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  • 1
    ISSN: 1432-0827
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary In this study, serum levels of classical serum markers of bone formation [carboxyterminal propeptide of procollagen type I (S-PICP), bone Gla protein (S-BGP)], and total alkaline phosphatase (S-AP)) were related to the calcium kinetic index of whole skeletal mineralization rate (m) by regression analysis in a variety of metabolic bone diseases. For each disease, the regression coefficient (r) as well as the fraction: standard error of estimate/mean dependent variable (SEE/Y) were determined. In a group of 19 normals, only the regression of S-PICP on m reached significance (r=0,53, P〈0.02, SEE/Y=0.44), whereas regressions of S-AP and S-BGP on m were nonsignificant. In a pooled material of high-and low-turnover bone diseases without mineralization defects or spinal fracture [myxedema, thyrotoxicosis, and primary hyperparathyroidism (n=48)], a highly significant positive regression of S-PICP on m was demonstrable (r=0.50, SEE/Y=0.63, P〈0.001). The regression coefficients obtained for S-BGP and S-AP were 0.74 (P〈0.001, SEE/Y=0.41) and 0.42 (P〈0.01, SEE/Y=0.55), respectively. When analyzing individual diseases in this group, significant differences among the three markers were detectable. In a group of 52 osteoporotics, S-PICP correlated significantly to m (r=0.49, P〈0.001, SEE/Y=0.50). Corresponding r-values for S-BGP and S-AP were 0.21 (NS) and 0.48 (P〈0.001, SEE/Y=0.61), respectively. Patients with histologically proven osteomalacia revealed no correlation between S-PICP and m. S-BGP and S-AP were, however. significantly correlated to m [r=0.92 (SEE/Y=0.46) and r=0.82 (SEE/Y=0.57), respectively], indicating that S-BGP and S-AP reflect mineralization activity, whereas S-PICP reflects matrix formation only. In order to study cellular production of the three formative markers, organ level production rate was normalized for bone turnover by division with m. For each marker, the fraction (bone marker concentration/m) was calculated and the means compared with normal controls. S-PICP/m was found to be lower than normal in primary hyperparathyroidism (P〈0.01) and thyrotoxicosis (P〈0.001). S-AP/m was elevated in myxedema (P〈0.05), osteoporosis (P〈0.001), and osteomalacia (P〈0.01). S-BGP/m only deviated significantly from normal in osteomalacia (P〈0.001). In conclusion, we found S-BGP to be a reliable marker of organ level mineralization rate in all diseases studied, whereas the regressions of S-AP and S-PICP revealed disease-specific discrepancies. This study also revealed significant alterations in the osteoblastic production rate of the three formative markers at the level of individual osteoblasts that have to be taken into account when comparing bone marker concentrations with other indices reflecting bone formation (e.g., calcium kinetics and histomorphometry).
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 26 (1978), S. 99-102 
    ISSN: 1432-0827
    Keywords: Bone biopsy ; Tetracycline Labeling ; Appositional Rate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary A histomorphometric evaluation of the iliac crest trabecular bone remodeling was performed after tetracycline double-labeling in 41 normal Danes (12 males and 29 females) aged 19 to 56 years. The fraction of formative (osteoid covered) and resorptive surfaces was unrelated to age but higher in males than in females (P〈0.02 andP〈0.05, respectively). The appositional rate (0.65±0.12 μm/day) was unrelated to age and sex, whereas the fractional labeled surfaces were higher (P〈0.01) in the males (0.18±0.08 μm2/μm2) than in the females (0.12±0.05 μm2/μm2), and among the females inversely related to age (R=−0.38,P〈0.05). The bone formation rate at BMU level (0.50±0.20 μm3/μm2/day) was unrelated to sex, but among the females inversely related to age R=−0.49,P〈0.01). The bone formation rate at tissue level was higher (P〈0.02) in the males (0.13±0.07 μm3/μm2/day) than in the females (0.07±0.03 μm3/μm2/day) and among the females inversely correlated to age (R=−0.43,P〈0.05). The age- and sex-dependent variations in the dynamic parameters underline the importance of a more elaborated normal material.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 26 (1978), S. 199-202 
    ISSN: 1432-0827
    Keywords: Fluoride ; Calcium ; Phosphate ; Parathyroid hormone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Fluoride 27 mg was given perorally to 14 subjects. It was found that the serum fluoride concentration increased followed by a decrease to normal levels during 24 h. Serum concentrations of calcium and phosphate decreased initially whereas those of serum immunoreactive parathyroid hormone increased. After 24 h the measured quantities were within normal limits. The results are discussed with reference to mineralization of hard tissues and to fluoride treatment of osteoporotic patients.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 21 (1985), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The prostaglandin E2 (PGE2) receptor on human peripheral blood monocytes is characterized. The receptor binding at physiological temperature and pH was saturable, specific, and reversible. Scatchard analysis of binding data revealed a linear plot giving a Kd= 1.1 ± 10-9mol/l and Bmax=4.1 fmol/107 cells, equal to 240 binding sites per cell. PGE2 increased intracellular cyclic adenosine 5′-monophosphate by a maximal factor of 3. PGF2α and archidonic acid had no stimulatory effects on adenyl cyclase, in accordance with their low binding to the cells. The characterization of the PGE2 receptor on human monocytes creates a basis for the study of the clinical significance of changes in PGE2-receptor binding in disease states involving PGE2-monocyte interactions such as various immunological disorders and bone resorption.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Comparative Biochemistry and Physiology -- Part A: Physiology 104 (1993), S. 483-484 
