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  • Lepidoptera  (146)
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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of nutrition 22 (1983), S. 185-194 
    ISSN: 1436-6215
    Keywords: sugar substitutes ; D-glucose ; bioavailability ; D-glucitol (D-sorbitol) ; D-mannitol ; Palatinit® ; D-glucosyl-α(1→1)-D-mannitol ; D-glucosyl-α(1→6)-D-glucitol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Zusammenfassung Zur Vertiefung des Verständnisses vom Stoffwechsel des Zuckeraustauschstoffes Palatinit® wurden seine zwei Bestandteile D-Glucosyl-α(1→1)-D-mannit und D-Glucosyl-α(1→6)-D-glucit [D-Glucosyl-α(1→6)-D-sorbit] nach dem Verfahren von Karimzadegan et al. auf ihre Glucose-Bioverfügbarkeit an ketotischen Ratten untersucht. Bei Umwandlungsraten in Glucose von 6 bzw. 20 % für Mannit und Glucit (Sorbit) sowie von 39 bzw. 42% für Glucosylmannit und Glucosylglucit erhält demnach der metabolische Glucose-Pool nicht das volle Glucose-Äquivalent aus diesen Verbindungen. Von dem Anteil an präformierter Glucose in den Glucosylhexiten — theoretisches Maximum 50 % — sind nur 36 % aus Glucosylmannit bzw. 32 % aus Glucosylglucit bioverfügbar. Die im Vergleich zur Theorie verminderte Bioverfügbarkeit von Glucose aus Palatinit® wird auf partiellen mikrobiellen Abbau in unteren Darmabschnitten zurückgeführt. Die an Ratten erhaltenen Ergebnisse werden auch für alle anderen Spezies gelten, welche in Caecum und/oder Colon Kohlenhydrate vergären. Die Unterschiede zwischen D-Glucosyl-α(1→1)-D-mannit und D-Glucosyl-α(1→6)-D-glucit werden durch unterschiedliche Verzögerung der Glucoseresorption im Dünndarm, wo auch D-Glucit angreift, bedingt. Die Ermittlung der Glucose-Bioverfügbarkeit gewährt weitgehende Einblicke in das Schicksal von Kohlenhydraten einschließlich der Symbiose zwischen Säugetier und Mikroorganismen im Dickdarm. Da ein ziemlich vollständiger Überblick über die metabolischen Konsequenzen nach ihrer Zufuhr erhalten wird, sollte das Verfahren zur Messung der Bioverfügbarkeit von Glucose daher bei Abschätzungen der Lebensmittelsicherheit anderer Zuckeraustauschstoffe ebenfalls angewandt werden.
    Notes: Summary For the sake of metabolic insight into the fate of the sugar substitute Palatinit®, its two components D-glucosyl-α(1→1)-D-mannitol and D-glucosyl-α(1→6)-D-glucitol [D-glucosyl-α-(1→6)-D-sorbitol] were assayed for glucose bioavailability by the procedure of Karimzadegan et al. using ketotic rats. With conversion rates into glucose of 6 and 20 %, respectively, for free mannitol and glucitol (sorbitol), 39 % for glucosylmannitol and 42 % for glucosylglucitol, the metabolic glucose pool of the rat does not receive the full carbohydrate complement of these compounds. The preformed glucose moiety of the glucosylhexitols is bioavailable by 36 and 32 %, respectively, from glucosylmannitol and glucosylglucitol, with 50 % as theoretical maximum. Less than theoretical bioavailability of glucose from Palatinit® is ascribed to microbial attack in the hindgut. The data on rats are held valid also for other species demonstrating carbohydrate fermentation in the caecum and/or colon. Differences between D-glucosyl-α(1→1)-D-mannitol and D-glucosyl-α(1→6)-D-glucitol are caused by a differential delay of glucose absorption in the small intestine, also exerted by D-glucitol. The deep metabolic insight offered by the glucose bioavailability assay into the fate of carbohydrates includes the mammal-microbial symbiosis in the large bowel. Since a rather complete survey of the metabolic consequences after their intake can be obtained, the assay system should be generally applied in assessments of food safety also of other sugar substitutes.
