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  • Articles  (100)
  • Calcification  (52)
  • pharmacokinetics  (48)
  • Springer  (100)
  • 2020-2020
  • 1970-1974  (100)
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  • Articles  (100)
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  • Springer  (100)
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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 10 (1972), S. 91-102 
    ISSN: 1432-0827
    Keywords: Hydroxyapatite ; Calcification ; Phases ; Growth ; Microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé La croissance cristalline de l'hydroxyleapatite à 25° et à pH constant de 7.4 a été étudiée à l'aide du microscope électronique à balayage. La technique reproductible de croissance par ensemencement à partir de solutions stables sursaturées est utilisée efficacement pour produire des échantillons de minéral à divers stades distincts de croissance. Des changements de phase sont observés avec le progrès de la croissance; ils correspondent dans le temps avec les résultats cinétiques obtenus antérieurement. Un essai de rationalisation est tenté à la lumière des mécanismes proposés pour la formation d'hydroxyleapatite dans des conditionsin vivo.
    Abstract: Zusammenfassung Das Kristallwachstum von Hydroxyapatit bei 25° und einem konstanten pH von 7,4 wurde mit Hilfe eines Raster-Elektronenmikroskopes studiert. Die reproduzierbare Technik des Keimwachstums aus stabilen übersättigten Lösungen wurde mit Erfolg verwendet, um Mineralproben in verschiedenen bestimmten Stadien des Wachstums zu erhalten. Phasenveränderungen wurden beim fortschreitenden Wachstum beobachtet, und diese stimmten zeitlich gut überein mit kinetischen Resultaten, über welche früher berichtet wurde. Es wurde versucht, diese Beobachtungen zu erklären in Anbetracht von Mechanismen, welche für die Bildung von Hydroxyapatit unterin vivo-Bedingungen vorgeschlagen wurden.
    Notes: Abstract The crystal growth of hydroxyapatite at 25° and at a constant pH of 7.4 has been studied with the aid of a scanning electron microscope. The reproducible technique of seeded growth from stable supersaturated solutions was used effectively to produce samples of the mineral at various distinct stages of growth. Phase changes were observed as the growth proceeded and these corresponded favorably in time with kinetic results reported earlier. An attempt was made to rationalize the observations in light of mechanisms proposed for the formation of hydroxyapatite under conditions foundin vivo.
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  • 2
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    Calcified tissue international 10 (1972), S. 136-141 
    ISSN: 1432-0827
    Keywords: Calcification ; Metal ; Experimental ; Rodent ; Fowl
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé L'injection sous-cutanée de solutions diluées d'acétate de plomb est suivie par une calcification autour des régions d'injection chez la souris, le rat, le lapin, le cobaye, le hamster et le poulet. Malgré les variations numériques des mastocytes présents dans les régions d'injection, une calcification marquée est observée. La réaction initiale est considérée comme une combinaison des ions de plomb avec les fibres collagènes, suivie par un afflux d'ions de calcium et phosphate, en provenance des capillaires locaux dilatés, avec calcification. Le rôle du mastocyte parait consister en une action dilatatrice locale des vaisseaux avec décharge de granules. Chez le poulet, bien que la séquence des évènements soit semblable, on n'observe pas de mastocytes dans les zones d'injection. D'autres vaso-dilatateurs peuvent done intervenir.
    Abstract: Zusammenfassung Mäuse, Ratten, Kaninchen, Meerschweinchen, Hamster und Küken, welchen Bleiacetat-Lösungen subcutan injiziert wurden, zeigten Verkalkungen rund um die Injektionsstelle. Trotz den unterschiedlichen Mengen von Mastzellen, welche sich bei diesen verschiedenen Tieren an der Injektionsstelle vorfanden, fand eine ausgeprägte makroskopische Verkalkung statt. Die Anfangsreaktion wird als eine Verbindung der injizierten Bleiionen mit Collagenfasern angesehen. Darauf folgt ein Zufluß von Calcium- und Phosphationen aus lokal dilatierten Capillaren und dann Verkalkung. Die Rolle der Mastzellen sieht man in ihrer Fähigkeit, lokale kleine Blutgefäße zu dilatieren, was einhergeht mit der Degranulation der Mastzellen. Beim Huhn ist der Ablauf der Ereignisse ähnlich, jedoch konnten keine Mastzellen rund um die Injektionsstelle gesehen werden. Deshalb ist es möglich, daß andere Vasodilatatoren ebenfalls an dem Vorgang beteiligt sind.
    Notes: Abstract The subcutaneous injection of dilute solutions of lead acetate in mice, rats, rabbits, guinea pigs, hamsters and chickens, was followed by calcification around the injection site. In spite of the variations in the number of mast cells present at the injection site in these different animals, marked macroscopic calcification occurred. The initial reaction is considered as a combination of the injected lead ions with collagen fibres. This is followed by an influx of calcium and phosphate ions from locally dilated capillaries followed by calcification. The role of the mast cell is considered to be that of dilating local small blood vessels associated with release of their granules. In the fowl, however, while the sequence of events was similar, mast cells were not seen around the injection site. Other vasodilators may, therefore, be involved in the process.
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  • 3
    ISSN: 1432-0827
    Keywords: Pyrophosphate ; Bone ; Cartilage ; Calcification
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Les concentrations de pyrophosphate inorganiques (PPi), d'orthophosphate et de calcium ont été déterminées dans le cartilage au repos, en prolifération, hypertrophique et calcifié au niveau d'épiphyses foetales de veaux et aussi dans l'os spongieux, périosté et compact. Dans les échantillons de cartilage, le contenu en PPi augmente progressivement dans l'ordre énoncé ci-dessus, de 8.59 μg P/g en poids sec de cartilage au repos à 236 μg P/g en poids sec dans le cartilage calcifié. Cependant, le rapport PPi sur orthophosphate suit une relation inverse: il est plus élevé dans la zone de repos et diminue considérablement lorsque le tissu se calcifie. Le rôle possible du PPi, en inhibant la précipitation de phosphate de calcium amorphe (ACP) et en ralentissant la transformation d'ACP en hydroxyleapatite (HA) dans les tissus calcifiés, est envisagé par rapport à d'autres facteurs, tels que le collagène, le magnésium, les phospholipides et les protéines-polysaccharides, qui peuvent aussi intervenirin vivo. Pour l'instant, aucun facteur isolé ne peut être considéré comme un régulateur physiologique certain.
    Abstract: Zusammenfassung Der Gehalt an anorganischem Pyrophosphat (PPi), Orthophosphat und Calcium wurde in ruhendem, proliferierendem, hypertrophischem und verkalktem Knorpel von foetalen Kalbsepiphysen und auch in spongiösem, periostalem und kompaktem Knochen gemessen. Bei den Knorpelproben nahm der Gehalt an PPi progressiv in der oben angegebenen Reihenfolge zu: von 8,59 μg P/g Trockengewicht in ruhendem Knorpel bis zu 236 μg P/g Trockengewicht in verkalktem Knorpel. Das PPi/Orthophosphat-Verhältnis hingegen verlief in umgekehrter Richtung; es war am höchsten in der ruhenden Zone und nahm dramatisch ab, wenn das Gewebe verkalkte. Die mögliche Rolle von PPi bei der Hemmung der Ausfällung von amorphem Calciumphosphat (ACP) und bei der Verlangsamung der Umwandlung von ACP in Hydroxyapatit (HA) in verkalkenden Geweben wird in bezug auf folgende anderen Faktoren, welche den Vorgang in vivo ebenfalls beieinflussen könnten, diskutiert: Collagen, Magnesium, Phospholipide und Proteinpolysaccharide. Bis jetzt war es nicht möglich, einen einzelnen Faktor als sicheren physiologischen Regulator zu identifizieren.
    Notes: Abstract The amounts of inorganic pyrophosphate (PPi), orthophosphate and calcium have been measured in resting, proliferating, hypertrophic and calcified cartilage from foetal calf epiphyses and also in cancellous, periosteal and compact bone. In the cartilage samples, the content of PPi increased progressively in the order named above, from values of 8.59 μg P/g dry weight in resting cartilage to 236 μg P/g dry weight in calcified cartilage. However, the ratio of PPi to orthophosphate followed the reverse relationship and was highest in the resting zone and fell dramatically as the tissue calcified. The possible role of PPi in inhibiting the precipitation of amorphous calcium phosphate (ACP) and in the slowing the transformation of ACP to hydroxyapatite (HA) in calcifying tissues is discussed in relation to other factors, such as collagen, magnesium, phospholipids and proteinpolysaccharides, which might also influence the processin vivo. At present, no single factor can be identified as a proven physiological regulator.
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  • 4
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    Calcified tissue international 14 (1974), S. 317-325 
    ISSN: 1432-0827
    Keywords: Calcification ; Neutral sites ; Elastin ; Calcium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Des études précédentes suggèrent la présence de groupements carboxyles, sulfhydriles et aminés dans les sites de liaison en calcium de l'élastine. La possibilité de l'existence de sites neutres de liaison en calcium au niveau de l'élastine a été étudiée dans ce travail. Une augmentation de la fixation du calcium au niveau de l'élastine est observée après des modifications de dissolution qui ont aussi provoqué des modifications de structure de la protéine. Dans des mélanges méthanol-H2O, les liaisons du calcium semblent indépendantes du pH et de la force ionique. Sur dix ions testés (Ca2+, CO2+, Na2+, Cu2+, Zn2+, Cr3+, Pb+2, K+, Rb+ et Mg2+) seule la liaison du calcium est nettement augmentée, lorsque le méthanol est ajouté. Il semble que les sites neutres sont importants pour les divers rapports entre calcium et élastine et servent, peut-être, comme centres de nucléation au cours de la calcification de la protéine.
    Abstract: Zusammenfassung Vorgängige Studien haben die Bedeutung der Carboxyl-, Sulfhydryl- und Aminogruppen als Stellen der Calciumbindung im Elastin gezeigt. Die vorliegende Arbeit hatte zum Ziel, die Rolle der neutralen Koordinationsstellen im Elastin als mögliche Calcium-Bindungsseite abzuklären. Die Calciumbindindung an das Elastin wurde durch solche Lösungsmittelveränderungen erhöht, die auch gleichartige Verschiebungen im Proteinmolekül bewirkten. In Methanol-Wasser-Mischungen schien die Calciumbindung nicht von Veränderungen des pH oder der Ionenstärke abhängig zu sein. Von 10 Ionen, bei welchen die Bindung überprüft wurde, war einzig diejenige des Calciums signifikant erhöht, wenn Methanol zugesetzt wurde. Es wird vorgeschlagen, daß die neutralen Stellen für die verschiedenen Vorgänge, bei welchen Calcium und Elastin beteiligt sind, eine wichtige Rolle spielen und vielleicht für die Verkalkung der Proteine als Nukleationszentren in Frage kommen.
    Notes: Abstract Previous studies have implicated carboxyl groups, sulphhydryl groups and amino groups as the sites for calcium binding in elastin. In this study, the concept was investigated that neutral co-ordinating sites in elastin may also provide calcium binding sites. Calcium binding to elastin was increased upon solvent changes which also effected conformational changes in the protein. In methanol-H2O mixtures calcium binding appeared to be independent of changes in pH and ionic strength. Of ten ions tested (Ca2+, Co2+, Na+, Cu2+, Zn2+, Cr3+, Pb+2, K+, Rb+, and Mg2+), only calcium binding was significantly increased when methanol was added. It is proposed that neutral sites are important to the various relationships involving calcium and elastin and perhaps serve as nucleation centers in the calcification of the protein.
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  • 5
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    Calcified tissue international 12 (1973), S. 117-124 
    ISSN: 1432-0827
    Keywords: Mouse ; Calcification ; Metals ; Mast Cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Des souris, ayant reçu par voie intra-veineuse une solution d'acétate de plomb, sont injectés par voie sous-cutanée avec du sulfate de polymixine B. Au niveau de ce dernier point d'injection, on observe des calcifications. L'examen histologique montre une dégranulation des mastocytes, une vaso-dilatation locale ainsi qu'une diffusion d'ions à partir des vaisseaux. Après 24 heures, des ions calcium et phosphate sont présents. En outre. des groupes de souris, pré-injectées par voie intraveineuse avec de l'acétate de plomb, reçoivent des extraits de granules de mastocytes, comportant du phosphate d'histamine, du sulfate de créatinine sérotonine, de l'héparine, du sulfate de chondroitine ou de l'acide hyaluronique. Seules les injections de sérotonine et d'histamine, connues comme vaso-dilatateurs et augmentant probablement la perméabilité capillaire, provoquent des calcifications. Il semble que le rôle des mastocytes dans la calcification soit lié principalement à la production d'une vasodilatation locale, avec perméabilité capillaire augmentée, plutot qu'à une action de liaison initiale des ions métalliques.
    Abstract: Zusammenfassung Nachdem Mäusen Bleiacetatlösungen intravenös eingespritzt worden waren, erhielten die Tiere Polymixin-B-Sulfat subkutan. Dies führte zu Verkalkung an der zweiten Injektionsstelle. Die histologische Untersuchung zeigte eine deutliche degranulation der Mastzellen, eine lokale Vasodilatation und das Austreten von Bleiionen aus diesen Gefäßen 24 Std nach der Injektion konnte eine groß Menge von Calcium- und Phosphationen eindeutig nachgewiesen werden. Weiter wurden Gruppen von Mäusen, die vorher Bleiacetat intravenös erhalten hatten. Bestandteile von Mastzellen-Granula injiziert. Diese bestanden aus Histaminphosphat, Serotonin-Creatinin-Sulfat, Heparin, Chondroitin-Sulfat oder Hyaluronsäure. Unter diesen exogenen Bestandteilen bewirkten nur Serotonin und Histamin eine Verkalkung. Beide sind starke Vasodilatatoren und erhöhen vermutlich die kapillare Permeabilität. Es wird postuliert, daß die Rolle der Mastzelle in der “calcergy” viel eher auf einer lokalen Vasodilatation mit erhöhter kapillarer Permeabilität als auf einer primären Bindung der Metallionen beruht.
    Notes: Abstract Mice previously injected intravenously with lead acetate solution were injected subcutaneously with Polymixin B Sulphate. This resulted in calcification at the latter injection site. Histological evidence showed marked mast cell degranulation, local vasodilation and the efflux of lead ions from these vessels. At twenty four hours after injection abundant calcium and phosphate ions were readily demonstrated. In addition, groups of mice pre-injected intravenously with lead acetate, were injected with constituents of mast cell granules. These included histamine phosphate, serotonin creatinine sulphate, heparin, chondroitin sulphate or hyaluronic acid. Of these exogenous constituents used, calcification was found only after serotonin and histamine injections, both of which are potent vasodilators and presumbly increase capillary permeability. It is postulated that the role of the mast cell in calcergy may be mainly that of producing local vasodilation with increased capillary permeability rather than the initial binding of metallic ions.
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  • 6
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    Calcified tissue international 12 (1973), S. 169-173 
    ISSN: 1432-0827
    Keywords: Calcification ; Histochemistry ; Autoradiography ; Fetal ; Mandible
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Des rats femelles reçoivent du45Ca ou du32P au 13ème et 18ème jour de la grossesse. Les coupes sériées des têtes de foetus sont étudiées par autoradiographie et par diverses méthodes histologiques pour déterminer la calcification. La détection la plus précoce de45Ca s'observe simultanément comme une réaction positive pour le calcium avec une des méthodes histologiques utilisées.32P est en évidence par les méthodes autoradiographiques un peu plus tard que le45Ca et sa présence coincide avec la réaction positive la plus précoce observée avec les autres méthodes histologiques utilisées. Les os de ces têtes foetales commencent à se calcifier selon un mode particulier commençant par la mandibule, puis l'os frontal et le maxillaire supérieur, suivis par les os nasaux, pariétaux et interpariétaux.
    Abstract: Zusammenfassung Weibliche Ratten erhielten45Ca und32P zwischen dem 13.–18. Tag der Schwangerschaft. Zur Ermittlung der Verkalkung wurden Serienschnitte der Köpfe ihrer Feten mittels Autoradiographie sowie durch verschiedene histologische Methoden untersucht. Das erste Auftreten von45Ca war ebenfalls von einer positiven Calciumreaktion mittels einer der verwendeten histologischen Methoden begleitet.32P wurde in der Autoradiographie erst etwas später als45Ca festgestellt und dessen Nachweis deckte sich mit den ersten positiven Reaktonen aller anderen verwendeten histologischen Methoden. Die Knochen in diesen Fetusköpfen begannen in einer bestimmten Sequenz zu verkalken: zuerst der Unterkiefer, dann das Stirnbein und der Oberkiefer, dann das Nasenbein, die Parietal- und Interparietalknochen.
    Notes: Abstract Female rats were given45Ca or32P from 13 to 18 days of pegnancy. Serial sections from the heads of their fetuses were studied by autoradiography, as well as by several histological methods for assessing calcification. The earliest detection of45calcium occured at the same time as a positive reaction for calcium with one of the histological methods used.32P was not detectable by autoradiographic methods until somewhat later than45Ca, and its presence coincided with the earliest positive reaction with all of the other histological methods employed. The bones in these fetal heads began to calcify in a partcular sequence, the mandible first, then the frontal bone and maxilla, followed by the nasal, parietal and interparietal bones.
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  • 7
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    Calcified tissue international 12 (1973), S. 209-216 
    ISSN: 1432-0827
    Keywords: Analysis ; Osteon ; Bone ; Composition ; Calcification
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Une étude microscopique de la composition du tissu osseux, réalisée initialement au niveau des ostéones, a été étendue à l'os lamellaire interstitiel périosté et aux ≪Mittellinien≫. Le phosphore, calcium, l'azote total, les mucopolysaccharides (sous forme d'hexosamines) et le collagène (sous forme d'hydroxyle-proline) ont été déterminés dans ce tissu au point de vue pondéral et volumétrique. Le calcium a également été déterminé dans les ostéones aux stades initial et final de la calcification. Malgré des rapports Ca/P sensiblement identiques, l'os lamellaire interstitiel périosté et les Mittellinien diffèrent en composition organique. L'os interstitiel a un contenu plus élevé en azote (absolu et par rapport au phosphore) et en hydroxyle-proline et azote non-collagénique que les Mittellinien. En étudiant les résultats sur la composition du tissu ostéoide, les ostéones à divers degrés de calcification et les structures décrites ci-dessus, on se rend compte de la composition variable du tissu osseux d'une plage à l'autre. D'après les résultats analytiques, il semble que dans tout processus de calcification rapide, des protéines non-collagéniques (probablement des protéoglycanes) sont présentes.
    Abstract: Zusammenfassung Eine Untersuchung der Zusammensetzung des Knochengewebes auf der Stufe mikroskopischer Strukturen, welche früher auf die Haversianischen Systeme begrenzt war, ist auf den interstitiellen Lamellenknochen des Periosts und auf die Mittellinien ausgedehnt worden. Phosphor, Calcium, Gesamtstickstoff, Mucopolysaccharide (als Hexosamine) und Kollagen (als Hydroxyprolin) wurden in diesen Materialien in bezug auf Gewicht und Volumen bestimmt. Calcium wurde auch in den Osteonen in der Anfangs- und Endphase der Verkalkung bestimmt. Trotz praktisch identischem Ca/P-Verhältnis unterscheiden sich interstitieller Lamellenknochen des Periosts und Mittellinien in ihrer organischen Zusammensetzung. Interstitieller Knochen hat einen höheren Gesamtstickstoffgehalt (absolut sowie auf Phosphorgehalt bezogen), ebenso mehr Hydroxyprolin und nicht-kollagenen Stockstoff als die Mittellinien. Eine Zusammenstellung von Daten über die Zusammensetzung des Osteoid-Gewebes, der Osteonen in verschiedenen Stadien der Verkalkung und der oben aufgeführten Strukturen zeigt, wie unterschiedlich die Zusammensetzung des Knochengewebes sogar von einer mikroskopischen Struktur zur angrenzenden sein kann. Es wurde versucht, aus den analytischen Daten eine allgemeine Regel betreffend den verkalkungsprozess zu erhalten, nämlich: Wo immer eine Verkalkung rasch stattfindet, sind nicht-kollagene Proteine (möglicherweise Proteoglycane) anwesend.
    Notes: Abstract A study of the composition of bone tissue at the level of microscopic structures, previously limited to the Haversian systems, has been extended to interstitial periosteal lamellar bone and to the “Mittellinien”. Phosphorus, calcium, total nitrogen, mucopolysaccharides (as hexosamines) and collagen (as hydroxyproline) were determined in these materials on both weight and volume basis. Calcium was also been determined in osteones at the initial and final stage of calcification. In spite of virtually identical Ca/P ratios, interstitial periosteal lamellar bone and Mittellinien differ in their organic composition. Interstitial bone has a higher total nitrogen content (both absolute and relative to phosphorus) as well as higher hydroxyproline and non-collagenous nitrogen than the Mittellinien. A compilation of data on the composition of osteoid tissue, osteones at different degrees of calcification and the above structures, shows how variable is the composition of bone tissue even from one microscopic structure to the one adjacent. Tentative indications of a general rule governing the process of calcification were obtained from the analytical data; namely that wherever calcification is taking place rapidly, non-collagenous proteins (possibly proteoglycans) are present.
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  • 8
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    Calcified tissue international 16 (1974), S. 227-237 
    ISSN: 1432-0827
    Keywords: Kinetics ; Calcification ; Secretion ; Protistan ; Coccolith
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract The calcified body scale (coccolith) of the unicellular marine algaHymenomonas carterae is composed of two morphologically distinct calcite elements which alternate about the perimeter of a complex, elliptical organic base. The coccoliths ofHymenomonas are formed intracellularly in a precise and orderly sequence of events within the single Golgi apparatus of the alga and then secreted to the anterior cell surface. This study demonstrates that the kinetics of this calcification-secretion process can be reproducibly determined by morphological means. Under standardized conditions, coccoliths are secreted at a rate of about ten per hour. In the absence of light this rate is significantly reduced. The procedure described for determining the kinetics of coccolith secretion inHymenomonas provides a simple, precise method for evaluating the results of experimental manipulation of this calcification-secretion system.
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  • 9
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    Calcified tissue international 16 (1974), S. 59-71 
    ISSN: 1432-0827
    Keywords: Apatite ; Calcification ; Pineal gland ; Calcospherulites ; Calculi
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract Calcifications of the pineal gland in the form of calcospherulites have been studied by optical microscopy, electron microscopy, electron probe analysis, X-ray diffraction, thermogravimetry, and infra-red and chemical analysis. Complex calcospherulite textures have been observed which have a granular substructure made up of apatite crystals averaging 218 Å in length and 38 Å in width. These apatite crystals appear to be a carbonate-containing hydroxyapatite, mineralogically similar to enamel.
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  • 10
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    Calcified tissue international 16 (1974), S. 109-127 
    ISSN: 1432-0827
    Keywords: Dentinogenesis ; Diphosphonates ; Calcification ; Collagen ; Electron Microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract The effects of high doses of ethylene-1-hydroxy-1,1-diphosphonate (EHDP) were investigated at the light microscopic and subcellular level. The administration of EHDP at a concentration of 7.5–10 mg P/kg body weight/day over a short period of time resulted in complete inhibition of crystal formation in predentin and pre-enamel. An increased predentin width was observed and within newly-formed predentin areas the formation ofcollagen fibrils was grossly disturbed. In addition, fine precipitates appeared in the ground substance. The presence of unusual thread-like elements within specific bodies in the cytoplasm of the odontoblastic processes may be indicative of an interference by EHDP in e.g. the synthesis of precollagen. The possibility of an inhibition by EHDP of the extracellular aggregation of collagen molecules is also discussed. EHDP further inhibited crystal formation within dentinal globules. Functioning ameloblasts were grossly affected in EHDP-treated rats, and it is suggested that this is related to an inhibition of crystal formation in pre-enamel.
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  • 11
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    Calcified tissue international 7 (1971), S. 103-107 
    ISSN: 1432-0827
    Keywords: Epiphysis ; Testosterone ; Calcification ; Actinomycin D
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Les métaphyses fémorales distales de souris impubères, traitées par le propionate de testostérone entre l'âge de 15 et 50 jours sont étudiées. La quantité de matrice collagénique ne change pas significativement avec le traitement. Elle diminue par traitement à l'Actinomycine D. Le degré de calcification est significativement augmenté par la testostérone, mais pendant une courte durée. Cet effet est inhibé par l'administration simultanée d'Actinomycine D. Les cartilages de conjugasion d'animaux, traités à la testostérone, montrent une augmentation transitoire, mais significative, du volume du cartilage hypertrophique. L'actinomycine D n'affecte ni l'involution normale de la métaphyse, ni l'hyperplasie du cartilage, en voie de maturation, produite par l'hormone. Le degré de maturation de la métaphyse es augmenté par la testostérone après l'âge de 30 jours.
    Abstract: Zusammenfassung Vor der Pubertät stehende Mäuse wurden im Altern von 15–50 Tagen mit Testosteron-propionat behandelt und anschließend deren distale Femurmetaphysen untersucht. Die Menge von kollagener Matrix wurde durch diese Behandlung nicht signifikant verändert; durch Actinomycin D-Gaben nahm siejedoch ab. Die Verkalkungsgeschwindigkeit war significant, aber nur kurz durch Testosteron erhöht. Diese Wirkung wurde durch die gleichzeitige Verabreichung von Actinomycin D gehemmt. Die Epiphysenscheibe der mit Testosteron behandelten Tiere zeigte eine vorübergehende, jedoch signifikante Volumenvergrößerung des hypertrophen Knorpels. Actinomycin D wirkte weder auf die normale Rückbildung der Scheibe, noch auf die durch das Hormon hervorgerufene Hyperplasie des reifenden Knorpels. Die Rückbildung der Epiphysenscheibe wurde erhöht, wenn Testosteron 30 Tagen alten Kücken verabreicht wurde.