    ISSN: 0300-9629
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 24 (1986), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The active vitamin D metabolite, 1,25-dihydroxycholecal ciferol induces differentiation of monocytes into macrophages. The pharmacological induction of differentiation of primitive, rapidly proliferating cell lines into more mature cells with lower proliferative potential is a new dimension in the treatment of myeloproliferative disorders, which may prove to be an important alternative to more traditional regimens, Furthermore, the cell primarily engaged in bone resorption-the osteoclast-represents another differentiated form of mononuclear phagocytes, and 1,25-dihydroxycholecalciferol increases the number of osteoclasts. Since the cellular action of 1,25-dihydroxycholecalciferol is exerted mainly through its binding to nuclear receptors, a detailed knowledge of ligand-receptor interactions is mandatory for future work in this area. In order to investigate the interaction between 1,25-dihydroxycholecalciferol and its receptor in mononuclear cells, the nuclear uptake of the hormone was studied using a whole cell assay. The nuclear uptake of l,25-dihydroxy[3H]cholecalciferol in human monocytes at physiological temperature and pH was saturable, specific, and fully reversible. When eight normal individuals were investigated, the maximal binding capacity (Bmax) was 0.4–8.4 fmol/106 cells and the dissociation constants (Kd) were 0.12–0.45 nmol/l. The characterization of the nuclear uptake of 1,25-dihydroxy [3H]cholecalciferol in intact human monocytes shows that it is mediated by binding of the ligand to a specific nuclear receptor. The binding to the nuclear receptor is the result of the passage of ligand across the cytoplasmic membrane and of the cytoplasmic transport of ligand. In contrast to conventional receptor assays in hypertonic cellular extracts, this system provides information on the role of the cytoplasmic membrane in relation to the nuclear uptake of 1,25-dihydroxycholecalciferol, which may be closer to in vivo cellular conditions.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0827
    Keywords: Osteoporosis ; Growth hormone ; Growth factors ; Proliferation ; Osteoblasts
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract Decreased osteoblastic activity seems to play an important role in the pathogenesis of postmenopausal osteoporosis. The aim of the present study was to examine the direct effects of human growth hormone (GH) on proliferation and differentiation of osteoblastic cells obtained from patients with postmenopausal osteoporosis and age-matched normals and to compare the cellular responses induced by GH between the two groups. Osteoblast cultures (human marrow stromal osteoblast-like cells) were established from bone marrow aspirates obtained from 9 osteoporotic patients and 12 age-matched normals. Effects on cell proliferation and cell differentiation markers [alkaline phosphatase (AP)], procollagen type I propeptide (PICP), and osteocalcin] were assessed. GH stimulated 3H-thymidine incorporation into DNA in cell cultures of osteoporotic patients to a maximum of 158±14% of no-treatment controls (n=9, P〈0.001) and to 203±52% (n=9, P〈0.001) in normals. GH increased cell number as measured by methylene blue (MB) assay in cells of osteoporotic patients to 138±10% (P〈 0.05, n=7) and in normals to 138±12 (P〈0.05, n=7). GH alone reduced cellular AP production: 61±3.8% (P〈0.05, n=7) versus 65±16% (P〈0.05, n=7) and cellular PICP production: 79±6% (P〈0.05, n=7) versus 69±16% (n.s., n=7), in cell cultures of osteoporotics and normals, respectively. 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) (10-9 M) alone increased AP production in cell cultures of osteoporotics to 193±23% (P〈0.01, n=7) and to 266±51% (P〈0.05, n=7) in cell cultures of normals. 1,25(OH)2D3 had no effect on PICP production in either culture. Combining GH and 1,25(OH)2D3 reduced 1,25(OH)2D3-stimulated levels of AP and osteocalcin. No statistically significant differences were observed in cell proliferation or cell differentiation responses between cell cultures of osteoporotic patients and normals. Our results demonstrate that osteoblastic cells obtained from osteoporotic patients exhibit normal responsiveness to short-term stimulation with GH in vitro and do not support the hypothesis of the presence of major defects in osteoblastic responsiveness to stimuli in patients with osteoporosis.
