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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 112 (1985), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0827
    Keywords: Osteopetrosis ; Diphosphonates ; Bone Resorption ; Mouse ; Calcium ; Tooth ; Bone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé L'effet de doses quotidiennes, administrées depuis la naissance, de deux types de diphosphonates, à savoir l'éthane-1-hydroxyle-1,1-diphosphonate (EHDP) et le dichlorométhylène diphosphonate (Cl2MDP), sur la croissance et le squelette de souris a été étudié. Les diphosphonates freinent la croissance: les incisives ne font pas leur éruption ou elle est plus tardive. La calcémie est normale. L'administration de Cl2MDP à une dose quotidienne de 10 mg P/kg/jour provoque des modifications squelettiques identiques à celles des souris grises létales atteintes d'ostéopétrose et les animaux meurent après quatre semaines de traitement. Par rapport aux témoins, les souris traitées présentent des os plus étroits, plus denses et plus déformés: les cavités médullaires sont comblées avec de l'os calcifié et du cartilage. La quantité totale de calcium d'un animal n'est pas augmentée par traitement au diphosphonate, par rapport à un témoin de même âge. Chez les souris grises létales et celles traitées aux diphosphonates, la plupart des anomalies est secondaire à une résorption osseuse diminuée. Ces résultats sont commentés en fonction de l'emploi des diphosphonates au cours de remaniements osseux pathologiques augmentés et en fonction du rôle de la résorption osseuse dans le maintien de la calcémie.
    Abstract: Zusammenfassung Mäuse erhielten von der Geburt an tägliche Dosen folgender zwei Diphosphonate: entweder Äthan-1-Hydroxy-1,1-Diphosphonat (EHDP) oder Dichloromethylen-Diphosphonat (Cl2MDP). Es wurde deren Wirkung auf das Wachstum und das Skelet untersucht. Die Diphosphonate verlangsamten das Wachstum, die Schneidezähne brachen nicht oder erst später durch, aber die Höhe des Plasmacalciums blieb normal. Die Verabreichung von Cl2MDP in Dosen von 10 mg P/kg/Tag führt zu Skeletveränderungen, welche denjenigen der „grey-lethal” osteopetrotischen Mäuse gleichen. Die Tiere sterben nach einer Behandlungsdauer von etwa 4 Wochen. Verglichen mit normalen Mäusen von ungefähr gleichem Alter hatten die behandelten Mäuse kleinere, dichtere und mehr keulenförmige Knochen, und die Markhöhlen waren gefüllt mit verkalktem Knochen oder Knorpel. Die Gesamtcalciummenge im Skelet wurde durch die Diphosphonatbehandlung nicht erhöht; dies ergab sich aus einem Vergleich mit der bei normalen Mäusen desselben Alters gefundenen Menge. Es wird vorgeschlagen, daß bei den „grey-lethal” und bei den Diphosphonat-behandelten Mäusen viele der Abnormalitäten als Folge der herabgesetzten Knochenresorption angesehen werden müssen. Die Ergebnisse werden einerseits im Hinblick auf den Gebrauch der Diphosphonate bei pathologischen Bedingungen eines erhöhten Knochenumbaus diskutiert; andererseits werden sie im Zusammenhang mit der Rolle der Knochenresorption bei der Erhaltung des Plasmacalcium-Spiegels besprochen.
    Notes: Abstract The effect of daily doses from birth of two diphosphonates, namely either ethane-1-hydroxy-1,1-diphosphonate (EHDP) or dichloromethylene diphosphonate (Cl2MDP), on the growth and the skeleton of mice has been studied. Diphosphonates slowed growth, the incisors did not erupt or erupted later, but the level of plasma calcium remained normal. The administration of Cl2MDP at a dose rate of 10 mg P/kg/day leads to skeletal changes that are similar to those observed in grey-lethal osteopetrotic mice, and the animals die after about four weeks of treatment. As compared with normal mice of similar age, treated mice had bones that were smaller, denser and more clubshaped, and the marrow cavities were filled with calcified bone or cartilage. The total amount of calcium in the carcass was not increased by diphosphonate treatment, as compared with the amount in normal mice of the same age. It is suggested that both in the grey-lethal and diphosphonate-treated mice many of the abnormalities are secondary to decreased bone resorption. The results are discussed with respect to the use of diphosphonates in pathological conditions of increased bone turnover and with respect to the role of bone resorption in the maintenance of plasma calcium levels.