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  • 2
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    Springer
    Monatshefte für Chemie 112 (1981), S. 149-156 
    ISSN: 1434-4475
    Keywords: Calcium ; Gallium ; Oxygen ; Single Crystal ; X-Ray
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The hitherto unknown compound Ca3Ga4O9 was prepared and investigated by X-ray single crystal methods. Ca3Ga4O9 has orthorhombic symmetry:a=1435.8;b=1682.5;c=532.1 pm; space group C 2v 11 −Cmm2,Z=6. The tetrahedra network (circles of 4 and 5 GaO4-tetrahedra) and the surrounding of Ca2+ are described and discussed with respect to other oxogallates.
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  • 3
    ISSN: 1570-7458
    Keywords: host-plant relations ; host variation ; Malacosoma americanum ; Malacosoma disstria ; Lasiocampidae ; Geometridae ; Lepidoptera ; niche breadth ; specialization ; plantinsect interactions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Zusammenfassung Raupen von Malacosoma americanum (F.), einer oligophagen Art, die sich vor allem auf Prunus und andern baumartigen Rosaceen entwickelt, wurden verglichen mit Raupen der polyphageren Verwandten M. disstria Hb. und zwar im Hinblick auf deren Empfindlichkeit auf Unterschiede im Blatt ihrer gemeinsamen Wirtspflanze, Prunus serotina Ehrh. Das Puppengewicht und die Entwicklungszeit bis zur Verpuppung wurden gemessen bei Raupen, welche auf Blättern von freiwachsenden und von beschatteten Jungpflanzen gezüchtet worden waren. Die Blattunterschiede hatten eine ausgesprochene Wirkung, aber es gab keine Unterschiede in der Reaktion der beiden Arten. Dieser Vergleich lässt vermuten, dass die Empfindlichkeit auf intraspezifische Unterschiede der Wirtspflanzenqualität bei wirtsspezifischen und polyphagen Arten gleich ist. Indessen dürften sich laut anderen Resultaten einige Insektenarten anders verhalten.
    Notes: Abstract Larvae of Malacosoma americanum (F.)(Lepidoptera: Lasiocampidae) an oligophagous species that feeds primarily on Prunus and other rosaceous trees, were compared to larvae of the more highly polyphagous congener M. disstria Hb., with respect to their sensitivity to variation in the foliage of a common host plant, Prunus serotina Ehrh. Pupal weight and time to pupation were measured on larvae reared on foliage from open-grown and from shaded saplings. The difference in foliage had a pronounced effect, but no difference was evident between the species in their response to the variation in foliage. This comparison implies that sensitivity to intraspecific variation in host quality does not differ between host-specific and generalized species. However, results from other species suggest that some species of insects do differ in this respect.
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  • 4
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    Entomologia experimentalis et applicata 30 (1981), S. 106-110 
    ISSN: 1570-7458
    Keywords: assimilation efficiency ; growth efficiency ; niche breadth ; specialization ; hostplant relations ; plant-insect interactions ; Malacosoma americanum ; Malacosoma disstria ; Lasiocampidae ; Lepidoptera
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Zusammenfassung Raupen von Malacosoma americanum, einer oligophagen Art, die sich vor allem auf Prunus und andern baumartigen Rosaceen. entwickelt, wurden mit Raupen der polyphageren Verwandten M. disstria in Hinblick auf die Verwertung der Blätter ihres gemeinsames Wirtes Prunus serotina verglichen. Wirerhielten ähnliche Werte wie sie früher für andere Lepidopteren publiziert worden waren und zwar in Bezug auf die üblichen Messwerte, Anteil verwertete Nahrung, Wachstum in Trockengewicht pro Einheit gefressene oder verwertete Nahrung. Zudem unterschieden sich die beiden Arten in keiner Masszahl für Effizienz. Unsere Resultate sind im Einklang mit der Folgerung, das spezialisierte phytophage Insekten ihre Wirtspflanzen nicht besser ausnützen als as polyphage Arten tun.