    Notes: Abstract The distal femoral metaphyses of prepubertal mice treated with testosterone propionate from 15 to 50 days of age were studied. The amount of collagenous matrix did not change significantly with treatment. It was depressed by treatment with Actinomycin D. The rate of calcification was significantly but briefly increased by testosterone. This effect was inhibited by the simulataneous administration of Actinomycin D. The epiphyseal plate of testosterone-treated animals showed a transitory but significant increase in the volume of hypertrophic cartilage. Actinomycin D did not affect either the normal involution of the plate or the hyperplasia of the maturing cartilage produced by the hormone. The rate of ageing of the epiphyseal plate was increased by testosterone after 30 days of age.
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  • 12
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    Calcified tissue international 7 (1971), S. 290-298 
    ISSN: 1432-0827
    Keywords: Proteinpolysaccharides ; Cartilage ; Calcification ; Binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Les protéines-polysaccharides (PP-L) de zones «au repos» et «en voie de calcification» de cartilage d'omoplate et de cloison nasale de veaux sont extraits à l'aide d'une solution aqueuse à 0.15 M KCl et fractionnés en une série de produits: PP-L3, PP-L4, PP-L5, PP-L6. Une fraction supplémentaire protéino-polysaccharidique, PP-L2, est extraite à partir des restes cartilagineux à l'aide d'hydroxylamine. Des différences de composition chimique parmi les fractions protéino-polysaccharides, obtenues à partir de ces trois sources de cartilage, son généralement faibles. La propriété de liaison du calcium des échantillons de PP-L, PP-L2, PP-L3, déterminée par la mesure de dialyse d'équilibre, semble principalement en rapport avec les contenus en acide uronique et en sulfate échangeable. L'application d'une technique d'échange cationique indique que le PP-L de zones «au repos» et «en voie de calcification» de cartilage de l'omoplate a des affinités identiques pour des quantités de calcium radioactif. Cependant, l'affinité de PP-L des deux zones de cartilage de l'omoplate pour des quantités de calcium radioactif est plus élevé que celle de PP-L de la cloison nasale. Les résultats obtenus ne montrent pas de différences suffisantes dans la composition chimique et l'affinité pour le calcium des protéines-polysaccharides de cartilage «au repos» et «en voie de calcification» de l'omoplate, pour rendre compte de l'enrichissement en calcium de la zone «en voie de calcification».
    Abstract: Zusammenfassung Proteinpolysaccharide (PP-L) von „ruhenden” und „verknöchernden” Zonen von Kalbs-Scapula-Knorpel und von Kalbs-Nasenseptum-Knorpel wurden mit wäßrigem 0,15 M KCl extrahiert und zu einer Serie von Produkten fraktioniert: PP-L3, PP-L4, PP-L5, PP-L6. Eine zusätzliche Proteinpolysaccharidfraktion, PP-L2, wurde mit Hydroxylamin aus den Knorpelrückständen extrahiert. Die Unterschiede in der chemischen Zusammensetzung zwischen den entsprechenden Proteinpolysacchariden von den drei Knorpel-Quellen waren im allgemeinen klein. Die Calciumbindungsfähigkeit der PP-L, PP-L2 und PP-L3-Proben, gemessen durch Gleichgewichtsdialyse, schien hauptsächlich deren Gehalt an Uronsäure und austauschbarem Sulfat wiederzugeben. Die Anwendung einer Kationenaustausch-Technik deutete darauf hin, daß PP-L von „ruhenden” und „verknöchernden” Zonen von Scapulaknorpel eine ähnliche Affinität für Tracermengen von Calcium hat. Jedoch war die Affinität von PP-L für Tracermengen von Calcium aus beiden Zonen von Scapulaknorpel größer als diejenige von PP-L aus dem Nasenseptum. Die aus dieser Studie hervorgehenden Daten zeigen nicht genügend Unterschiede an zwischen der chemischen Zusammensetzung und der Calcium-affinität von Proteinpolysacchariden aus „ruhendem” und „verknöcherndem” Scapulaknorpel, um die Calciumaufnahme in der „verknöchernden” Zone zu erklären.
    Notes: Abstract Proteinpolysaccharide (PP-L) of “resting” and “ossifying” zones of calf scapular cartilage and of calf nasal septum cartilage was extracted with aqueous 0.15 M KCl and fractionated into a series of products: PP-L3, PP-L4, PP-L5, PP-L6. An additional proteinpolysaccharide fraction, PP-L2, was extracted from the cartilage residues with hydroxylamine. Differences in chemical composition among corresponding proteinpolysaccharides obtained from the three cartilage sources were, in general, small. The calcium binding capacity of the PP-L, PP-L2, and PP-L3 samples, as measured by equlibrium dialysis, appeared to reflect principally their uronic acid and exchangeable sulfate contents. Application of a cation exchange technique indicated that PP-L from “resting” and “ossifying” zones of scapular cartilage had similar affinities for tracer quantities of calcium. However, the affinity of PP-L from both zones of scapular cartilage for tracer quantities of calcium was greater than that of PP-L from nasal septum. The data obtained from this study do not indicate sufficient differences between the chemical composition and calcium affinity of proteinpolysaccharides from “resting” and “ossifying” scapular cartilage to account for the calcium uptake in the “ossifying” zone.
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  • 13
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    Calcified tissue international 9 (1972), S. 109-121 
    ISSN: 1432-0827
    Keywords: Arthritis ; Phosphonates ; Bone ; Resorption ; Pathology ; Calcification
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé De l'adjuvant de Freund, constitué deMycobacterium butyricum tués, en suspension dans de l'huile minérale, provoque une arthrite chez les rats qui rappelle certaines formes d'arthrites chez l'Homme. L'arthrite comporte une inflammation de tissu mou, une formation de pannus et deux ostéopathies distinctes, une résorption ossuse accélérée et une formation anormale d'os périarticulaire. L'étidronate disodique, administré à raison de 4 mg/kg/jour par voie cutanée, à partir de l'injection de l'adjuvant, inhibe nettement la résorption osseuse, la formation de pannus, l'érosion inflammatoire de cartilage et la formation d'os pathologique, en rapport avec l'adjuvant. Après arrêt du traitement à l'étidronate disodique, la formationd'os pathologique devient visible radiographiquement deux semaines après l'arrêt du traitement. Le rôle de l'étidronate disodique sur la régulation de la résorption osseuse et sur la concentration du calcium et du phosphate, dans les tissus environnants, ainsi que les rapports des phénomènes arthritiques avec ce type d'expérience sont envisagés. Les résultats suggèrent la possibilité de l'emploi de l'étidronate disodique dans certaines formes d'arthrites humaines.
    Abstract: Zusammenfassung Freund's Adjuvans, das aus abgetötetem und in Mineralöl suspendiertem Mycobacterium butyricum besteht, verursacht bei Ratten eine arthritische Reaktion, welche gewissen Arthritisformen beim Menschen ähnlich ist. Die arthritische Reaktion besteht in einer Entzündung der Weichteile, einer Pannusbildung und zwei verschiedenen Osteopathien, ferner in einer beschleunigten Knochenresorption und einer abnormen periartikulären Knochenbildung. Wird gleichzeitig mit der Verabreichung des Adjuvans Dinatriumetidronat in einer Dosis von 4 mg/kg/Tag subcutan gegeben, so werden sowohl die Knochenresorption, als auch die Pannusbildung, die entzündliche Knorpelerosion und die mit der Adjuvansgabe verbundene pathologische Knochenbildung merklich gehemmt. Wurde die Dinatriumetidronat-Behandlung abgebrochen, so wurde die pathologische Knochenbildung innerhalb 2 Wochen nach Behandlungsabbruch röntgenologisch sichtbar. Die Kontrollfunktion des Dinatriumetidronates bei der Knochenresorption und bei der Calcium- und Phosphatkonzentration in den umliegenden Geweben, sowie die Beziehung dieser Substanz zu den arthritischen Prozessen, wie sie bei diesem Rattenversuch vorliegen, werden besprochen. Auf Grund dieser Resultate ist eine potentielle Anwendung des Dinatriumetidronates bei gewissen Formen der menschlichen Arthritis denkbar.
    Notes: Abstract Freund's Adjuvant, consisting of deadMycobacterium butyricum suspended in mineral oil, produces an arthritic response in rats which resembles certain forms of arthritis in man. The arthritic response consists of soft tissue inflammation, pannus formation and two separate osteopathies; accelerated bone resorption and abnormal periarticular bone formation. Disodium etidronate administered at 4 mg/kg/day subcutaneously from the time of adjuvant injection markedly inhibited bone resorption, pannus formation, inflammatory erosion of cartilage, and the pathologic bone formation associated with the adjuvant model. When the disodium etidronate treatments were discontinued, the pathologic bone formation became radiologically visible within two weeks after cessation of treatment. The role of disodium etidronate in controlling bone resorption and surrounding tissue concentration of calcium and phosphate and the relation to arthritic processes in this rat model are discussed. The data suggest a potential use of disodium etidronate in some forms of human arthritis.
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  • 14
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    Calcified tissue international 14 (1974), S. 229-244 
    ISSN: 1432-0827
    Keywords: Teeth-enamel ; Histocytochemistry ; Calcification
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Des études histochimiques et d'affinités tinctoriales sont menées sur des germes dentaires de foetus de veauxin situ, fixés dans du chlorure de cyanure ou du formol. La concentration en protéine décroit avec la maturation de l'émail. Le tissue est divisé en deux bandes distinctes: une région externe d'émail nouvellement formé et une région interne d'émail en maturation. L'émail mature, défini antérieurement par méthode biochimique, n'a pas été étudié. L'histidine, présente dans l'émail, est aisément traitée par l'iode: le traitement au benzol n'a pas d'effet. La tyrosine est mise en évidence par deux méthodes dans les deux types d'émail et décroit légèrement au cours de la maturation. La transition est progressive. Des groupements sulfhydriles sont présents dans l'émail jeune, mais non dans l'émail en voie de maturation, avec une transition nette entre les deux zones. Le tryptophane est présent dans toute l'épaisseur de l'émail. L'arginine ne réagit pas bien par la méthode de Sakaguchi, mais on peut la mettre en évidence en bloquant par la fluorodinitrobenzène les colorants anioniques. La lysine est présente et diminue avec la maturation. Les résidus d'acide carboxyliques sont mis en évidence dans les deux types d'émail, mais des bandes distinctes et moins de résidus sont observés au cours de la maturation. Les affinités tinctoriales anioniques à diverses concentrations de sels montrent que la concentration critique en électrolytes de l'émail est relativement élevée et semblable à celle de la kératine. Les affinités tinctoriales cationiques indiquent que l'ionisation des groupements d'acide carboxylique peut être supprimée dans l'émail jeune, mais non dans l'email en voie de maturation. L'émail jeune a les caractéristiques histochimiques d'une kératine, mais non pas l'émail mature, qui ressemble à un groupe de protéines globulaires ectodermiques.
    Abstract: Zusammenfassung Histochemische Methoden und Farbbindungs-Untersuchungen wurden an Zahnkeimen von Kalbsembryonen in situ, welche in Cyanurchlorid oder Formalin fixiert worden waren, ausgeführt. Die Proteinkonzentration nahm mit dem Reiferwerden des Schmelzes ab. Das Gewebe wurde in zwei genau abgegrenzte Bänder unterteilt, einen äußeren Bereich aus neu gebildetem Schmelz und einen inneren Bereich aus reifendem Schmelz. Was früher biochemisch als reifer Schmelz definiert wurde, wurde nicht untersucht. Histidin lag im Schmelz vor und konnte leicht iodiert werden, eine Benzoilierung fand jedoch nicht statt. Zwei verschiedene Tyrosinanalysen bestätigen dessen Gegenwart in neugebildetem und reifendem Schmelz, wobei es aber beim Reifeprozess etwas abnahm. Der Übergang zeigte sich fließend. Sulphydryl-Gruppen waren in neugebildetem, aber nicht in reifendem Schmelz vorhanden, wobei sich ein abrupter Übergang zwischen den beiden Zonen fand. Tryptophan konnte durch die gesamte Schmelzbreite nachgeweisen werden. Argininrückstände reagierten kaum auf die Sakaguchi-Methode, aber sie konnten durch die anionische Farbstoffe blockierende Fluorodinitrozenzen-Methode nachgewiesen werden. Lysin war anwesend und nahm im Laufe des Reifeprozesses ab. Carboxylsäure-Rückstände wurden in reifendem und neugebildetem Schmelz nachgewiesen, jedoch mit scharfer Abgrenzung und deutlich weniger Rückständen in reifendem Schmelz. Die Bindung mit anionischen Farbstoffen bei verschiedenen Salzkonzentrationen zeigte, daß die kritische Elektrolyten-Konzentration nicht besonders hoch und derjenigen von Keratin ähnlich ist. Untersuchungen mit kationischen Farbstoffen deuteten an, daß die Ionisierung von Carboxylsäure-Gruppen in neugebildetem, nicht aber in reifendem Schmelz, unterdrückt werden kann. Neugebildeter Schmelz hat die histochemische Eigenschaften von Keratin; reifender Schmelz hingegen hat diese Eigenschaft nicht und gleicht eher einem Vertreter der Gruppe der ektodermalen globulären Proteine.
    Notes: Abstract Histochemical methods and dye binding studies were carried out on foetal calf tooth germsin situ fixed in cyanuric chloride or formalin. Protein concentration decreased upon maturation of enamel. The tissue was divided into two distinct bands, an outer region of newly formed enamel and an inner region of maturing enamel. What has previously been defined biochemically as mature enamel was not investigated. Histidine was present in enamel and easily iodinated but protected from benzoylation. Two methods for tyrosine analysis confirm its presence in both newly formed and maturing enamel but with some decrease upon maturation. The transition was gradual; Sulphydryl groups were present in newly formed, but not in maturing, enamel, with abrupt transition between the two zones. Tryptophane was demonstrated throughout the entire thickness of enamel. Arginine residues were not very reactive to Sakaguchi's method but they were demonstrable by fluorodinitrobenzene blockade of anionic dyes. Lysine was present, decreasing upon maturation. Carboxylic acid residues were demonstrated in both maturing and newly formed enamel but with distinct banding and noticeably fewer residues in maturing enamel. Anionic dye binding at various salt concentrations showed that the critical electrolyte concentration of enamel is moderately high and similar to that of keratin. Cationic dye binding studies indicated that ionization of carboxylic acid groups in newly formed enamel, but not maturing enamel, might be suppressed. Newly formed enamel has the histochemical characteristics of a keratin but maturing enamel does not, more nearly resembling one of a group of ectodermal globular proteins.
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  • 15
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    Calcified tissue international 14 (1974), S. 275-281 
    ISSN: 1432-0827
    Keywords: Calcification ; Cartilage ; Lipids ; Membranes ; Vesicles
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Les vésicules matricielles sont des particules extracellulaires, entourées par une membrane, qui sont nombreuses dans la matrice du cartilage en voie de calcification et qui sont en rapport morphologique avec le dépôt minéral. Les vésicules matricielles et les cellules de l'épiphyse d'os longs d'embryons de veaux sont libérées par digestion grâce à la collagénase et séparées par centrifugation différentielle. Les vésicules ainsi obtenues sont riches en lipides et contiennent significativement plus de sphingomyéline et phosphatidyl sérine que les fractions cellulaires. Le rapport moles de cholestérol sur moles de phospholipides totaux est plus élevé dans les vésicules que dans les cellules; ce résultat est en accord avec l'origine des vésicules au niveau des membranes cellulaires des chondrocytes.
    Abstract: Zusammenfassung Matrixvesikel sind extrazelluläre, membrangebundene Teilchen, welche in der Matrix von verkalkendem Knorpel gehäuft vorkommen und welche in morphologischem Zusammenhang mit der Mineralablagerung in diesem Gewebe stehen. Matrixvesikel und Epiphysenzellen aus Röhrenknochen von Kalbsembryonen wurden mittels Collagenaseverdauung freigesetzt und durch Differential-Zentrifugierung getrennt. Die Vesikelpräparate waren reich an Lipidien und enthielten bedeutend mehr Sphingomyelin und Phosphatidylserin als die Zellfraktionen. Das molare Verhältnis Cholesterol/Gesamtlipide war in den Vesikeln höher als in den Zellen; dieser Befund stimmt mit der Tatsache überein, daß die Vesikel ihren Ursprung in den Plasmamembranen der Chondrozyten haben.
    Notes: Abstract Matrix vesicles are extracellular, membrane-bounded particles which are abundant in the matrix of calcifying cartilage and which are morphologically related to the deposition of mineral in this tissue. The matrix vesicles and cells of the epiphyses of the long bones of fetal calves were liberated by digestion with collagenase and separated by differential centrifugation. Vesicle preparations were found to be lipid-rich and to contain significantly more sphingomyelin and phosphatidyl serine than cellular fractions. The ratio, moles cholesterol to moles total phospholipid, was higher in vesicles than in cells, a finding which is consistent with vesicles having their origins in the plasma membranes of the chondrocytes.
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  • 16
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    Calcified tissue international 10 (1972), S. 269-279 
    ISSN: 1432-0827
    Keywords: Calcification ; ATP ; Magnesium ; Plaque ; Amorphous
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé L'injection sous-cutanée de solutions de Ca ATP provoque, chez le Rat, la formation de plaques rugueses et circonscrites, de couleur blanche, contenant du phosphate de calcium amorphe (Ca/P 1.3, 1.5). Des dépôts denses, en forme de bâtonnets, orientés le long des éléments fibreux, entourent les vaisseaux sanguins et sont situés dans le tissu conjonctif souscutané. La réaction observée est proportionnelle à la dose utilisée, la quantité de calcium de la plaque étant environ 100 fois celle de la quantité injectée. Ces résultats semblent indiquer que le phosphate de calcium, formé à partir du Ca ATP, dans le tissu sous-cutané actif en ATP-ase, est susceptible de provoquer un phénomène de cristallisation par nucléation. L'injection d'une solution de Ca Cl2, ayant la même concentration en calcium que la solution Ca ATP ou d'une solution de phosphate de sodium, ayant la même concentration en phosphore que Ca ATP, ne provoque pas de plaques. Cependant, l'injection d'une solution contenant du Ca2+ et du PO 4 3− forme de la plaque, en quantité inférieure à celle provoquée par l'injection de Ca ATP. A l'aide d'une dose d'injection type, contenant des concentrations accrues de magnesium, on observe la formation de plaques dont la taille et le poids en cendres sont inversement proportionnels au rapport Mg/Ca de la solution injectée. Dans ce système, il semble que le rapport Mg/Ca puisse affecter le processus de calcification et qu'il puisse aussi inhiber la calcification de tissus mous, en controlant les rapports locaux Mg/Ca.
    Abstract: Zusammenfassung Die subkutane Injection von CaATP-Lösungen in Ratten führte zur Bildung von weißen, umschriebenen, sandigen Plättchen, welche amorphes Calciumphosphat enthielten (Ca/P 1,3; 1,5). Dichte, rutenförmige Ablagerungen fanden sich entlang den fibrösen Elementen und umgaben Blutgefäße im subkutanen Bindegewebe. Diese Reaktion hing von der Dosis ab; die Menge des Calciums in den Plättchen entsprach etwa der hundertfachen eingespritzten Menge. Diese Ergebnisse lassen vermuten, daß das Calciumphosphat, welches im ATPase-aktiven subcutanen Gewebe aus CaATP gebildet wurde, als Keim für die Kristallisation wirken kann. Die Injektion einer Lösung von CaCl2, welche dieselbe Konzentration hatte wie das Calcium in der CaATP-Lösung, oder einer Natriumphosphatlösung, welche dieselbe Phosphorkonzentration wie CaATP hatte, erzeugte keine Plättchen. Hingegen erzeugte die Injektion einer Lösung, welche Ca2+ und PO 4 3− enthielt, Plättchen, die jedoch kleiner waren als diejenigen nach der Injektion von CaATP. Bei Verwendung einer Standard-Injektionsdosis, welche zunehmende Mengen von Magnesium enthielt, wurden Plättchen gebildet, deren Größe und Aschgewicht umgekehrt proportional zum Mg/Ca-Verhältnis in der eingespritzten Lösung waren. Die Ergebnisse bei diesem System lassen vermuten, daß das lokale Mg/Ca-Verhältnis den Kalzifikationsprozeß beein-flussen kann. Aus diesen Befunden folgt, daß es möglich sein könnte, die Weichteilverkalkung durch die Kontrolle der lokalen Mg/Ca-Verhältnisse zu hemmen.
    Notes: Abstract Injection of CaATP solutions subcutaneously in rats resulted in the formation of white, circumscribed, gritty plaques containing amorphous calcium phosphate (Ca/P 1.3–1.5). Dense, rod-shaped deposits were oriented along the fibrous elements and surrounding blood vessels in the subcutaneous connective tissue. The response was dose related, the amount of plaque calcium being about 100 times the amount injected. These results suggest that the calcium phosphate formed from CaATP in the ATPase active subcutaneous tissue may nucleate crystallization. Injection of a solution of CaCl2 having the same concentration as the calcium in the CaATP solution, or of a sodium phosphate solution having the same concentration of phosphorus as the CaATP, did not produce plaques. However, injection of a solution containing both Ca2+ and PO 4 3− produced plaques, although smaller than those formed by injection of CaATP. Using as standard CaATP injection dose containing increasing amounts of magnesium, plaques were formed whose size and ashed weight were inversely proportional to the Mg/Ca ratio in the solution injected. In this system, the results suggest that the local ratio of Mg/Ca may affect the calcification process. A corollary to this conclusion is that it may be possible to inhibit soft tissue calcification through control of the local Mg/Ca ratios.
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  • 17
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    Calcified tissue international 16 (1974), S. 93-107 
    ISSN: 1432-0827
    Keywords: Dentinogenesis ; Globules ; Pyrophosphatase ; Calcification ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract Three-day-old rats were fixed by perfusion with glutaraldehyde and thin slices were cut of the first molar germs. The slices were treated with EDTA and “activated” with buffered solutions containing Mg2+, Ca2+ or Zn2+. Incubation was carried out in buffered solutions (pH 8.5) containing inorganic pyrophosphate and Pb2+. In the Mg2+-activated specimens incubation products were localized to the plasma membranes in the stratum intermedium and the subodontoblastic area. Lead deposits were found on the periphery of the dentinal globules. Incubation products were more randomly distributed in Ca2+-activated specimens whereas those activated with Zn2+ displayed a deposition of lead precipitates mainly corresponding to that seen after activation with Mg2+. The findings are discussed in reference to the localization of alkaline phosphatase in the dentin-producing tissues and it is proposed that the results are indicative of the presence of an inorganic pyrophosphatase in these tissues.
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    Calcified tissue international 16 (1974), S. 169-182 
    ISSN: 1432-0827
    Keywords: Histochemistry ; Alkaline phosphatases ; Calcification ; Bone ; Teeth
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract Activity of alkaline phosphatases in unfixed cold microtome setions from the lower first molar area of newborn mice was recorded by histochemical methods. A substrate specificity test included the following phosphate compounds: ATP, CTP, GTP, UTP, ADP, AMP, GP, PPi, MDP and naphthol AS-TR phosphate. Intense staining was obtained in osteoblasts, stratum intermedium of the enamel organ and odontoblasts with all the substrates, except PPi and MDP. Staining of skeletal muscle fibres was obtained only with triphosphates as substrates. Addition of-SH groups decreased the hydrolysis of triphosphate compounds in cells involved in mineralization while the hydrolysis of monophosphate was inhibited. In contrast triphosphatase activity in striated muscle was enhanced when-SH compounds were added. Demineralization with EDTA diminished the cytoplasmic staining but induced a nuclear staining in hard tissue forming cells when triphosphates were used as substrates. No cytoplasmic and only slight nuclear staining was seen with GP or AMP as substrates. The triphosphate hydrolyzing capacity of tongue muscle fibres was, however, increased after the decalcification treatment. Addition of Mg2+ ions to the incubation media distinctly lowered the hydrolysis of triphosphates in the investigated tissues whereas the hydrolysis of ADP, AMP, GP and naphthol AS-TR phosphate remained unchanged. In view of the findings the triphosphatase activities at alkaline pH of muscle fibres and of cells related to hard tissue formation are considered to be due to activity of separate enzymes. The orthophosphate liberating enzyme activities at alkaline pH in osteoblasts, stratum intermedium and odontoblasts may be expressions of the catalytic functions of one common enzyme. Furthermore, the results indicate that CaATP might be the substrate used by the alkaline ATPase in mineralizing areas.
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  • 19
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    Calcified tissue international 13 (1973), S. 63-72 
    ISSN: 1432-0827
    Keywords: Structure ; Poly(glycol monomethacrylate) ; Gel ; Implants ; Calcification
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Abstract L'effet de la structure physique et des modification chimiques de gels de poly(glycol monométhacrylate) sur la calcification d'implants tests a été étudié. Alors que les modifications chimiques du poly(glycol monométhacrylate) osseux, obtenu par introduction de groupes formateurs d'ions, n'affectent pas le processus de calcification, on observe un effet net de la structure physique du polymère par action du rapport monomère: eau sur le processus de calcification des implants. Des gels homogènes et microporeux montrent rarement une calcification autor de l'implant; dans les gels macroporeux, la calcification s'observe massivement autour de l'implant, en cas de porosité élevée en son centre. Ce phénomène a été expliqué par la pénétration diverse par du tissu néoformé ainsi que par la possibilité de pénétration d'éléments nutritifs cellulaires, liée à la porosité de l'implant.
    Abstract: Zusammenfassung Die Wirkung der physikalischen Struktur und der chemischen Veränderung von Poly-(Glycol-Monomethacrylat)-Gelen auf die Verkalkung von Implantat-Proben wurde untersucht. Die chemische Veränderung der Poly(Glycol-Monomethacrylat)-Grundstruktur, hervorgerufen durch das Beifügen ionogener Gruppen, hatte auf den Verkalkungsprozeß keine Wirkung; die physikalische Struktur des Polymers hingegen hatte eine markante Wirkung auf den Verkalkungsprozeß der Implantate, welche durch das Verhältnis Monomer: Wasser bestimmt wurde. Homogene und kleinporöse Gele zeigten ganz ausnahmsweise eine Verkalkung am Rande des Implantats; in großporösen Gelen erfolgte massive Verkalkung am Rande des Implantats, bei höherer Porosität in dessen Zentrum. Dieses Phänomen wird zurückgeführt auf den unterschiedlichen Grad, in welchem das neu gebildete Gewebe das Implantat durchdringt und auf die verschiedene Zugänglichkeit der Nahrung der eindringenden Zellen, welche von der Porosität des Implantats abhängt.
