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Biomedical subjects

J C Netelenbos

Publications and source records attributed to J C Netelenbos.

At least 19 recordsLinked to original sources
PubMed1995

Insulin-like growth factor binding proteins-2 and -3 stimulate growth hormone receptor binding and mitogenesis in rat osteosarcoma cells.

GH exerts its biological actions on osteoblasts through a specific high affinity receptor expressed on these cells. GH receptor binding is positively modulated by a number of factors, including retinoic acid and dexamethasone, whereas fetal calf serum strongly decreases the binding. To identify responsible factors in serum, components of serum, the insulin-like growth factors (IGFs)-I and -II, and IGF binding proteins (IGFBPs)-2 and -3 were tested for a possible negative modulatory role. IGF-I and -II decreased [125I]hGH binding at an optimal concentration of 30 ng/ml for IGF-I and 100 ng/ml IGF-II, reducing the binding to 51% and 55%, respectively, of control values. A stimulation of [125I]hGH binding was observed with IGFBP-2 as well as IGFBP-3, inducing an increase to 148% and 151% of control binding at an optimal concentration of 3000 ng/ml for both peptides. The effects of all peptides were dependent on the incubation time, being significantly increased after 8 h of incubation and reaching the full effect thereafter. The effects were declined at 24 h compared with 16 h for IGFBP-2 and -3 but not for IGF-I and -II. Coincubation of the cells with IGF-I and -II and IGFBP-2 and -3 neutralized the effects of the factors alone. In conclusion, these results show that IGF-I and -II on the one hand and IGFBP-2 and -3 on the other hand exert opposite actions on [125I]hGH binding, IGFBP-2 and -3 exerting probably an IGF-independent effect. Further, IGF-I and -II decreased GH receptor messenger RNA (mRNA) levels, as quantified by a solution hybridization ribonuclease protection assay, from 8.65 +/- 1.78 attomoles (amol)/microgram DNA (control) to 2.4 +/- 0.68 and 2.16 +/- 0.92 amol/microgram DNA, respectively. IGFBP-2 increased GH receptor mRNA levels from 5.26 +/- 1.17 (control) to 13.19 +/- 3.48. Incubation with IGFBP-3 did not result in stimulation of GH receptor mRNA levels (8.59 +/- 2.91 amol/microgram DNA). This shows that the mechanism of regulation of the GH receptor is, except for IGFBP-3, at least in part on the mRNA level. Lastly, IGFBP-2 and IGFBP-3 are mitogenic for UMR-106.01 rat osteosarcoma cells, inducing an increase in cell number to 125% and 142% of control cell counts after 48 h of incubation with 1000 ng/ml IGFBP-2 and -3, whereas IGF-I, IGF-II and Long R3 IGF-I did not stimulate proliferation. IGFBP-2 and -3 potentiate hGH induced mitogenesis at low hGH concentrations of both factors, whereas at higher concentrations no such effect is observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

The relation between periodontitis and systemic bone mass in women between 46 and 55 years of age.

It has been suggested that periodontitis and systemic bone mass might be related. In order to evaluate this possible relationship, we performed an intra-oral examination and measured lumbar bone mineral density (lumbar BMD) and metacarpal cortical thickness (MCT) in 286 female volunteers between 46 and 55 years of age. In addition, the alveolar bone height was measured on bite wing radiographs of the dentate subjects. Of the subject, n = 60 (21%) were edentulous. Compared to the dentate subjects, the lumbar BMD and MCT of the edentulous women were not significantly different. In the dentate subjects, no significant correlation was observed between the clinical parameters of periodontitis (mean probing depth, occurrence of bleeding after probing and number of missing teeth) and the bone mass parameters (lumbar BMD and MCT); nor was a significant relation observed between the bone mass measurements and alveolar bone height. We therefore suggest that systemic bone mass is not an important factor in the pathogenesis of periodontitis.

Absorptiometry, Photon↗
PubMed1991

Biochemical parameters of bone turnover during ten days of bed rest and subsequent mobilization.