    Notes: Abstract Larvae of Malacosoma americanum (F.) an oligophagous species that feeds primarily on Prunus and other rosaceous trees, were compared to larvae of the more highly polyphagous congener M. disstria Hb., with respect to the efficiency of utilization of the foliage of a common host plant, Prunus serotina Ehrh. We obtained values similar to those reported for other Lepidoptera for the commonly used measures of the fraction of ingested food that was assimilated, and for the growth in dry weight per unit of food ingested or assimilated. Moreover, the two species did not differ in any measure of efficiency. Our results are compatible with the conclusion that specialized phytophagous insects do not use their host plants with greater physiological efficiency than do generalized insects.
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  • 5
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    Entomologia experimentalis et applicata 34 (1983), S. 174-178 
    ISSN: 1570-7458
    Keywords: Lepidoptera ; Pyralidae ; Maruca testulalis ; Pod borer ; Development ; Nutritional suitability ; Host plant ; Crotalaria ; Vigna unguiculata
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Résumé Les possibilités de développement larvaire de Maruca testulalis sur les fleurs de huit espèces végétales ont été examinées en laboratoire. La comparaison a porté sur Crotalaria retusa, C. juncea, C. saltiana, C. misereniensis, C. mucronata, C. amazonas, Cajanus cajan et l'hôte principal de cette chenille, Vigna unguiculata. En tenant compte de la mortalité larvaire et des indices de croissance (G.I.), ces plantes ont été divisées en trois catégories principales: 1 celles provoquant une mortalité larvaire de 0–30% et ayant des G.I. ≥60%, constituent les plantes hôtes convenables (Vigna unguiculata seule); 2 les plantes qui provoquent une mortalité larvaire de 30≤50% et ont des G.I. de 30 à 60% de la plante hôte principale (Cajanus cajan, Crotalaria amazonas, C. saltiana, C. mucronata; 3 les plantes qui causent 50–100% de mortalité larvaire et dont les G.I. sont inférieurs à 30% de la plante hôte principale (Crotalaria retusa, C. juncea, C. misereniensis). Les résultats déjà publiés sur les choix du lieu de ponte des femelles et l'utilisation de C. juncea comme plante piège, sont discutés à la lumière de ces données nouvelles.
    Notes: Abstract Flowers of eight plant species were evaluated under laboratory conditions for their suitability as larval growth media for the cowpea pod borer, Maruca testulalis. The plants tested were Crotalaria retusa, C. juncea, C. saltiana, C. misereniensis, C. amazonas, Cajanus cajan and the principal host of the borer, Vigna unguiculata (cowpea), was included for comparison. Based on the data obtained on larval mortality and growth indices (GI) the plants were divided into 3 categories namely: I: Those causing 0–30% mortality and having GI value ≥60% form suitable host plants. This group only included V. unguiculata. — II: Those plant species causing 30≤50% larval mortality and having GI value 30%≤60% of the principal host plant (Cajanus cajan, Crotalaria amazonas, C. saltiana, C. mucronata). This group of species is marginally suitable as hosts. — III: Plants causing 50–100% larval mortality and having GI value ≤30% of principal host plant (C. retusa, C. juncea and C. misereniensis). Previously published data on the oviposition preference of the adult moth are discussed in the light of the present findings and the use of C. juncea as a possible trap crop.