    Notes: Abstract The effect of the physical structure and chemical modification of poly(glycol monomethacrylate) gels on the calcification of test implants has been studied. While the chemical modification of the poly(glycol monomethacrylate) backbone by the introduction of ionogenic groups did not affect the process of calcification, there was a substantial effect of the physical structure of the polymer, as determined by the monomer: water ratio, on the process of calcification of the implants. Homogenous and microporous gels showed calcification in the margin of the implant only exceptionally; in macroporous gels calcification occurred massively in the margin of the implant and in the case of a higher porosity in its centre. This phenomenon has been explained by the different degree to which the implant is penetrated by the newly formed tissue, as well as by the difference in accessibility of nutrition to the penetrating cells depending on the porosity of the implant.
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  • 20
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    Calcified tissue international 13 (1973), S. 335-337 
    ISSN: 1432-0827
    Keywords: Bone ; Morphogenesis ; Calcification
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
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  • 21
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    Calcified tissue international 14 (1974), S. 31-48 
    ISSN: 1432-0827
    Keywords: Bone ; Cartilage ; Calcification ; Collagen ; Phosphate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Une méthode pour l'étude de la croissance des os longs de foetus de rat, en culture d'organe, dans un milieu chimiquement défini, a été mise au point. Les extrémités cartilagineuses et les parties centrales de l'os sont analysées séparément pour leur croissance et minéralisation en étudiant leur contenu en collagène, calcium et phosphate, poids sec, et incorporation de proline marquée en hydroxyproline. La croissance et la minéralisation des parties centrales osseuses sont plus lentes dans un milieu chimiquement défini qu'in vivo. La croissance peut être accélérée en ajoutant au milieu des acides aminés non essentiels, de l'albumine ou du sérum. Les extrémités cartilagineuses présentent une augmentation plus importante en poids et contenu en collagène que les parties centrales et l'adjonction de diverses substances a moins d'effet sur la croissance. La croissance et la minéralisation des parties centrales sont augmentées en élevant la concentration du milieu en phosphate de 1.5 à 4.5 mM, avec ou sans adjonction de sérum ou d'albumine. A une concentration faible de calcium (0.5 mM), la croissance et la minéralisation des parties centrales sont arrêtées. A une concentration faible en magnésium (0.5 mM), la minéralisation est augmentée, mais la croissance est arrêtée.
    Abstract: Zusammenfassung Es wird eine Methode beschrieben, mit welcher das Wachstum der Röhrenknochen von Rattenembryos in einem chemisch bestimmten Medium in Organkultur untersucht werden kann. Die Knorpelenden und Knochenschäfte wurden gesondert auf Wachstum und Mineralisation geprüft, indem Collagen-, Calcium- und Phosphatgehalt, das Trockengewicht und der Einbau von markiertem Prolin in Hydroxyprolin gemessen wurden. Wachstum und Mineralisation des Knochenschaftes waren langsamer in einem chemisch bestimmten Medium als in vivo. Das Wachstum konnte beschleunigt werden, indem dem Medium nicht-essentielle Aminosäuren, Albumin oder Serum beigegeben wurden. Die Knorpelenden zeigten eine viel stärkere Zunahme an Gewicht und Collagengehalt als die Schäfte, und Anreicherung des Mediums hatte weniger Wirkung auf ihr Wachstum. Das Wachstum und die Mineralisation der Knochenschäfte nahmen zu, wenn die Phosphatkonzentration im Medium zwischen 1,5 und 4,5 mM erhöht wurde, und zwar unabhängig davon, ob dem Medium Serum oder Albumin beigegeben wurde oder nicht. Bei niederer Calciumkonzentration (0,5 mM) im Medium wurden Wachstum und Mineralisation der Knochenschäfte beeinträchtigt. Bei niedriger Magnesiumkonzentration (0,5 mM) wurden die Mineralisation erhöht, das Wachstum hingegen gehemmt.
    Notes: Abstract A method for studying the growth of fetal rat long bones in a chemically defined medium in organ culture is described. Cartilage ends and bone shafts were analyzed separately for growth and mineralization by measuring the collagen, calcium, and phosphate content, dry weight, and incorporation of labeled proline into hydroxyproline. Growth and mineralization of the bone shaft were slower in a chemically defined medium thanin vivo. Growth could be enhanced by supplementation of the medium with non-essential amino acids, albumin or serum. Cartilage ends showed a greater increase in weight and collagen content than the shafts, and medium supplements had less effect on their growth. Bone shaft growth and mineralization were enhanced by increasing medium phosphate concentration over a range of 1.5 to 4.5 mM whether or not the medium was supplemented with serum or albumin. At a low medium calcium concentration (0.5 mM) bone shaft growth and mineralization were impaired. At a low magnesium concentration (0.5 mM) mineralization was enhanced, but growth was impaired.
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  • 22
    ISSN: 1432-0827
    Keywords: Dentin ; Calcification ; Pyrophosphate ; Enzyme
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Après incubation de coupes de germes de molaires de rats, fixés aux aldéhydes, dans une solution alcaline de pyrophosphate de plomb, une réaction positive de coloration au sulfure est localisée au niveau du front de minéralisation de la dentine, dans le stratum intermedium et les cellules sous-odontoblastiques. Au microscope électronique, le nombre et la taille de cristaux, en forme d'aiguilles, sont augmentés dans la zone en voie de minéralisation (denture intermédiaire). Un fin précipité est surtout observé dans les noyaux du stratum intermedium et les cellules sous-odontoblastiques. Les effects de l'EDTA, Zn2+, Ca2+, Mg2+ et citrate sont aussi étudiés et la probabilité d'activité en pyrophosphatase inorganique est discutée en fonction des dépôts de plomb observés. L'action d'une pyrophosphatase inorganique sur la précipitation du phosphate de plomb ne peut être exclue. Cependant, la réaction de coloration peut être aussi due à une absorption non catalysée de composé de plomb sur les cristaux d'apatite.
    Abstract: Zusammenfassung Schnitte von Ratten-Molarkeimen, die mit Aldehyd fixiert und in einer alkalischen Blei-Pyrophosphat-Lösung inkubiert wurden, zeigten an folgenden Stellen eine positive Sulfid-Färbungsreaktion: in der Mineralisierungsfront des Dentins, im Stratum intermedium, und in den subodontoblastischen Zellen. Elektronenmikroskopisch waren Anzahl und Größe der sichtbaren, nadelartigen Kristallite in der Mineralisationszone (intermediäres Dentin) erhöht. Ein feiner Niederschlag konnte vorwiegend in den Nuclei des Stratum intermedium und der subodontoblastischen Zellen beobachtet werden. Es wurde zudem die Wirkungsweise von EDTA, Zn2+, Ca2+, Mg2+ und Zitrat untersucht. Schließlich wird die Wahrscheinlichkeit einer Aktivität von anorganischer Pyrophosphatase im Zusammenhang mit den beobachteten Bleiablagerungen besprochen. Daß anorganische Pyrophosphatase bei der Fällung von Bleiphosphat eine Rolle Spielt, ist nicht auszuschließen. Allerdings kann die Farbreaktion auch durch nicht-katalysierte Adsorption der Bleiverbinding an die Apatitkristalle bedingt sein.
    Notes: Abstract After incubation of aldehyde-fixed sections of rat molar germs in an alkaline solution of lead pyrophosphate, a positive sulphide staining reaction was observed in the mineralization front of the dentin, in the stratum intermedium, and in the subodontoblastic cells. In the electron microscope, the number and size of visible needle-like crystallites was increased in the mineralization zone (intermediate dentin). A fine precipitate was observed predominantly in the nuclei of the stratum intermedium and subodontoblastic cells. The effects of EDTA, Zn2+, Ca2+, Mg2+ and citrate were also studied and the probability of inorganic pyrophosphatase activities is discussed in relation to the observed lead deposits. The interaction of an inorganic pyrophosphatase cannot be excluded in the precipitation of lead phosphate. However, the staining reaction may also be due to uncatalyzed adsorption of the lead compound onto the apatite crystals.
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  • 23
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    Calcified tissue international 5 (1970), S. 108-114 
    ISSN: 1432-0827
    Keywords: Calcification ; Microchemistry ; Osteoid ; Osteones ; Density ; Analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Abstract Les modifications chimiques qui ont lieu au cours de l'ossification ont été déterminées au moyen de l'analyse de quelques-uns des composants inorganiques tenant au liseré préosseux et aux ostéons, soit au stade initial de la calcification qu'au stade final. Les composants considérés ont été les suivants: azote et phosphore totaux, mucopolysaccarides (titulés comme héxosamines), collagène (titulé comme hydroxyproline) et eau. Rapportées ci-bien au poids qu'au volume, ces données analytiques ont fourni les informations suivantes: a) au cours de l'ossification du liseré préosseux, jusqu'au degré le plus complet de la calcification de l'ostéon, le taux d'hydroxyproline reste pratiquement constant; au contraire l'azote total acuse une légère diminution au moment où la calcification se complète; b) par rapport au liseré préosseux, les ostéons au stade initial de la calcification montrent une chute significative des mucopolysaccarides (héxosamines); c) une diminution remarquable de l'azote non-collagénique s'avére au cours de la phase où les ostéons complétent leur calcification; d) selon les prévisions, le phosphore, c'est à dire l'élément représentatif de la fraction minérale, va augmentant avec régularité dès que la calcification s'amorce jusqu'au moment où elle devient complète. En concluant, l'ossification au niveau des systémes d'Havers s'accompagne d'une chute des mucopolysaccarides au moment où la calcification s'amorce et d'une réduction remarquable d'un composant azoté non-collagénique lorsque la calcification se compléte.
    Abstract: Zusammenfassung Zum Nachweis der chemischen Veränderungen, die während des Verkalkungsprozesses im Knochen vorgehen, wurden einige anorganische und organische Komponenten am isolierten Osteoidsaum und an Osteonen im Anfangs- und im Endstadium der Verkalkung bestimmt. Es handelt sich dabei um Messungen von Gesamtstickstoff, Gesamtphosphor, Mucopolysacchariden (in Form von Hexosamin), Kollagen (in Form von Hydroxyprolin) und des Wassergehaltes. Die ermittelten Resultate, sowohl auf Gewicht als auf Volumen bezogen, lassen nachstehende Folgerungen zu: a) während des ganzen Ossifikationsprozesses vom Osteoidsaum bis zu den stark verkalkten Osteonen bleibt der Hydroxyprolin-Gehalt praktisch konstant, während jener des Gesamtstickstoffes gegen das Ende der Verkalkung leicht zurückgeht; b) im Vergleich zur nicht-verknöcherten Vorstufe zeigen teilweise verkalkte Osteone eine signifikante Abnahme von Hexosamin; c) wurden wenig verkalkte mit stark verkalkten Osteonen verglichen, so konnte bei den letztgenannten eine beträchtliche Abnahme des nicht-kollagengebundenen Stickstoffes beobachtet werden; d) wie zu erwarten war, nimmt der Gehalt an anorganischem Phosphor im Verlaufe der Verkalkung regelmäßig zu. Zusammenfassend kann gesagt werden, daß die an isolierten Haversschen Systemen untersuchten Verkalkungsvorgänge im Anfangsstadium durch eine Abnahme der Mucopolysaccharide und am Ende der Verkalkung durch eine Verminderung des nicht-kollagen-gebundenen Stickstoffes geprägt sind.
    Notes: Abstract In order to establish the chemical modifications which may occur, at a microscopic level, during the calcification process in bone, some inorganic and organic components have been determined in isolated samples of osteoid tissue and in osteones at the initial and final stage of calcification. Total nitrogen, total phosphorus, mucopolysaccharides (as hexosamine), collagen (as hydroxyproline) and water content have been determined on both a weight and volume basis in these materials. The following conclusions can be drawn from the analytical data: a) throughout the calcification process from osteoid tissue to the osteones at the highest degree of mineralization, hydroxyproline remains practically constant, while total nitrogen reveals a slight decrease as calcification goes to completion; b) partially calcified osteones show a significant decrease of hexosamine, compared with osteoid tissue; c) a dramatic decrease of non-collagenous nitrogen has been observed in highly calcified osteones compared with those calcified to a lesser degree; d) inorganic matter (phosphorus), as expected, regularly increases from osteoid tissue to highly calcified osteones. Studied at the level of isolated Haversian systems, calcification is associated with a decrease of mucopolysaccharides at its onset and a decrease of a non-collagenous, nitrogencontaining material near its completion.
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  • 24
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    Calcified tissue international 6 (1970), S. 20-31 
    ISSN: 1432-0827
    Keywords: Calcification ; Metals ; Apatite ; Collagen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Plusieurs sels métalliques (par ex., PbCl2, HoCl3, FeCl2, CrCl3) favorisent la précipitation d'apatite lorsqu'ils, sont ajoutés à une solution calcifiante. Toutefois, seuls certains d'entre eux (par ex., PbCl2, HoCl3) ont cette même propriété lorsqu'ils sont administrés à des rats. Lorsqu'injecté par voie sous-cutanée, le FeCl2 se dépose surtout à la surface de fibrilles collagènes bien développées. Il augmente les concentrations locales de calcium et de phosphore sans toutefois produire d'apatite. Au contraire, l'acétate de plomb administré de la même façon produit rapidement l'accumulation d'une substance cristalline (probablement du triphosphate de, plomb); il se dépose autour des faisceaux collagènes et endommage d'une façon plus marquée que le FeCl2 les éléments cellulaires du tissu, conjonctif;, finalement, il conduit à la formation d'apatite.
    Abstract: Zusammenfassung Viele Metallsalze (z. B. PbCl2, HoCl3, FeCl2, CrCl3) fördern in einer geeigneten Lösung die Ausfällung von Apatit; werden sie jedoch Ratten verabfolgt, so entfalten nur einige (z. B. PbCl2, HoCl3), diese Wirkung. Nach subcutaner Injektion ist FeCl2 größtenteils an der Oberfläche gut geformter kollagener Fibrillen abgelagert; es erhöht die örtliche Konzentration von Calcium und Phosphor, führt aber nicht zur Bildung von Apatit. Andererseits ruft Bleiacetat (in gleicher Weise verabreicht) eine frühe Anhäufung von kristallinem Material hervor (wahrscheinlich Bleitriphosphat); es lagert sich um Kollagenbündel herum ab und schädigt die Bindegewebszellen mehr als FeCl2. Schließlich führt es zu Apatitbildung.
    Notes: Abstract Many metallic salts (e.g., Pbcl2, HoCl3, FeCl2 CrCl3) favor the precipitation of apatite when added to a calcifying solution; however, only some of them (e.g., PbCl2, HoCl3) have the same actionin vivo. FeCl2 injected subcutaneously is deposited mostly on the surface of well-formed collagen fibrils; it increases the local concentrations of calcium and phosphorus but does not produce apatite. On the other hand, lead acetate (administered by the same route) produces an early accumulation of a crystalline material (probably lead triphosphate); it is deposited around collagen bundles and has, a more damaging effect on the cellular components of connective tissue than FeCl2. Eventually, it gives way to apatite formation.
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  • 25
    ISSN: 1432-0827
    Keywords: Bone ; Epiphyses ; Calcification ; Physiologic ; Phospholipids ; Phosphorus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Neuf polets, âgés de huit semaines, ont reçu 1 mCi de32P orthophosphate par voi intrapéritonéale. Ils ont été sacrifiés 2, 14, 38, 86 et 169 heures asprès injection. Les épiphyses des os longs ont été prélevées et séparés en cartilage au repos, cartilage en voie de prolifération, cartilage en voie de calcification et os spongieux primitif. Les lipides sont extraits: chaque tissu est déminéralisé et les lipides sont extraits à nouveau. On détermine ainsi le contenu en lipides totaux et en phospholipides, ainsi que leurs divers types et l'activité spécifique relative: Le contenu lipidique total de tous les tissus épiphysaires est de 1,35 à 4,52% en poids sec de matrice déminéralisée. La fraction phospholipipidique constitue environ la moitié des lipides. Dans les régions à contenu élevé en calcium, plus de phospholipides sont extraits après déminéralisation qu'avant. Des phospholipides neutres constituten 80–90% des phospholipides totaux dans les extraits réalisés avant déminéralisation, et seulement 48–65% dans les extraits après déminéralisation. La quantité des phospholipides, éthanolamine et sérine, est variable dans les diverses zone épiphysaires. La quantité et les types de phospholipides et leur rapport avec le degré de calcification concordent avec les résultats publiés pour les tissus de veaux. Les courbes d'activité spécifique démontrent une activité réduite au niveau de cartilage au repos et des échange très actifs en phospholipides dans les trois autres zones épiphysaires. Les divers types de phospholipides ont des activités métaboliques nettement différentes les uns par rapport aux autres. Les modes d'échanges particuliers de la phosphatidyle ethanolamine, de la phosphatidyle sérine et de la phosphatidyle inositol, au niveau du cartilage en voie de prolifération et de calcification, suggérent un rôle spécial de ces lipides dans le mécanisme de las croissance et de la calcification.
    Abstract: Zusammenfassung Neun achtwöchige Hühner erhielten intraperitoneal 1 mCi32P-Orthophosphat und wurden 2, 14, 38, 86 und 169 Std nach der Injektion getötet. Die Epiphysen der Röhrenknochen wurden seziert und ruhende, proliferierende und verkalkende Knorpel, sowie primäre Spongiosa voneinander getrennt. Die Lipide jeder Zone wurden extrahiert, jedes Gewebe wurde demineralisiert und die Lipide erneut extrahiert. Der Gehalt der Extrakte an Gesamtlipden und Phospholipiden sowie die Art der Phospholipide wurden bestimmt und die relative spezifische Aktivität: gemessen. Der Gehalt an Gesamtlipiden aller epiphysischen Gewebe betrug 1,35–4,52% des Trockengewichtes der demineralisierten Matrix. Phospholipide machten ungefähr die Hälfte der Gesamtlipide aus. In den Zonen mit hohem Calciumgehalt konnten mehr Phospholipide nach der Demineralisation als vorher extrahiert werden. Die neutralen Phospholipide entsprachen in vor der Demineralisation erhaltenen Extrakten 80–90% und in jenen nach der Demineralisation nur 48–65% der gesamten Phospholipide. Die Aethanolamin- und Serinphospholipidmengen variierten bedeutend in den verschiedenen Zonen der Epiphyse. Die Menge und die Art der Phospholipide und ihr Verhältnis in bezug auf Verkalkungsgrad waren in Einklang mit den Werten, die für das Kalb angegeben werden. Die Kurven der relativen spezifischen Aktivität zeigten ein träges metabolisches Muster im ruhenden Knorpel und einen sehr aktiven Phospholipidumsatz in den drei anderen Zonen der Epiphyse. Die verschieden gearteten Phospholipide zeigten untereinander merklich verschiedene metabolische Muster. Die speziellen Eigenschaften der Umsatzsmuster von Phosphatidyläthanolamin, Phosphatidylserin und Phosphatidylinositol in proliferierendem und verkalkendem Knorpel lassen vermuten, daß diese Lipide spezielle Funktionen im Wachstums- oder Verkalkungsprozeß ausüben.
    Notes: Abstract Nine eight-week old chicks were given32P orthophosphate, 1 mCi, intraperitoneally and killed 2, 14, 38, 86, and 169 hours after injection. Long bone epiphyses were dissected and separated into resting cartilage, proliferating cartilage, calcifying cartilages, and primary spongiosa. Lipids were extracted from each zone, each tissue was demineralized, and lipids were extracted again. The extracts were analyzed for total lipid and phospholipid content, types of phospholipids, and relative specific activity. Total lipid content of all epiphyseal tissues was 1.35 to 4.52% of the dry demineralized matrix weight. Phospholipid was about half the total. In the zones with higher calcium content more phospholipid was extracted after demineralization that before. Neutral phospholipids were 80 to 90% of the total phospholipids in predemineralization extracts and only 48 to 65% in extracts after demineralization. The amount of ethanolamine and serine phospholipids varied considerably in different epiphyseal zones. The amount and types of phospholipid and their relation to degree of calcification corroborated data reported for the calf. Relative specific activity curves revealed a sluggish metabolic pattern in resting cartilage and very active phospholipid turnover in the other three epiphyseal zones. The different types of phospholipids had markedly different metabolic patterns from each other. Special features of the turnover patterns of phosphatidyl ethanolamine, phosphatidyl serine, and phosphatidyl inositol in proliferating and calcifying cartilage suggest special roles of these lipids in the growth or calcification process.
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  • 26
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    Calcified tissue international 6 (1970), S. 162-167 
    ISSN: 1432-0827
    Keywords: Raman Spectroscopy ; Collagen ; Calcification
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Des spectres Laser de Raman de tibias de boeuf et de tendons de rat reconstitués ont été réalisés et comparés avec le spectre infra-rouge de tissu calcifié, et de collagène. Les raies les plus intenses dans le tissue calcifié sont liées aux systèmes phosphates, symétriques: cependant certains systèmes des corps vertébraux et les chaines secondaires du collagène sont aussi apparents. Il semble que la proline et la phénylalamine du collagène particitpent au spectre. Le spectre Raman du collagène reconstitué est difficile à distinguer du fond fluorescent. Seules 6 bandes distinctes ont pu, etre obtenues elles se répartissent entre les peptides et des chaines secondaires. Les différences êntre le collagène reconstitué et calcifié semblent provenir de la dénaturation partielle du premier dans le faisceau laser. Les autres différences semblent liées à des différences chimiques vraies.
    Abstract: Zusammenfassung Die Laser-Ramanspektren von Ochsentibia und von rekonstituierter Rattenschwanzsehne wurden aufgenommen und mit den Infrarotspektren von verkalktem Gewebe und Kollagen verglichen. Die intensivsten Ramanbanden der verkalkten Gewebe wurden von den symmetrischen Phosphatschwingungen verursacht; einige der Schwingungen des Grundgerüstes und der Seitenketten sind jedoch ebenfalls sichtbar. Es weist einiges darauf hin, daß sowohl das Prolin als auch das Phenylalanin des Kollagens zum Spektrum beitragen. Das Ramanspektrum Nur 6 klar abgetrennte Banden, die sich auf Peptide und Seitenkettenschwingungen verteilten, wurden erhalten. Die Unterschiede zwischen den Spektren von redonstituiertem und verkalktem Kollagen können auf eine teilweise Denaturierung des ersteren im Laserstrahl zurückgeführt werden. Andere Unterschiede scheinen rein chemischer Natur zu sein.
    Notes: Abstract Laser Raman spectra of ox tibia and of reconstituted rat tail tendon have been obtained and have been compared with the infrared spectra of calcified tissue and collagen. The most intense Raman bands in the calcified tissue originate from the symmetric phosphate modes; however, several of the backbone and side chain modes of collagen are also apparent. There is some evidence that both proline and phenylalamine in the collagen contribute to the spectrum. The Raman spectrum of reconstituted, collagen was difficult to separate from the fluorescence background. Only six distinct bands could be obtained, divided between peptide and sidechain modes. Differences between reconstituted and calcified collagen spectra may originate from partial denaturation of the former in the laser beam. Other differences seem to be genuine chemical manifestations.
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  • 27
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    Calcified tissue international 6 (1970), S. 173-182 
    ISSN: 1432-0827
    Keywords: Calcification ; Fluoride ; Aorta ; Calcium ; Phosphate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Le rapport entre le fluor et la calcification de l'aorte a été étudié chez le rat intact et au niveau d'une préparationin vitro de l'aorte thoracique, incubée dans du sérum. La vitamine D3 provoque une augmentation de dix fois la concentration en calcium et une augmentation de douze fois la concentration en phosphate de l'aorte. Le fluor n'a pas d'action sur le dépot du calcium, mais il freine l'augmentation du phosphore de l'aorte des animaux traités à la vitamine D3. Chez les rats témoins, le fluor n'affecte pas l'incorporation du calcium ou du phosphore. La concentration en fluor des aortes des rats, ne recevant que de l'huile de germe de blé par sonde gastrique, n'est pas modifiée par l'administration prolongée de 50 p.p.m. de F à l'eau potable. La vitamine D3 provoque une augmentation de neuf fois la concentration en fluor de l'aorte de rats recevant du fluor dans l'eau potable, lorsqu'on les compare à ceux soumis à la vitamine D3 et à l'eau distillée. Is apparait ainsi que l'exposition prolongée à de l'eau potable fluorée ne favorise pas un début de calcification aortique et n'induit pas de calcification par l'intermédiaire de la vitamine D3. La coloration de von Kossa démontre une calcification intense des aortes de rat recevant de la vitamine D3. Une absence totale de dépôts calciques est notée chez les rats recevant seulement de l'eau distillée. La coloration à la résorcine-fuchsine vert de méthyle, pour la mise en évidence de fibres élastiques, montre une destruction de ces dernières dans les régions de calcification chez les rats recevant la vitamine D3. Ces lésions des fibres élastiques ne sont pas visibles chez les rats ne recevant que du fluor.