Immobilization is associated with increased bone resorption. To investigate the early onset of increased bone resorption, we evaluated 14 patients who were immobilized for 10 days because of lumbar disc protrusion. The fasting urinary hydroxyproline/creatinine ratio increased significantly after four days (P less than 0.01), reached a peak after 10 days (16.4 +/- 3.3 mumol/mmol, 27.6 +/- 8.8 mumol mmol, P less than 0.01) and returned slowly to baseline values after mobilization. The fasting urinary calcium creatinine ratio followed a similar pattern. Serum calcium and phosphate increased during immobilization (P less than 0.01). Serum 1,25-dihydroxyvitamin D decreased significantly during immobilization (98 +/- 33 pmol/l vs. 79 +/- 36 pmol/l, P less than 0.05), and reached a nadir one week after mobilization (P less than 0.01). We conclude that there is an early significant increment in resorption parameters, with a slow return during the mobilization period. Serum 1,25-dihydroxyvitamin D is suppressed as a result of the increased serum calcium and serum phosphate levels.

Adult↗
PubMed1991

Short-term effects of Org OD 14 and 17 beta-oestradiol on bone and lipid metabolism in early post-menopausal women.

The effects of 8 weeks of daily oral treatment with 1 mg 17 beta-oestradiol (E2), 2.5 mg Org OD 14 [7 alpha, 17 alpha)-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one) , a steroid with weak androgenic, weak oestrogenic and weak progestational activity, or placebo on calcium and lipid metabolism were compared in 21 healthy, early post-menopausal women in a randomised double-blind study. The treatment period was followed by a treatment-free period of 8 weeks to study the reversibility of drug-induced effects. The results show that both E2 and Org OD 14 reduce bone resorption, as indicated by the decreases in the urinary hydroxyproline/creatinine and calcium/creatinine ratios in 2-h fasting urine. In contrast to E2, Org OD 14 did not reduce serum calcium levels. As regards lipid parameters, E2 reduced the concentration of serum cholesterol and Org OD 14 decreased serum levels of high-density-lipoprotein cholesterol and triglycerides. All these effects appeared to be reversible after cessation of treatment. It is concluded that both of these steroids reduce bone resorption in early post-menopausal women, but that their mechanisms of action are most likely different.

Anabolic Agents↗
PubMed1991

Stimulation and suppression of intact parathyroid hormone (PTH1-84) in normal subjects and hyperparathyroid patients.

OBJECTIVE: Because of an overlap between serum PTH values in healthy controls and hyperparathyroid patients we sought to evaluate a short stimulation and suppression test for differentiating the two groups. SUBJECTS: Subjects were 34 patients with primary hyperparathyroidism (PHPT) and 25 healthy controls. DESIGN: After stimulation with intravenous EDTA (10 mg/kg body weight in 5 minutes) blood samples were obtained for up to 15 minutes. After an oral calcium dose of 1 g, blood samples were obtained at 1 and 2 hours. After an intravenous calcium dose (2.5 mg/kg body weight in 30 seconds), blood samples were obtained serially for 20 minutes. MEASUREMENT: Serum PTH(1-84) was measured by a double antibody technique. RESULTS: The intravenous EDTA test resulted in an average 2.6-fold increase of serum PTH(1-84) in hyperparathyroid patients, whereas it increased 10.5-fold in controls. A response was absent in three of 23 patients. There was an overlap in results between patients with mild hyperparathyroidism and controls. The oral calcium dose decreased serum PTH(1-84) in patients to 0.73 and in controls to 0.55 of the basal value, but six of 15 patients and two of 12 controls did not respond. The intravenous calcium test resulted in a drop of serum PTH(1-84) in hyperparathyroid patients to 0.51 and in control subjects to 0.40 of the basal value, and non-responders were not observed. There was a strong correlation between the responses to the EDTA and the calcium infusion tests in the patients (r = 0.97, P less than 0.01). Fasting serum calcium and serum PTH(1-84) showed a positive correlation in PHPT patients (r = 0.75, P less than 0.001) and a negative correlation in control subjects (r = -0.41, P less than 0.05). Based on these relationships, hyperparathyroid patients and controls could be completely separated. CONCLUSION: The wide range of responses to stimulation and suppression tests and the correlation between these responses in hyperparathyroid patients indicate various degrees of autonomy. As the response to these tests is less marked in patients than in controls and both groups still overlap, these tests are not useful for the diagnosis of primary hyperparathyroidism.