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  • 6
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    Entomologia experimentalis et applicata 34 (1983), S. 203-205 
    ISSN: 1570-7458
    Keywords: Lepidoptera ; Sesiidae ; Synanthedon vespiformis ; Paranthrene tabaniformis ; Chamaesphecia empiformis ; Chamaesphecia tenthrediniformis ; Attractants ; Pheromones ; Clearwing moths ; Nemapogon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
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  • 7
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    Entomologia experimentalis et applicata 30 (1981), S. 280-292 
    ISSN: 1570-7458
    Keywords: Allozyme variation ; Lepidoptera ; Yponomeuta padellus ; evolutionary stages ; F-statistics ; panmixis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Résumé Le degré de différenciation génétique en allozymes à des niveaux divers de divergence évolutive (populations conspécifiques, sibling species et non-sibling species) d'Yponomeuta a été déterminé. Les distances génétiques entre des sibling species ou des non-sibling species sont très larges. Il en est conclu que de telles estimations ne fournissent pas beaucoup d'informations sur le phénomène de spéciation même. Des coéfficients de reproduction consanguine (F ST) ont été calculés pour des populations d'Y. padellus provenant de six plantes-hôtes. La valeur moyenne F STest .030±.012. Les valuers de F ST des populations recueillies sur Crataegus, (plante-hôte habituelle d'Y. padellus), sont inférieures 2–3.5 fois à celles des populations de l'ensemble des autres plantes-hôtes. L'apparition de races en fonction de l'hôte, mesurée par les différences importantes dans de fréquences des allozymes entre populations sympatriques sur plusieurs plantes-hôtes, a été examinée dans quatre régions. Il apparaît ainsi que la formation de races en fonction de l'hôte se produit chez Y. padellus et que la spéciation sympatrique est un évènement très vraisemblable.
    Notes: Abstract The amount of genetic differentiation at various levels of evolutionary divergence (conspecific populations, sibling species and non-sibling species) in Yponomeuta was determined. Genetic distances between siblings or non-siblings were found to cover a wide range. It is concluded that such estimates do not give much information on the speciation process itself. Inbreeding coefficients were calculated for populations of Y. padellus from a total of six host plants. The grand mean F ST value is 0.030±0.012. F ST values for populations sampled from Crataegus, the common food plant of Y. padellus, are 2–3.5 times smaller than those for populations from the other food plants taken together. Host race formation, as measured by significant differences in allozyme frequencies between sympatric populations on two or more food plants, was investigated in four areas. Host race formation seems to occur in Y. padellus and sympatric speciation is a likely event.
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  • 8
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    Entomologia experimentalis et applicata 34 (1983), S. 20-26 
    ISSN: 1570-7458
    Keywords: Dioryctria abietella ; Cone pyralid ; Lepidoptera ; Pyralidae ; Sex pheromone, (Z,E)-9,11-tetradecadienyl acetate ; Single sensillum recordings ; Electroantennography ; Gas chromatography ; Mass spectrometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Résumé L'analyse en chromatographie gazeuse associée à une détection électroantennographique a montré que l'acétate (Z,E)-9,11-tétradécadiényle (Z,E)-9,11–14:Ac est l'un des composants de la phéromone de Dioryctria abietella Schiff (Lepid.: Pyralidae). Couplage chromatographie en phase gazeuse spectrometrie de masse a montré la présence d'acétate tétradécadiényle avec un spectre de masse et un indice de rétention identiques au Z,E-9,11–14:Ac Un récepteur cellulaire sensible à la fois au Z,E-9,11–14:Ac et à un extrait de la femelle a été identifié sous l'antenne du mâle. Les analyses des antennogrammes et de la cellule isolée ont étayé la caractérisation du composant de la phéromone comme étant Z,E-9,11–14:Ac. Un récepteur cellulaire additionnel sensible à l'acétate (Z.)-9-tétradécadiényle et à l'acétate (Z.E.)-9,12-tétradécadiényle a été trouvé sur l'antenne du mâle, mais il n'était pas activé par l'extrait de la femelle. Sur le terrain Z,E-9,11–14:Ac, présenté seul, attirait des nombres importants de mâles de D. abietella. L'addition de l'acétate (Z)-9-tétradécényle a inhibé l'attraction des mâles par les pièges.