    Abstract: Zusammenfassung Wir haben die Wirkung von Fluorid auf der Verkalkung der Aorta anhand folgender zwei Systeme untersucht: bei der Rattein vivo undin vitro an der Aorta thoracica, die in Serum inkubiert wurde. Durch Vitamin D3 wurde bei den Kontrollratten eine 10fache Erhöhung der Calcium-Konzentration und eine 12fache Zunahme des Phosphatgehaltes der Aorta verursacht; Fluorid beeinflußte diese Calcium-Ablagerung nicht, blockierte dagegen die Zunahme des Phosphors in der Aorta der mit Vitamin D3 behandelten Tiere. Bei den mit Maisöl behandelten Ratten beeinträchtigte Fluorid weder die Ablagerung von Calcium noch von Phosphor. Die Fluorid-Konzentration in den Aorten jener Ratten, die nur Maisöl durch die Magensonde erhielten, wurde selbst durch eine langfristige Einnahme von 50 ppm F enthaltendem Trinkwasser nicht beeinflußt. Die Aorten der mit Vitamin D3 behandelten Ratten, deren Trinkwasser Fluorid zugesetzt worden war zeigten im Vergleich zu den Vitamin D3-Ratten, die nur destilliertes Wasser erhielten, eine 9fache Zunahme der Fluoridkonzentration. Somit scheint es, daß Fluorid im Trinkwasser über lange Zeit eingenommen weder eine Verkalkung der Aorta auslöste, noch eine durch Vitamin D3 verursachte Verkalkung zu potenzieren vermochte. Mit der von Kossa-Färbung konnten ausgeprägte Aortenverkalkungen der mit Vitamin D3 behandelten Ratten nachgewiesen werden, wogegen keine pathologischen Kalkablagerungen bei jenen Ratten gefunden wurden, die nur destilliertes Wasser erhielten. Die für elastische Fasern spezifische Resorcin-Fuchsin-Methylgrün-Färbung zeigte Zerstörungen in den Verkalkungszonen bei den mit Vitamin D3 behandelten Ratten, welche aber bei den Tieren, die nur Fluorid erhielten, nicht vorhanden waren. Fluorid schien das histologische Bild der Aorten von Ratten mit Vitamin D3-Gaben nicht zu verändern. Imin vitro-Modell wurden Aortae thoracicae von Ratten während 24 Stdn in Rattenserum inkubiert, welches45Ca sowie 0,14, 0,56 und 1,12 ppm F enthielt. Alle drei Fluoridkonzentrationen hemmten die Aufnahme von45Ca in signifikanter Weise.
    Notes: Abstract The relation between fluoride and calcification of the aorta has been studied in two systems: the intact rat and anin vitro preparation of the thoracic aorta incubated in serum. Vitamin D3 produced a ten-fold increment in calcium concentration and a twelve-fold increase in phosphate levels of the dry aorta. Fluoride did not affect the deposition of calcium, but significantly blocked the increase in phosphorus in the aorta of the vitamin D3-treated animals. In control rats, fluoride did not affect the incorporation of either calcium or phosphorus. The concentration of fluoride in the aortas of rats receiving only corn oil by intubation was not affected by long term exposure to drinking water containing 50 ppm F. Vitamin D3 produced a nine-fold increase in fluoride concentration in the aorta of the rats receiving fluoride in the drinking water when compared to the vitamin D3 rats receiving distilled water. It appears that long-term exposure to fluoride in the drinking water neither initiates calcification in the aorta nor potentiates calcification induced by vitamin D3. Von Kossa stain showed pronounced calcification of the aortas in rats receiving vitamin D3 but none was seen in the rats receiving distilled water alone. Resorcin-fuchsin-methyl green stain for elastic fibers showed destruction in regions of calcification in rats receiving vitamin D3 but not in those receiving fluoride alone. Fluoride did not appear to alter the histological picture seen in the aortas of rats receiving vitamin D3. In thein vitro model, rat thoracic aortas were incubated for 24 hours in rat serum containing45Ca and 0.14, 0.56 and 1.12 ppm F. Fluoride at all levels significantly inhibited45Ca uptake.
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  • 28
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    Calcified tissue international 6 (1970), S. 239-248 
    ISSN: 1432-0827
    Keywords: Apatite ; Calcification ; Collagen ; Tendon ; X-ray diffraction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Des études de diffraction aux rayons X sont réalisées au niveau du tendon calcifié de la patte de dinde pour déterminer l'effet de la minéralisation sur certaines propriétés structurales du collagène. Le résultat le plus important indique que la première raie équatoriale du collagène de tendon calcifié, fraichement prélevé, présente une équidistance intermédiaire entre les valeurs de collagène déssèché et du collagène frais non calcifié. Comme cette équidistance parait traduire fidèlement le degré d'humidité du collagène, il semble que la minéralisation réduit la quantité d'eau associéein vivo avec le composant collagènique du tissu. La présence du minéral semble augmenter la résistance du collagène à une dénaturation thermique permanente.
    Abstract: Zusammenfassung Es wurden Röntendiffraktionsuntersuchungen an calcifizierten Truthahnbeinsehnen durch geführt, um die Wirkung der Mineralisation auf einige der strukturellen Eigenschaften von Collagen festzustellen. Die wichtigste Beobachtung war, daß die erste äquatoriale Reflexion von Collagen in frish herauspräparierten calcifizierten Sehnen einen d-Wert aufwies, der zwischen den Werten für trockenes Collagen und frisches, nicht mineralisiertes Collagen liegt. Da dieser d-Wert empfindlich auf den Feuchtigkeitsgrad des Collagens reagiert, lassen diese Resultate vermuten, daß die Mineralisation die Wassermenge reduziert, welche sich in vivo mit der Collagenkomponente im Gewebe verbinden kann. Es wurde auch beobachtet, daß die Anwesenheit von Mineral den Widerstand von Collagen gegen bleibende thermale Denaturierung heraufzusetzen scheint.
    Notes: Abstract X-ray diffraction studies were conducted on calcified turkey leg tendon to establish the effect of mineralization on some of the structural properties of collagen. The principal finding was that the first equatorial reflection of collagen in freshly-excised calcified tendon had a d-spacing intermediate between the values for dried collagen and fresh unmineralized collagen. Since this spacing is a sensitive monitor of moisture levels in collagen, the data suggest that mineralization reduces the amount of water than can associatein vivo with the collagen component in tissue. It was also found that the presence of mineral appears to increase the resistance of collagen to permanent thermal denaturation.
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  • 29
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    Calcified tissue international 7 (1971), S. 220-231 
    ISSN: 1432-0827
    Keywords: Bicarbonate ; Alkalosis ; Calcification ; Cartilage ; Carbonic anhydrase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Le mécanisme de l'élévation du (HCO 3 − ) dans les liquides extracellulaires du cartilage (Cfl) a été étudié au niveau, de métaphyses tibiales de Rat. Au cours d'étudesin vitro, les courbes pH- $$P_{CO_2 } $$ dans une lymphe synthétique ne sont pas modifiées de façon nette par des protéines-polysaccharides ou par une protéine cationique. (HCO 3 − ) de Cfl, aspiré à partir de pièces métaphysaires, incubées isolément, décroit rapidement en fonction du temps. Les résultats de ces deux expériences semblent infirmer un rôle des sécrétions cartilagineuses comme cause de gradients sang— Cfl (HCO 3 − ) in vivo. L'acétazolamide, administré à des ratsin vivo, réduit le gradient sang —Cfl (HCO 3 − ) jusqu'à, un seuil non dosable. Cette action ne peut être attribuée à l'acidose généralisée, produite par l'acétazolamide, étant donné que les rats témoins, ayant une acidose généralisée similaire, provoquée par un traitement à NH4Cl, présentent un gradient sang —Cfl (HCO 3 − ) net. La répartition de l'activité en anhydrase carbonique dans les tissus épiphysaires et métaphysaires de rats identiques est déterminée par micro-analyse. L'activité enzymatique n'est pas détectée dans des échantillons cartilagineux, mais est retrouvée, de façon significative, dans les structures adjacentes. L'activité en anhydrase carbonique, mesurée dans les structures adjacentes, est considérée comme les lieux de sécrétion d'HCO 3 − . Le rôle éventuel des capillaires épiphysaires et métaphysaires et des cellules osseuses dans la sécrétion d'HCO 3 − , est envisagé.
    Abstract: Zusammenfassung Der mechanismus, durch welchen (HCO 3 − ) in extrazellulären Knorpelflüssigkeiten (fl) der Wachstumsplatten von Rattentibiae erhöht ist, wurde untersucht. Beiin vitro Versuchen mit einer synthetischen Lymphe waren die pH- $$P_{CO_2 } $$ Kurven weder durch Proteinpolysaccharide noch durch kationisches Protein nachweisbar verändert. In Cfl, welche aus isolierten Inkubaten von Wachstumsknorpel entnommen wurden, nahm (HCO 3 − ) in Funktion der Zeit ebenfalls rasch ab. Die Resultate beider Experimente sprechen dagegen, daß die Knorpelsekretein vivo als Ursache der Blut-Cfl (HCO 3 − )- Gradienten in Betracht kommen. Acetazolamid, das Ratten verabreicht wurde, erniedrigte den Blut-Cfl (HCO 3 − )-Gradienten auf ein nicht mehr nachweisbares Niveau. Dieser Effekt konnte nicht einer durch Acetazolamid hervorgerufenen generalisierten Acidose zugeschrieben, werden, da Kontrollratten mit einem ähnlichen Grad von generalisierter Acidose, welche von einer NH4Cl-Behandlung herrührte, einen ansehnlichen Blut-Cfl (HCO 3 − )-Gradienten aufrechterhielten. Die Verteilung der Kohlensäureanhydrase-Aktivität in epiphysären und metaphysären Geweben von gleichartigen Ratten wurde durch Mikroanalyse bestimmt. Eine enzymatische Aktivität konnte in den Knorpelproben nicht nachgewiesen werden, wurde jedoch in signifikanten Mengen in den angrenzenden Geweben gefunden. Es wurde die Hypothese aufgestellt, daß die Stellen, wo diese Kohlensäureanhydrase-Aktivität in angrenzenden Geweben gemessen wurde, den Sekretionsstellen von HCO 3 − entspricht. Die mögliche Beteiligung von epiphysären und metaphysären Capillargefäßen und von Knochenzellen an, der HCO 3 − -Sekretion wird diskutiert.
    Notes: Abstract The mechanism by which (HCO 3 − ) is elevated in extracellular cartilage fluids (Cfl) of rat tibial growth plates was investigated. Inin vitro studies, the pH- $$P_{CO_2 } $$ curves in a synthetic lymph were not detectably altered by proteinpolysaccharides or by a cationic protein. Also, (HCO 3 − ) in Cfl aspirated from isolated incubates of growth cartilage decreased rapidly as a function of time. Results of both of these experiments mitigated against a role for cartilage secretions as the cause of blood-Cfl (HCO 3 − ) gradientsin vivo. Acetazolamide administered to ratsin vivo reduced the blood-Cfl (HCO 3 − ) gradient to an undetectable level. This effect could not be attributed to systemic acidosis produced by acetazolamide since control rats with a similar degree of systemic acidosis resulting from NH4Cl treatment, maintained a substantial blood-Cfl (HCO 3 − ) gradient. The distribution of carbonic anhydrase activity in epiphyseal and metaphyseal tissues of similar rats was determined by microassay. Enzymatic activity was not detected in cartilage samples, but was found in significant amounts in adjacent structures. This carbonic anhydrase activity measured in adjacent structures was hypothesized to represent sites of HCO 3 − secretion. The possible involvement in HCO 3 − secretion of epiphyseal or metaphyseal capillaries and bone cells is discussed.
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  • 30
    ISSN: 1432-0827
    Keywords: Calcification ; Physiology ; Dentin ; Glycoproteins ; Golgi ; Odontoblasts
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé La synthèse et la sécrétion de la glycoprotéine matricielle de la dentine sont étudiées par radioautographie des odontoblastes et de la dentine d'incisives de rats. Ces derniers reçoivent, par voie intraveineuse, du3H-fucose. A des intervalles de temps variés, ils sont sacrifiés par perfusion intra-cardiaque de glutaraldéhyde. Les radioautographies de specimens démineralisés sont préparées pour la microscopie optique et électronique. Des grains d'argent se situent au niveau de l'appareil de Golgi 5–10 minutes après injection, mais sont absents dans les autres régions. A 35 minutes, les grains sont visibles à la base du prolongement odontoblastique et dans les ramifications voisines, en association avec des granules allongés, limités par une membrane: quelques grains se localisent dans la matrice prédentinaire adjacente. A 4 heures, on observe une réaction de la jonction dentine-prédentine, où un matériel granulaire dense est associé aux fibres de collagène. Ces résultats confirment que l'odontoblaste synthétise une glycoprotéine contenant du fucose, et indiquent que le3H-fucose est ajouté a la glycoprotéine en voie de formation dans l'appareil de Golgi: cette glycoprotéine migre ensuite dans le prolongement odontoblastique, puis est déchargée dans la matrice. Une certaine quantité de glycoprotéine s'accumule dans la région où la prédentine se transforme en dentine. Ce matériel granulaire observé à ce niveau, pourrait indiquer un dépôt de glycoprotéine. Comme cette région coincide avec le front de minéralisation, le dépôt de glycoprotéine marquée pourrait coincider avec le début de cette minéralisation.
    Abstract: Zusammenfassung Synthese und Sekretion des Glucoproteins der Dentinmatrix wurden anhand von Autoradiographien der Odontoblasten und des zugehörigen Dentins an Rattenschneidezähnen untersucht. Zu diesem Zweck erhielten die Ratten3H-Fucose i.v. An verschiedenen Zeitpunkten danach wurden sie durch intrakardiale Perfusion mit Glutaraldehyd getötet. Autoradiographien von entkalkten Proben wurden anschließend für Licht-und EM-Autoradiographie präpariert. 5–10 min nach Injektion ist der Golgi-Apparat mit Silberkörnern bedeckt; die übrigen Regionen der Odontoblasten und des umgebenden Prädentins und Dentins sind jedoch frei davon. Nach 35 min werden die Körner auch über der Basis der Odontoblastenfortsätze und ihrer nächsten Verzweigungen beobachtet; sie sind verbunden mit membranbegrenzten, dort lokalisierten, länglichen Granula. Einige wenige Körner befinden sich über der angrenzenden Prädentinmatrix. Nach 4 Std zeigt sich über der Matrix eine Reaktion auf der Dentinseite der Prädentin-Dentin-Berührungszone, wo ein elektronenundurchlässiges, granuläres Material mit kollagenen Fasern verbunden vorliegt. Mit diesen Beobachtungen kann belegt werden, daß die Odontoblasten fucosehaltiges Glucoprotein synthetisieren und sie weisen darauf hin, daß sich3H-Fucose mit dem sich bildenden Glucoprotein im Golgi-Apparat verbindet. Dieses Glucoprotein wandert später zu den Odontoblastenfortsätzen und wird dann an die Matrix abgegeben. Ein großer Teil des Glucoproteins sammelt sich an jener Stelle an, wo Prädentin zu Dentin umgewandelt wird. Beim hier beobachteten, granulären Material kann es sich um den morphologischen Beweis für das abgelagerte Glucoprotein handeln. Da die Verkalkungsgrenze sich an dieser Stelle befindet, kann die Ablagerung von markiertem Glucoprotein mit der beginnenden Verkalkung in Zusammenhang gebracht werden.
    Notes: Abstract The synthesis and secretion of the matrix glycoprotein of dentin was investigated by radioautography of the odontoblasts and associated dentin in the rat incisor. To this end, rats received3H-fucose intravenously. At various times thereafter, they were sacrificed by intracardiac perfusion with glutaraldehyde. Demineralized specimens were then prepared for light and electron microscope autoradiography. Silver grains overlie the Golgi apparatus 5–10 min after injection, but are absent over other regions of the odontoblasts and adjacent predentin and dentin. By 35 min, grains are observed over the base of the odontoblastic processes and their nearby branches, in association with membrane-limited elongated granules located therein; a few grains are located over the adjacent predentin matrix. At 4h, a reaction is seen over the matrix on the dentin side of the predentin-dentin junction where an electron-dense granular material is associated with collagen fibers. These findings provide evidence that odontoblasts synthesize fucose-containing glycoprotein, and indicate that3H-fucose is added to forming glycoprotein in the Golgi apparatus; this glycoprotein later migrates to the odontoblastic processes and is then discharged into the matrix. Much of the glycoprotein accumulates at the site where predentin transforms into dentin. The granular material observed at this location may be morphological evidence of the glycoprotein being deposited. Since this is also the site of the mineralization front, the deposition of labeled glycoprotein may be related to the onset of mineralization.
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  • 31
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    Calcified tissue international 9 (1972), S. 67-79 
    ISSN: 1432-0827
    Keywords: Bone ; Calcium ; Calcification ; Mitochondria ; Cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Quatre vingt quinze pour cent du total du calcium et phosphate d'homogénats cellulaires, isolés mécaniquement de l'os, sédimentent avec des particules sub-cellulaires par centrifugation à 15000×G. Une méthode, destinée à isoler et à purifier partiellement cette fraction, riche en calcium, est mise au point par digestion enzymatique avec de la désoxyribonucléase et ultracentrifugation dans 70% de saccharose. Le fragment obtenu contient 10% de produit minéral, sous forme de complexe calcium-phosphate, et des protéines et lipides. Des quantités importantes de phospholipides et RNA sont notées, ainsi que des quantités faibles d'hexosamine et d'acide sialique. Les essais enzymatiques et la microscopie électronique indiquent que la fraction contient plusieurs types différents de particules cytophoniques, mais leur contenu en calcium n'a pu être déterminé.
    Abstract: Zusammenfassung Es wurde festgestellt, daß 95% des gesamten Calcium-und Phosphatgehaltes in Zellhomogenaten, welche mechanisch aus Knochen isoliert wurden, mit subzellulären Teilchen in einem Zentrifugenfeld von 15000×G sedimentieren. Zur Isolation und teilweisen Reinigung dieser calciumreichen Fraktion wurde eine Methode entwickelt, die auf enzymatischer Verdauung mit Desoxyribonuclease und Ultrazentrifugation mittels 70% Sucrose basiert. Der entstandene Niederschlag enthielt 10% Mineral, der in Form eines Calciumphosphat-Komplexes vorlag und einen hohen Gehalt an Protein und Lipid aufwies. Es fanden sich ferner signifikante Mengen von Phospholipid und RNS, dagegen nur kleine Mengen von Hexosamin und Sialsäure. Enzymbestimmungen und Elektronenmikroskopie zeigten, daß die gefundene Fraktion mehrere, sich voneinander unterscheidende Typen von Cytoplasmapartikeln enthielt; ihr Calciumgehalt konnte jedoch anhand der verfügbaren Resultate nicht bestimmt werden.
    Notes: Abstract Ninety-five percent of the total calcium and phosphate in homogenates of cells isolated mechanically from bone was found to sediment with subcellular particles in a centrifugal field of 15000×G. A method was devised for the isolation and partial purification of this calcium-rich fraction by enzymatic digestion with deoxyribonuclease and ultracentrifugation through 70% sucrose. The resultant pellet was 10% mineral, present as some form of calcium-phosphate complex, and was rich in protein and lipid. Significant amounts of phospholipid and RNA were present also, but only small amounts of hexosamine and sialic acid. Enzyme assays and electron microscopy indicated that the fraction contained several different types of cytoplasmic particles but those which contained calcium could not be determined from available data.
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  • 32
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    Calcified tissue international 5 (1970), S. 261-269 
    ISSN: 1432-0827
    Keywords: Calcification ; Hydroxyapatite ; Connective tissue ; Crystallization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé L'étude morphologique du minéral osseux au microscope électronique montre plusieurs microcristaux en forme de minces plaques, à côté des bien connues petites aiguilles. Par la méthode stéréoscopique, on peut démontrer que les petites aiguilles sont en effet des plaquettes vues selon la direction de la moindre épaisseur.
    Abstract: Zusammenfassung Die morphologische Untersuchung von Knochenmineral am Elektronemikroskop zeigt mehrere Mikrokristalle in Form von dünnen Plättchen, neben den bereits bekannten kleinen Nadeln. Mittels der stereoskopischen Methode kann nachgewiesen werden, daß es sich bei den kleinen nadelförmigen Kristallen in Wirklichkeit um Kantansichten von Plättchen handelt.
    Notes: Abstract In ultrathin sections of bone specimens observed in the electron microscope, many apatite microcrystals having a plate-like habit are clearly visible, besides the well-known needleshaped forms. Stereoscopic views demonstrate that the needle-like microcrystals are actually the edge view of small, thin platelets.
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  • 33
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    Calcified tissue international 5 (1970), S. 196-205 
    ISSN: 1432-0827
    Keywords: Carbonic anhydrase ; Calcification ; Physiology ; Mollusca
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Le manteau des moules d'eau douce est responsable du dépôt du calcaire de la coquille. Au moins 2 compartiments du calcium peuvent être mis en évidence dans ce tissu. Le premier correspond à la forme ionisée, le second est une forme liée qui peut être séparée par centrifugation d'un homogénat. Les échanges entre ces 2 compartiments sont étudiés. Dans les homogénats des variations de la pression partielle du CO2 entrainent des variations du pH insuffisantes pour expliquer le passage du calcium d'une forme vers l'autre. L'anhydrase carbonique contrôle ces échanges qui sont inhibés en présence de diamox. Le rôle physiologique de ce mécanisme est discuté.
    Abstract: Zusammenfassung Der Mantel der Süßwasser-Muschel ist für die Kalkablagerung in der Muschel-Schale verantwortlich. 1. Mindestens 2 Calcium-Kompartimente können in diesem Gewebe festgestellt werden. Das erste entspricht einer ionisierten Form, das zweite einer gebundenen Form, welche durch Zentrifugieren eines Homogenates abgetrennt werden kann. 2. Die Austausche zwischen diesen 2 Kompartimenten wurden studiert. Die Veränderungen der Homogenate, die durch Änderungen des CO2-Partialdruckes bedingt sind, genügen nicht, um den Übergang vom einen in das andere Kompartiment zu erklären. Diese Austausche werden durch die Kohlensäureanhydrase kontrolliert und bei Anwesenheit von Diamox gehemmt. 3. Die physiologische Rolle dieses Mechanismus wird diskutiert.
    Notes: Abstract The mantle of fresh water lamellibranchs is responsible for the deposition of calcium in the shell. 1. At least 2 calcium pools can be shown to occur in this tissue. The first corresponds to an ionised form, the second to a bound form which may be separated by the centrifugation of a homogenate. 2. Exchanges between these 2 compartments are studied. The variations of pH in homogenates as a result of changes in the partial pressure of CO2 cannot entirely explain calcium translocation from one pool to the other. These exchanges, which are inhibited in the presence of diamox, are controlled by carbonic anhydrase. 3. The physiological role of this mechanism is discussed.
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  • 34
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    Calcified tissue international 5 (1970), S. 270-276 
    ISSN: 1432-0827
    Keywords: Ultrastructure ; Cartilage ; Calcification
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Une solution de sulfate de chrome est utilisée à la fois comme fixateur, colorant et agent de déminéralisation pour l'étude ultrastructurale de cartilage, en voie de minéralisation. Cette technique permet de mettre en évidence un “fantôme cristallin” organique, en rapport avec chaque cristal. L'intérêt du sulfate de chrome comme agent de déminéralisation est souligné.
    Abstract: Zusammenfassung Bei Ultrastrukturuntersuchungen von mineralisierendem Knorpel wurde eine Chromsulfatlösung als Agens zur kombinierten Fixation, Färbung und Demineralisierung verwendet. Diese Technik zeigte das Vorhandensein eines organischen “Kristallschattens”, der jedem Kriställchen zugehört. Die Tauglichkeit von Chromsulfat als demineralisierendes Agens wird besprochen.
    Notes: Abstract A solution of chromium sulphate was used as a combined fixative, stain and demineralizing agent for the ultrastructural study of mineralizing cartilage. This technique revealed the presence of an organic ‘crystal ghost’ associated with each crystallite. The effectiveness of chromium sulphate as a demineralizing agent is discussed.
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  • 35
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    Calcified tissue international 6 (1970), S. 1-10 
    ISSN: 1432-0827
    Keywords: Bone ; Dentin ; Enamel ; Lipids ; Calcification
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Le but de cette étude est l'analyse des lipides des tissus calcifiés au niveau de la dentine et de l'émail bovins et de l'os cortical humain. Les lipides extraits des tissues pulvérisés sont analysés qualitativement par chromatographie sur colonne. Des échantillons ont été déminéralisés et une seconde extraction a permis de comparer les résultats obtenus avec ceux de la première analyse. Les acides gras des lipides osseux sont étudiés par chromatographie en phase gazeuse et comparés à ceux de l'os spongieux et des expaces médulaires. Les tissus calcifiés contiennent du cholestérol et ses esters, des monoglycérides, des diglycérides, des triglycérides, des acides gras libres et divers phospholipides. A part certains cas, et en particulier l'émail bovin, où l'on n'a pas pu identifier des phospholipides, ces derniers sont constitués par de la lécithine, la lyso-lécithine, l'éthanolamine de phosphatidyle, la sphingomyéline, ainsi que par des substances qui pourraient être de l'acide phosphatidique et de la cardiolipine. La sérine de phosphatidyle a pu être isolée de la dentine bovine, seulement après déminéralisation, mais a pu être extrait de l'os à la avant et, après traitement à l'EDTA. D'autres lipides sont recueillis après déminéralisation à l'EDTA et une seconde dé minéralisation. Les lipides totaux extraits sont d'environ 20.28 mg/100 grammes de dentine, 1.97 mg/100 grammes d'émail et 2005 mg/100 grammes, d'os humain. Le constituant lipidique principal de l'os cortical humain est le triglycéride et la composition en acide gras est identique à celle de l'os spongieux et de la moëlle.