Adolescent↗
PubMed1991

Effect of a single infusion of aminohydroxypropylidene on calcium and bone metabolism in healthy volunteers monitored during 2 months.

Recently, bisphosphonates have been used to prevent postmenopausal bone loss. As the effects of bisphosphonates on normal bone metabolism are unknown, 3-amino-1-hydroxypropylidene-1,1-diphosphonate (APD) was studied in healthy subjects. The effects of a single 20-mg APD infusion on biochemical parameters of calcium and bone metabolism were investigated during 2 months in 10 healthy male volunteers. This single moderate dose of APD reduced biochemical parameters of bone resorption during the time of follow-up. After 2 months, urinary hydroxyproline excretion was still below the basal level. The decreased serum calcium levels did not return to basal values. Biochemical parameters of bone formation, serum alkaline phosphatase and osteocalcin, showed a slight increase during the first month after stimulation of the parathyroids and a corresponding increase in serum 1,25-dihydroxyvitamin D. These formation parameters decreased thereafter, probably representing coupling between bone resorption and bone formation.

24,25-Dihydroxyvitamin D 3↗
PubMed1991

Calcium supplementation reduces vertebral bone loss in perimenopausal women: a controlled trial in 248 women between 46 and 55 years of age.

To study the effect of calcium supplementation on perimenopausal bone loss, 295 women were randomized into a control group and 2 supplementation groups receiving, respectively, 1000 and 2000 mg elemental calcium/day for a period of 2 yr. We observed a significant decrease in lumbar bone loss in relation to the calcium supplementation (mean loss after 2 yr of 3.5% in the control group vs. 1.3% and 0.7% in the 1000 and 2000 mg groups, respectively), a significant increase in urinary calcium excretion, and a significant decrease in the urinary hydroxyproline/creatine ratio, serum alkaline phosphatase, osteocalcin, and 1,25-dihydroxyvitamin D. The effect of calcium supplementation on lumbar bone loss was significant in the first year of supplementation, but not in the second. However, the urinary hydroxyproline/creatinine ratio and the serum alkaline phosphatase level remained significantly decreased in the treatment groups at the end of the study; this was not the case for serum osteocalcin. Calcium supplementation did not have a significant effect on metacarpal cortical bone loss. The difference in biochemical parameters between the 2 supplementation groups was small. No significant interaction was observed between the menopausal status of the subjects and the effect of calcium supplementation. We conclude that calcium supplementation retards lumbar bone loss in the first year of calcium supplementation by reducing bone turnover. However, the effect on lumbar bone loss over a longer time span is still uncertain.

Alkaline Phosphatase↗
PubMed1990

Human pharmacokinetics of orally administered strontium.

Pharmacokinetics of orally administered SrCl2 (2.5 mmol) were studied in six healthy male volunteers. In the overall plasma concentration time (C-t) curves, two absorption phases were observed due to two dominant intestinal absorption loci. A method was devised to obtain separately the plasma C-t curves associated with each of the two absorption loci (curve 1 and curve 2). These curves and the overall plasma C-t curve were analyzed with a nonlinear estimation program (PCNONLIN). Pharmacokinetic parameters (mean +/- SD, n = 6) calculated from the overall curve were as follows: peak plasma concentration (Cmax) 3.55 +/- 1.22 micrograms/ml and area under the plasma C-t curve (AUC affinity) 9138 +/- 1930 micrograms.min/ml. The pharmacokinetic parameters calculated from curve 1 were as follows: terminal plasma elimination half-life time 47.3 +/- 7.9 hour, the plasma elimination half-life time of the preceding phase 5.2 +/- 3.3 hour, Cmax 1 3.09 +/- 0.95 micrograms/ml, the first-order absorption rate constant for absorption locus 1 (Ka,1) 5.7 +/- 1.2 * 10(-2) minute-1 and the time lag (tlag,1) 11.7 +/- 7.9 minute. In three of the subjects the pharmacokinetic parameters of absorption locus 2 could be evaluated: Ka,2 = 4.6 +/- 0.4 * 10(-2) minute-1, tlag,2 = 77.3 +/- 4.0 minute, tmax,2 = 153 +/- 16 minute, Cmax,2 = 0.9 +/- 0.4 micrograms/ml and AUC 2 affinity = 1204 +/- 565 micrograms. minute/ml. and AUC2 affinity = 0.14, indicating that 14% of the absorbed dose was absorbed via the second locus.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1990

Lower mobility and markers of bone resorption in the elderly.