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  • 8
    ISSN: 1432-0827
    Keywords: Bone mineral density ; Deoxypyridinoline ; Osteocalcin ; Pyridinoline ; Salmon calcitonin ; Suppositories
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract The objective of this study was to test the efficacy and safety of salmon calcitonin (sCT) suppository in postmenopausal women with previous hip fractures as an inhibitory agent of bone loss. The study was a single blind, randomized, and placebo-controlled trial comparing three parallel groups of patients. Fifty-four healthy women were randomly allocated to 1 year's treatment with either sCT 100 IU/6 times a week, 200 IU/3 times a week, or placebo/6 times a week. All groups received a calcium supplement of 500 mg daily. Fifteen patients left the study before its end, six of those due to adverse events, such as abdominal and rectal pain, nausea, headache, and diarrhea. Bone mineral density of the spine and the femoral neck was measured every 26 weeks, and biochemical markers of bone turnover were measured at baseline and week 12, 26, and 52. There were no significant changes in bone mineral density in the spine and in the hip in any of the treatment groups. No significant changes were observed in serum alkaline phosphatase, serum osteocalcin, urine hydroxyproline, and urine pyridinoline or deoxypyridinoline. Conclusively, we did not observe any significant effect on bone metabolism in women with postmenopausal osteoporosis after 1 year of treatment with sCT suppositories at the doses used.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0827
    Keywords: Growth hormone ; Osteoblast ; Growth factors ; Osteoporosis ; Bone cell cultures ; Bone formation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary In this study we investigated the direct, shortterm effects of human growth hormone (hGH) on the biology of normal adult human osteoblast-like (hOB) cells cultured from trabecular bone explants. In Subconfluent cultures, hGH stimulated hOB proliferation in a dose-dependent fashion (P〈0.001, n=15) with half-maximal effects at a concentration of 10 ng/ml. These mitogenic effects were detectable within 24 hours as shown by bromodeoxyuridine labeling. In confluent cultures containing mainly quiescent cells, hGH increased levels of alkaline phosphatase (P〈0.05, n=10) and to a lesser degree levels of procollagen type I carboxyterminal propeptide (PICP) (P=0.07, n=9). Effects on osteocalcin (bone GLa protein, BGP) levels were highly variable among different cell strains and only 7 of 10 cell strains showed a stimulatory response (P=0.16). We also studied the effects of hGH on osteoblastic production of insulin-like growth factor I (IGF-I) and IGF-II as well as the production of GH-dependent, insulin-like growth factor binding protein 3 (IGFBP-3). Under basal conditions, human osteoblasts produced IGF-II and IGFBP-3 in the conditioned medium. When stimulated with hGH, minor insignificant increase in both IGF-II and IGFBP-3 (125% and 126% of control, respectively) were detectable. No IGF-I was detectable in the conditioned medium under basal conditions or after stimulation with hGH. In conclusion, the results obtained in this study suggest that GH exerts direct anabolic effects on human osteoblasts.
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  • 10
    ISSN: 1432-0827
    Keywords: Renal osteodystrophy ; Hyperparathyroidism ; Adenylate cyclase ; Phospholipase C ; 1,25-Dihydroxyvitamin D3 ; Bone turnover ; Histomorphometry ; Rat model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract Predicting the course of parathormone (PTH)-elicited bone turnover in both humans and experimental rat models with moderate chronic uremia, using only standard clinical chemistry analyses, is often difficult. Consequently, rat bone from 1+2/3 nephrectomized animals, after 230 days of progressive renal failure, was examined for PTH-stimulated adenylate cyclase (AC) and phospholipase C (PLC) activities. Correlations to biological parameters related to the function of bone and kidney were made. Reduced renal function was demonstrated by increased serum creatinine; circulating 1,25 dihydroxyvitamin D3 below detection level; diminished renal PTH-elicited AC activity; and decreased urinary cAMP excretion. PTH-activated renal PL-C was also reduced. However, no significant differences were seen in urine creatinine, calcium, phosphate, and hydroxyproline, nor in serum PTH, alkaline phosphatase, calcium, and phosphate. Notwithstanding, renal osteodystrophy developed as estimated by increased plasticity of the long bones, as well as reduction of the diaphyseal (Dd) and inner femoral midshaft (Di) diameters. Femoral cancellous bone exhibited a substantial elevation of both eroded surface (ES) and osteoid surface (OS) as well as a marked reduction in trabecular bone volume (TBV). Calvarial PTH-activated AC was enhanced, whereas corresponding PL-C was markedly reduced. PTH-enhanced AC correlated positively with ES and negatively with Di, respectively. PTH-enhanced PL-C, however, correlated positively with bone calcium content and negatively with ES. Our results indicate that bone modeling and remodeling are to a large extent related to PTH-elicited signaling systems, and cannot easily be predicted by standard clinical chemistry analyses.
    Type of Medium: Electronic Resource
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