    Abstract: Zusammenfassung Drei verschiedene Materialien wurden untersucht: bovines Dentin, boviner Schmelz und menschliche Corticalis. Die aus den pulverisierten Geweben extrahierten Lipide wurden qualitativ mittels Säulenchromatographie analysiert. Die Proben wurden ebenfalls demineralisiert und ein zweites Mal extrahiert, damit die Resultate mit denjenigen vor der Demineralisation verglichen werden konnten. Die Fettsäuren der Knochenlipide wurden mittels Gaschromatographie untersucht und mit den Fettsäuren der Spongiosa und des Markes verglichen. In den verkalkten Geweben fanden sich Cholesterol, Cholesterolester, Monoglyceride, Diglyceride, Triglyceride, freie Fettsäuren und verschiedene Phospholipide. Mit einigen Ausnahmen, wie z. B. in bovinem Schmelz, wo Phospholipide nicht nachgewiesen werden konnten, bestanden diese Phospholipide aus Lecithin, Lysolecithin, Phosphatidyläthanolamin, Lysophosphatidyläthanolamin, Phosphatidylinositol, Sphingomyelin und Substanzen, welche Phosphatidsäure und Cariolipin sein könnten. Aus bovinem Dentin konnte Phosphatidylserin nur nach Demineralisation extrahiert werden; aus Knochen ließ es sich jedoch sowohl vor wie nach EDTA-Behandlung entfernen. Zusätzliche Lipide wurden aus Proben gewonnen, wenn diese mit EDTA demineralisiert und ein zweites Mal extrahiert wurden. Die gesamte aus den Geweben extrahierte Lipidmenge betrug im Mittel 20,28 mg/100 g Dentin, 1,97 mg/100 g Schmelz und 2005 mg/100 g menschlichen Knochen. Der Hauptteil der Lipide aus menschlicher Corticalis bestand aus Triglyceriden und die Zusammensetzung der Fettsäuren entsprach jener im Mark und in der Spongiosa.
    Notes: Abstract Three different materials were studied: bovine dentin, bovine enamel, and human cortical bone. Lipids extracted from pulverized tissues were analyzed qualitatively by paper chromatography and quantitatively by column chromatography. Sample materials were also demineralized and extracted a second time so that results could be compared to those obtained prior to demineralization. Fatty acids of bone lipids were investigated by vapor phase chromatography and compared to the fatty acids of trabecular bone and bone marrow. Calcified tissues were found to contain cholesterol, cholesterol esters, monoglycerides, diglycerides, triglycerides, free fatty acids, and various phospholipids. With some exceptions, such as bovine enamel where phospholipids could not be identified, these included lecithin, lysolecithin, cephalin, lysocephalin, monophosphoinositide, sphingomyelin, and substances which might be phosphatidic acid and cardiolipin. Phosphatidylserine was extractable from bovine dentin only after demineralization, but was removable from bone both before and after EDTA treatment. Additional lipids were obtained from sample materials if they were demineralized with EDTA and extracted a second time. The total lipids extracted from the tissues averaged 20.28 mg/100 g dentin, 1.97 mg/100 g enamel, and 2,005 mg/100 g human bone. The major portion of human cortical bone lipids was triglyceride and the fatty acid composition was similar to that of marrow and trabecular bone.
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    Calcified tissue international 9 (1972), S. 310-324 
    ISSN: 1432-0827
    Keywords: Strontium ; Calcification ; Collagen ; Nucleation ; Exchange
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Une matrice non calcifiée de tendon de bœuf fixe environ 2 μ moles de Sr2+/100 mg de matrice. La fixation de Sr2+ est inhibée par du Mg2+, du Ca2+ et de l'urée, mais n'est pas modifiée par le phosphate inorganique, le phosphonoacétate ou le méthylène-diphosphonate. Le Sr2+ inhibe la calcification réticulaire et cette inhibition est inversée par le Ca2+, mais non par HPO 4 2− . Bien que la formation réticulaire d'apatite de strontium ne soit pas induite par cette matrice, une précipitation élevée de Sr2+ est observée au niveau de la matrice déjà calcifiée. Cette dernière ne nécessite pas l'addition de phosphate. Ce phénomène s'accompagne par une libération presque équimolaire de Ca2+ de la phase soluble et il est inhibé par des composés qui inhibent également les réactions d'échange du45Ca2+ et du32P-HPO 4 2− . Ces résultats semblent indiquer que le Sr2+ peut se fixer à la matrice par un processus sensible au Mg2+ et à l'urée, ainsi que par incorporation à la phase minérale liée à la matrice. Ce dernier mécanisme pourrait se produire par échange isoionique nécessitant l'adjonction de phosphate. Le rapport possible de ces observations avec les diverses étapes de la calcification est envisagé.
    Abstract: Zusammenfassung Nichtverkalkte Matrix aus Rindersehne bindet ungefähr 2 μMol Sr2+/100 mg Matrix. Die Aufnahme von Sr2+ wird durch Mg2+, Ca2+ und Harnstoff gehemmt, jedoch durch anorganisches Phosphat, Phosphonoacetat oder Methylendiphosphonat nicht beeinflußt. Sr2+ hemmt die Netto-Verkalkung, und diese Hemmung wird durch Ca2+, aber nicht durch HPO 4 2− verhindert. Obschon die Netto-Strontiumapatitbildung durch diese Matrix nicht angeregt wird, wurde eine erhöhte Sr2+-Aufnahme durch vorgängig verkalkte Matrix beobachtet. Für diese Aufnahme wird kein zusätzliches Phosphat benötigt; sie wird von einer nahezu äquimolaren Ca2+-Abgabe an die lösliche Phase begleitet und von Substanzen gehemmt, welche auch die45Ca2+- und32P-HPO 4 2− -Austauschreaktionen hemmen. Diese Resultate können in dem Sinne interpretiert werden, daß Sr2+ fähig ist, sich durch einen Mg2+-und Harnstoff-empfindlichen Vorgang, sowie durch Einbau in die Matrix-gebundene Mineralphase an die Matrix zu binden. Es wird vorgeschlagen, daß dieser Einbau durch einen heteroionischen Austauschmechanismus geschieht, welcher mit dem isoionischen Austausch, der zusätzlich Phosphat benötigt, nicht identisch ist. Es wird diskutiert, ob diese Beobachtungen möglicherweise mit einem in mehreren Schritten ablaufenden Verkalkungsprozeß im Zusammenhang stehen.
    Notes: Abstract Uncalcified matrix derived from beef tendon will bind approximately 2 μmoles Sr2+/100 mg matrix. Sr2+ uptake is inhibited by Mg2+, Ca2+ and urea but is not influenced by inorganic phosphate, phosphoacetate, nor methylenediphosphonate. Sr2+ inhibits net calcification and this inhibition is reversed by Ca2+ but not by HPO 4 2− . Although net strontium apatite formation is not induced by this matrix, an elevated Sr2+ uptake by previously calcified matrix was observed. The latter does not require added phosphate, is accompanied by a nearly equimolar release of Ca2+ to the soluble phase and is inhibited by compounds that also inhibit the45Ca2+ and32P-HPO 4 2− exchange reactions. These results are interpreted to indicate that Sr2+ can bind to the matrix by a Mg2+ and urea-sensitive process as well as by incorporation into the matrix-bound mineral phase. It is proposed that the latter occurs by a heteroionic exchange mechanism that is not identical to the isoionic exchange which requires added phosphate. The possible relationship of these observations to a multi-step calcification process is discussed.
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  • 37
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    Calcified tissue international 7 (1971), S. 277-289 
    ISSN: 1432-0827
    Keywords: Calcification ; Collagen ; Catalysis ; Inhibition ; Tendon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Les propriétés d'inhibition de la calcification réticulaire et des réactions d'échanges de H32PO4 et45Ca2+, induites par la matrice calcifiée de tendon de boeuf, ont été étudiées pour divers produits. L'inhibition des deux types de réaction, par la méthylènediphosphonate et une fraction dérivée de l'urine humaine peut être diminuée en augmentant la proportion de la phase minérale liée. Mg2+ n'inhibe pas les réactions d'échanges, mais l'inhibition de la calcification réticulaire peut être inversée en augmentant la concentration en Ca2+ de la phase soluble; mais une telle réaction ne peut être obtenue ni par le phosphate inorganique, ni en augmentant la proportion du minéral lié. Le phosphono-acétate inhibe la calcification réticulaire, mais non les réactions d'échanges, et l'inhibition n'est diminuée ni en augmentant la concentration en Ca2+ ou HOP4 2−, ni en augmentant la proportion du minéral lié. Les actions d'inhibition peuvent s'expliquer par leur interaction avec la matrice insoluble, bien que l'affinité pour le méthylènediphosphonate et l'inhibiteur urinaire soit plus grande que pour les autres produits testés. Un mécanisme catalytique hétérogène et multifonctionnel est proposé pour la calcification matricielle du tendon. Selon ce mécanisme, la calcification matrieielle est catalysée par une entité macromoléculaire, sensible à l'urée, qui contient un minimum de trois régions actives. La première est une région sensible au Mg et capable de se lier avec Ca2+, qui facilite la réaction avec HPO4 2− de la phase soluble pour constituer un complexe Ca−P au niveau d'une deuxième région sensible au phosphonoacétate. Le complexe Ca−P réagit ensuite avec une troisième région matricielle pour la formation de la phase minérale et la croissance cristalline. Les agrégats Ca−P, qui sont présents au niveau des régions en voie de croissance, fournissent les ions mobiles qui participent aux réactions d'échanges45Ca et H32PO4 2− et qui constituent aussi les zones de liaison pour le méthylènediphosphonate, ainsi que pour les inhibiteurs sériques et urinaires de la calcification.
    Abstract: Zusammenfassung Die Hemmeigenschaften von verschiedenen Substanzen in bezug auf effekte Verkalkung sowie die45Ca2+ und H32PO4 2− Austauschreaktionen, hervorgerufen durch verkalkte Rindersehnenmatrix, wurden untersucht. Die Hemmung beider Reaktionen durch Methylendiphosphonat und durch eine aus menschlichem Urin gewonnene Fraktion kann bei Erhöhung der Menge der gebundenen Mineralphase herabgesetzt werden. Mg2+ hemmt die Austauschreaktionen nicht; die Hemmung der effektiven Verkalkung durch Mg2+ kann jedoch aufgehoben werden, indem die Konzentration von Ca2+ in der löslichen Phase erhöht wird; dies gilt nicht, wenn anorganisches Phosphat zugefügt oder die Menge des gebundenen Minerals erhöht wird. Phosphonoacetat hemmt die effektive Verkalkung, nicht aber die Austauschreaktionen. Dabei wird die Hemmung weder durch Erhöhung der Konzentration von Ca2+ oder HPO4 2−, noch durch Erhöhung der Menge gebundenen Minerals vermindert. Die Hemmwirkungen können durch ihre Wechselwirkung mit der unlöslichen Matrix erklärt werden, obwohl die Affinität für Methylendiphosphonat und den Urin-Hemmkörper größer ist als für die anderen Substanzen. Ein polyfunktioneller, heterogener, katalytischer Mechanismus für die Sehnenmatrixverkalkung wird vorgeschlagen. Nach diesem Schema wird die Matriverkalkung durch einen Harnstoff-empfindlichen, makromolekulären Stoff katalysiert, der im Minimum drei aktive Zentren enthält. Das erste ist ein Mg-empfindliches, Ca2+-bindendes Zentrum, welches das zusammenwirken der löslichen Phase mit HPO2 2− erleichtert, um einen Ca−P-Komplex an einem zweiten, Phosphonoacetat-empfindlichen Zentrum zu bilden. Dieser Ca−P-Komplex reagiert darauf mit einem dritten Zentrum auf der Matrix, um die Bildung der Mineralphase auszulösen und das Kristallwachstum anzuregen. Die an den Wachstumsstellen vorliegenden Ca−P-Aggregate liefern jene mobilen Ionen, welche an den45Ca und H32PO4 2− Austauschreaktionen teilnehmen; diese bilden auch die Bindungsstellen für Methylendiphosphonat sowie für die Serum- und Urinverkalkungshemmer.
    Notes: Abstract The inhibitory properties of several compounds with respect to net calcification and the45Ca2+ and the H32PO4 exchange reactions induced by calcified bovine tendon matrix have been investigated. The inhibition of both reactions by methylenediphosphonate and a fraction derived from human urine can be decreased by increasing the amount of the bound mineral phase. Mg2+ does not inhibit the exchange reactions but the inhibition of net calcification by Mg2+ can be reversed by increasing the concentration of Ca2+ of the soluble phase but not by inorganic phosphate or by increasing the amount of bound mineral. Phosphonoacetate inhibits net calcification but not the exchange reactions and the inhibition is decreased neither by increasing the concentration of Ca2+ or HPO4 2− nor by increasing the amount of bound mineral. The inhibitory effects can be explained by their interaction with the insoluble matrix, although the affinity is greater for methylene diphosphonate and the urine inhibitor than for the other compounds. A polyfunctional heterogeneous catalytic mechanism for tendon matrix calcification is proposed. According to this scheme, matrix calcification is catalyzed by a urea-sensitive macromolecular assembly that contains a minimum of three reactive sites. The first is a Mg-sensitive, Ca2+-binding site that facilitates the interaction with HPO4 2− of the soluble phase to form a Ca−P complex at a phosphonoacetate-sensitive second site. This Ca−P complex then reacts with a third matrix site for mineral phase initiation and crystal growth. The Ca−P aggregates present in the growth sites provide those mobile ions which participate in the45Ca and H32PO4 2− exchange reactions and which also constitute the binding sites for methylenediphosphonate as well as the serum and urine calcification inhibitors.
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    Calcified tissue international 8 (1971), S. 83-86 
    ISSN: 1432-0827
    Keywords: Bone ; Strontium ; Calcium ; Vitamin D ; Calcification
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Des poulets sont nourris avec une alimentation contenant 0,5% de Ca et 0,5% de Sr, plus diverses concentrations de vitamine D3. La moitié des besoins en calcium pour la croisance corporelle chez le poulet est assurée par le Sr, tant que la concentration en Vitamine D3 est maintenue entre 500 et 1000 ICU/kg de nourriture. Les besoins totaux en calcium pour la croissance ne sont pas couverts par le Sr. Bien que Sr soit incorporé dans l'os lorsque l'alimentation renferme de faibles doses de vitamine D3, le contenu total en cendre, ainsi que le contenu en calcium, sont diminués.
    Abstract: Zusammenfassung Eine Untersuchung an Hühnern, welche Futter mit 0,5% Ca und 0,5% Sr und verschieden hohen Vitamin D3-Zusätzen erhielten, läßt vermuten, daß die Hälfte des für das Körperwachstum des Huhnes benötigent Ca durch Sr ersetzt werden kann, solange das Vitamin D3 in der Höhe von 500–1000 IE/kg Futter gehalten wurde. Die Gesamtmenge des für das Knochenwachstum benötigten Ca konnte jedoch nicht durch Sr ersetzt werden. Obschon Sr bei niederem Vitamin D3-Gehalt der Nahrung im Knochen eingebaut wurde, waren sowohl der totale Aschegehalt als auch der Calciumgehalt vermindert.
    Notes: Abstract An investigation involving chicks fed diets with 0.5% Ca and 0.5% Sr supplemented with various levels of vitamin D3 suggests that one-half of the Ca requirement of body growth in the chick is met by Sr as long as the vitamin D3 level was maintained at 500 to 1000 ICU/kg foodstuff. The entire Ca requirement for bone growth could not, however, be met by Sr. Even though Sr was incorporated into the bone when low levels of vitamin D3 were fed in the diet, the total ash content, as well as Ca content, was reduced.
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    Calcified tissue international 8 (1971), S. 154-164 
    ISSN: 1432-0827
    Keywords: Calcium ; Phosphate ; Fluoride ; Calcification ; Tooth Enamel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Les dépôts simultanés en calcium, phosphate et fluorure et le taux de formation en ion hydrogène, pendant la minéralisation, de surfaces d'émail, attaquées par des acides, sont mesurés du point de vue cinétique dans un système fermé. Le taux de dépôt en calcium et phosphate, à partir de la solution, dépend des concentrations en fluorure et du pH. Les proportions de calcium par rapport au phosphate et de calcium par rapport au fluor suggère la formation de fluoroapatite ou de fluorohydroxyleapatite sur l'émail. L'adjonction d'ions hydroxyles pour maintenir un pH constant au moment du dépôt minéral, dépasse les ions phosphates totaux qui se déposent. Ce fait semble indiquer la possibilité d'une hydrolyse de phosphate acide pendant le dépôt minéral.
    Abstract: Zusammenfassung In einem geschlossenen System wurden die gleichzeitigen Ablagerungen von Calcium, Phosphat und Fluorid sowie die Geschwindigkeit der Wasserstoffionenproduktion während der Mineralbildung an säureverätzten Zahnschmelz-Oberflächen kinetisch gemessen. Die Ablagerungsgeschwindigkeiten von Calcium und Phosphat aus der Lösung hingen von den Fluoridkonzentrationen und dem pH ab. Das Verhältnis von Calcium zu Phosphat und von Calcium zu Fluorid zeigte die Bildung von Fluorapatit oder Fluorhydroxyapatit auf dem Zahnschmelz an. Die Hydroxylionenzugaben, welche nötig waren, um das pH während der Mineralablagerung konstant zu halten, überschritten die totalen, aus der Lösung ausgeschiedenen Phosphationen. Dies weist auf die Möglichkeit hin, daß während der Mineralablagerung eine saure Phosphat-Hydrolyse stattfindet.
    Notes: Abstract Concurrent calcium, phosphate and fluoride depositions, and the rate of hydrogen ion production, during formation on acid etched enamel surfaces were kinetically measured in a closed system. The deposition rate of calcium and phosphate from solution was dependent on the fluoride concentrations and pH. The proportions of calcium to phosphate and calcium to fluoride indicated fluorapatite or fluorhydroxyapatite formation on the enamel. The hydroxyl ion additions to maintain constant pH, concurrent with mineral deposition, exceeded the total phosphate ions deposited from solution. This indicates the possibility that acid phosphate hydrolysis occurs during mineral deposition.
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    Calcified tissue international 8 (1971), S. 287-303 
    ISSN: 1432-0827
    Keywords: Calcification ; Bone ; Matrix ; Apatite ; Nucleation ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Du collagène d'os compact de mouton est préparé par décalcification dans I'EDTA et à partir de tendons de queux de rats, par extraction dans l'acide acétique et reconstitution dans NaCl. Le dépôt d'apatite dans le collagène osseux de mouton dans une solution de calcification métastable est étudié chimiquement et par microscopie électronique. Le collagène osseux est un bon catalyseur de nucléation pour le dépôt minéral, alors que le collagène de tendons de rat ne l'est pas. Le dépôt minéral du collagène osseux se produit en deux phases cinétiques séparées, une phase rapide de nucléation et une croissance cristalline, donnant naissance à de petits ilots calcifiés et une seconde phase lente de croissance dans des régions ne comportant pas de zones catalytiques. La seconde phase de dépôt minéral paraît être le résultat d'une diffusion inhibée d'ions à travers les fibrilles collagènes alignées, laissant de larges régions de collagène sans minéral, bien que le tampon reste hautement sursaturé. La microscopie électronique permet de penser que les zones de catalyse pourraient avoir un rapport avec la périodicité de 640 Å de collagène, mais l'importance d'un matériel noncollagènique, lié au collagène, n'est pas à exclure. L'activité catalytique faible du collagène reconstitué n'est pas liée à la présence d'inhibiteurs faiblement liés, bien que des inhibiteurs puissent être intimement liés à ce type de collagène, qui pourrait être absent du collagène osseux. La différence d'activité catalytique pourrait intervenir dans la calcification physiologique. Une hypothèse plus générale pour la nucléation de la phase minérale dans les systémes biologiques est nécessaire.
    Abstract: Zusammenfassung Kollagen wurde aus kompaktem Schafsknochen mittels EDTA-Entkalkung und aus Rattenschwanzsehnen durch Essigsäureextraktion und Rekonstitution mit NaCl gewonnen. Die Apatitablagerung aus einer metastabilen Verkalkungslösung auf Schafsknochenkollagen wurde chemisch und im Elektronenmikroskop untersucht. Es zeigte sich, daß das Knochenkollagen ein guter Nukleationskatalysator für die Mineralablagerung ist, was beim Rattenschwanzkollagen nicht zutraf. Im Knochenkollagen erfolgte die Mineralablagerung in zwei getrennten kinetischen Phasen: einer raschen Phase der Nukleation und des Kristallwachstums, welche kleine verkalkte Inseln entstehen läßt, und einer zweiten langsamen Phase, welcher das Wachstum in Bezierken, die keine katalytischaktiven Stellen einschließen, zuzuschreiben ist. Diese zweite Phase der Mineralablagerung wird als Resultat einer verminderten Ionendiffusion durch die enganeinanderliegenden Kollagenfibrillen angesehen, wodurch weite Kollagenbereiche ohne Mineral bleiben, obwohl der Puffer stark übersättigt ist. Elektronenmikrographien ließen vermuten, daß die katalytischaktiven Stellen in einem gewissen Verhältnis zur 640 Å-Periodizität des Kollagens stehen; es konnte jedoch nicht ausgeschlossen werden, daß nicht-kollagenhaltiges Material, welches an Kollagen gebunden ist, ebenfalls eine Rolle spielt. Die schlechte katalytische Aktivität des rekonstituierten Kollagens konnte nicht auf die Anwesenheit von schwachgebundenen Hemmstoffen zurückgeführt werden, obwohl Inhibitoren stark an dieses Kollagen gebunden sein könnten, die jedoch im Knochenkollagen nicht vorhanden sind. Die Unterschiede in der katalytischen Aktivität können mit der physiologischen Verkalkung in Beziehung stehen. Eine allgemeinere Hypothese für die Nukleation einer Mineralphase in biologischen Systemen wäre erforderlich.
    Notes: Abstract Collagen was prepared from compact sheep bone by decalcification with EDTA and from rat tail tendons by acetic acid extraction and reconstitution with NaCl. The deposition of apatite in sheep bone collagen in a metastable calcification solution was studied chemically and by electron microscopy. The bone collagen was shown to be a good nucleation catalyst for mineral deposition, while rat tail collagen was a poor catalyst. Mineral deposition in bone collagen occured in two separate kinetic phases, a rapid phase of nucleation and crystal growth, giving rise to small calcified islands, and a second slow phase, ascribed to growth in regions not involving the catalytic sites. This second phase of mineral deposition is considered to be the result of impaired ion diffusion through the closely-aligned collagen fibrils, thus leaving large areas of the collagen free of mineral even though the buffer remains highly supersaturated. Electron micrographs suggested that the catalytic sites might be in some relationship to the 640 Å periodicity of collagen, but a role for non-collagenous material bound to the collagen has not been excluded. The poor catalytic activity of reconstituted collagen was not due to the presence of loosely-bound inhibitors, although inhibitors could be strongly bound to this type of collagen and be absent from bone collagen. The differences in catalytic activity may have a bearing on physiological calcification. A more general hypothesis for nucleation of a mineral phase in biological systems is required.
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    Calcified tissue international 9 (1972), S. 122-130 
    ISSN: 1432-0827
    Keywords: Tetracycline ; Development ; Calcification ; Statolith ; Nematocysts ; Aurelia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé L'effet de la tétracycline HCl sur la synthèse de statolithes de sulfate de calcium chezAurelia a été étudié. La tétracycline inhibe la synthèse de statolithes et nématocystes à un stade précoce de strobilation. La tétracycline, cependant, n'est pas incorporée dans les statolithes ou nématocystes en formation. Comme la tétracycline ne se combine pas avec le calcium des statolithes de sulfate de calcium dihydraté d'Aurelia, l'explication des effets d'inhibition sur la différenciation de statolithes et nématocystes ne semble pas liée avec un facteur en rapport avec l'incorporation. Des étudesin vitro de quatre systèmes inorganiques de calcium et de tétracycline montrent que le sulfate de calcium dihydraté (gypse) n'incorpore pas la tétracycline: il en est de même de son équivalent isostructural, le phosphate de calcium hydrogéné dihydraté (brushite). Le carbonate de calcium et le phosphate de calcium (apatite) incorpore la tétracycline. L'explication des différences de comportement du calcium peut être liée à la structure cristalline des composés respectifs, et, en particulier, au fait que l'ion Ca est prêt ou non à réagir avec la tétracycline.
    Abstract: Zusammenfassung Es wird über die Wirkung von Tetracyclinchlorhydrat auf die Synthese von Calciumsulfat-Statolithen beiAurelia berichtet. Wird das Tetracyclin in einem Frühstadium der Strobilation verabreicht, so hemmt es die Synthese der Statolithen und der Nematocysten. Das Tetracyclin wird jedoch nicht in die sich bildenden Statolithen oder Nematocysten eingebaut. Da sich das Tetracyclin nicht mit dem Calcium der Calciumsulfatdihydrat-Statolithen derAurelia verbindet, so kann dessen Hemmwirkung auf die Statolithen und die sich differenzierenden Nematocysten offenbar nicht mit einem einbaubedingten Faktor erklärt werden. Untersuchunge, die in vitro mit vier verschiedenen anorganischen Calciumsalzen und Tetracyclin ausgeführt wurden, zeigten, daß weder Calciumsulfatdihydrat (Gips), noch dessen isotrukturelles Aequivalent Calciumhydrogenphosphatdihydrat (Bruschit) Tetracyclin einbauen. Dagegen inkorporieren Calciumcarbonat und Calciumphosphat (Apatit) das Tetracyclin. Die Erklärung für dieses unterschiedliche Verhalten der Calciumsalze findet sich in der Kristallstruktur der betreffenden Verbindungen, d.h. es hängt davon ab, ob das Calciumion ür die Reaktion mit Tetracyclin leicht verfügbar ist.
    Notes: Abstract The effect of tetracycline HCl on synthesis of calcium sulphate statoliths inAurelia is reported. Tetracycline inhibits synthesis of statoliths and nematocysts when administered at an early stage of strobilation. The tetracycline, however, is not incorporated into the developing statoliths or nematocysts. As the tetracycline does not combine with the calcium of the calcium sulfate dihydrate statoliths ofAurelia, an explanation for its inhibitory effects on statoliths and nematocyst differentiation apparently does not rest with an incorporation-related factor. In vitro studies of four inorganic calcium systems and tetracycline revealed that calcium sulfate dihydrate (gypsum) did not incorporate tetracycline nor did its isostructural equivalent, calcium hydrogen phosphate dihydrate (brushite). Calcium carbonate and calcium phosphate (apatite) did incorporate tetracycline. The explanation for these different behaviors of calcium can be found in the crystal structure of the respective compounds, namely, whether or not the Ca ion is readily available to react with tetracycline.
