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  • II  (1)
  • Key words:Bone turnover – Immunosuppressive drugs – Liver disease – Liver transplant – Osteoporosis  (1)
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  • 1
    Electronic Resource
    Electronic Resource
    Increased activity of the insulin-like growth factor system in mesangial cells cultured in high glucose conditions. Relation to glucose-enhanced extracellular matrix production (1996)
    Springer
    Diabetologia 39 (1996), S. 775-784 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Insulin-like growth factor-I ; II ; binding proteins ; receptors ; transforming growth factor-b ; extracellular matrix ; mesangial cell ; diabetes mellitus.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Recent evidence suggests that several growth factors participate in diabetic glomerular disease by mediating increased extracellular matrix accumulation and altered cell growth and turnover leading to mesangial expansion. Transforming growth factor (TGF)-β has been demonstrated to be upregulated both in vivo and in vitro, whereas studies on the activity of the renal insulin-like growth factor (IGF) system in experimental diabetes have provided conflicting results. We investigated the effects of prolonged exposure (4 weeks) of cultured human and rat mesangial cells to high (30 mmol/l) glucose vs iso-osmolar mannitol or normal (5.5 mmol/l) glucose levels on: 1) the autocrine/paracrine activity of the IGF system (as assessed by measuring IGF-I and II, IGF-I and II receptors, and IGF binding proteins); and, in parallel, on 2) TGF-β1 gene expression; 3) matrix production; and 4) cell proliferation. High glucose levels progressively increased the medium content of IGF-I and the mRNA levels for IGF-I and IGF-II, increased IGF-I and IGF-II binding and IGF-I receptor gene expression, and reduced IGF binding protein production. TGF-β1 transcripts and matrix accumulation and gene expression were increased in parallel, whereas cell proliferation was reduced. Iso-osmolar mannitol did not affect any of the above parameters. These experiments demonstrated that high glucose levels induce enhanced mesangial IGF activity, together with enhanced TGF-β1 gene expression, increased matrix production, and reduced cell proliferation. It is possible that IGFs participate in mediating diabetes-induced changes in matrix turnover leading to mesangial expansion, by acting in a paracrine/autocrine fashion within the glomerulus. [Diabetologia (1996) 39: 775–784]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050510
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Long-Term Persistence of Low Bone Density in Orthotopic Liver Transplantation (2000)
    Springer
    Osteoporosis international 11 (2000), S. 417-424 
    Details
    ISSN: 1433-2965
    Keywords: Key words:Bone turnover – Immunosuppressive drugs – Liver disease – Liver transplant – Osteoporosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: We determined bone density and metabolism in 46 patients (35 males, 11 females) who had undergone liver transplantation 1–48 months previously. Twenty-one patients were then followed for the next 24 months. At each visit, blood and urine samples for bone and liver metabolism parameters, as well as spinal and femoral dual-energy X-ray absorptiometry (DXA) scans, were obtained. Basal spinal and femoral density was low (p〈0.001). Patients with pre-transplant cholestatic diseases had lower spinal density than all the other subjects (p〈0.05) and the cumulative methylprednisolone intake was an independent negative predictor of total hip density (p〈0.02). At baseline, urinary hydroxyproline and N-telopeptide were at the upper normal level and decreased only after 24 months of follow-up (p〈0.05). During the first year of follow-up, femoral density decreased (p〈0.05) and a partial recovery was observed for both spine and femur after 24 months. After 12 months, femoral bone density was negatively associated with serum cyclosporin A levels (p〈0.005) and cumulative methylprednisolone intake (p〈0.05), while the percent decrease in spinal density after the first 12 months was negatively predicted by mean daily methylprednisolone intake (p〈0.05). In patients with pre-transplant cholestatic diseases, femoral and spinal density increased after the first (p〈0.05) and second year (p〈0.05), respectively. In patients with previous post-necrotic cirrhosis, femoral density decreased after 12 months (p〈0.05) and was still lower than baseline after 24 months (p〈0.05). However, at the end of the study the cumulative percentage of femoral neck osteoporosis was 43%. In conclusion, an elevated prevalence of spinal and femoral osteoporosis is present even many years after liver transplantation, with immunosuppressive treatment and pre-transplant liver disease being the most important pathogenetic factors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001980070109
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    Paper (German National Licenses)
    Fulltext
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