    Notes: Summary Gas chromatographic analyses coupled with electro-antennographic detection indicated that (Z,E)-9,11-tetradecadienyl acetate (Z,E-9, 11–14:Ac) is a pheromone component of the cone pyralid Dioryctria abietella. Gas chromatographic-mass spectrometric analyses confirmed the presence of a tetradecadienyl acetate with mass spectrum and retention index identical to Z,E-9,11–14:Ac. A receptor cell sensitive to both Z,E-9,11–14:Ac and the female extract was identified on the male antenna. An additional receptor cell sensitive to (Z)-9-tetradecenyl acetate and (Z,E)-9,12-tetradecadienyl acetate was found on the male antenna but was not activated by the female extract. In the field Z,E-9,11–14:Ac presented alone attracted significant numbers of male D. abietella. Addition of (Z)-9-tetradecenyl acetate inhibited the attraction of males to traps.
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  • 9
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    Entomologia experimentalis et applicata 36 (1984), S. 15-16 
    ISSN: 1570-7458
    Keywords: sex attractants ; Lepidoptera ; Noctuidae ; Orthosia incerta ; Orthosia cruda ; fruit pest ; Z9-14:Ac ; Z9-14:Ald ; Z11-16:Ac ; Z11-16:Ald
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
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  • 10
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    Entomologia experimentalis et applicata 34 (1983), S. 65-70 
    ISSN: 1570-7458
    Keywords: Insect growth regulators ; Anti-juvenile hormone ; Fluoromevalonate ; Precocious metamorphosis ; Premature pupation ; Ecdysis ; Fall webworm ; Hyphantria cunea ; Lepidoptera ; Arctiidae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Zusammenfassung Fluormevalosäure (FMev), bekannt als ein spezifischer Inhibitor der Biosynthese des Juvenilhormons (JH) in Insekten, wurde in 0,1–50 μg/Tier Dosis topikal an 3., 4. und 5. Larvenstadien von Hyphantria cunea getestet. Die Raupen wurden auf einem semi-synthetischen, künstlichen Nährboden bei 25° und unter Langtagsbedingungen (18 : 6 St., Licht/Dunkel) gezüchtet. Diese Verbindung rief drei verschiedene Typen spezifischer Reaktionen hervor: 1) verfrühte Metamorphose, 2) gehemmte Häutung und 3) verlängerte Larvenentwicklung. Vor der verfrühten Verpuppung wurde normales Verhalten beobachtet. Die Larven des 3. oder 4. Stadiums häuteten sich meist erst nach einem interkalaren Larvenstadium in verfrühte Puppen. Unter den drei Larvenstadien erwies sich das 5. Stadium gegen die Anti-JH-Verbindung am empfindlichsten. In allen getesteten Entwicklungsphasen wiesen die frisch gehäuteten Larven die höchste Empfindlichkeit gegen FMev auf. Nach der Häutung wurde stufenweises Absinken der FMev-Empfindlichkeit beobachtet, im 5. Larvenstadium verursachte die Verbindung jedoch selbst am letzten Tag des Wachstums zu einen relativ hohen Prozentzahl verfrühte Verpuppung. Eine zweite typische Wirkung von FMev war die Hemmung der Häutungsprozesse. Zwei grundlegende Stufen der Häutungsstörungen unterschieden sich voneinander: 1) Als Folge der Anwendung hoher Dosen von FMev konnte die Mehrzahl der Raupen die alte Larvenkutikula nicht öffnen und ging deswegen in kurzer Zeit zugrunde. 2) Bei Behandlung mit niedrigen Dosen der Anti-JH-Verbindung häuteten sich einige Hyphantria-Larven scheinbar normal; nach der Häutung waren aber alle unfähig, die normalen Bewegungen und die Nahrungsaufnahme fortzusetzen. Auch die vorzeitigen Puppenhäutungen wurden in meisten Fällen durch die Anti-JH-Behandlung gehemmt. Die morphogenetischen Wirkungen von FMev konnten durch eine topikale Behandlung mit Hydroprene, einem hochaktiven JH-Analogen, vollständig oder teilweise verhindert werden.
