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  1. Artikel ; Online: Calcimimetics and calcilytics--fooling the calcium receptor.

    Steddon, Simon J / Cunningham, John

    Lancet (London, England)

    2005  Band 365, Heft 9478, Seite(n) 2237–2239

    Abstract: Context: Just a decade after the the calcium-sensing receptor (CaR) was identified, pharmacological manipulation of the CaR is about to enter routine practice. For hyperparathyroid states, calcimimetics, which increase activation of the CaR, have been ... ...

    Abstract Context: Just a decade after the the calcium-sensing receptor (CaR) was identified, pharmacological manipulation of the CaR is about to enter routine practice. For hyperparathyroid states, calcimimetics, which increase activation of the CaR, have been licensed in Europe and the USA. Calcilytics, which decrease CaR function and increase secretion of parathyroid hormone (PTH), might allow the anabolic effects of PTH on bone to be harnessed for the prevention and treatment of osteoporosis.
    Starting point: In a multicentre randomised double-blind placebo-controlled study, Munro Peacock and colleagues recently confirmed the efficacy of the oral calcimimetic cinacalcet for achieving long-term reductions in serum calcium and PTH concentrations in primary hyperparathyroidism (J Clin Endocrinol Metab 2005; 90: 135-41). The arrival of a non-surgical option for this common disorder is important. WHAT NEXT? Study in primary and uraemic secondary hyperparathyroidism will indicate whether the efficacy of calcimimetic agents extends into the longer term. The extracellular relation between the CaR and its ligands and the intracellular signalling cascades that modify PTH gene transcription and secretion need further study. Drugs acting on the CaR might treat other disorders of bone remodelling, including osteoporosis. CaR expression in tissues beyond those involved in mineral ion homoeostasis should remain an important focus of research.
    Mesh-Begriff(e) Bone Diseases, Metabolic/drug therapy ; Calcium/agonists ; Calcium/metabolism ; Cinacalcet Hydrochloride ; Humans ; Hypercalcemia/drug therapy ; Hyperparathyroidism/drug therapy ; Hyperparathyroidism/metabolism ; Hyperparathyroidism, Secondary/drug therapy ; Hyperparathyroidism, Secondary/metabolism ; Naphthalenes/therapeutic use ; Parathyroid Hormone/secretion ; Receptors, Calcium-Sensing/drug effects ; Receptors, Calcium-Sensing/physiology
    Chemische Substanzen Naphthalenes ; Parathyroid Hormone ; Receptors, Calcium-Sensing ; Cinacalcet Hydrochloride (1K860WSG25) ; Calcium (SY7Q814VUP)
    Sprache Englisch
    Erscheinungsdatum 2005-06
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 3306-6
    ISSN 1474-547X ; 0023-7507 ; 0140-6736
    ISSN (online) 1474-547X
    ISSN 0023-7507 ; 0140-6736
    DOI 10.1016/S0140-6736(05)66782-7
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: New prospects for the management of renal bone disease.

    Steddon, Simon J / Fan, Stanley L S / Cunningham, John

    Nephron. Clinical practice

    2005  Band 99, Heft 1, Seite(n) c1–7

    Abstract: The last decade has been a remarkably productive one in the field of bone biology. New insights into the maintenance of a normal bone microenvironment have led to significant advances in our understanding of many important skeletal disorders, including ... ...

    Abstract The last decade has been a remarkably productive one in the field of bone biology. New insights into the maintenance of a normal bone microenvironment have led to significant advances in our understanding of many important skeletal disorders, including renal osteodystrophy. Novel targets for therapeutic manipulation have been exposed and encouraging progress made towards new treatments. In addition, just as clinical studies have alerted us to the potential hazards of vascular calcification, basic science has unearthed the intimate nature of the relationship between the previously separate disciplines of bone and vascular biology. The clinical nephrologist, however, may be forgiven a little cynicism at this point. If such progress has been made, why do the same proverbial difficulties confront us in day-to-day practice? Control of phosphate remains inadequate, despite a literature which constantly reaffirms its crucial importance, and parathyroid hyperplasia seems inevitable in many patients. Furthermore, even the satisfaction of successful control of serum parathyroid hormone concentration must now be tempered by disquiet regarding the skeletal and cardiovascular consequences of oversuppression. This review aims to provide an update of the latest developments in relevant skeletal research and to assess how recently acquired knowledge may improve clinical nephrological practice over the next five years.
    Mesh-Begriff(e) Animals ; Bone Remodeling/physiology ; Calcium/blood ; Carrier Proteins/physiology ; Chronic Kidney Disease-Mineral and Bone Disorder/diagnostic imaging ; Chronic Kidney Disease-Mineral and Bone Disorder/physiopathology ; Chronic Kidney Disease-Mineral and Bone Disorder/therapy ; Cinacalcet Hydrochloride ; Humans ; Hyperparathyroidism/drug therapy ; Hyperplasia ; Membrane Glycoproteins/physiology ; Naphthalenes/therapeutic use ; Osteoclasts/physiology ; Parathyroid Glands/pathology ; Parathyroid Hormone/blood ; Parathyroidectomy ; RANK Ligand ; Radiography ; Receptor Activator of Nuclear Factor-kappa B ; Vitamin D/analogs & derivatives
    Chemische Substanzen Carrier Proteins ; Membrane Glycoproteins ; Naphthalenes ; Parathyroid Hormone ; RANK Ligand ; Receptor Activator of Nuclear Factor-kappa B ; TNFRSF11A protein, human ; TNFSF11 protein, human ; Vitamin D (1406-16-2) ; Cinacalcet Hydrochloride (1K860WSG25) ; Calcium (SY7Q814VUP)
    Sprache Englisch
    Erscheinungsdatum 2005
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Review
    ZDB-ID 207121-6
    ISSN 1660-2110 ; 1423-0186 ; 2235-3186 ; 1660-8151 ; 0028-2766
    ISSN (online) 1660-2110 ; 1423-0186 ; 2235-3186
    ISSN 1660-8151 ; 0028-2766
    DOI 10.1159/000081787
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: New Prospects for the Management of Renal Bone Disease