Immobilization may lead to severe bone loss. Physical activity decreases with age and lower mobility might influence bone loss. We have evaluated the degree of mobility and parameters of bone turnover in 70 residents of a nursing home (mean age +/- SD 81 +/- 9 years) and 68 residents of an old people's home (mean age +/- SD 84 +/- 6 years). The mobility was assessed with a standing and walking score from 1 (severely disabled) to 5 (standing/walking without help). When the subjects were arranged according to increasing walking score from 1 to 5, fasting urinary hydroxyproline/creatinine ratio gradually decreased from 31 +/- 19 to 14 +/- 5 mumol/mmol (P less than 0.001). There was also a significant linear decrease of fasting urinary calcium/creatinine ratio, and serum calcium concentration and a significant increase of serum albumin and 1,25-dihydroxyvitamin D concentrations with increasing walking score. These data indicate that lower mobility in the elderly leads to higher bone resorption, which may suppress the formation of 1,25-dihydroxyvitamin D.

Aged↗
PubMed1990

Growth hormone (replacement) therapy in adults: bone and calcium metabolism.

Calcium uptake from the gut is increased by GH effects on vitamin D metabolism or action. Bone metabolism is stimulated by many factors, of which GH and insulin-like growth factor I (IGF-I) are only two examples. From various animal and human data, it can be shown that GH and IGF-I seem to influence bone formation more than bone resorption. However, GH excess, as seen in acromegaly, does not result in increased bone mass. GH was used to treat osteoporosis in a few clinical trials. In only one, in combination with calcitonin, an increase in bone mass was observed. In GH-deficient adult patients, substitution therapy resulted in a temporary increase in serum calcium levels. Effects on bone mineral mass were only found in a pilot study performed by us in a group of 8 GH-deficient adult patients. The mean increase of bone mineral mass was 0.04 g hydroxyapatite/cm2, p less than 0.05. These data indicate that GH substitution can result in increased bone mass.

Bone and Bones↗
PubMed1989

Selective determination of hydroxyproline in urine by high-performance liquid chromatography using precolumn derivatization.

A method to measure total hydroxyproline in human urine was developed. Primary amino acids were derivatized with ortho-phthaldialdehyde, followed by derivatization of imino acids with 9-fluorenylmethyl chloroformate. The fluorescent 9-fluorenylmethyl chloroformate derivatives were separated by reversed phase high-performance liquid chromatography. 3,4-Dehydroproline was used as internal standard. Calibration curves for hydroxyproline and internal standard were linear from 1 to 200 pmol injected. Both within- and between-run precision were below 3.2%. Analytical recovery of hydroxyproline added to urine samples was 99.2 +/- 2.6%. Values for excreted hydroxyproline were determined by analysis of urine samples from adult volunteers. The hydroxyproline/creatinine ratio was found to be 15.8 +/- 4.6 mmol/mol (range 7.0-27.3) with no significant sex-related difference.

Chromatography, High Pressure Liquid↗
PubMed1989

The effect of cross-gender hormonal treatment on bone metabolism in male-to-female transsexuals.

A deficiency of sex hormones leads in both sexes to increased bone loss, and hormonal substitution can prevent this. The effect of the change of hormonal environment on bone metabolism in transsexuals is unknown. Transilial bone biopsies were obtained from 23 male-to-female transsexuals (mean age +/- SD, 38.0 +/- 11.7 years) after estrogen (ethinylestradiol, 100 micrograms/day) and antiandrogen treatment (cyproterone acetate, 100 mg/day) for 8-41 months. Histomorphometric data were compared with those from 11 healthy men (39.6 +/- 9.4 years). There was no difference in bone volume, bone surface, or trabecular thickness between transsexuals and controls. Eroded surface and osteoclast number were not different between the groups. The osteoid volume, surface, and thickness were significantly lower in the transsexuals than in the controls. The mineral apposition rate and adjusted apposition rate were normal, but mineralizing surface and bone formation rate were suppressed in the transsexuals compared with data reported from the literature. The results indicate that antiandrogen and estrogen treatment in male-to-female transsexuals may suppress bone turnover and is not associated with bone loss.

