-like calcitonin in serum in contrast to young women.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Midmolecular parathyroid hormone-related peptide in serum during pregnancy, lactation and in umbilical cord blood.

Indications of an important physiological role of parathyroid hormone-related peptide (PTHrP) for fetal calcium homeostasis, maternal-fetal calcium transport and reproduction have accumulated over recent years. The PTHrP concentrations were measured by an earlier developed midregion radio-immunoassay in serum from lactating healthy females and umbilical cord blood and compared with levels in age-matched non-pregnant or lactating females. The PTHrP concentrations could be measured in all samples after silica cartridge C18 extraction of 10-12 ml of serum. The concentrations were significantly higher during lactation (mean +/- SD: 0.72 +/- 0.14 pmol/l, N = 22) and in umbilical cord blood (0.85 +/- 0.18 pmol/l, N = 12) compared with healthy age-matched women (0.48 +/- 0.09 pmol/l, N = 10, p < 0.001). The molecular forms of PTHrP were also studied in an age-matched control group, in pregnant women and in umbilical cord blood by gel chromatography in a fast protein liquid chromatography system of Sep-Pak-extracted pooled serum. In all three groups we found heterogeneity of the molecular forms with two predominant peaks. The smallest fragment had a molecular weight of 4-6 kD while the largest form appeared as a high-molecular-weight molecule. In conclusion, the concentrations of midmolecule PTHrP fragments in serum are elevated during lactation and in umbilical cord blood. Because the midregion of PTHrP has unique actions, our results indicate that PTHrP may play an important physiological role for the mother and for the maternal-fetal calcium transport.

Chromatography, Liquid↗

Sensitive time-resolved fluoroimmunoassay of salmon calcitonin.

A two-site assay was developed by use of the "dissociation and enhancement lanthanide fluoroimmunoassay" (DELFIA) technique for determination of salmon calcitonin (SCT) in serum after administration to osteoporotic patients. Polyclonal antibodies were produced in rabbits immunized with SCT coupled to ovalbumin. After affinity purification, the antibodies were used both as immobilized capture antibodies and as Eu-chelate-labeled signal antibodies. A sensitive assay with a detection limit of 1.1 pmol/L was achieved, and no cross-reaction with human calcitonin was observed. The intra- and interassay CVs were < 12% (n = 10) and < 15% (n = 4), respectively. Analytical recovery of SCT added to serum was 91% +/- 3% (mean +/- SD, n = 4). SCT was measurable in all the samples from eight osteoporotic patients after subcutaneous SCT administration. We conclude that this new sensitive and specific two-site DELFIA can reliably measure SCT in serum.

Aged↗

Human parathyroid hormone (1-34) and (1-84) increase the mechanical strength and thickness of cortical bone in rats.

An anabolic effect on bone of intermittent parathyroid hormone (PTH) treatment has been found in patients with osteoporosis and also in experimental animals. Controversies exist, however, about whether the positive effect on the trabecular bone balance occurs at the expense of the cortical bone. We examined the biomechanical quality of cortical bone after intermittent treatment with different doses of PTH and, furthermore, compared the effects of PTH-(1-34) and PTH-(1-84). Groups of rats were treated with biosynthetic human PTH-(1-34) or PTH-(1-84), 1.1, 3.3, 10, or 30 nmol/kg/day for 30 days. No changes in the body weights and no changes in the lengths of the femora were observed after the PTH treatments. The biomechanical properties were analyzed by means of a materials-testing machine. A dose-related increase in the bending strength and stiffness of the femora was found, and this increase in mechanical strength corresponds with a 9-12% increase in the cross-sectional area of the femoral diaphyses. The deflection capability and energy absorption were not influenced by any of the PTH treatments. No differences were found between the effects of PTH-(1-34) or PTH-(1-84) on the biomechanical properties of the femora. Consequently, intermittent treatment with biosynthetic PTH-(1-34) or PTH-(1-84) increased the formation of cortical bone, and the biomechanical competence of the femora was found to be preserved.

Animals↗

Regulation of insulin-like growth factor binding protein-5 messenger ribonucleic acid expression and protein availability in rat osteoblast-like cells.