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  • 3
    ISSN: 1432-0827
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0827
    Keywords: Bone ; Vitamin D ; Resorption ; Calcium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Deux métabolites de la vitamine D3, le 25-hydroxycholecalciferol (25-OHD3) et 1,25-dihydroxycholecalciferol (1,25-(OH)2D3), stimulent la résorption osseuse dans deux systèmestests alors que la vitamine D3 est inactive. Ces substances sont testées a) en comparant directement leur action dans les explants osseux de calottes craniennes de sourisin vitro et b) en les injectant dans de jeunes souris et en mesurant le degré de résorptionin vitro, lorsque les explants sont réalisés 18 heures après l'injection. Dans les deux tests, le métabolite 1,25 est environ 100 fois plus puissant que 25-OHD3. La courbe dose-résponse de 1,25-(OH)2D3 indique que des doses au-dessus d'environ 0.2 ng/g de poids corporel sont capables d'induire une augmentation de la résorption osseuse chez de jeunes souris normales. Ces résultats montrent que 1,25-(OH)2D3 est une des substances connues les plus actives qui agit sur le métabolisme osseux. Le rôle possible de 1,25-(OH)2D3 sur la mobilisation normale du calcium osseux est envisagé.
    Abstract: Zusammenfassung Bei Anwendung zweier verschiedener Versuchsanordnungen konnte gezeigt werden, daß die beiden Vitamin D3-Metaboliten 25-Hydroxycholecalciferol (25-OHD3) und 1,25-Dihydroxycholecalciferol (1,25-(OH)2D3) als starke Stimulatoren der Knochenresorption wirken, während sich Vitamin D3 selbst inaktiv verhält. Diese Substanzen wurden folgendermaßen geprüft: a) durch direkten Vergleich ihrer Wirkung auf Knochenexplantate (Hälften von Mäusecalvarien)in vitro und b) indem die Metaboliten jungen Mäusen injiziert wurden und der Resorptionsgrad an Explantaten 18 Std nach Injektionin vitro gemessen wurde. Bei beiden Versuchsanordnungen war der 1,25-Metabolit etwa 100mal wirksamer als der 25-OHD3-Metabolit. Aus der Dosiswirkungskurve für 1,25-(OH)2D3 geht hervor, daß es möglich ist, mit Dosen über ca. 0,2 ng/g Körpergewicht bei normalen jungen Mäusen bereits eine erhöhte Knochenresorption auszulösen. Diese Resultate zeigen, daß 1,25-(OH)2D3 eine der wirksamsten bisher bekannten Substanzen ist, die auf den Knochenmetabolismus einwirken können. Die Ergebnisse werden im Zusammenhang mit der Rolle, die das 1,25-(OH)2D3 bei der normalen Freisetzung von Calcium aus dem Knochen spielt, besprochen.
    Notes: Abstract Two metabolites of vitamin D3, 25-hydroxycholecalciferol (25-OHD3) and 1,25-dihydroxy-cholecalciferol (1,25-(OH)2D3) are potent stimulators of bone resorption in two test systems whereas vitamin D3 itself is inactive. These substances were tested (a) by directly comparing their action on bone explants of mouse half-calvariain vitro, and (b) by injecting them into young mice and measuring the degree of resorptionin vitro when explants were made 18 hours atter the injection. In both tests the 1,25-metabolite was about 100 times more potent than 25-OHD3. The dose-response curve for 1,25-(OH)2D3 indicates that doses above about 0.2 ng/g body weight are capable of inducing an increase in bone resorption in normal young mice. These data show that 1,25-(OH)2D3 is one of the most potent substances known that affects bone metabolism. The results are discussed in relation to the possible role of 1,25-(OH)2D3 in the normal mobilization of calcium from bone.