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    Calcified tissue international 10 (1972), S. 128-135 
    ISSN: 1432-0827
    Keywords: Bone ; Embryo ; Calcification ; Phosphate ; Pyrophosphate ; Carbonate ; Apatite
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé La maturation chimique et physique du sel osseux est étudiée par l'obervation des caractéristiques stoichiométriques et aux infra-rouges d'os embryonnaire d'oiseaux, du début jusqu'à la fin de la croissance adulte après éclosion. La succession des transformations chimiques de l'os en voie de développement montre surtout un rapport inverse entre le phosphate acide et le carbonate, ainsi que la formation de CO3-apatite. Ces résultats semblent indiquer que le CO 3 2− est substitué au HPO 4 2− au cours de la synthèse du CO3-apatite de l'os.
    Abstract: Zusammenfassung Die chemischen und physikalischen Umwandlungen zum stabilen Knochensalz in Hühnerknochen wurden anhand serienmäßiger Beobachtungen seiner stöchiometrischen Zusammensetzung und seiner infraroten Charakteristika untersucht; diese Beobachtungen erstreckten sich über die Zeit der frühen embryonalen Mineralablagerung bis zur vollständigen Reife nach dem Ausbrüten. Die Sequenz der chemischen Umwandlungen im sich entwickelnden Knochen zeigte hauptsächlich ein entgegengesetztes Verhältnis zwischen saurem Phosphat und Carbonat, das mit der Bildung von Carbonatapatit zusammenfällt. Diese Resultate weisen darauf hin, daß HPO 4 2− bei der Synthese von Carbonatapatit im Knochen durch CO 3 2− substituiert wird.
    Notes: Abstract The chemical and physical maturation of the bone salt was studied by serial observations on its stoichiometric and infrared characteristics in avian bone from early embryonic mineral deposition to full maturity after hatching. The sequence of chemical transformations in the developing bone showed most predominantly an inverse relationship between acid phosphate and carbonate, coincident with the formation of CO3-apatite. The data are consistent with the view that CO 3 2− is substituted for HPO 4 2− in the synthesis of CO3-apatite in bone.
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    Calcified tissue international 15 (1974), S. 31-44 
    ISSN: 1432-0827
    Keywords: Calcification ; Regeneration ; Repair ; Shell ; Mollusc
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Une régénération de la coquille induite expérimentalement chez l'excargot terrestreOtala lactea a été utilisée pour l'étude du substratum sur le type de régénération minérale. Des subsrats, comportant le periostracum de quatre espèces de mollusques, des répliques de surfaces et la membrane externe de la coquille de poule, ont été insérés au niveau de la région de reconstitution de la coquilled'Otala. Les divers types de dépôt de carbonate de calcium sont étudiés en microscopie électronique par balayage. Les types minéraux, formés sur les substrats mis en place, se conforment à la microtopographie des surfaces et se trouvent être nettement différents du type minéral observé au cours d'une régénération normale de la coquille. Les types minéraux de la surface minérale externe normale de la coquille de quatre espèces de mollusques semblent identiques aux types individuels de surface du periostracum sur lequel les cristaux de la coquille se déposent. Il semble que ce type de surface minérale externe de la coquille se forme par l'interaction de cristaux de CaCO3 qui se développent dans une matrice organique au contact du periostracum. La coquille normaled'Otala est constituée d'aragonite à orientation hautement préférentielle. La coquille régénérée contient de la calcite et de l'aragonite orientées au hasard. Le rapport aragonite-calcite est très variable et parait indépendant des substrats expérimentaux placés dans la région de régénération.
    Abstract: Zusammenfassung Der Einfluß der Unterlage auf die Art der Mineral-Neubildung im Gehäuse der Landschnecke,Otala lactea, wurde mit dem Raster-Elektronenmikroskop untersucht, indem in der Regenerationszone Fremdkörper eingeschoben wurden. Diese Fremdkörper waren Periostraca von vier anderen Molluskenarten, Plastikabdrücke von Periostraca oder der äußeren Mineral-Oberfläche normaler Gehäuse und die äußere Membran einer Hühnereierschale. Die Oberflächenstruktur des Kalziumkarbonats, das auf diesen Unterlagen abgelagert wurde, entsprach der Mikrotopographie der Unterlags-Oberfläche und war deutlich verschieden von der Mineraloberflächenstruktur bei normaler Regenerierung des Gehäuses. Die Strukturen der normalen Mineraloberflächen der vier Molluskenarten entsprachen der Struktur der Periostracum-Oberfläche, auf welcher die Kalziumkarbonat-Kristalle abgelagert werden. Die Mineraloberflächenstruktur des Gehäuses ergibt sich vermutlich durch die Wechselwirkung zwischen den Kalziumkarbonat-Kristallen, welche in einer organischen Matrix wachsen und der Berührung mit dem Periostracum. Das normale Mineral von Otala-Gehäusen besteht aus Aragonit in ganz bestimmter Anordnung. Regeneriertes Gehäuse enthielt Kalzit in zufälliger Anordnung und Aragonit, meist auch in zufälliger Anordnung. Das Verhältnis Aragonit/Kalzit variierte stark und schien unabhängig von der experimentellen Unterlage zu sein.
    Notes: Abstract Experimentally induced shell repair in the land snailOtala lactea has been employed to study the influence of the substratum on microtopography of the surface of mineral deposited by molluscs. Substrata, including the periostraca of four species of molluscs, surface replicas, and the outer membrane of the eggshell of the hen, have been inserted in the area of shell repair inOtala, and the topographical patterns of deposition of calcium carbonate have been observed by scanning electron microscopy. The mineral patterns formed on all inserted substrata conformed to the microtopography of the surfaces and were distinctly different from that of normal shell regeneration. The topography of the normal outer mineral surface of the shell of four species of molluscs were observed to conform to the topography of the periostraca on which the crystalline shell is deposited. It is inferred that the topography of the outer mineral surface of the shell probably results from the interaction of crystals of aragonite and calcite growing in an organic matrix and in contact with the periostracum. Normal shell ofOtala consists of fine-grained aragonite in highly preferred orientation. Regenerated shell contains calcite grains in random orientation and aragonite, usually in random orientation. The aragonite-to-calcite ratio varies widely and appears to be independent of experimental substrata placed in the area of repair.
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    Calcified tissue international 13 (1973), S. 173-185 
    ISSN: 1432-0827
    Keywords: Calcification ; Apatite ; Whitlockite ; Amorphous
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Des études cristallographiques, spectroscopiques et chimiques ont permis de mettre en évidence deux types distincts de phosphate de calcium dans les tissus de patients, atteints de troubles rénaux chroniques. Les dépôts des calcifications périarticulaires sont des apatites contenant des carbonates, alors que ceux trouvés dans les tissus viscéraux calcifiés sont soit des micro-cristaux de whitlockite de magnésium ou un précurseur de ce composé. Les clichés de diffraction aux rayons X sont de type apatitique pour les calcifications tumorales et amorphe pour les calcifications viscérales. Il semble que la présence de magnésium facilite la formation de ce dernier type en inhibant la cristallisation de l'apatite et en stabilisant la phase amorphe comme dans les systèmes synthétiques.
    Abstract: Zusammenfassung Kristallographische, spektroskopische und chemische Untersuchungen belegen die Anwesenheit von zwei bestimmten Arten von Calciumphosphat-Ablagerungen in den Geweben von Patienten mit chronischem Nierenversagen. Die Ablagerungen, welche in periartikulären Verkalkungen gefunden wurden, sind Karbonat-enthaltendes Apatit; diejenigen in visceralen Geweben sind entweder Kleinkriställchen von Magnesium-Whitlockit oder eine direkte Vorstufe davon. Röntgendiffraktionsspektren dieser beiden Ablagerungsarten zeigen, daß tumorale Verkalkungen apatitartig und viscerale Verkalkungen amorph sind. Es wird vorgeschlagen, daß die Anwesenheit von Magnesium die Bildung dieser zweiten Art der Calciumablagerung begünstigt, indem es die Apatitbildung stört und die amorphe Phase stabilisiert, was in synthetischen Systemen beobachtet werden konnte.
    Notes: Abstract Crystallographic, spectroscopic and chemical studies demonstrate the presence of two distinct types of calcium phosphates deposits in tissues of patients with chronic renal failure. Deposits found in periarticular calcifications are carbonate-containing apatite, while those found in calcified visceral tissues are either microcrystallites of magnesium whitlockite or an immediate precursor of this compound. X-ray diffraction patterns of these two types show tumoral calcification to give an apatitic pattern and visceral calcification, an amorphous one. It is suggested that the presence of magnesium promotes the formation, of this latter type of calcium deposit by disturbing the crystallization of the apatite and stabilizing the amorphous phase as observed in synthetic systems.
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    Calcified tissue international 15 (1974), S. 201-212 
    ISSN: 1432-0827
    Keywords: Ultrastructure ; Alkaline Phosphatase ; Calcification
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Des cals expérimentaux de neuf jours, formés au niveau de radius de jeunes rats, sont traités par la méthode calcium-cobalt de Gomori (1939) pour la mise en évidence ultrastructurale de la phosphatase alcaline afin d'étudier son rôle éventuel dans le dépôt du calcium. L'activité enzymatique apparait initialement sous forme de précipités globulaires en dehors de la membrane cellulaire de jeunes chondroblastes hypertrophiques. Ce précipité donne ensuite naissance à des corps sphériques de phosphatase alcaline qui se forme près de la cellule. Ces corps sphériques s'observent dans une zone intermédiaire plus éloignée. Une formation de cristaux en aiguilles (apparemment une calcification) se développe dans des corps isolés ou agrégés, laissant voir nettement leurs limites, même lorsque la calcification est plus avancée au point qu'on ne peut plus distinguer des cristaux individuels. Au niveau des coupes témoins, traitées de façon identique mais sans substrat ou avec de l'E.D.T.A., on n'observe ni précipité enzymatique ou corps sphériques. L'aspect des dépôts cristallins dans des corps qui contiennent de la phosphatase alcaline ne peut s'expliquer que par l'existence d'une association étroite entre enzymes et calcification.
    Abstract: Zusammenfassung Neun Tage alter experimenteller Kallus an Radii von jungen Ratten wurde mit Gomori's (1939) Calcium-Kobalt Methode untersucht, um die Verteilung der alkalischen Phosphatase und ihre Beziehung zur Calciumablagerung ultrastrukturell zu demonstrieren. Enzymaktivität zeigte sich zuerst als globulares Präzipitat außerhalb der Zellmembran von Knorpelzellen im Beginn der Hypertrophie. Aus dieser Präzipitatschicht entstanden dann gerundete Körperchen, die sich von der Zelle abtrennten. Solche Körperchen wurden auch in größerer Entfernung von der Zelle beobachtet, d.h. in einer Zwischenzone zwischen benachbarten Zellen. Nadelförmige Kristalle, wahrscheinlich von Calcium-Salzen, wurden in einzelnen oder aggregierten Körperchen beobachtet. Die äußere Zone der Körperchen blieb jedoch deutlich sichtbar, selbst dann, wenn der Calciumgehalt derart zugenommen hatte, daß einzelne Kristalle nicht länger erkennbar waren. In Kontrollen, die in gleicher Weise behandelt waren, aber ohne Substrat oder mit Zufügung von EDTA, wurden weder Präzipitate noch Körperchen beobachtet. Das Auftreten von Calciumablagerungen in alkalischer Phosphatase enthaltenden Körperchen scheint kaum anders erklärbar als durch eine enge funktionelle Verbindung zwischen Enzym und Calciumablagerung.
    Notes: Abstract Nine day old experimental calluses in radii of young rats were treated with Gomori's (1939) calcium-cobalt method to demonstrate ultrastructurally the presence of alkaline phosphatase in a search for its possible role in the desposition of calcium. Enzyme activity first appeared as globule-like precipitates outside the cell membrane of early hypertrophic cartilage cells. This precipitate layer then seemed to give rise to spherical bodies of alkaline phosphatase which occur at a slight distance from the cell. The spherical bodies were also observed further away from the cell in an intermediate zone between neighboring cells. Needle-like crystal formation, apparently calcification, occurred inside single or aggregated bodies, leaving their peripheral rim clearly visible, even when calcification had increased to such an extent that individual crystals could no longer be recognised. In controls, treated in the same way but without substrate, or with EDTA, no enzyme precipitate or spherical bodies were seen. The appearance of crystalline deposits in bodies which contain alkaline phosphatase seems difficult to explain on any other basis than that there is a close functional association between the enzyme and calcification.
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    Calcified tissue international 16 (1974), S. 315-320 
    ISSN: 1432-0827
    Keywords: Ossification center ; Calcification ; Femoral head ; Estrogen ; Hypophysectomy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract In Wistar rats, calcified centers normally appeared in the epiphyseal cartilage of the femoral heads by 21 days of age, but ossification centers were not observed until the animals were at least 6 weeks old. The effects of hypophysectomy, performed when the rats were 13 days old, and estradiol, 5 μg per g body weight injected subcutaneously on the day of birth and subsequently every second day, were investigated. All animals were sacrificed when 21 days old and the development of calcified centers examined radiographically and histologically. At this time there were fewer calcified centers in the femoral heads of the hypophysectomized rats than in those of the control animals, but there was no significant difference between the number of calcified centers in the estradiol-treated hypophysectomized rats and the controls. Estradiol-injected rats developed calcified centers at a nearlier stage than hypophysectomized rats receiving estradiol injection. These findings are interpreted to show that hypophysectomy produces the opposite effect to estradiol treatment on the development of calcified centers in the femoral heads of rats.
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    Calcified tissue international 5 (1970), S. 247-260 
    ISSN: 1432-0827
    Keywords: Carbonic Anhydrase ; Calcification ; Physiologic ; Mollusca
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé L'étude du mécanisme impliqué dans la régulation des échanges entre les différents compartiments du calcium dans le manteau des lamellibranches d'eau douce montre: 1) La nécessité d'une localisation topographique proche des éléments intervenant dans le mécanisme étudié. Ces éléments sont: les réserves de calcium et l'anhydrase carbonique. 2) Par des expériences effectuées sur des homogénats ou des observations histologiques que les réserves de calcium se présentent sous la forme de petits granules calcifiés extracellulaires, localisés dans le tissu interstitiel du manteau. 3) Par des observations sur la sédimentation d'homogénats que l'enzyme se trouve liée aux granules calcifiés. Enfin l'intérêt d'une telle liaison enzyme-substrat est discuté.
    Abstract: Zusammenfassung Es wurde der Mechanismus der Austauschregulation zwischen den verschiedenen Calciumkompartimenten im Mantel der Süßwasser-Lamellibranchen untersucht. Dabei ergab sich: 1. Die an dieser Regulation beteiligten Substanzen, nämlich die Calciumreserven und die Kohlensäureanhydrase, müssen topographisch nahe beeinander liegen. 2. Die Calciumreserven kommen als kleine extrazelluläre verkalkte Granula vor, die im interstitiellen Gewebe des Mantels lokalisiert sind (belegt durch Versuche an Homogenaten und durch histologische Untersuchungen). 3. Sedimentationsbeobachtungen an Mantelhomogenaten lassen vermuten, daß das Enzym an die verkalkten Granula gebunden ist. Die Rolle einer solchen Enzym-Substrat-Einheit wird diskutiert.
    Notes: Abstract A study of the mechanism of exchange regulation between the different calcium pools in freshwater lamellibranch mantle shows: 1) that the substances concerned in this regulation, namely the calcium reserves and carbonic anhydrase, must be topographically in close proximity, 2) that the calcium reserves occur as small extracellular calcified granules localised in the interstitial tissue of the mantle (evidence both from experiments on homogenates and from histological examination), and 3) that observations on the sedimentation in mantle homogenates suggest that the enzyme is bound to the calcified granules. The role of such an enzyme-substrate unit is discussed.
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    Calcified tissue international 5 (1970), S. 317-326 
    ISSN: 1432-0827
    Keywords: Mollusc ; Calcification ; Amino acids ; Protein ; Polysaccharides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Le byssus calcifié d'Anomia comporte une fraction minérale importante (96 à 98%) constituée essentiellement d'aragonite et de traces de calcite. La composition en acides aminés de la fraction organique est caractéristique des sécrétions calcifiées en général, mais diffère toutefois de celle de la coquille des Bivalves. Les oses neutres représentent 3,4% du poids de la matrice organique, les hexosamines 19,2% (essentiellement de la glucosamine).
    Abstract: Zusammenfassung Der verkalkte Byssus vonAnomia besteht aus einer anorganischen Hauptfraktion (96–98%), die vorwiegend aus Aragonit und Spuren von Calcit aufgebaut ist. Die Aminosäuren-Zusammensetzung der organischen Fraktion ist charakteristisch für die verkalkten Sekretionen im allgemeinen, weicht jedoch von jener der zweischaligen Muscheln ab. Die neutralen Kohlenhydrate machen 3,4% des Gewichtes der organischen Matrix, die Hexosamine (hauptsächlich Glucosamin) 19,2% aus.
    Notes: Abstract The calcified byssus ofAnomia consists largely of mineral (96–98%) made up principally of aragonite with traces of calcite. The amino-acid composition of the organic fraction is characteristic of calcified secretions in general, but differs in some ways from those of bivalve shells. Neutral sugars represent 3.4% of the weight of the organic matrix, hexosamines (principally glucosamine) 19.2%.
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    Calcified tissue international 5 (1970), S. 21-29 
    ISSN: 1432-0827
    Keywords: Phospholipids ; Bone ; Calcification
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Les phospholipides neutres, tels que la sphingomyéline, la lécithine et la phosphatidyléthanolamine, sont les phosphatides principaux de l'os compact bovin. Ces lipides constituent plus de 90% des phospholipides de l'os, avant déminéralisation, et plus de 60% des phosphatides totaux extraits de ce tissu. Après déminéralisation, les solvants lipidiques neutres extraient des phospholipides neutres et acides de la matrice osseuse. Le traitement final de la matrice osseuse avec un mélange de solvants acides permet de récupérer une faible quantité de phosphatides acides et neutres. Pour expliquer la nécessité d'une déminéralisation au cours de l'extraction lipidique, il est possible que les lipides de l'extrait, obtenu après déminéralisation. soient liés à la phase minérale de l'os. Afin d'exclure la possiblité que cette extraction soit dûe simplement aux cristaux d'apatite, pouvant agir comme obstacle à la diffusion du solvant, l'effet de l'extraction lipidique sur des fractions de particules osseuses de diverses tailles a été étudié. La composition des extraits lipidiques n'est pas liée à la taille des particules: le minéral osseux ne parait done pas constituer un obstacle au passage des solvants lipidiques.
    Abstract: Zusammenfassung Die neutralen Phospholipide Sphingomyelin, Lecithin und Phosphatidyläthanolamin sind die wichtigsten Phosphatide des kompakten Rinderknochens. Zusammengenommen machen diese Lipide über 90% der Phospholipide, welche vor der Demineralisation dem Knochen entzogen worden sind und über 60% der aus diesem Gewebe extrahierten totalen Phosphatide aus. Nach der Demineralisation konnten mit neutralen Lösungsmitteln für Lipide ein weiterer Anteil an neutralen und eine beträchtliche Menge an sauren Phospholipiden aus der Knochenmatrix extrahiert werden. Am Schluß wurde die Knochenmatrix mit einem angesäuerten Lösungsmittelgemisch behandelt, und es konnte eine kleine Menge saurer sowie neutraler Phosphatide aus dem Gewebe extrahiert werden. In Anbetracht der notwendigen Demineralisierung bei der Lipidextraktion wurde vorgeschlagen, daß die Lipide aus dem nach Demineralisation gewonnenen Extrakt an die Mineralphase des Knochens gebunden sind. Um die Möglichkeit auszuschließen, daß dieser Extrakt lediglich durch die Apatit-Kristalle bedingt ist, die die Diffusion des Lösungsmittels verhindern, wurde die Wirkung der Lipidextraktion auf Knochenpulver verschiedener Partikelgrößen geprüft. Jedoch besteht keine Beziehung zwischen der Zusammensetzung des Lipidextraktes und der Größe der Partikel. Daraus folgt, daß das Knochenmineral den Durchgang der Lipidextraktionsmittel in das Gewebe nicht verhindert.
    Notes: Abstract The neutral phospholipids sphingomyelin, lecithin and phosphatidylethanolamine were the principal phosphatides of compact bovine bone. Together, these lipids accounted for over 90% of the phospholipids removed from bone, prior to demineralization, and for over 60% of the total phosphatides extracted from this tissue. Following demineralization, neutral lipid solvents removed a further quantity of neutral, and a considerable number of acidic, phospholipids from the bone matrix. A final treatment of the bone matrix with an acidified solvent mixture removed a small number of acidic, as well as neutral, phosphatides from the tissue. To account for the necessity of the demineralization step in the lipid extraction procedure, it was suggested that lipids of the post-demineralized extract were bound to the mineral phase of bone. To exclude the possibility that this extract was merely due to the apatite crystallites acting as a solvent diffusion barrier, the effect of the lipid extraction of bone of different particle size was examined. However, it was found that the composition of the lipid extracts was not related to the particle area; hence, it was inferred that the bone mineral was not obstructing the passage of the lipid extractants in the tissue.
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    Calcified tissue international 6 (1970), S. 81-92 
    ISSN: 1432-0827
    Keywords: Calcification ; Collagen ; Kinetics ; Matrix ; Ions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Ce travail montre que les fibres contenant du collagène, et provenant de tendons de boeuf, induisent le dépôt d'ions calcium et phosphates à partir de solutions stables. Il se forme ainsi une phase minérale, liée à la matrice, qui participe aux réactions d'échange avec45Ca2+ et32P-HPO 4 2 -, présents dans la phase soluble. Les vitesses d'échange et le dépôt au niveau de la matrice augmentent lorsque la quantité de minéral lié est augmentée. Cependant, à des concentrations élevées de minéral lié, la vitesse de dépôt du calcium matriciel tend à approcher une valuer limite, indiquant la présence d'un facteur de limitation, ou d'une étape faisant intervenir l'ion calcium, qui ne participe pas à la réaction d'échange du calcium. Ces études montrent aussi que les inhibiteurs de la réaction générale de calcification peuvent être définies par leurs effects différents sur l'échange et le dépôt de l'ion matriciel. Une fraction peptidique acide, dérivée de l'urine, et l'acide méthylène-diphosphonique inhibent la calcification matriciel ainsi que les deux réactions d'échange, alors que Mg2+ et F− inhibent la calcification matricielle, mais n'inhibent pas les réactions d'échange. Les résultats obtenus indiquent que les réactions d'échanges ne sont pas liés à la réversibilité du mécanisme de la calcification matricielle, mais constituent une réaction d'équilibre indépendante d'ions mobiles de la phase minérale liée avec ceux de la phase soluble.
    Abstract: Zusammenfassung Diese Untersuchung zeigt, daß collagenhaltige, aus Rindersehnen gewonnene Fasern die Aufnahme von Calcium- und Phosphationen aus stabilen Lösungen veranlassen; dadurch entsteht eine an die Matrix gebundene Mineralphase, welche an Austauschreaktionen mit in der löslichen Phase vorliegenden45Ca2+- und32P-HPO 4 2 -Ionen teilnimmt. Es zeigte sich, daß die Geschwindigkeit von Austausch und effektiver Aufnahme bei Erhöhung der gebundenen Mineralmenge zunahm. Ist jedoch viel Mineral gebunden, so hat die effektive Calcium-aufnahmegeschwindigkeit die Tendenz, einen Grenzwert zu erreichen, was die Beteiligung einer geschwindigkeitsbegrenzenden Stelle oder Stufe vermuten läßt, wobei das an der Calcium-austauschreaktion nicht teilnehmende Calciumion einbezogen wird. Diese Untersuchungen zeigen auch, daß Inhibitoren der gesamten Verkalkungsreaktion im Hinblick auf ihre unterschiedlichen Wirkungen auf Austausch und effektive Ionenaufnahme charakterisiert werden können. Eine saure Peptidfraktion aus Urin sowie Methylendiphosphonate hemmen die effektive Verkalkung und zudem beide Austauschreaktionen, während Mg2+ und F− wohl die effektive Verkalkung, aber nicht die Austauschreaktionen hemmen. Diese Ergebnisse deuten darauf hin, daß die Austauschreaktionen nicht auf der Reversibilität des effektiven Verkalkungsvorgangs beruhen, sondern daß sie ein unabhängiges Gleichgewicht zwischen mobilen Ionen der gebundenen Mineralphase und der löslichen Phase darstellen.
    Notes: Abstract This investigation demonstrates that collagen-containing fibers derived from beef tendon will induce the uptake of calcium and phosphate ions from stable solutions to form a matrix-bound mineral phase that will participate in exchange reactions with45Ca2+ and32P-HPO 4 2 -present in the soluble phase. The rates of exchange and net uptake were found to be increased by increasing the amount of bound mineral. However, at elevated levels of bound mineral the rate of net calcium uptake tends to approach a limiting value, suggesting the involvement of a rate-limiting site or step involving the calcium ion that does not participate in the calcium exchange reaction. These studies also reveal that inhibitors of the overall calcification reaction can be characterized with respect to their differential effects on exchange and net ion uptake. An acidic peptide fraction derived from urine and methylenediphosphonic acid inhibit net calcification as well as both exchange reactions whereas Mg2+ and F− inhibit net calcification but do not inhibit the exchange reactions. These results indicate that the exchange reactions are not due to the reversibility of the net calcification reaction but constitute an independent equilibration of mobile ions of the bound mineral phase with those of the soluble phase.