PTH treatment of UMR 106-01 rat osteosarcoma cells increased 20- to 100-fold medium levels of a discrete insulin-like growth factor binding protein (IGFBP) with M(r) of 29K. Northern analysis of UMR cellular RNA hybridized with a specific IGFBP-5 complementary DNA probe indicated a 6.0-kilobase transcript induced within 2 h in PTH-treated cells. IGFBP-5 messenger RNA (mRNA) abundance was maximal around 6 h and remained elevated after 24 h of treatment. Another rat osteosarcoma cell line (ROS 17/2.8) did not express IGFBP-5 mRNA and did not secrete 29K IGFBP. Induction of IGFBP-5 mRNA by PTH was blocked when RNA synthesis in UMR cells was inhibited by actinomycin D (Bu)2cAMP mimicked the effect of PTH on IGFBP-5 mRNA expression and protein secretion. In addition, a monoclonal antibody against IGF-I (Sm 1.2) inhibited the PTH-induced increase in medium IGFBP-5 without influencing IGFBP-5 transcript levels. Direct addition of IGF-I to UMR cell cultures increased medium IGFBP-5 levels approximately 14-fold, with a modest effect on IGFBP-5 mRNA levels. Studies comparing IGF-I, IGF-II, different IGF-I analogs, and insulin indicated that the predominant IGF effect on IGFBP-5 accumulation was type I IGF receptor independent. Thus, in UMR 106-01 cells, PTH and IGF-I increase extracellular concentrations of IGFBP-5 via distinct but coordinate mechanisms; PTH acts primarily to induce IGFBP-5 mRNA expression through a cAMP-mediated mechanism, and IGF-I appears to interact directly with IGFBP-5 protein to promote its accumulation.

Animals↗

Plasma calcitonin, IGF-I levels and vertebral bone mineral density in hyperprolactinemic women during bromocriptine treatment.

Hyperprolactinemia is associated with decreased bone mineral density, which may be caused by the hypogonadism and hypoestrogenicity noticed in patients with hyperprolactinemia. Since calcitonin inhibits the bone resorption, and insulin-like growth factor I (IGF-I) has important anabolic effects on the skeleton, lack of one or both peptides may contribute to the development of osteopenia. We therefore measured the plasma calcitonin and IGF-I levels in nine women with hyperprolactinemia caused by a prolactin-producing pituitary tumor. The calcium-stimulated C-cell reactivity was studied by measuring calcitonin in plasma during a calcium clamp before and after normalization of serum prolactin during treatment with bromocriptine. Basal CT levels were measurable but lower than in healthy controls. Basal IGF-I levels and calcium-stimulated plasma calcitonin were normal in the hyperprolactinemic state and similar to the calcitonin and IGF-I levels during bromocriptine treatment. The serum prolactin levels decreased (p < 0.001) and the serum estradiol levels increased (p < 0.001). The bone mineral density of the lumbar spine increased significantly during treatment. Thus, basal plasma CT levels are slightly reduced in hyperprolactinemic women. However, the reversible osteopenia in hyperprolactinemic women is less likely to be caused by inhibited IGF-I secretion or by deficient CT levels since the CT response to calcium is normal. In addition, bromocriptine treatment with normalization of prolactin levels is beneficial for the bone mineral content in this condition.

Adult↗

Parathyroid hormone (1-34) and (1-84) stimulate cortical bone formation both from periosteum and endosteum.

The anabolic effect of intermittent treatment with parathyroid hormone (PTH) on cortical bone was investigated. Groups of rats were injected with human PTH (1-34) or PTH (1-84), 1.1, 3.3, 10, and 30 nmol/kg/day for 30 days. A dose-related increase in bone formation rate at the femoral middiaphysis was found at both the periosteum and the endosteum and also an increase in bone mass, with no change in the bone lengths or body weight gain of the rats. The highest mineral apposition rate, as analyzed by tetracycline labeling, was found at the periosteal postero-medial aspect and at the endosteal anterior aspect. This pattern of bone modeling was also found in the PTH-treated animals, although more and more areas were included in bone mineral apposition. The PTH treatments did not change the porosity of the cortical bone nor the concentration and biochemical stability of the collagen. The highest doses of PTH resulted in a slight reduction in the ash concentration of cortical bone. No differences were found between the effects of PTH (1-34) and PTH (1-84) on bone formation rate, bone mass, porosity, and biochemical parameters. Consequently, intermittent treatment with PTH increased the formation of cortical bone dose dependently, at both the periosteum and the endosteum and increased the bone mass of these growing rats, with no change in the body weight gain or femoral growth rate compared with the control animals. The responses of the cortical bone modeling were increased by the PTH treatments without changing its direction or pattern.

Animals↗

Occurrence of ophthalmopathy after treatment for Graves' hyperthyroidism. The Thyroid Study Group.