    Steddon, Simon J. / Fan, Stanley L.S. / Cunningham, John

    Nephron Clinical Practice

    2005  Band 99, Heft 1, Seite(n) c1–c7

    Abstract: The last decade has been a remarkably productive one in the field of bone biology. New insights into the maintenance of a normal bone microenvironment have led to significant advances in our understanding of many important skeletal disorders, including ... ...

    Abstract The last decade has been a remarkably productive one in the field of bone biology. New insights into the maintenance of a normal bone microenvironment have led to significant advances in our understanding of many important skeletal disorders, including renal osteodystrophy. Novel targets for therapeutic manipulation have been exposed and encouraging progress made towards new treatments. In addition, just as clinical studies have alerted us to the potential hazards of vascular calcification, basic science has unearthed the intimate nature of the relationship between the previously separate disciplines of bone and vascular biology. The clinical nephrologist, however, may be forgiven a little cynicism at this point. If such progress has been made, why do the same proverbial difficulties confront us in day-to-day practice? Control of phosphate remains inadequate, despite a literature which constantly reaffirms its crucial importance, and parathyroid hyperplasia seems inevitable in many patients. Furthermore, even the satisfaction of successful control of serum parathyroid hormone concentration must now be tempered by disquiet regarding the skeletal and cardiovascular consequences of oversuppression. This review aims to provide an update of the latest developments in relevant skeletal research and to assess how recently acquired knowledge may improve clinical nephrological practice over the next five years.
    Schlagwörter Osteodystrophy ; Adynamic bone disease ; Bone remodelling ; Calcium ; Phosphorus ; Vitamin D
    Sprache Englisch
    Verlag S. Karger AG
    Erscheinungsort Basel
    Erscheinungsland Switzerland
    Dokumenttyp Artikel ; Online
    ZDB-ID 207121-6
    ISSN 1660-2110 ; 1423-0186 ; 0028-2766 ; 1660-8151 ; 1660-2110 ; 0028-2766 ; 1660-8151
    ISSN (online) 1660-2110 ; 1423-0186
    ISSN 1660-2110 ; 0028-2766 ; 1660-8151
    DOI 10.1159/000081787
    Datenquelle Karger Verlag

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  4. Artikel: New Prospects for the Management of Renal Bone Disease

    Steddon, Simon J. / Fan, Stanley L.S. / Cunningham, John

    Nephron Clinical Practice

    2005  Band 99, Heft 1, Seite(n) c1–c7

    Abstract: The last decade has been a remarkably productive one in the field of bone biology. New insights into the maintenance of a normal bone microenvironment have led to significant advances in our understanding of many important skeletal disorders, including ... ...