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    Calcified tissue international 7 (1971), S. 307-317 
    ISSN: 1432-0827
    Keywords: Ultrastructure ; Cartilage ; Calcification ; Inorganic ; Organic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé La phase organique (ou fantôme des cristaux) associéc à chaque cristal, ainsi que la substance de base associée à chaque cristal, ainsi que la substance de base associée à chaque amas cristallin, sont mises en évidence au niveau du cartilage calcifié en utilisant le sulfate de chrome basique comme agent de fixation, de coloration et de déminéralisation. Le traitement ultérieur du tissu, à l'aide de papaïne ou d'hyaluronidase, indique que les fantômes cristallins constitutent un complexe protéino-polysaccharidique et que la substance de base est formée par une protéine associée à un polysaccharide acide. Les rapports entre phases inorganique et organique sont discutés.
    Abstract: Zusammenfassung Die organische Phase (oder Kristallit-Schatten), die zu jedem Kristallit gehört, sowie das Hintergrundmaterial, das zu jeder Kristallitgruppe gehört, wurden in calcifiziertem Knorpel sichtbar gemacht. Zu diesem Zweck wurde basisches Chromsulfat als ein kombiniertes Fixierungs-, Färbe- und Demineralisierungsmittel verwendet. Nachfolgende Behandlung des Gewebes mit Papain oder Hyaluronidase läßt vermuten, daß die Kristallitschatten einen Proteinpolysaccharidkomplex darstellen und daß das Hintergrundmaterial hauptsächlich aus Protein mit einigen sauren Polysacchariden besteht. Die Beziehung zwischen anorganischen und organischen Phasen wird diskutiert.
    Notes: Abstract The organic phase (or crystallite ghost) associated with each crystallite, together with the background material associated with each crystallite cluster, was demonstrated in calcified cartilage using basic chromium sulphate as a combined fixative, stain, and demineralizing agent. Subsequent treatment of the tissue with papain, or with hyaluronidase, suggests that the crystallite ghosts represented a protein-polysaccharide complex and that the background material was principally protein together with some acid polysaccharide. The relationship between inorganic and organic phases is discussed.
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    European journal of clinical pharmacology 5 (1972), S. 44-52 
    ISSN: 1432-1041
    Keywords: alprenolol ; serum drug level ; exercise ; man ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of alprenolol on heart rate and systolic blood pressure were studied in healthy subjects during standardized exercise on a bicycle ergometer. In one series of experiments, in which serum concentrations of alprenolol were also measured, the effects of single oral doses of 50, 100 and 200 mg of alprenolol and a placebo were compared by a double blind cross-over technique. In a second series of experiments 100 mg alprenolol was given four times in one day and the effect was followed for up to eighteen hours after the last dose. — Alprenolol diminished the expected increase in heart rate and systolic blood pressure during exercise. The reduction of exercise tachycardia in a given individual was linearly related to the logarithm of the dose or the serum concentration of alprenolol. The serum concentrations required for a given reduction of exercise tachycardia varied almost one hundred-fold amongst the subjects studied. The biological availability of alprenolol was dose-dependent, probably due to a limited capacity biotransformation of the drug before it entered the general circulation. After a single dose the serum level of alprenolol and its chronotropic effect diminished at a rate corresponding to an elimination half life of about two hours. This rate of elimination was consistent with that calculated from the results of the four dose study.
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    European journal of clinical pharmacology 5 (1973), S. 174-180 
    ISSN: 1432-1041
    Keywords: Tricyclic antidepressant ; nortriptyline ; metabolism ; urine ; pharmacokinetics ; twins ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The urinary excretion of nortriptyline (NT) and five of its metabolites was studied by quantitative gas chromatography in 22 twins and 7 unrelated healthy subjects after single (1 mg/kg) and multiple oral doses (0.4 mg/kg t.i.d.) of NT hydrochloride. A mean recovery of 62% of the dose was found after both single and multiple doses. The metabolite pattern in the urine was qualitatively and quantitatively identical in the two regimes, but there were marked variations in the pattern of metabolites between individuals. The disappearance rate of NT from the plasma was mainly determined by the metabolism of NT to 10-hydroxynortriptyline, which varied considerably between individuals. The data suggest that in certain rapid NT metabolizers, the upper limit for the overall clearance of NT from the plasma (if extrahepatic metabolism is assumed to be negligible) might be set by the blood flow through the liver.
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    European journal of clinical pharmacology 6 (1973), S. 268-270 
    ISSN: 1432-1041
    Keywords: Diphenhydramine ; orphenadrine ; gas-liquid chromatography ; N-selective detector ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A method is described for the assay of nanogram quantities of diphenhydramine and orphenadrine in human plasma. The procedure employs gas-liquid chromatography and a high sensitivity nitrogen detector. It has been used to assay diphenhydramine in plasma after oral administration of therapeutic doses.
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    European journal of clinical pharmacology 6 (1973), S. 234-238 
    ISSN: 1432-1041
    Keywords: Phenobarbital ; neonate ; maternal-fetal exchange ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations of phenobarbital were measured in 18 newborn infants for one to two weeks after birth. The drug had been administered prenatally to the mothers as part of treatment for maternal hypertension or toxaemia. The plasma half-life of the drug in the infants (77–404 h) was inversely correlated with the extent of prenatal exposure to it. In three infants a bi-phasic plasma curve was found as there was a sudden change from slow to fast disappearance on the 5th to 7th day of life.
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  • 56
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    European journal of clinical pharmacology 7 (1974), S. 407-414 
    ISSN: 1432-1041
    Keywords: Diuretic ; indapamide ; human pharmacology ; toxicology ; pharmacokinetics ; TLC assay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacology, toxicology and kinetics of a new diuretic indapamide, have been studied in six normal volunteers following a single oral dose of 40 mg. Pronounced diuresis was found, commencing three hours after ingestion, with a peak urinary flow at four to six hours, and continuing for a total of thirty-six hours. A fall in systolic standing blood pressure occurred twenty four hours after ingestion, coincident with the period of maximum dehydration. Free water clearance rose, accompanied by increased urinary losses of Na+, K+ and Cl− and alkalinisation of the urine comparable to the actions of benzothiadiazines. Total urinary losses of Ca2+, Mg2+ and PO 4 3− rose in spite of a fall in urinary concentrations of these ions. The Ca2+ effect compares with the acute ionic effects of other diuretics. No renal, hepatic or haematological toxic effect was demonstrated. The blood sugar level was not disturbed. Serum uric acid rose to abnormal levels although the change did not reach statistical significance. — A thin layer chromatographic method, with a sensitivity limit of 0.1 µg/ml., has been developed for the assay of indapamide in urine. The urinary excretion rates of the volunteers measured over forty-eight hours indicate that the drug is rapidly absorbed with a peak excretion, 2.9±1.3 µg/min occurring three hours after ingestion. The drug is eliminated bi-phasically with an initial short rapid elimination followed by a slower exponential decline with a mean elimination half-life of 10.3 ± 3.9 h. The mean urinary excretion of unchanged indapamide over forty-eight hours was 4.4±1.4% of the administered dose. — It is concluded that indapamide is an effective long-acting diuretic with comparable action to the benzothiadiazine diuretics, but without an effect on blood sugar level in single doses in normal subjects. In contrast with other diuretics, indapamide appears to be extensively metabolised in man, and its longer duration of action to be related to a longer elimination half-life.
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  • 57
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    Keywords: Oral antidiabetic drug ; butylbiguanide ; pharmacokinetics ; two-compartment open model ; plasma concentration ; liver concentration ; intestine concentration ; man
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 50 mg14C-Butylbiguanide was administered intravenously to 4 diabetic patients and 100 mg14C-butylbiguanide orally to 5 further diabetics. The concentrations of the drug in plasma, intestinal fluid, intestinal epithelium and liver tissue were determined and the renal excretion of the biguanide measured. Irregularities in the plasma concentration curve were observed which appeared as systematic deviations from the ideal curve of a biexponential function. Because these deviations occurred only in the middle phase of the plasma concentration curve, it was nevertheless possible to calculate the pharmacokinetic parameters of butylbiguanide by use of a two-compartment open model. The principal pharmacokinetic parameters were determined according to this model after intravenous dosing and the following mean values were obtained:t 1/2 (β)=4.6 h (β=0.15 h−1),C P 0 =0.85µg/ml,V D =218 l,V T =157 l,V P =62 l,k 12=0.69 h−1,k 21=0.44 h−1,k el =0.54 h−1. Within 48 h after administration, an average of 72.4% of the intravenous and 74.4% of the oral dose had been excreted in the urine. Total clearance (Cl tot) averaged 536 ml/min and renal clearance (Cl ren) 393 ml/min. High concentrations of butylbiguanide were observed in the intestinal fluid (100–700 mg/ml) 20–40 min after oral administration. It was found that the drug accumulates in intestinal fluid, intestinal epithelium and liver tissue, and that it is secreted into the intestinal lumen. The concentrations of butylbiguanide in intestinal and liver tissue were 10–46 times higher than in plasma. The secretion of biguanide into the intestinal lumen may occur via the bile or the intestinal mucosa, but there is no evidence of significant biliary excretion of butylbiguanide.
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    European journal of clinical pharmacology 7 (1974), S. 295-305 
    ISSN: 1432-1041
    Keywords: Mestranol ; ethynyloestradiol ; contraceptive compounds ; demethylation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The oestrogenic activity of mestranol depends on its demethylation to ethynyloestradiol. The reaction has been studied in man. The compound disappeared exponentially from plasma during the first 4 h after i.v. injection of [4-14C-] mestranol. The “metabolic clearance” for this phase amounted to 31.8 1/day per kg body weight. Methoxy-3H-labelled mestranol was prepared for the further studies, because if it is demethylated, the tritium would be transferred to HTO, which would equilibrate immediately with body water. The appearance in body water of tritium from [methoxy-3H-] mestranol could be described by two exponential functions, which corresponded to bi-phasic disappearance of the original compound from plasma. The rate constant of the first stage was: γ1=0.835 h−1, and of the second: γ2=0.034 h−1. HTO radioactivity was eliminated from the body by exchange of water. From the data obtained, a three-compartment model was constructed of the transfer of tritium from [methoxy-3H-] mestranolinto body water, which permitted computer simulation of the partial processes. The compartmental analysis suggested that mestranol differed from ethynyloestradiol mainly in the delayed and protracted manner in which hormonally active oestrogen entered the circulation. The proportion of [methoxy-3H-] mestranol demethylated to ethynyloestradiol (demethylation ratio) varied little, 53.7±5.0% (x±SD; n=6), and was consistent with clinical observations that mestranol is half as potent an oestrogen as ethynyloestradiol. Thus, the dose of mestranol required to produce a given effect has to be twice as large as that of ethynyloestradiol.
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    European journal of clinical pharmacology 6 (1973), S. 44-53 
    ISSN: 1432-1041
    Keywords: Nortriptyline ; pharmacokinetics ; plasma clearance ; gas chromatography — mass spectrometry ; pharmacogenetics ; twins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five identical (monozygotic) and 6 fraternal (dizygotic) sets of healthy twins between 47 and 53 years of age were given a single oral dose of nortriptyline (NT) hydrochloride 1 mg/kg. The plasma half-life, the apparent volume of distribution, and the plasma clearance of NT were estimated for each subject as well as the urinary excretion rate of conjugated and unconjugated 10-hydroxynortriptyline (10-OH-NT). “Steady-state” plasma levels predicted from the reciprocal single dose plasma clearance rate of NT agreed well with those observed in a previous study of the same twins 2 years previously. In the present study, there was a 5-fold range of the plasma half-lives and 2-fold variation in the apparent volume of distribution of NT (assuming complete availability on oral administration). No correlation was found between the plasma half-life and the apparent volume of distribution. Analysis of variance showed that most of the variability between persons in plasma half-life, apparent volume of distribution and conjugation of 10-OH-NT was genetically determined. The plasma half-life and apparent volume of distribution may contribute independently to the total interindividual variability of the “steady-state” plasma level of NT.
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    European journal of clinical pharmacology 4 (1971), S. 54-58 
    ISSN: 1432-1041
    Keywords: pharmacokinetics ; infusion ; plasma expander ; blood level fluctuation ; sulfonamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Description / Table of Contents: Summary A hypothetical pharmacokinetic model is reported which describes the decreasing fluctuations in the blood levels of a sulfonamide during infusion of a plasma expander. Its concentration in the serum increases reciprocally with the amount of plasma expander infused. These procedures can be described by simple equations, and it is possible therefore, to calculate the dose required to maintain a constant blood level during the infusion.
    Notes: Zusammenfassung Es wird über ein hypothetisch-pharmakokinetisches Modell berichtet, welches sich mit der absinkenden Serumkonzentration eines Sulfonamids nach Infusion eines Plasmaexpanders beschäftigt. Die Serumkonzentration fällt reziprok zur infundierten Menge des Plasmaexpanders ab. Die Vorgänge lassen sich durch einfache Gleichungssysteme beschreiben. Es gelingt daher, eine Zusatzdosis zu berechnen, welche den bei Infusionsbeginn bestehenden Plasmaspiegel annähernd konstant erhält.
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    European journal of clinical pharmacology 5 (1972), S. 58-61 
    ISSN: 1432-1041
    Keywords: Pralidoxime chloride ; pharmacokinetics ; anti-cholinesterase poisoning
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A dose of 1.0 g (10.0–14.0 mg/kg body weight) of pralidoxime mixed with various cholinolytics was given by i.m. injection to 29 healthy male subjects. A concentration of pralidoxime in blood of 4 µg/ml was reached after 5 to 10 min with all the mixtures and was maintained for about 1 to 2 h. The calculated half lives of pralidoxime in three groups of subjects were 62.2, 60.0 and 61.8 min., respectively. — The urinary excretions of pralidoxime during the first 4 h after the injections averaged 75.0, 79.6 and 69.6 per cent, respectively, of the total amount given. — The results are compared with published information about similar oximes.
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    European journal of clinical pharmacology 7 (1974), S. 375-380 
    ISSN: 1432-1041
    Keywords: Tranexamic acid ; pharmacokinetics ; man ; antifibrinolytic agents ; renal clearance ; two-compartment model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of tranexamic acid has been investigated in two healthy volunteers. The behaviour of the drug can be described in terms of a two compartment open model; the disposition (biological) half-life was 2.7 h and 1.9 h, respectively. In five normal volunteers the mean total recovery in urine 48 h after dosing was 94.8%. The renal clearance in the two subjects, adjusted to 1.73 m2 body surface area, was 135 and 132 ml/min/1.73 m2, respectively, indicating that tranexamic acid is eliminated by glomerular filtration and that neither tubular excretion nor absorption takes place.
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    European journal of clinical pharmacology 7 (1974), S. 381-385 
    ISSN: 1432-1041
    Keywords: Phenazone ; pharmacokinetics ; plasma half-life ; gas chromatographic analysis ; intra-individual variability
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Intra-individual variability in the plasma half-life of phenazone has been studied in 16 healthy, young volunteers. Phenazone was analysed by a simple gas chromatographic method, which is specific in relation to known metabolites; 4′-methylphenazone was employed as the internal standard. Phenazone was given on two occasions, two or three months apart, in oral doses of 10 mg/kg. The plasma half-life determined from five time points was 10.9±1.5 h and 11.2±1.3 h respectively, on the two occasions. The mean intra-individual variability (0.86 h) was close to the methodological error of 4%.
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    European journal of clinical pharmacology 7 (1974), S. 25-29 
    ISSN: 1432-1041
    Keywords: Pindolol ; uraemia ; pharmacokinetics ; β-blockade
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The elimination of pindolol in 25 patients with various degrees of renal failure has been studied after an intravenous dose of 3 mg. A linear correlation was not found between the elimination rate of pindolol and the endogenous creatinine clearance, and the half-life of the unchanged drug was independent of the severity of the renal failure. This implies greater metabolism of pindolol in anuric patients and the extrarenal elimination rate constantk mwas increased. Three patients with severe renal failure were given 3 mg14C-pindolol. They showed almost constant plasma levels of radio-activity for 6 h and then slow excretion with a half-life of 48 h, because of accumulation of metabolites in the blood. Up to 90% of the metabolites are glucuronides and sulphates which have no beta-blocking or other clinical activity. Thus, to produce beta-adrenergic blockade the same dose of indolol is required in healthy patients as in those with uraemia.
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    European journal of clinical pharmacology 7 (1974), S. 59-60 
    ISSN: 1432-1041
    Keywords: Pizotifen ; isonicotinylhydrazine ; orexigen ; tuberculosis ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pizotifen (BC 105) has an orexigenic effect in patients with pulmonary tuberculosis. As these cases are often treated with isonicotinylhydrazine (INH), any effect of one of these drugs on the absorption of the other has been examined in a cross-over study in 8 healthy male volunteers. No difference was found between the absorption of INH given alone or together with pizotifen. It should be safe, therefore, to employ the combination of the orexigenic drug and INH in the treatment of tuberculosis as there will be no change in the concentration of therapeutic drug achieved.
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    European journal of clinical pharmacology 7 (1974), S. 31-37 
    ISSN: 1432-1041
    Keywords: Diphenylhydantoin ; uraemia ; protein binding ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Diphenylhydantoin (2 mg/kg) was infused intravenously in four uraemic patients and four healthy volunteers and its plasma concentration measured during and after the infusion. The plasma concentrations were considerably lower in the uraemic subjects and the apparent volume of distribution was higher. These observations could be explained by the lower plasma protein binding of diphenylhydantoin in the uraemics. The overall elimination rate constant β was greater (shorter half-life) in the uraemic patients. This difference could not be explained by reduced plasma protein binding, but it might be due to induction of diphenylhydantoin metabolism in the uraemic state. it is concluded that monitoring of the plasma levels of drugs in uraemic patients should be combined with determination of the extent to which the compounds are bound to plasma proteins.
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    European journal of clinical pharmacology 4 (1972), S. 233-240 
    ISSN: 1432-1041
    Keywords: Sulphamethoxazole ; trimethoprim ; pharmacokinetics ; uraemia ; sulphonamides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of sulphamethoxazole (SMZ) and trimethoprim (TMP) have been investigated in four healthy volunteers, 15 patients with stable chronic renal failure and 3 patients on regular dialysis. The dosage schedule was 400 mg of SMZ and 80 mg of TMP orally every 12 h. The plasma concentrations and urinary excretion have been analysed in terms of a one compartment open model, allowing for elimination by renal excretion and metabolic processes. — At equilibrium the plasma concentrations of unchanged sulphonamide showed no significant correlation with the degree of renal impairment. The accumulation of TMP increased slightly without affecting the concentration ratio of both agents in plasma. In contrast, increasing accumulation of metabolized SMZ was demonstrated in the presence of renal insufficiency. Indirect evidence indicates that rising metabolite levels under these circumstances may lead to a displacement of unchanged sulphonamide from protein binding sites. — The cumulative urinary excretion amounted to 82.4% of the dose of sulphonamide administered, which probably corresponds to the fraction of the compound absorbed. The urinary concentration of biologically active SMZ was slightly below the plasma level, especially in advanced renal failure, but it remained above the minimum inhibitory concentrations reported in the literature. The concentration of TMP in urine was considerably higher than in plasma, it decreased with loss of renal function as did active SMZ.
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    European journal of clinical pharmacology 4 (1972), S. 191-195 
    ISSN: 1432-1041
    Keywords: Amobarbital ; pentobarbital ; barbiturates ; gas chromatography ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Gas chromatographic methods are described for the assay of amobarbital and pentobarbital in 500 µl samples of plasma, in concentrations down to 250 ng/ml. After ether extraction at pH 5.5, the barbiturates are reextracted into an alkaline solution of trimethylanilinium hydroxide and are determined quantitatively by gas chromatography as their dimethylated derivatives. The method has been used successfully in volunteers receiving therapeutic doses of these bariturates.
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    European journal of clinical pharmacology 6 (1973), S. 181-186 
    ISSN: 1432-1041
    Keywords: Phenothiazines ; thioridazine ; serum levels ; pharmacokinetics ; man
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The rate of absorption of thioridazine varied greatly in ten healthy volunteers who took 100 mg in the morning after an overnight fast. The peak level in blood was also variable and it was reached 1 1/4 to 4 h after dosing. Maximal concentrations in the blood varied widely from 0.13 µg/ml to 0.52 µg/ml. No relation was found between the weight or sex of the subjects and the pharmacokinetics of the drug. The serum half life of thioridazine in three healthy volunteers was 9, 10 and 10 h respectively. In a group of 22 patients receiving less than 5 mg/kg body weight a day, there was a strong correlation between the dose and the morning or evening concentration of thioridazine in the blood. A positive correlation was also observed between the age of the patient and the serum level in those who received doses of less than 5 mg/kg body weight.
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    European journal of clinical pharmacology 7 (1974), S. 51-58 
    ISSN: 1432-1041
    Keywords: Rifampicin ; plasma level ; pleural fluid concentration ; microbiological assay ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Single oral doses of rifampicin (RMP) were given to 31 patients with pleural effusions of various aetiologies. The concentrations of RMP and its active metabolites in pleural fluid and plasma were determined by an agar diffusion method using paper discs as diffusion centres. The plasma concentrations reached a peak within 3 h and then declined monoexponentially; in pleural fluid, RMP concentration rose slowly to reach a plateau that lasted for several hours. There were marked differences between subjects in the observed concentrations of RMP. During the first 12 h the plasma levels exceeded those in pleural fluid, but after 24 h the concentration of RMP in pleural fluid was higher than in plasma. If multiple oral doses of RMP 10 mg/kg b. w. are given every 24 h, as is common in the treatment of tuberculosis, therapeutic concentrations may be expected in pleural fluid for the major part of each day.
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  • 71
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    European journal of clinical pharmacology 6 (1973), S. 88-92 
    ISSN: 1432-1041
    Keywords: Noradrenaline pools ; 7-3H-noradrenaline ; neuro-effector junction kinetics ; pharmacokinetics ; sympathoadrenergic activity
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A two-compartment model of 73HNA distribution has been developed for studying sympatho-adrenergic activity in intact man. After infusion of 73HNA at constant speed in resting normal subjects, the decay curves of the plasma concentration and urinary excretion of 73HNA were plotted against time. Analysis of the curves yielded constants and indirect indications about noradrenaline exchange processes in the extracellular environment. Complete evaluation of the neuronal pools and of the pathways of biosynthesis and metabolism was impossible, but it seemed likely that 73HNA entered small neuronal pools that underwent rapid exchange with the extracellular environment, a point of some interest in clinical and pharmacologic investigations.
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  • 72
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    European journal of clinical pharmacology 6 (1973), S. 137-140 
    ISSN: 1432-1041
    Keywords: Urography ; Hypaque® ; Urovist® ; pharmacokinetics ; renal failure
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Comparative tests were carried out, using a radioactive tracer method, on the pharmacokinetics of sodium and methylglucamine diatrizoate. A biological model was simulated using an analogue computer; and the rate and elimination constants, the elimination half life, and the ratio of tissue entry to tissue elimination constants were calculated. Over the period of time required for X-ray diagnosis, the two salts of the contrast medium acid which were tested did not alter the pharmacokinetics of the contrast medium itself.
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  • 73
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    European journal of clinical pharmacology 6 (1973), S. 245-250 
    ISSN: 1432-1041
    Keywords: Procaine amide ; N-acetylprocaine amide ; sustained-release ; pharmacokinetics ; ventricular arrhythmia
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ten patients with acute myocardial infarction were studied during treatment with either a conventional or a new sustained-release preparation of procaine amide in order to compare fluctuations in plasma concentration and urinary excretion of the drug during “steady state” conditions. Procaine amide in plasma was measured by spectrofluorimetry and the urine concentration of it and its major metabolite, N-acetylprocaine amide, by gas chromatography. The average fluctuation of plasma concentrations was 3.5±0.1 µg/ml during treatment with sustained-release tablets (dosage interval 8 h) and 4.2±0.4 µg/ml during treatment with ordinary tablets (dosage interval 4 h), i. e. it was 20% greater during treatment with the conventional preparation. There was no difference between the two preparations in recovery of the drug from urine (sustained-release tablets 85.4±3.0%; and conventional tablets 90.3±5.4%). Thus, the new sustained-release preparation of procaine amide administered 3 times daily produced the same range of plasma levels as the identical dose of conventional tablets given 6 times a day.
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  • 74
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    European journal of clinical pharmacology 6 (1973), S. 261-267 
    ISSN: 1432-1041
    Keywords: Alclofenac ; antiphlogistic ; man ; pharmacokinetics ; dosage regimes ; plasma levels
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A one compartment open model has been found to fit plasma concentration data previously obtained in man after single oral doses of alclofenac; the parameters of the model are: $${\text{t}}_{\tfrac{{\text{1}}}{{\text{2}}}} $$ abs=1.3±0.7h, $${\text{t}}_{\tfrac{{\text{1}}}{{\text{2}}}} $$ el=3.5±1.2h, Vd/F=17±6. The model has been used successfully to predict steady-state plasma levels of alclofenac after multiple oral doses. One treatment schedule (initial dose 500 mg, maintenance dose 250 mg five times a day) was administered to two volunteers for five days and the plasma levels of alclofenac determined daily. The latter were in good agreement with computer predictions based on the model. It is now possible, therefore, to select the most suitable dosage regimes for this drug.
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  • 75
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    European journal of clinical pharmacology 7 (1974), S. 17-24 
    ISSN: 1432-1041
    Keywords: Pindolol ; beta-blockade ; pharmacokinetics ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of absorption, distribution and excretion of pindolol have been investigated in 17 volunteers after an oral dose or intravenous infusion of 5 mg. The calculated absorption was 92%. The time course of the plasma levels appeared to follow first order kinetics with an apparent half life of 3.6 (oral) and 3.1 (i.v.) hours. The cumulative urinary excretion att=∞ was 36.1% and 39.2% of the dose administered, respectively, indicating extensive metabolism of the drug. The distribution volume was 136 l. Peak plasma levels were found 80 min after oral administration and they showed up to 4-fold variation after identical doses. Renal clearance was 216 ml×min−1 and total clearance was 483 ml×min−1. In plasma 57% of pindolol was bound to protein.
