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Biomedical subjects

S Ljunghall

Publications and source records attributed to S Ljunghall.

At least 109 records · Page 6Linked to original sources
PubMed1995

[Vitamin D and osteoporosis].

Vitamin D constitutes a complex endocrine-regulated system, and is both a prohormone for the endogenous synthesis of the active hormone, calcitriol, and a vitamin which may be administered to supply the organism's requirements. No single test or investigation is available for the demonstration of vitamin D deficiency. Both vitamin D intake and ability to synthesise vitamin D decrease with increasing age, and particularly the elderly in institutionalised care are at risk of developing vitamin D deficiency. Iceland excepted, mean daily vitamin D consumption in the Nordic countries is less then 5 micrograms; and in approximately 10-25 per cent of the population, daily intake is less than 2.5 micrograms which is insufficient to maintain an adequate serum calcidiol concentration in individuals unexposed to sunlight. The recommended daily intake of 5 micrograms, currently adopted in the Nordic countries, may be too low-an intake of 10 micrograms is probably necessary to satisfy requirements in the elderly.

Adrenal Cortex Hormones↗
PubMed1994

Competitive PCR demonstrates that 9-cis retinoic acid induces cellular retinoic acid-binding protein-II more efficiently than all-trans retinoic acid in human osteosarcoma cells.

Cellular retinoic acid-binding proteins (CRABPs) are thought to play a key role in the regulation of the levels of retinoic acid (RA) available to interact with the nuclear receptors. In this study we have used reverse transcription (RT) and competitive polymerase chain reaction (cPCR) to investigate the effects of RA on CRABP-II expression levels in the human osteosarcoma cell line MG-63. Two different isomers of RA, all-trans (at) and 9-cis RA, were chosen since at-RA but not 9-cis RA binds to CRABP-II. Cells were treated with 10(-6) M at-RA or 9-cis RA for 24 h. Following RNA preparation and RT, cPCR was performed using constructed internal standards for CRABP-II and beta-actin. While no change occurred in the beta-actin control, an approximate two-fold increase of CRABP-II mRNA levels was seen in cells treated with at-RA and at least a four-fold increase with 9-cis RA. Thus, although 9-cis RA does not bind to CRABP-II, it induces CRABP-II expression more efficiently than at-RA in human osteosarcoma cells.

Base Sequence↗
PubMed1994

Adult human osteoblast-like cells do not express insulin-like growth factor-I.

Previous studies using cultures of fetal rodents calvaria have indicated an important role for insulin-like growth factor-I (IGF-I) in the local control of bone formation. In this study, we have examined the expression of IGF-I in adult human osteoblast-like (hOB) cells. To detect very low levels and to distinguish between the two IGF-I mRNA transcripts Ea and Eb, which are formed by alternate splicing, we have used the reverse transcriptase-polymerase chain reaction (RT-PCR). Expression of both Ea and Eb IGF-I mRNA transcripts were found in human liver and in placenta. However, neither Ea nor Eb IGF-I mRNA could be detected under basal conditions or after stimulation with growth hormone in normal hOB cells and two human osteosarcoma cell lines with osteoblastic properties, SaOS-2 and MG-63. We conclude that adult hOB cells do not synthesize IGF-I. Thus, in contrast to its crucial role as a local regulator of skeletal remodeling in fetal rodent bone, IGF-I does not appear to have this autocrine function in adult human bone.

Base Sequence↗
PubMed1994

Growth hormone-dependent insulin-like growth factor binding protein is a major determinant of bone mineral density in healthy men.

To establish the major determinants of bone mass, we assessed relationships between bone mineral density (BMD) and height, weight, body mass index (BMI), muscle strength, physical capacity (VO2max), body composition, serum concentrations of insulin-like growth factor I (IGF-I), growth hormone (GH), the GH-dependent IGF binding protein (IGFBP-3), testosterone, sex hormone binding globulin (SHBG), osteocalcin, and parathyroid hormone (PTH) in 38 healthy men between 25 and 59 years of age. Values of BMD at all sites (total body, lumbar spine, and hip) were strongly correlated with IGFBP-3 (r = 0.51-0.64, p < 0.001 at all sites), and total-body BMD was also significantly correlated with IGF-I (r = 0.43, p = 0.01). BMD measurements of the total body and of the different sites of the hip were negatively correlated with age and positively with weight, BMI, muscle strength, VO2max, and fat-free weight. IGF-I and IGFBP-3 were both positively related to muscle strength and VO2max. In a stepwise forward multiple-regression analysis, the best model was obtained for the femoral neck, where IGFBP-3, GH, PTH, age, IGF-I, and BMI explained 77% of the variation in BMD. The partial regression coefficients of IGFBP-3, PTH, and BMI were all positive, whereas age, GH, and IGF-I were negatively correlated with BMD. In summary, IGFBP-3 correlated better with BMD than any other study parameter. The findings indicate that GH is of importance for bone mass and suggest that IGFBP-3 not only reflects the integrated GH secretion but also has a direct role in the endocrine regulation of bone metabolism.