BACKGROUND: Ophthalmopathy caused by Graves' disease may first appear or worsen during or after treatment for hyperthyroidism. It is not known, however, whether choosing to treat hyperthyroidism with antithyroid drugs, iodine-131, or surgery affects the development or aggravation of Graves' ophthalmopathy. METHODS: We studied 168 patients with hyperthyroidism caused by Graves' disease, stratified into two age groups--20 to 34 years (54 patients, group 1) and 35 to 55 years (114 patients, group 2). The patients in group 1 were randomly assigned to treatment with methimazole for 18 months or subtotal thyroidectomy, and those in group 2 to either of these two treatments or to iodine-131 therapy. All the patients received thyroxine to avert hypothyroidism, except those treated with iodine-131, who received thyroxine only if hypothyroidism developed. The duration of follow-up was at least 24 months. RESULTS: Twenty-two patients (13 percent) had infiltrative Graves' ophthalmopathy at randomization. During follow-up, ophthalmopathy developed for the first time in 22 patients (13 percent) and worsened in 8 patients (5 percent). The frequency of the development or worsening of ophthalmopathy was similar among the patients in group 1 (medical therapy, 4 of 27 patients [15 percent]; and surgery, 3 of 27 patients [11 percent]). In group 2, ophthalmopathy developed or worsened in 4 of the 38 patients (10 percent) treated medically, 6 of the 37 patients (16 percent) treated surgically, and 13 of the 39 patients (33 percent) given iodine-131 (P = 0.02 for the comparison between the iodine-131 subgroup and the others combined). The risk of the development or worsening of ophthalmopathy increased as pretreatment serum triiodothyronine concentrations increased. CONCLUSIONS: As compared with other forms of antithyroid therapy, iodine-131 is more likely to be followed by the development or exacerbation of Graves' ophthalmopathy.

Adult↗

Parathyroid hormone-related peptide in human milk measured by a mid-molecule radioimmunoassay.

Several peptide hormones and growth factors have been found in human milk, and we present here the results of measurements of parathyroid hormone-related peptide (PTHrP). A radioimmunoassay (RIA) using a polyclonal antiserum against the mid-region of the molecule has been developed. In milk collected during the first 6 days after parturition, the PTHrP concentrations showed large interindividual variations ranging from 0.3 to 13.7 nmol-Eq/L (0.5 to 24.4 ng-Eq/mL) (n = 67) and increased between days 3 and five postpartum. PTHrP also increased during the first 4 collecting days when measured in milk from the same mother during a prolonged period. On fast-protein liquid chromatography (FPLC), the bulk of PTHrP eluted with a molecular weight of approximately 10 to 12 kd after treatment with urea. After mid-molecule immunoaffinity extraction of PTHrP from milk, higher levels were obtained by the mid-molecule RIA than by an aminoterminal assay, indicating that all fragments did not contain the aminoterminal. Parts of immunoextracted milk PTHrP stimulated cyclic adenosine monophosphate (cAMP) production in rat osteosarcoma cell line, UMR-106. In conclusion, we have found PTHrP-like immunoreactivity in human milk using a mid-region RIA. Parts of the immunoextracts also contained the aminoterminal and possessed PTH-like bioactivity. Whether PTHrP in human milk plays a physiological role in the maternal breast or in the newborn gastrointestinal tract is unknown, but the present observations demonstrate that a portion of the PTHrP is at least potentially biologically active.

Biological Assay↗

Expression of the thyroid hormone receptor, the oncogenes c-myc and H-ras, and the 90 kD heat shock protein in normal, hyperplastic, and neoplastic human thyroid tissue.

Expression of the thyroid hormone receptor (TR beta), the 90 KD heat shock protein (HSP 90), and the oncogenes H-ras and c-myc mRNA in normal hyperplastic, and neoplastic human thyroid tissue was investigated by Northern blot and slot blot analyses. The TR beta mRNA was present in all normal and neoplastic thyroid tissue samples. The levels were significantly higher in normal and hyperplastic tissues (7.91 +/- 0.48 and 7.60 +/- 0.68 arbitrary units, respectively) than in neoplastic tissues (3.82 +/- 0.67) (p < 0.001). H-ras and c-myc mRNA were also detected in glandular tissue specimens, but no significant difference was observed in their expression levels. Furthermore, there was a tendency to a negative correlation between the level of TR beta and c-myc mRNA (p = 0.06). In normal thyroid tissue, HSP 90 mRNA levels were significantly higher than in hyperplastic and papillary carcinoma tissue specimens (p < 0.001). These results indicate that mRNA of TR beta and HSP 90 (the latter only in papillary thyroid carcinoma) are expressed in relation to the degree of cellular differentiation. Furthermore, the presence of TR beta in normal thyroid tissue implies that T3 and T4 may be involved in the regulation of their own production via TR beta activated feedback mechanism(s).

Adult↗

Inhibition by human interleukin-1 alpha of parathyroid hormone-related peptide effects on renal calcium and phosphorus metabolism in the rat.