    Notes: Summary Fluoromevalonate (FMev, ZR-3516) known as an inhibitor of JH biosynthesis was topically applied in 0.1 to 50 μg/specimen doses to the 3rd, 4th, and 5th instar caterpillars of Hyphantria cunea Drury. The anti-JH compound induced 3 main types of specific responses: 1) precocious metamorphosis, 2) inhibition of ecdysis, and 3) prolongation of larval development. Precocious pupation was accompanied by behavioural events typical of normal pupation. Third and 4th instar larvae metamorphosed prematurely mostly with the intervention of an intercalary larval instar. The 5th instar exhibited the highest sensitivity to the anti-JH agent. Within each larval stage the freshly moulted insects proved to be the most susceptible to FMev. Afterwards, the incidence of morphogenetic reaction gradually decreased with age. In another fraction of Hyphantria larvae not responding with precocious pupation, FMev evoked varying degrees of ecdysial disturbance which always resulted in the death of caterpillars. In most cases the anti-JH compound inhibited the premature pupal moult, too, and these affected insects died as tanned pharate pupae. A complete or partial “rescue” from the effects of FMev was elicited, if simultaneously or subsequently, a single topical dose of a JH analogue, hydroprene was also administered.
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  • 11
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    Entomologia experimentalis et applicata 30 (1981), S. 123-127 
    ISSN: 1570-7458
    Keywords: Sex Pheromones ; Repellent ; Heliothis armigera ; Heliothis zea ; Lepidoptera ; Noctuidae ; cotton bollworm ; corn earworm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Résumé L'examen en olfactomètre a porté sur les réactions face à d'autres femelles de la même espèce, de femelles vierges ou ayant copulé d'Heliothis armigera Hübner et H. zea Boddie. Le lot comprenait 8 femelles, vierges ou ayant copulé en présence d'une femelle vierge ou ayant copulé. Les 4 combinaisons possibles de femelles vierges et de femelles ayant copulé ont été examinées avec 12 répétitions pour chaque espèce. Un extrait de l'extrémité de l'abdomen de femelles vierges d'une espèce a été présenté aux femelles de l'autre espèce pour examiner les possibilités de réactions interspécifiques aux phéromones. Pour chaque espèce, les réactions interspécifiques de répulsion entre femelles ont été hautement significatives par rapport aux témoins, à l'exception toutefois des réactions de femelle ayant copulé face à des femelles ayant elles aussi copulé. Les répulsions moyennes chez H. armigera et H. zea pour les 8 femelles de chaque expérience ont été: a) vierges en présence d'une vierge: 7,33 et 7,66; b) vierges en présence d'une femelles ayant copulé: 5,76 et 5,58; c) femelles ayant copulé en présence d'une vierge: 4,67 et 4,83. Les différences sont hautement significatives entre chaque paire de moyennes et entre chaque paire et le lot témoin; 3,17; 3,17; 3,42; 4,00 pour H. armigera; 3,17; 3,50; 2,83 et 3,75 pour H. zea. Les femelles vierges des deux espèces, H. armigera et H. zea ont présenté une réaction de répulsion en présence d'un extrait de l'abdomen de l'autre espèce; les répulsions moyennes étant respectivement 5,53 et 5,33 contre 3,83 et 3,58 pour le lot trémoin. On peut en conclure que ces répulsions doivent entraîner une tendance à la répartition uniforme.
    Notes: Abstract An olfactometer was used to determine the effect of pheromones released by females of the bollworms Heliothis armigera (Hübner) and H. zea (Boddie) on females of the same species. Four combinations of virgin and mated females were tested for repellency of one to the other. Evidence is presented that females of the two bollworms were repelled by females of the same species. In addition, extracts of virgin female abdomens of each species repelled virgin females of the other species.