Absorptiometry, Photon↗
PubMed1994

Intact serum parathyroid hormone levels increase during running exercise in well-trained men.

The purpose of this study was to examine the influence of exercise on the serum concentrations of intact parathyroid hormone (PTH). Serum PTH and plasma lactate were measured in 15 well-trained men, 9 long-distance runners and 6 fire-fighters, during two running exercises. Test one consisted of 40-minute treadmill running with a step-wise increased load and test two consisted of 50-minute treadmill running with a constant velocity. When the load was step-wise increased, the PTH concentrations increased moderately at the slower running paces but reached a final value that was about 50% higher than the starting value. This rise occurred despite a concomitant increase of total serum calcium from 2.38 +/- 0.06 to 2.49 +/- 0.05 mmol/liter (P < 0.01). During the constant running exercise, the long-distance runners, but not the fire-fighters, displayed a significant increase in PTH concentrations although the rise in total serum calcium was similar in both groups. There was a weak correlation between the changes in PTH and lactate in both exercises. The findings demonstrate that both high and low intensity exercise enhance release of PTH in long-distance runners through a mechanism that does not involve serum calcium. This relationship might be of importance for bone mass in men performing long-distance training.

Adult↗
PubMed1994

Monoclonal antibodies against the putative divalent cation-receptor that is located on parathyroid cells do not stain isolated rat osteoclasts.

It has been reported that osteoclastic function is regulated by calcium-induced alterations in cytoplasmic free calcium ([Ca2+]i), possibly through a specific receptor. We have investigated whether osteoclasts, isolated from neonatal rat long bones, possess the divalent cation-receptor that has been demonstrated on parathyroid cells. Studies with fura-2 loaded adherent single cells showed that an increase in extracellular Ca2+ ([Ca2+]e) from 0.5 mM to 10 mM resulted in an increase in [Ca2+]i in isolated rat osteoclasts, from a basal value of 94.7 +/- 16.2 to 150.6 +/- 22.4 nM (means +/- SEM; n = 14). The shape and time course of the [Ca2+]i increase varied considerably from cell to cell. Less than half of the cells responded with a rapid transient increase whereas the rest responded with a slow increase that reached a plateau within 1-2 minutes. When [Ca2+]e was changed back to 0.5 mM, a slow decrease in [Ca2+]i was monitored. Immunohistochemical staining with two different monoclonal antibodies, recognizing the putative Ca2+ receptor on parathyroid cells, did not indicate any staining on freshly isolated rat osteoclasts. Thus, our data demonstrate that an increase in [Ca2+]e causes an elevation of [Ca2+]i in osteoclasts. This increase is not mediated via the putative cation-receptor found on parathyroid cells.

Animals↗
PubMed1994

Acute effects of high-dose chemotherapy followed by bone marrow transplantation on serum markers of bone metabolism.

There is an interplay between the cells in the bone marrow and the surrounding bone tissue, but little is known about the effects of myeloablative treatment followed by bone marrow transplantation on bone metabolism. We have therefore investigated 24 patients undergoing bone marrow transplantation (14 autologous, 10 allogeneic) for hematological malignancies. Serum concentrations of parathyroid hormone (PTH), albumin-modified calcium, and biomarkers for bone turnover--osteocalcin, bone alkaline phosphatase (B-ALP), and carboxyterminal cross-linked telopeptide of type I collagen (ICTP)--were measured. The samples were collected before myeloablative treatment, on the day of bone marrow infusion and 1, 2, 3, and 12 weeks thereafter. A serum PTH peak was consistently seen the day after total body irradiation, but no long-term effects on PTH/calcium homeostasis were observed. Bone formation as reflected by serum osteocalcin and B-ALP decreased, with nadir levels 2 to 3 weeks after marrow infusion. A simultaneous increase in bone resorption (increased S-ICTP) occurred. Pretreatment values were not completely regained 12 weeks after transplantation. The findings indicate that bone tissue is affected by myeloablative treatment, and the changes in biomarkers imply a net loss of bone over the study period.