    Körperschaft Department of Renal Medicine and Transplantation, Bart’s and the London NHS Trust Department of Nephrology, The Middlesex Hospital, University College London Hospitals, London, UK
    Abstract The last decade has been a remarkably productive one in the field of bone biology. New insights into the maintenance of a normal bone microenvironment have led to significant advances in our understanding of many important skeletal disorders, including renal osteodystrophy. Novel targets for therapeutic manipulation have been exposed and encouraging progress made towards new treatments. In addition, just as clinical studies have alerted us to the potential hazards of vascular calcification, basic science has unearthed the intimate nature of the relationship between the previously separate disciplines of bone and vascular biology. The clinical nephrologist, however, may be forgiven a little cynicism at this point. If such progress has been made, why do the same proverbial difficulties confront us in day-to-day practice? Control of phosphate remains inadequate, despite a literature which constantly reaffirms its crucial importance, and parathyroid hyperplasia seems inevitable in many patients. Furthermore, even the satisfaction of successful control of serum parathyroid hormone concentration must now be tempered by disquiet regarding the skeletal and cardiovascular consequences of oversuppression. This review aims to provide an update of the latest developments in relevant skeletal research and to assess how recently acquired knowledge may improve clinical nephrological practice over the next five years.
    Schlagwörter Osteodystrophy ; Adynamic bone disease ; Bone remodelling ; Calcium ; Phosphorus ; Vitamin D
    Sprache Englisch
    Erscheinungsdatum 2005-01-14
    Verlag S. Karger AG
    Erscheinungsort Basel, Switzerland
    Dokumenttyp Artikel
    Anmerkung Minireview
    ZDB-ID 207121-6
    ISSN 1660-2110 ; 1423-0186 ; 2235-3186 ; 1660-8151 ; 0028-2766
    ISSN (online) 1660-2110 ; 1423-0186 ; 2235-3186
    ISSN 1660-8151 ; 0028-2766
    DOI 10.1159/000081787
    Datenquelle Karger Verlag

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  5. Artikel: Impaired release of interleukin-6 from human osteoblastic cells in the uraemic milieu.

    Steddon, Simon J / McIntyre, Christopher W / Schroeder, Neil J / Burrin, Jacky M / Cunningham, John

    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

    2004  Band 19, Heft 12, Seite(n) 3078–3083

    Abstract: Background: Osteoblast-derived interleukin-6 (IL-6) affects bone metabolism and is linked with a number of pathological states characterized by increased bone resorption, including osteoporosis and renal osteodystrophy. To examine the possibility that ... ...

    Abstract Background: Osteoblast-derived interleukin-6 (IL-6) affects bone metabolism and is linked with a number of pathological states characterized by increased bone resorption, including osteoporosis and renal osteodystrophy. To examine the possibility that uraemia directly influences the release of this cytokine in bone, we have investigated the effect of human uraemic serum on the release of IL-6 from human osteoblast-like cells.
    Methods: Individual serum samples collected from healthy male volunteers or male haemodialysis patients prior to and during a dialysis treatment were assayed for IL-6, interleukin-1beta (IL-1beta) and soluble IL-6 receptor (sIL-6R) using specific enzyme-linked immunosorbent assays. MG-63 and SaOS-2 cells were cultured in media containing pooled sera from both groups and alongside matching charcoal-stripped sera. IL-6 concentrations were determined in harvested cell supernatants after 24 h. In further experiments, media containing individual sera obtained from five patients at regular intervals during their haemodialysis treatment were incubated with MG-63 cells to determine the effects of the dialysis process on IL-6 secretion.
    Results: Haemodialysis patients had significantly higher (n = 10, P < 0.001) circulating concentrations of IL-6 (7.0 +/- 1.6 pg/ml) than normal subjects (0.4 +/- 0.1 pg/ml), but there were no significant differences in the concentrations of either IL-1beta or sIL-6R. These serum concentrations did not change significantly during 80 min of dialysis. IL-6 release by MG-63 cells incubated with charcoal-stripped serum from normal or from uraemic subjects was similar. Incubation with untreated sera from normal subjects increased IL-6 release by approximately 6-fold above the charcoal-stripped control, whereas sera from uraemic subjects increased IL-6 release by only approximately 2- to 3-fold (normal vs uraemic of 6878 +/- 595 and 2579 +/- 169 pg/ml, respectively, P < 0.001). Similar results were seen with SaOS-2 cells. Haemodialysis did not restore the capacity of uraemic serum to augment IL-6 release to the same degree as normal serum.
    Conclusions: These data show that the augmentation of IL-6 release from human osteoblastic cells after incubation with normal serum is greater than after uraemic serum. This may indicate the presence of an inhibitor of IL-6 release in uraemic serum that is involved in the deranged bone turnover of uraemic patients.
    Mesh-Begriff(e) Cells, Cultured ; Culture Media ; Humans ; Interleukin-1/blood ; Interleukin-6/secretion ; Kidney Failure, Chronic/blood ; Kidney Failure, Chronic/immunology ; Kidney Failure, Chronic/therapy ; Kinetics ; Male ; Osteoblasts/immunology ; Receptors, Interleukin-6/blood ; Reference Values ; Renal Dialysis ; Uremia/blood ; Uremia/immunology ; Uremia/therapy
    Chemische Substanzen Culture Media ; Interleukin-1 ; Interleukin-6 ; Receptors, Interleukin-6
    Sprache Englisch
    Erscheinungsdatum 2004-12
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 90594-x
    ISSN 1460-2385 ; 0931-0509
    ISSN (online) 1460-2385
    ISSN 0931-0509
    DOI 10.1093/ndt/gfh491
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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