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  • 12
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    Entomologia experimentalis et applicata 34 (1983), S. 155-162 
    ISSN: 1570-7458
    Keywords: Hymenoptera ; Braconidae ; Lepidoptera ; Nymphalidae ; Apanteles bignellii ; Euphydryas aurinia ; Multivoltinism ; Synchronisation ; Weather
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Zusammenfassung In einer Population von Euphydryas aurinia (Rottemburg) bei Oxford, England treten während einer Generation von E. aurinia drei Normalgenerationen von Apanteles bignellii Marshall auf. Jede Generation des Parasitoids kann charakterisiert werden durch das befallende Wirtsstadium und durch die aus einem Wirt schlüpfende Zahl Parasitoide. Parasitoide schlüpfen in Normalgenerationen aus dem 3., dem 4. und dem 6. Stadium des Wirts; in Ausnahmegenerationen schlüpfen sie aus dem 2. und 5. Stadium. Bis zu 70 Parasitoide können aus einer Altraupe (6. Stadium) schlüpfen und die Dauer dieses Stadiums kann bis auf 2 Wochen verlängert werden. Die Ausnahmegenerationen von A. bignellii aus Zweitlarven dürften aus Eiablagen in frühe Erstlarven stammen. Fünftlarven des Wirts, aus denen Parasitoide schlüpfen, sind ungewöhnlich klein und fressen nicht; sie dürften das Resultat sein eines Uebermasses von Apenteles-Eiern, die in frühe Viertlarven gelegt wurden. Die Synchronisation zwischen dem Parasitoiden und dem Wirt während der Zeit, da E. aurinia im Puppen-, Adult- oder Eistadium ist, wird aufrechterhalten durch ein verlängertes Coconstadium von Apanteles. Die Puppen des Parasitoiden entwickeln sich normal und die Adulten schlüpfen, bleiben aber bis 4 Wochen lang im Cocon, bevor sie sich eine Ausgangsöffnung machen. Das Wetter kann den Parasitierungsgrad der letzten Wirtsstadien beeinflussen. Wenn der Frühling kalt ist mit klarem Himmel, kann die Synchronisierung zwischen Parasitoiden, die aus Viertlarven des Wirts schlüpfen und potentiellen Fünft- und Sechtstlarven des Wirts schlecht werden. Die Entwicklung von Apanteles-Puppen wird durch die Umgebungstemperatur beeinflusst, während E. aurinia-Larven ihre Temperatur erhöhen, indem sie sich sonnen und deshalb rasch wachsen. Wenn die Parasitoiden unter solchen Bedingungen schlüpfen, sind die meisten potentiellen Wirte schon verpuppt und damit nicht mehr geeignet für die Parasitierung. Die Mechanismen der Synchronisation und der Wettereinfluss auf diese Vorgänge wird diskutiert.
    Notes: Abstract The gregarious endoparasite, Apanteles bignellii Marshall is specific to the nymphalid butterfly, Euphydryas aurinia (Rottemburg) in the British Isles. The synchronisation between host and parasitoid is described at a site near Oxford, England where both occur. Three regular generations of A. bignellii occur in one generation of the host in the studied population. Relevant features of the biology of A. bignellii and E. aurinia are described, including a method of distinguishing the number of Apanteles larval instars based upon shed cuticle remnants. Mechanisms for host-parasitoid synchronisation are outlined, especially a protracted parasitoid cocoon stage when the host is unavailable for attack during the chrysalis, adult and egg stages. Cool, but sunny weather conditions in spring can influence the degree of parasitisation experienced by final instar host caterpillars. The timing of adult A. bignellii emergence and subsequent attack on early instar hosts can lead to additional, partial, generations of parasitoids from second and fifth instar hosts.
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    Entomologia experimentalis et applicata 35 (1984), S. 159-167 
    ISSN: 1570-7458
    Keywords: Lepidoptera ; Geometridae ; Ectropis excursaria ; larval dispersal ; colour polymorphism ; phototaxis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Zusammenfassung Acht Experimente wurden durchgeführt, um einige der Faktoren zu studieren, die das Wanderverhalten der Larven (Raupen) eines polyphagen Geometriden (Ectropis excursaria (Guenée)) beein-flussen. 1. Larven sind positiv phototaktisch. Die positive Phototaxis ist negativ mit Fasten, Alter und Populationsdichte korreliert. Bei hohen Temperaturen ist sie nicht mehr nachweisbar. 2. Das Wanderverhalten der Larven wird durch die Populationsdichte beeinflußt, wodurch annähernd eine konstante Dichte erhalten bleibt. Das Verhalten der individuellen Larven is dabei nicht statistisch homogen. Es gibt ‘Wanderer’ und ‘Nicht-Wanderer’. 3. Diese Verhaltensunderschiede stehen möglicherweise im Zusammenhang mit physiologischen und morphologischen Faktoren, die den individuellen Fortpflanzungserfolg und das überleben beeinflussen können; ‘Wanderer’ sind dunkler, entwickeln sich schneller und das Gewicht ihrer Puppen ist niedriger als das der ‘Nicht-Wanderer’. 4. Eine der larvalen Farbvarianten zeigte eine Präferenz für einen von zwei angebotenen Hintergründen.