Adolescent↗
PubMed1994

Effects of infusion of parathyroid hormone and primary hyperparathyroidism on formation and breakdown of type I collagen.

The influence of chronic and acute exposure to parathyroid hormone (PTH) on formation and breakdown of type I collagen, using two recently developed radioimmunoassays for serum PICP (the carboxyterminal propeptide of type I procollagen) and serum ICTP (the carboxyterminal telopeptide of type I collagen), have been evaluated. Fasting morning values were obtained from 18 women with primary hyperparathyroidism (HPT) and an equal number of age-matched, healthy controls. A 24-hour infusion of synthetic human parathyroid hormone (PTH 1-38) was performed in 14 healthy females. The patients with HPT had higher values for serum ICTP than the controls (6.0 +/- 3.0 and 4.1 +/- 2.1 micrograms/liter; P < 0.05), whereas the serum PICP concentrations were not different (170 +/- 72 and 151 +/- 65 micrograms/liter; n.s.). During infusion of PTH in healthy subjects, there was an increase of the serum ICTP concentrations (from 3.6 +/- 1.3 to 4.4 +/- 1.8 micrograms/liter; P < 0.001) whereas those of serum PICP decreased (from 185 +/- 78 to 118 +/- 42 micrograms/liter; P < or = 0.0001). The increase of serum ICTP during infusion of PTH was positively related to the increase of serum calcium and other indices of bone resorption, i.e., fasting urinary excretions of hydroxyproline and calcium. The decrease of serum PICP was also related to the changes of serum ICTP and hydroxyproline in urine, serum calcium, and alkaline phosphatase but not to osteocalcin, an established marker of osteoblastic activity. The findings support the fact that serum ICTP is a valuable method for evaluating bone resorption and is also easy to perform.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

On the interplay between insulin secretion and sensitivity as determinants of glucose tolerance.

Both insulin secretion and sensitivity have been claimed to be the main characteristics in the determination of future deterioration in glucose tolerance. In this cross-sectional study insulin secretion and insulin sensiturity were determined in 228 subjects with varying degrees of glucose tolerance. Insulin secretion was measured in an intravenous glucose tolerance test (IVGTT) and insulin sensitivity by the hyperinsulinaemic euglycaemic clamp test. Both the early insulin response in the IVGTT (increment) and the glucose disposal rate in the clamp test (M-value) were found to be related hyperbolically to fasting glucose (r = -0.63 and -0.66, respectively; both P < 0.0001) and in a second-order polynomial manner to the glucose disappearance rate (k-value) in the IVGTT (r = 0.53 and 0.48, respectively; both P < 0.0001). Multiple regression analysis showed the insulin increment in the IVGTT and the M-value in the clamp test to be equally important determinants of glucose tolerance, together explaining about 50% of the variation in fasting glucose and the k-value in the IVGTT. In conclusion, in this cross-sectional study insulin secretion and sensitivity studied over a broad range of glucose tolerance were found to be of almost equal importance in the determination of glucose tolerance. However, low levels of insulin increment in the IVGTT were more often associated with glucose intolerance than was a low insulin sensitivity.

Aged↗
PubMed1994

Risk factors for fractures of the distal forearm: a population-based case-control study.

To evaluate the risk factors for early osteoporosis in consecutive patients with fracture of the distal forearm, a population-based case-control study was carried out using postal questionnaires supplemented by interviews when necessary. All men and women between the ages of 40 and 80 years who were resident in the County of Uppsala (population 265,000) and who sustained a fracture of the distal forearm during a defined 12-month period were initially included. Of 427 cases, 385 (90.2%) replied. Those with previous fragility fractures were excluded, leaving 367 patients in the study (mean age 61.9 +/- 10.6 years): 302 women (mean age 62.8 +/- 10.1 years) and 65 men (mean age 57.5 +/- 11.8 years). For each patient an age- and sex-matched control without previous fragility fractures was selected from the population register. The questionnaire concerned heredity, diseases and medications, general health, tobacco smoking and physical activity. Reproductive variables and postmenopausal hormone replacement therapy were analyzed extensively. In neither sex were any significant, consistent differences found with regard to chronic diseases, medications, physical activity or smoking. In females heredity for fractures (odds ratio, OR = 1.46) was associated with an increased risk. Nulliparous women had an increased risk of forearm fractures (OR = 1.72) while late menopause (OR = 0.95) and postmenopausal oestrogen therapy > 2 years (OR = 0.44) appeared to be protective. It is concluded that lifestyle factors did not discriminate between fracture patients and controls in this strict population-based investigation, suggesting that in affluent Western societies, with their high fracture rate, most individuals have an osteoporosis-prone way of life.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Distal radius fracture is an early sign of general osteoporosis: bone mass measurements in a population-based study.