Humoral hypercalcemia of malignancy (HHM) is at least partly caused by tumor secretion of PTH-related peptide (PTHrP), but there is growing evidence for cosecretion with PTHrP of other bone-resorbing peptides, such as the cytokine interleukin-1 alpha (IL-1 alpha). Administration of PTHrP in vivo and in vitro generally mimics the actions of PTH itself, with increases in both resorption and formation of bone. However, bone in HHM is characterized by uncoupling of bone turnover, with increased resorption and decreased formation. We performed experiments to determine whether IL-1 alpha might alter the effects of PTHrP and produce uncoupling. Thus, we administered to 100-g male rats by sc osmotic minipumps synthetic PTHrP-(1-34) alone (2 micrograms/100 g/day), recombinant IL-1 alpha alone (1.5 micrograms/100 g/day), both peptides together at the previous doses, or vehicle only. We infused 5 groups of 12 rats each (PTHrP, IL-1 alpha, PTHrP plus IL-1 alpha, ad libitum fed control, and controls pair-fed to the PTHrP plus IL-1 alpha group) for 14 days. At the end of the study, blood and urine were taken for chemical measurements, and tibias and femurs were harvested for histomorphometry and extraction of RNA from periosteal cells. As expected, PTHrP induced hypercalcemia, relative hypophosphatemia, phosphaturia, and reduced bone mass. Osteoblast number was increased, but osteoclast number was not. Indices of bone formation were unchanged or reduced. The dose of IL-1 alpha chosen had no statistically significant effect, except for reduced longitudinal bone growth, but when combined with PTHrP, IL-1 alpha reduced hypercalcemia, hypophosphatemia, and phosphaturia. In contrast to the blood and urine effects, IL-1 alpha did not interact significantly with PTHrP's effect on bone measurements. Northern analysis of periosteal cell mRNA showed that PTHrP reduced expression of osteocalcin, but not glyceraldehyde-3-phosphate dehydrogenase; IL-1 alpha had no additional effect. These data suggest that 1) continuously administered PTHrP alone may induce uncoupled bone turnover with decreased cortical bone formation; 2) IL-1 alpha appears to inhibit strongly the renal effects of PTHrP and weakly (if at all) its actions on bone and, thus, to decrease its hypercalcemic, phosphaturic, and hypophosphatemic actions; and 3) cosecretion of IL-1 alpha, and possibly other peptide cytokines, with PTHrP may modify the clinical expression of HHM.

Animals↗

Parathyroid hormone-related peptide, measured by a midmolecule radioimmunoassay, in various hypercalcaemic and normocalcaemic conditions.

The diagnosis of humoral hypercalcaemia of malignancy often presents considerable clinical problems. We have studied parathyroid hormone-related peptide (PTHrP) in serum from patients with humoral hypercalcaemia of malignancy (N = 22), hypercalcaemia of malignancy with skeletal metastases (17), histologically confirmed primary hyperparathyroidism (21) and hypercalcaemic patients with various benign diseases (9). PTHrP measurements were also made in normocalcaemic patients with various malignancies (23), endocrine diseases (13), sarcoidosis (22) and chronic renal failure (17). PTHrP was measured by a novel radioimmunoassay using rabbit antibodies directed towards the midregion of the molecule. Immuno- or silica cartridge extraction of serum before radioimmunoassay enabled us to measure PTHrP in all samples, which may add further information about circulating forms of PTHrP. PTHrP was clearly elevated in patients with humoral hypercalcaemia of malignancy (5.0 +/- 4.7 pmol/l) (mean +/- SD, N = 12) and when the kidney function was impaired (4.0 +/- 0.9 pmol/l) (N = 15) (silica cartridge extraction), whether the subject was hypercalcaemic or not. Some patients with endocrine diseases, including two with primary hyperparathyroidism, had slightly elevated serum PTHrP concentrations, while they were normal in sarcoidosis. In healthy subjects the levels were 1.1 +/- 0.5 pmol/l (N = 15) after immunoextraction and 0.8 +/- 0.2 pmol/l (N = 33) after silica cartridge extraction.

Aged↗

A rapid extraction method for serum calcitonin.

A rapid, simple and reliable extraction method for calcitonin from serum has been developed. 2 volumes of acidic ethanol and 1 volume of serum were mixed, centrifuged, and the supernatant was evaporated to dryness. The extracts were reconstituted in assay buffer before radioimmunoassay was performed. Basal concentrations of calcitonin after extraction were 5.4 +/- 3.0 pg-equivalents/ml (mean +/- SD), females, n = 48 and 8.8 +/- 5.5 pg-equivalents/ml, males, n = 42. Calcitonin was detectable in serum from all males and from 90% of the females. The concentrations in males were significantly higher (P less than 0.001). There was a more pronounced calcitonin response in males (n = 12) than in females (n = 12) to a calcium clamp (P less than 0.01). Gel chromatography of serum from patients with medullary thyroid carcinoma on a Sephadex G-75 column and a TSK G 2000 SW column in a fast protein liquid chromatography system, disclosed that the ethanol extraction excluded the high mol mass forms of calcitonin. We propose the acidic ethanol extraction as a convenient method for routine measurements of calcitonin.

Calcitonin↗