Adult↗
PubMed1989

Perimenopausal bone mass and risk factors.

We studied the effect of menopausal status and risk factors on lumbar bone mineral density (BMD) and metacarpal cortical thickness (MCT) in 286 women of 46-55 years of age. Body mass index (height/weight) was measured and the family history of osteoporosis, reproductive history, menopausal status, calcium intake, amount of physical activity and the consumption of tobacco and alcohol were assessed. Lumbar BMD and MCT decreased substantially in the perimenopausal and postmenopausal period. In the premenopausal women a significant (P = 0.03) lower lumbar BMD was observed in the lowest tertile of calcium intake (less than or equal to 900 mg/day) compared to the highest tertile (greater than or equal to 1200 mg/day). This difference was not apparent in the peri- and postmenopausal women. This suggests that dietary calcium intake is more important in the development and/or maintenance of peak bone mass, than in the modulation of postmenopausal bone loss. Apart from menopausal status and low calcium intake, no other significant determinant of bone mass could be identified. We conclude, therefore, that the assessment of risk factor status is not an efficient tool for the identification of perimenopausal women with low bone mass.

Bone Density↗
PubMed1989

Pharmacokinetics of 24,25-dihydroxyvitamin D3 in humans.

Pharmacokinetic properties of pharmacological doses of 24,25-dihydroxyvitamin-D3 [24,25(OH)2D3] were determined in healthy volunteers. Four male subjects received 25 micrograms of 24,25(OH)2D3 as an intravenous bolus injection. Plasma concentrations of 24,25(OH)2D3, 25-hydroxyvitamin D and 1,25-dihydroxy-vitamin D were monitored during 14 days. In addition, serum ionized calcium, total calcium, inorganic phosphate, albumin, creatinine and intact hPTH(1-84) were measured during 14 days. The concentration-time curve of 24,25(OH)2D3 could be described by a two-exponential curve with half-lives of 3.0 +/- 0.9 hrs and 8.2 +/- 2.9 days (mean +/- SD). The volume of distribution was 0.19 +/- 0.02 liters/kg. None of the mentioned biochemical parameters, except serum 24,25(OH)2D3, changed markedly. In 18 subjects suffering from primary hyperparathyroidism, taking 25 micrograms of 24,25(OH)2D3 daily during three months, an average plateau level of 39 +/- 12 nmol/l of serum was observed. Bioavailability as estimated from this plateau level was approximately 70%.

24,25-Dihydroxyvitamin D 3↗
PubMed1989

Quantification of strontium in plasma and urine with flameless atomic absorption spectrometry.

This analytical method for determination of Sr in plasma and urine involves flameless atomic absorption spectrophotometry (FAAS). Drying, charring, and atomization were optimized with respect to temperature, temperature ramp, and duration for Sr in dilute HNO3 and Sr in plasma diluted 20-fold with dilute HNO3. Calibration curves (r greater than 0.995) were linear in the concentration range 5-250 micrograms/L for Sr in various media, with intercepts negligibly small except for the calibration curves in 1:1-diluted plasma and undiluted urine. The estimated detection limits for Sr in 20-fold-diluted plasma and 50-fold-diluted urine were 2 and 3 micrograms/L, respectively. Endogenous Sr in plasma and urine was estimated at 16 (SD 8) micrograms/L and 158 (SD 26) micrograms/L (n = 6), respectively. Intra- and interassay CVs were 9.1% and 5.3% for 20-fold-diluted plasma at a Sr concentration of 25 micrograms/L, and 6.9% and 4.8% at a concentration of 250 micrograms/L. The respective CVs were 8.2% and 1.2% for 50-fold-diluted urine at the low concentration, and 4.0% and 4.6% at the high concentration. In a pharmacokinetic pilot study of 2.5 mmol of Sr orally administered to a healthy volunteer, the peak plasma concentration of Sr, 4.4 mg/L, decayed bi-exponentially [t1/2, alpha = 24 h, t1/2, beta = 77 h]; the estimated first-order absorption rate constant was 0.005 min-1; and the observed decay (day 0-6) of the urinary Sr/creatinine ratio closely paralleled the plasma decay [t1/2 = 70 h].

Administration, Oral↗