To evaluate the bone mass by bone density measurements in patients with distal radius fracture, a prospective open case-control study was carried out in the county of Uppsala, Sweden, with population-based cases and controls. There were 111 patients with a distal radius fracture who were otherwise healthy and aged 53-76 years, together with 60 healthy controls of similar age, sex and menopausal status. The main outcome measures were bone mineral density (BMD) in the lumbar spine and hip measured with dual-energy X-ray absorptiometry, and in the (non-fractured) distal forearm determined by single-photon absorptiometry. It was found that at all measuring sites BMD was significantly lower in cases than in controls. The difference in the distal forearm was around 20% (p < 0.001) and in the spine and hip 5%-8% (p < 0.05-0.001). In the healthy subjects there were positive correlations (r = 0.39-0.65; p < 0.002) between the forearm BMD and that of both the spine and hip, whereas in the patients with distal radius fracture there was only a weak correlation between the forearm and spine BMD (r = 0.28; p < 0.05) and no association between the BMD of the forearm and hip (r < 0.01). It is concluded that patients with distal radius fracture who are otherwise healthy have a preferential bone loss at the distal forearm but also a generally low bone mass. Patients with fracture of the distal radius fracture should be considered for prophylactic measures against osteoporosis.

Age Factors↗
PubMed1994

Serum calcium and the ECG in patients with primary hyperparathyroidism.

Primary hyperparathyroidism (HPT) is associated with cardiovascular disease, but there are no systematic studies on the electrocardiographic findings in HPT. Preoperative electrocardiograms from 139 patients with primary HPT and 97 control patients were therefore investigated. Serum calcium levels were found to be significantly correlated to the QRS amplitude (r = .26, P < .002), ST-segment duration (r = -.55, P < .0001), QT interval (r = -.64, P < .0001), and T wave duration (r = .19, P < .009). These relations were still significant when the influence of age, sex, and blood pressure level were taken into account in the multiple regression analysis. Thus, the electrocardiograms from HPT patients, compared to normocalcemic control patients, showed a shorter duration of the ST-segment, representing the systolic interval, and an increased amplitude of the QRS complex, representing ventricular muscle mass. Furthermore, the duration of the T wave was significantly prolonged in HPT patients. The hemodynamic effects of these findings have to be further evaluated.

Aged↗
PubMed1994

Circulating levels of insulin-like growth factor-I and -II, and IGF-binding protein-3 in inflammation and after parathyroid hormone infusion.

In order to assess if the anabolic action of PTH is related to changes in circulating levels of insulin-like growth factor-I and -II (IGF-I and -II), and IGF binding protein 3 (IGFBP-3), 24 h of PTH infusion was performed in healthy women and in patients with rheumatoid arthritis (RA), a state where both bone metabolism and PTH secretion is influenced by the inflammatory activity. The patients with RA had lower basal levels of both IGF-I and -II than the healthy controls (P < 0.05). In neither group did the IGFs change after 24 h of PTH administration, while IGFBP-3 was significantly increased in the healthy controls (4600 +/- 1200 to 5750 +/- 2200 micrograms/l, P < 0.05). IGFBP-3 was not affected by PTH infusion in patients with RA when the disease had high activity, but when inflammation had subsided they responded with a similar increase in IGFBP-3 as the control group and basal IGF-I and -II levels were normalised. Since IGFBP-3 can enhance the anabolic action of IGF-I, increased IGFBP-3 levels after PTH infusion may reflect a mechanism by which PTH is anabolic for bone. Inflammation may inhibit bone formation via decreased serum levels of IGFs and blocked IGFBP-3 response to PTH.

Adult↗
PubMed1994

Interleukin-1 beta induces cyclic AMP formation in isolated human osteoblasts: a signalling mechanism that is not related to enhanced prostaglandin formation.