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  • 5
    ISSN: 1432-0827
    Keywords: Coronal suture ; Mechanical stress ; Neutral metalloproteinases ; Collagenase inhibitor ; Matrix degradation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The application of a continuous tensile mechanical stress (30g) to explants of coronal sutures from newborn rabbits (1–2 days) produced increases in enzyme activity of 33.7% for collagenase, 95.2% for gelatinase, and 35.9% for NMP III over a 4-day culture period. All three activities were in latent form and required activation with either 4-APMA or trypsin. The increases in enzyme activities were not accompanied by an alteration in the degradation of structural proteins. This was due to the ability of the cells to synthesize an inhibitor (mol wt 29,000 daltons) which complexed the increased quantities of enzyme. This necessitated a substantial stimulation of inhibitor production because there was still a residue of free inhibitory activity in the media of stressed cultures after 4 days. We previously showed using the same model system that coronal sutures respond to tensile mechanical stress by a two-fold increase in collagen synthesis. The present data suggest that when the priority of the cell population is the synthesis of structural proteins, the inhibitor, in addition to preventing the hydrolysis of newly synthesized peptides, also maintains matrix degradation at normal turnover levels.
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  • 6
    ISSN: 1432-0827
    Keywords: Collagenase ; Inhibitor ; Bone resorption ; Hormone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Half-calvariae from 1-week-old mice were cultured for 3 days with daily medium changes. Collagenase and the synthesized collagenase inhibitor were measured in the media from untreated explants and from explants treated with agents that alter bone resorption. Collagenase from untreated explants was in a latent form that could be activated by either trypsin or 4-aminophenylmercuric acetate. The molecular weight of the latent collagenase was 60,000 by gel filtration, that of the activated enzyme 50,000, and that of the collagenase inhibitor 30,000. Activated enzyme from both untreated and treated explants gave the typical ¾ and ¼ fragments when reacted with collagen. Vitamin A and 1,25-dihydroxycholecalciferol increased the production of collagenase and reduced that of inhibitor. In the case of vitamin A treated-explants, inhibitor levels in the media fell to zero during the first day, after which active enzyme became detectable. These results suggest that agents that induce resorption change the ratio of enzyme to inhibitor in favor of active enzyme. By itself hydrocortisone depressed latent enzyme production but had no effect on inhibitor. Hydrocortisone did not affect the resorption induced by vitamin A but partially suppressed enzyme production. Calcitonin alone did not alter the production of free inhibitor and caused a small increase in latent collagenase production. Calcitonin prevented the induction of resorption by vitamin A but did not affect the changes in enzyme and inhibitor levels associated with this resorbing agent. We suggest that calcitonin mainly affects the mechanisms involved with mineral removal and the differentiation of osteoclasts and has no direct role in the control of matrix catabolism. The depressive effect of hydrocortisone on enzyme production may be of greater importance in nonmineralized tissues. Because calcitonin can prevent osteoclastic resorption even when active enzyme is detectable, the production of active enzyme may lead to bone matrix resorption only after other mechanisms involved in demineralization operate.
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  • 7
    ISSN: 1432-0827
    Keywords: Streptococci ; Cell walls ; Bone resorption ; Protein ; DNA synthesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Cell wall components fromStreptococcus mutans NCTC 10449 andStreptococcus sanguis ATCC 10558 stimulated the release of45Ca from prelabeled mouse calvariae in organ culture. Bone resorbing activity was not blocked by fetal calf serum. It was, however, blocked by calcitonin, an inhibitor of osteoclast-mediated bone resorption. Indomethacin, a prostaglandin synthetase inhibitor, partially blocked endogenous but not antigen-stimulated45Ca release, suggesting that antigen-stimulated bone resorption was not mediated by prostaglandins. The antigen preparations also had an inhibitory effect on the incorporation of3H-proline and3H-thymidine into explants of rabbit and rat calvariae, respectively. The inhibitory effect of antigen on3H-proline incorporation was not altered by the presence of calcitonin, which suggests that it represented a real inhibition of protein synthesis and not a reflection that the bones were resorbing. These findings indicate that plaque bacterial antigens may contribute directly to the progressive loss of alveolar bone during periodontal disease. The assumption that only Gram-negative organisms play an important role in the etiology of periodontal disease appears incorrect.
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  • 8
    ISSN: 1432-0827
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] TIMP was sequenced after purification from human amniotic fluid10 and from the culture media of human fetal lung fibroblasts (American Type Culture Collection CCL153). Figure la compares these N-terminal sequences with that published for a collagenase inhibitor11, with properties similar to TIMP8, ...
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  • 10
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Periodontology 2000 14 (1997), S. 0 
    ISSN: 1600-0757
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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