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  • 76
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    European journal of clinical pharmacology 7 (1974), S. 119-124 
    ISSN: 1432-1041
    Keywords: Anticonvulsants ; phenytoin ; diphenylhydantoin ; bioavailability ; generic inequivalence ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma levels of phenytoin (diphenylhydantoin, DPH) in epileptic patients were significantly higher after treatment with either of two preparations containing the sodium salt of DPH, than after treatment with the same dose of the free acid. This was confirmed in both short and long term studies, and in the latter increased plasma levels of DPH were accompanied by better control of generalized seizures. The degree of acute side-effects in 6 out of 10 patients whose treatment was changed from DPH-acid to DPH-sodium was proportional to the plasma level of DPH; the latter varied from 22.8 to 34.9 µg/ml in affected patients. After a single oral dose in healthy volunteers, the sodium salt of DPH showed much better bioavailability than the free acid. The differences in bioavailability in patients and volunteers probably depended on differences in particle size in the preparations of the sodium salt of DPH and its free acid. The excipient, lactose or starch, did not seem to affect the bioavailability of the two formulations of sodium-DPH.
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  • 77
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    European journal of clinical pharmacology 7 (1974), S. 217-225 
    ISSN: 1432-1041
    Keywords: Rifampicin ; p-aminosalicylic acid ; drug interaction ; isoniazid ; pharmacokinetics ; antituberculous therapy
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Single oral doses of rifampicin (10 mg/kg body weight), p-aminosalicylic acid (0.2 g/kg), isoniazid (10 mg/kg), or rifampicin and either p-aminosalicylic acid or isoniazid, were given to 69 tuberculous patients with normal renal and hepatic function. Ten-fold interindividual differences were observed in the peak serum concentrations and half-lives of rifampicin; its half-life was reduced from 4.3 h after the first dose to 3.1 h after the third dose, possibly due to self-induction of its own metabolism. No effect on its serum concentration or half-life, nor on those of isoniazid, were found after simultaneous oral administration of the two drugs. After treatment with rifampicin and p-aminosalicylic acid, the peak serum level of the former was delayed from 2 to 4 h, it was reduced from 8.0 to 3.8 µg/ml, and the mean area under the serum concentration curve throughout the entire 8 h study period was also lowered by about half. Individual patients did not attain therapeutically effective peak serum concentrations of rifampicin if also treated withp-aminosalicylic acid. The interaction observed between the two drugs is probably due to impaired gastrointestinal absorption of rifampicin, either by alteration of its physico-chemical properties or by a decrease in the gastric emptying rate combined with more rapid intestinal transit. The combination of these two drugs is unsuitable for the routine chemotherapy of tuberculosis.
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  • 78
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    European journal of clinical pharmacology 7 (1974), S. 249-252 
    ISSN: 1432-1041
    Keywords: Practolol ; renal failure ; uraemia ; beta-blockade ; pharmacokinetics ; man
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of renal failure on the excretion of oral doses of practolol has been studied. The plasma half-life increased up to 6.6 times normal and the cumulative urinary excretion of the drug was reduced. There was a linear correlation between the overall elimination rate constant of practolol and inulin and creatinine clearances. A linear correlation was also found between the renal clearances of practolol and inulin. The dose of practolol required for maintenance therapy should be reduced in patients with impaired renal function.
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  • 79
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    European journal of clinical pharmacology 3 (1970), S. 3-11 
    ISSN: 1432-1041
    Keywords: Amphetamine ; drug dependence ; pharmacokinetics ; amphetamine psychosis
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eighteen subjects with amphetamine psychosis were studied with respect to fluid balance, intensity and duration of psychotic symptoms, urinary and plasma amphetamine levels and the relative amounts of unchanged drug and metabolites in urine. On admission to hospital about half of the psychotic patients were dehydrated, the water lack being up to 6.7% of total body weight. The dehydrated subjects had lower renal clearances of amphetamine because of lower rates of urine production. As noted previously there was a strongly positive correlation between urinary pH and the half life (T 1/2) of plasma amphetamine, with an increase inT 1/2 of about 7 h for every unit increase in urinary pH. Patients with alkaline urine had intense psychoses lasting for about 4 1/2 days after the last dose of amphetamine. In patiens with acid urine, the psychotic symptoms were milder, and of about 2 days duration. No correlation was found between the degree of psychosis in different subjects and the plasma levels of the drug. — The ratio between the amounts of labelled metabolites and unchanged drug excreted in urine rose for each day after administration of3H-amphetamine, implying a slower excretion rate for the metabolites than for the parent drug. The relative proportion of metabolites was higher in patients with an alkaline urine, being more than 90% after the first day. — When amphetamine (200 mg i.v.) was given to nonpsychotic, dependent subjects, the peak plasma levels (mean 423 ng/ml) exceeded the highest levels observed during the first day in psychotic patients. However, no psychotic symptoms were observed in these subjects. The volumes of distribution calculated from the monoexponential elimination curves were higher than those previously reported in nondependent subjects. — With an alkaline urine a group of nonpsychotic amphetamine-dependent subjects had significantly longer plasmaT 1/2 (p〈0.05) than a group of drug-naive control subjects. The results suggest that increased tissue binding may be a component in tolerance to amphetamine in dependent humans.
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  • 80
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    European journal of clinical pharmacology 4 (1971), S. 32-37 
    ISSN: 1432-1041
    Keywords: Glibenclamide ; pharmacokinetics ; metabolism ; potentiation of hypoglycemic action ; phenylbutazone
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    Topics: Chemistry and Pharmacology , Medicine
    Description / Table of Contents: Summary Metabolically healthy subjects were given an intravenous injection of 1,13 mg14C-labelled glibenclamide (HB 419). The plasma level, renal elimination of the radioactivity and metabolism of the substance were investigated. Two minutes after administration the HB 419 is virtually present only in the blood and at the end of the distribution period mostly in the extracellular space. 53% of the radioactivity is excreted via the kidneys in the form of metabolites. If glibenclamide is administrated in the same way to the same subjects after pretreatment with phenylbutazone there are no differences in the course of the plasma levels or the rate of elimination from the blood. There is, however, a significant difference in the excretion of the radioactivity in the urine. In the presence of phenylbutazone significantly less HB 419 metabolite is excreted renally. In view of the known alternative route of elimination it is suggested that the amount not excreted in the urine is in compensation eliminated via the bile. There was no difference in the metabolism of glibenclamide between the control and phenylbutazone treated groups. The potentiation by phenylbutazone of HB 419 action, and probably also that of other antidiabetic sulphonylureas, must therefore be due predominantly to other causes (Communication III).
    Notes: Zusammenfassung Stoffwechselgesunde Versuchspersonen erhielten14C-markiertes Glibenclamid in einer Dosis von 1.13 mg/Vpn i.v. gespritzt. Plasmaspiegelverläufe, renale Elimination der Radioaktivität und die Metabolisierung der Substanz wurden untersucht. Zwei Minuten nach der Applikation ist HB 419 praktisch nur im Blutund nach Abschluß der Verteilung weitgehend im Extracellulärraum vorhanden. 53% der Radioaktivität werden über die Nieren in Form von Metaboliten ausgeschieden. Wird den gleichen Probanden nach Prämedikation mit Phenylbutazon Glibenclamid in gleicher Weise verabfolgt, ergibt sich kein Unterschied hinsichtlich der Plasmaspiegelverläufe und der Eliminationsgeschwindigkeit aus dem Blut. Ein signifikanter Unterschied besteht jedoch in der Ausscheidung der Radioaktivität in den Harn (26.3%). In Gegenwart von Phenylbutazon wird ein signifikant geringerer Anteil von HB 419-Metaboliten renal eliminiert. Aufgrund des bekannten zweiten Ausscheidungsweges wird vermutet, daß der fehlende Anteil kompensatorisch über die Galle eliminiert wird. Die Metabolisierung von Glibenclamid weist keine Differenzen zwischen Phenylbutazon-und Kontroll-Gruppe auf. Die Wirkungspotenzierung von HB 419 — wahrscheinlich auch diejenige anderer antidiabetisch wirksamer Sulfonylharnstoffe — durch Phenylbutazon dürfte demnach überweigend andere Ursachen haben. (Mitteilung III).
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    European journal of clinical pharmacology 3 (1970), S. 36-42 
    ISSN: 1432-1041
    Keywords: Sulphonamides ; sylfametopyrazine ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of sulfametopyrazine were studied for seven days after a single oral dose of 2 g. in healthy volunteers in order to establish its chemotherapeutic value. — The appearance and disappearance of the drug in the plasma were evaluated both for compounds with a free amino group and for total sulphonamides. The half-life and absorption, distribution, elimination and excretion coefficients were calculated, as well as the concentrations in plasma water and interstitial fluid. The estimated drug concentrations in the urine agreed with those calculated from the excretion coefficients. — In all subjects at the end of the seventh day the concentrations in all body compartments of active compounds exceeded the minimum required for a therapeutic effect. The highest concentrations found in the urine were always significantly lower than the drug's basal solubility at pH 5, thus excluding any risk of crystalluria.
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  • 82
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    European journal of clinical pharmacology 3 (1971), S. 221-228 
    ISSN: 1432-1041
    Keywords: Biguanides ; butylbiguanide ; pharmacokinetics ; sustained release form
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In man, after oral administration of 50 mg14C-butylbiguanide, the maximum serum concentration was 26–41 µg/100 ml. The biguanide was eliminated with an average half-life of 2h. 84% of the dose administered was found excreted unchanged in the urine. — After administration of14C-butylbiguanide in a sustained release form (Silubin® retard), the drug was slowly released and its serum concentration remained almost constant for up to 7 h.
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  • 83
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    European journal of clinical pharmacology 4 (1972), S. 137-141 
    ISSN: 1432-1041
    Keywords: Fentanyl ; pharmacokinetics ; neuroleptanalgesia ; analogue computer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma levels and urinary excretion of3H-fentanyl were studied in 5 human subjects after intravenous injection of this drug. After an initial rapid decline, the plasma level of fentanyl decreased slowly and approximately exponentially. The plasma concentration of metabolites remained almost steady from 1–3 h after injection. More than 60% of the administered radioactivity was excreted through the kidneys within 4 days. Only a small proportion of it was unchanged fentanyl. The rates of fall of plasma concentration and of urinary excretion were slower in man than in rabbits. — The time courses of plasma concentrations and of urinary excretion were simulated on an analogue computer. The results support the assumption that the different time courses of concentrations in man and rabbits are caused by slower metabolism in man. It seems likely that redistribution plays a dominant part in the short duration of action of fentanyl in man.
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  • 84
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    European journal of clinical pharmacology 4 (1972), S. 150-157 
    ISSN: 1432-1041
    Keywords: Antibiotics ; pharmacokinetics ; microbiological assay ; drug control ; neonatal septicaemia
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The various steps of a paper disc micromethod for quantitative determination of plasma concentrations of antibiotics is described. Only 10 µl of plasma is needed for a single determination, allowing easy and repeated capillary sampling. Separate assay was attempted of three antibiotics in a mixture (streptomycin, cloxacillin and ampicillin), both by use of selective inhibitors (semicarbazide, penicillinase) in the culture medium and by choosing suitable strains of bacteria. In this way, it was possible to determine streptomycin and cloxacillin separately when all three antibiotics were present simultaneously in the plasma. The assay of ampicillin, however, was always influenced by the presence of even small concentrations of cloxacillin. The 95% confidence intervals of the standard curves for the three antibiotics are presented. — The method is suitable both for pharmacokinetic studies and for routine clinical control of plasma antibiotic levels, even in premature children.
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  • 85
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    Cell & tissue research 103 (1970), S. 192-217 
    ISSN: 1432-0878
    Keywords: Cartilage ; Calcification ; Calcifying globules
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    Topics: Biology , Medicine
    Notes: Summary The cartilage matrix in which the early calcium salts are deposited has been studied in the tibial epiphyses and in the costo-chondral junctions of 30-day-old guinea pigs. The results may be summarized as follows: (1) Structures of globular shape (“globules”) are to be found throughout the entire epiphyseal plate. (2) They have a homogeneous matrix and are bounded by a membrane. (3) Early calcification occurs in globules. Calcification of collagen fibrils seems to occur later. (4) The earliest mineral deposited would seem to consist of tiny granules about 20 Å in diameter. Then apatite crystals are laid down, initially in small clusters and later filling the globules completely. (5) The globules are strongly osmiophilic. They seem to contain a fair amount of neutral polysaccharides, but no acid polysaccharides except a coating on their outer membrane. Hyaluronidase digestion does not affect globules. Papain digestion makes them more reactive to uranium and lead. (6) Globules are of cellular origin but they are almost certainly not pre-formed in the chondrocytes. Finally, the present paper advances the hypothesis that some globules derive from degenerating chondrocytes and others from the processes of normal chondrocytes.
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    Journal of pharmacokinetics and pharmacodynamics 1 (1973), S. 51-68 
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; cancer chemotherapy ; cell kinetics ; mathematical model ; cell cycle specific drugs
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    Topics: Chemistry and Pharmacology
    Notes: Abstract Predictive models have been developed to simulate cancer cell populations under treatment with cytotoxic drugs, with both direct-acting and cell cycle specific drugs being considered. Models of cell growth kinetics have been combined with simple pharmacokinetic models to complete the cell-drug interaction system. The models depend on knowing the distribution of generation time in the cell population, the cell-drug interaction, and the local concentration of the drug at the effective site. All of the quantities can be obtained, in principle, from separate experiments and combined to form a model describing several aspects of the cell-drug response system.
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  • 87
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    Journal of pharmacokinetics and pharmacodynamics 1 (1973), S. 497-520 
    ISSN: 1573-8744
    Keywords: tissue distribution ; plasma protein binding ; tissue protein binding ; fat/water partition coefficient ; volumes of distribution ; corticosterone ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The concentration of a drug at its site of action will be affected by the ability of the drug to distribute to and pass through various membranes and tissues. Mechanisms of drug distribution are summarized in this paper and include the differences between intracellular and extracellular pH,active transport systems for drugs, distribution of drugs between fat and water in adipose tissues, the reversible binding of drugs to phospholipids and to various macromolecules including proteins, nucleic acid, and melanin. These mechanisms usually tend to decrease the concentration of unbound drugs at their sites of action, but usually not to the extent one would predict on the basis of in vitrobinding studies. The effects of drug distribution in altering the biological half-lives of drugs in the body are discussed as well as the interrelationship between the kinetic volumes of distribution for drugs and blood flow rates through the organs that eliminate these drugs. These concepts are illustrated for corticosterone levels following intravenous bolus injections and infusions into rats.
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    Journal of pharmacokinetics and pharmacodynamics 1 (1973), S. 341-361 
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; pharmacokinetic models ; bioavailability ; clinical metabolic profile ; chronic dosing regimens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The present status of pharmacokinetics is reviewed. Pharmacokinetic models and the basic concepts involved in applying models to blood, urine, bile, and tissue levels of drugs and metabolites are discussed. An outline of methods for pharmacokinetic analyses is proposed. Special emphasis is given to the determination of bioavailability of a drug from various dosage forms. Uses of pharmaco-kinetics in determining sites of drug action and in determining a clinical metabolic profile are suggested. The perturbations of magnitudes of pharmacokinetic parameters among individuals challenged with the drug can be used as a diagnostic tool in evaluating the state of dynamic processes, the presence of metabolic diseases and genetic abnormalities, and the failure of physiological functions. The use of pharmacokinetics and the prediction of chronic dosing regimens are reviewed. Typical curves depicting predicted blood levels on repetitive dosing are presented.
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    Journal of pharmacokinetics and pharmacodynamics 2 (1974), S. 123-148 
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; computer program ; NONLIN ; data weighting ; isoniazid
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    Topics: Chemistry and Pharmacology
    Notes: Abstract Several important statistical aspects of pharmacokinetic analyses by digital computer are discussed. These include selection of appropriate equations, weighting of data, precision of parameter estimates, comparisons of parameters, analysis of weighted residuals, and criteria useful in the selection of particular models. Data obtained after administration of isoniazid and isonicotinuric acid to man are analyzed to illustrate the usefulness of the discussed methods.
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    Journal of pharmacokinetics and pharmacodynamics 1 (1973), S. 521-540 
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; polygenically controlled disease states ; pharmacokinetic twin studies ; pharmacokinetic heritability ; ethanol ; antipyrine ; phenylbutazone ; bishydroxycoumarin.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The application of pharmacokinetics to the elucidation of polygenic factors involved in drug disposition is discussed in the context of three questions: (a)How extensive is the variation among individuals in rate of plasma clearance for commonly used drugs? (b)If appreciable variation occurs, what are the relative contributions of genetic and environmental factors to its maintenance? (c) What role is played by polygenic factors in maintaining this variation?Large variance in plasma decay rates for phenylbutazone, ethyl biscoumacetate, antipyrine, isoniazid, and nortriptyline is noted throughout the general population. However, these large variations appear to be controlled predominately by genetic rather than by environmental factors on the basis of studies run on identical and fraternal twins. At the present time, an individual's capacity to metabolize drugs and the effects of various conditions in altering that basal, genetically determined capacity seem to be best indicated by measurements of the plasma antipyrine half-life. While the theoretical advantages of obtaining blood concentrations of drugs as a guide to their more rational administration are evident, several practical problems are discussed in this paper.
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    Journal of pharmacokinetics and pharmacodynamics 2 (1974), S. 495-509 
    ISSN: 1573-8744
    Keywords: hepatobiliary transport ; rat ; bromphenol blue ; pharmacokinetics ; roles of liver cytoplasmic Y- and Z-binding proteins and T binder
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    Topics: Chemistry and Pharmacology
    Notes: Abstract A new pharmacokinetic model is proposed to explain the hepatobiliary transport of a nonmetabolized sulfonic acid dye, bromphenol blue, which is actively transported from the bloodstream into bile. This model has the advantage of taking into account the roles of the liver cytoplasmic Y- and Z- binding proteins and T binder.
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  • 92
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    Keywords: digoxin ; pharmacokinetics ; two-compartment model ; three-compartment model ; radioimmunoassay
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    Topics: Chemistry and Pharmacology
    Notes: Abstract An experiment has been carried out in man designed to compare the fit of a two- and a three-compartment pharmacokinetic model to experimentally determined serum digoxin concentration-time data following rapid intravenous injection of 1.0 mg of the drug. Digoxin was administered to five healthy male volunteers, blood samples were withdrawn repetitively over a period of 72 hr, and samples were assayed using a 125 I radioimmunoassay. Appropriate equations describing two- and three-compartment open models were fitted to the experimental data using weighted nonlinear least squares regression analysis. It was demonstrated that the three-compartment fit resulted in a statistically significant reduction in residual error, a marked improvement in the randomness of scatter of the experimental data about the serum digoxin-time curve, and better agreement of the predicted serum concentration-time curve with experimental serum digoxin concentrations. Thus the three-compartment open model is the simplest pharmacokinetic model consistent with the data observed in this experiment.
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    Journal of pharmacokinetics and pharmacodynamics 1 (1973), S. 137-163 
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; nonlinear regression ; drug distribution ; compartmental models ; computer program ; BASIC ; time sharing ; spectinomycin ; naloxone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract COMPT, a computer program for optimizing the solution of integral compartmental models of drug distribution by nonlinear regression analysis, is written in extended BASIC for use in time-sharing computer systems. It is based on Hartley's modification of the Gauss-Newton gradient method. The characteristics and features of the program are indicated, and the program source listing is presented. This version of COMPT is designed to solve the two-compartment open model of intravenous drug administration. Examples of the results of the operational program are presented. The program is modifiable to permit analytical solutions for other types of systems described by nonlinear equations.
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    Journal of pharmacokinetics and pharmacodynamics 1 (1973), S. 175-200 
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; cancer chemotherapy ; pharmacodynamics ; cell kinetics ; vincristine ; vinblastine ; arabinosylcytosine ; cyclophosphamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A pharmacodynamic model is proposed and equations are developed for the quantitative analysis of dose-time-cell-survival curves produced by the administration of cell-cycle-specific chemo-therapeutic agents. The essential feature of the model is an irreversible, bimolecular mechanism of drug-receptor interaction which serves as the interface between the pharmacokinetics of the drug and the cell-cycle-cell-proliferation kinetics of the normal and neoplastic cells. A preliminary cell system which allows adequate characterization of the experimental data is a two-compartment model where cells are assumed to exist in their proliferative and nonproliferative phases. The chemotherapeutic model was used to analyze dose-time-cell-survival curves found in the literature for the effects of vincristine, vinblastine, arabinosylcytosine, and cyclophosphamide on lymphoma and hematopoietic cells in the mouse femur. Similarity in the values of the “cell-kill” constants for these drugs on the two cell types indicates that, in the cell systems studied, the proliferative state of the cells is the primary in vivodeterminant of selective chemotherapy.
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  • 95
    ISSN: 1573-8744
    Keywords: absorption ; amphetamine ; bioavailability ; elimination ; pharmacokinetics ; phentermine ; resin-bound drugs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Plasma levels of amphetamine and phentermine have been measured in man in a crossover study of the pharmacokinetics of these agents following oral administration of resin-bound and soluble salt formulations. The one-compartment open model with first-order drug absorption was fitted to the data from each subject by nonlinear regression methods and provided an excellent fit. Relative bioavailability of the two salts did not differ for either drug. In both cases the rate constant for absorption was significantly lower and less variable for the resinated compound.
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  • 96
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    Journal of pharmacokinetics and pharmacodynamics 1 (1973), S. 295-305 
    ISSN: 1573-8744
    Keywords: diazoxide ; pharmacokinetics ; stable-isotope dilution ; GC-mass fragmentography ; solubility ; excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A specific, sensitive, and accurate assay for diazoxide in human plasma and urine samples was developed utilizing stable-isotope dilution-GC-mass fragmentography. 3-Trideuterodiazoxide (d 3-diazoxide) served as internal standard, and diazoxide was N-methylated with diazomethane prior to GC. Plasma elimination half-lives of diazoxide ranged within 20–53 hr in four severely hypertensive patients, which did not correlate with endogenous plasma creatinine levels. A rapid infusion over 10–15 sec of an antihypertensive dose presumably resulted in a very transient precipitation of diazoxide due to its limited solubility of approximately 380 Μg/ml plasma. Urinary excretion accounted for 4–6% of the dose within 24 hr after administration in the four patients studied and totalled 19% and 22% in two patients. Renal clearance of diazoxide was below 1 ml/min on the first day following administration and increased to 2–3 ml/min on consecutive days. It was concluded that renal excretion of diazoxide is self-limited by antihypertensive doses in severely hypertensive patients. The major route of elimination in these patients may be due to metabolism.
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  • 97
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    Journal of pharmacokinetics and pharmacodynamics 1 (1973), S. 89-98 
    ISSN: 1573-8744
    Keywords: clindamycin ; clindamycin-2-palmitate ; clindamycin-2-hexadecylcarbonate ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract To determine the bioavailability of clindamycin from the microbiologically inactive clindamycin-2-palmitate and clindamycin-2-hexadecylcarbonate in man, a three-way crossover study was conducted with oral administration of the two esters and clindamycin hydrochloride. In each case, serum clindamycin bioactivity concentrations were fitted to a one-compartment open model with an initial lag time. Analysis of variance of measured quantities (serum concentrations and urinary excretion) and of derived pharmacokinetic parameters showed that for every comparison except maximum serum concentrations clindamycin-2-palmitate was not significantly different (at p=0.05) from clindamycin hydrochloride. Clindamycin-2-hexadecylcarbonate gave significantly different values from those for the hydrochloride in all cases except the rate constant and half-life for elimination from the serum. The palmitate was the superior ester and was bioequivalent to the hydrochloride in man.
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  • 98
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    Journal of pharmacokinetics and pharmacodynamics 2 (1974), S. 347-364 
    ISSN: 1573-8744
    Keywords: metoprolol ; β-receptor antagonist ; pharmacokinetics ; disposition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics of 3H-metoprolol, a new selective β 1-receptor antagonist, have been studied in healthy volunteers by following the plasma concentrations and the urinary excretion of the unchanged compound and its total radioactive metabolites after oral and intravenous administration. The compound was rapidly and completely absorbed after oral administration, and about 40% of the dose reached the systemic circulation. The estimated half-life of the absorption process was 10 min. Metoprolol was extensively distributed to extravascular tissues, with the half-life of the distribution phase close to 12 min. About 95% of the dose was excreted in the urine within 72 hr, mainly in metabolized form. The elimination halflife of the compound was close to 3 hr as was also the half-life of the total metabolites after oral administration. After intravenous administration, the elimination half-life of the metabolites was raised to 5 hr, indicating that the route of administra tion might influence the metabolic pathways of the parent compound.
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  • 99
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    Bulletin of experimental biology and medicine 78 (1974), S. 1150-1152 
    ISSN: 1573-8221
    Keywords: methindione ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The pharmacokinetics of the new anticonvulsant, methindione, carbon-labeled in the carbonyl and N-methyl groups, was studied in experiments on rats. Methindione is quickly absorbed from the gastro-intestinal tract and passes easily through tissue barriers. The highest concentration of methindione in the brain is observed 15–30 min after administration. The metabolism of methindione and its elimination from the tissues take place rapidly. In most tissues only 6–23% of its maximal concentration still remains after administration of the drug. Metabolites of methindione, labeled in the carbonyl group, are excreted mainly through the kidneys, but metabolites labeled in the N-methyl group are excreted chiefly through the lungs.
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  • 100
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    Bulletin of experimental biology and medicine 78 (1974), S. 1379-1381 
    ISSN: 1573-8221
    Keywords: fluorouracil ; pharmacokinetics ; radiometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The dynamics of the concentration of radioactivity in the blood serum, organs, and urine was investigated after intravenous injection of 5-fluorouracil-2-C14 into rats. The preparation is rapidly absorbed from the blood into the tissues in which it accumulates rapidly in high concentrations and it is excreted quickly from the body. The half-elimination period of 5-fluorouracil in the blood is 15 min. It is excreted chiefly by extrarenal routes.
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