Interleukin-1 (IL-1) is a potent stimulator of bone resorption. Induction of osteoclastic bone resorption by various endocrine or paracrine factors is mediated via the osteoblasts. We have therefore investigated the effects of IL-1 beta on cell signalling in isolated human osteoblasts. Special interest was focused on prostaglandin synthesis, since indomethacin, an inhibitor of prostaglandin synthesis, partly inhibits IL-1-induced bone resorption. IL-1 beta, at and above 0.3 pM, dose dependently stimulated PGE2 formation in isolated human osteoblasts, with half maximal stimulation, EC50, at 3 pM. Treatment with the calcium ionophore A23187 (1 microM), or with forskolin (30 microM), also stimulated PGE2 formation in human osteoblasts. The time-course for IL-1 beta-induced PGE2 formation was similar to that of forskolin, with a significant increase in the formation of PGE2 seen after 1 h. In contrast, A23187-induced PGE2 formation was seen within minutes. IL-1 beta stimulated the accumulation of cyclic AMP in isolated human osteoblasts incubated for 15 min. This increase in cyclic AMP formation was not secondary to PGE2 formation since it was not blocked by the addition of indomethacin (1 microM). Pretreatment with the phosphodiesterase inhibitor IBMX did not augment IL-1 beta-induced PGE2 formation, nor did the protein kinase A inhibitor Rp-cAMPs inhibit IL-1 beta-induced PGE2 formation, suggesting that cyclic AMP does not mediate the stimulatory effect of IL-1 on PGE2 formation. We conclude that IL-1 beta enhances the formation of cyclic AMP as well as PGE2 in primary cultures of isolated human osteoblasts. The IL-1 beta-induced cyclic AMP formation is, however, not related to the enhanced prostaglandin formation. The findings implicate that both cyclic AMP- and PGE2-formation in osteoblasts might be involved as independent mediators of IL-1 beta-induced bone resorption.

1-Methyl-3-isobutylxanthine↗
PubMed1994

Blood pressure reaction during the intraoperative and early postoperative periods in patients with primary hyperparathyroidism.

Hypertension is a well known finding in primary hyperparathyroidism (HPT). In the present study, systolic blood pressure (SBP) and heart rate were recorded before, during and after surgery for HPT in 101 patients (mean serum calcium 2.96 +/- 0.22 mmol/l) and compared to 91 scheduled general surgical patients matched for age, sex, duration of surgery and type of general anesthesia. The HPT patients displayed an increased mean SBP, given as mean +/- standard deviation, both before (147 +/- 28 vs 131 +/- 25 mm Hg in controls) and during surgery (142 +/- 24 vs 117 +/- 21 mm Hg in controls) as well as postoperatively (141 +/- 23 vs 118 +/- 17 mm Hg in controls, all p < 0.0001). The preoperative SBP was correlated to both the intraoperative and postoperative SBP (r = 0.59 and r = 0.61, both p < 0.00001). However, the blood pressure elevation during and after surgery was still significant (both p < 0.001) when corrected for the influence of the preoperative blood pressure level using multiple regression analysis. The heart rate was increased in the HPT subjects only in the postoperative period (88 +/- 12 vs 83 +/- 12 beats/min in controls, p < 0.007). In conclusion, the systolic blood pressure was found to be elevated both before, during and after surgery in HPT subjects when compared to a general surgical population. In the postoperative period, also the heart rate was increased in the HPT subjects. These findings suggest an increased cardiovascular response to surgical stress in HPT subjects.

Aged↗
PubMed1994

Influences of different antihypertensive treatments on indices of systemic mineral metabolism.

A negative calcium balance has previously been described in human hypertension with low levels of plasma ionized calcium (Ca2+) and an increased urinary excretion of calcium. The cause of this disturbance in mineral metabolism is not known, nor is it known if this derangement could be abolished if blood pressure is reduced by antihypertensive treatment. In the present investigation, the effects of antihypertensive monotherapy on serum and fasting urinary electrolytes were studied. For 3 to 6 months, 319 hypertensive patients entered 17 study groups, each group using one of the following antihypertensive drugs: dilevalol, metoprolol, antenolol, pindolol, propranolol, hydrochlorothiazide, bendrofluomethiazide, furosemide, spironolactone, doxazocine, prazocine, diltiazem, verapamil, nifedipine, isradipine, captopril, or lisinopril. Treatment with different beta-blockers, as well as diuretics, reduced the fasting urinary calcium excretion (P < .001). However, while the beta-blockers increased the proportion of the ionized form of calcium in blood (Ca2+) (P < .001), Ca2+ was further decreased by diuretic treatment (P < .05). Angiotensin converting enzyme inhibitors caused no major changes in mineral metabolism while of the calcium antagonists studied only verapamil raised the levels of Ca2+ (P < .01). No significant relationship between the changes in mineral metabolism and the reduction in blood pressure was observed in any of the treatment groups. Of the antihypertensive drugs used in the present study, beta-blockers appeared to reverse the basic abnormality with regard to calcium balance, suggesting that the activity of the sympathetic nerve system is involved in the disturbed calcium metabolism seen in hypertensive patients.

Adrenergic beta-Antagonists↗