    Notes: Abstract The dispersive behaviour of larvae of a polyphagous, wide-spread geometrid (Ectropis excursaria (Guenée)) was studied by examining responses to environmental and endogenous variables. It was found that differences in behaviour can be affected by environmental factors such as light, temperature, density, and plant background as well as some physiological and morphological features. The implications of these relationships are discussed as adaptative strategies to a varying environment.
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  • 14
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    Entomologia experimentalis et applicata 35 (1984), S. 177-193 
    ISSN: 1570-7458
    Keywords: induction of feeding preference ; host plants ; non-host plants ; Manduca sexta ; Sphingidae ; Lepidoptera
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Résumé Vingt-deux espèces de plantes, dont 10 planteshôtes (Solanées), ont été testés comme plantes alimentaires pour des chenilles de ler stade de Manduca sexta. Sur cet ensemble, seulement 12 plantes (dont 9 plantes hôtes) induisaient la prise de nourriture et permettaient la croissance jusqu'au 5ème stade. La diversité des résultats suggère que les plantes pouvaient être classées en hôtes, non-hôtes acceptables et non-hôtes refusés. En utilisant le test du choix alimentaire préférentiel entre deux rondelles de feuilles, les chenilles néonates de ler stade ont préféré nettement les plantes-hôtes aux autres. Cette préférence initiale pour les plantes-hôtes était préservée quand les cheniles étaient élevées sur plantes-hôtes, mais devenait moins nette ou disparaissait pour des chenilles élevées sur d'autres plantes acceptées. Ainsi l'oligophagie ches M. sexta n'est pas induite, mais doit être héritée. Les chenilles néonates, aussi bien que celles de 5ème stade, présentent des préférences hiérarchisées parmi les plantes hôtes ou non. La seule frontiere nette observée était entre espèces de plantes acceptables ou non. Les hiérarchies préférentielles des chenilles du 5ème stade différaient légèrement lors-qu'elles avaient été élevées sur deux plantes-hôtes différentes. La différence essentielle était l'observation d'une préférence accrue pour l'espèce ayant servi à l'élevage, mais deux autres plantes-hôtes changaient aussi de position hiérarchique. La cause de ces changements de préférence a été approfondie, les chenilles étant élevées sur des feuilles de chaque espèce acceptable (hôte ou non). Leurs préférences alimentaires ont été définies en utilisant des combinaisons diverses (hôte x hôte, hôte x non-hôte acceptable, non-hôte acceptable x non-hôte acceptable). L'induction de la préférence alimentaires a été obtenue dans ces trois associations. Ceci montre que l'induction des choix alimentaires chez M. sexta n'est pas limitée aux plantes-hôtes. Le degré d'induction de la préférence alimentaire variait de très fort à indécelable; il dépendait de l'association examinée. La source de la variabilité de cette induction a été examinée en fonction de la relation entre la force de l'induction et les rapports taxonomiques des plantes associées. La relation obervée était inversée pour M. sexta. L'examen des données de la littérature ont révélé une relation du même type pour les autres espèces de Lépidoptères.
    Notes: Abstract Ten host plant (Solanaceae) and twelve non-host plant species were tested as foodplants for first instar larvae of the tobacco hornworm, Manduca sexta. Only nine host and three non-host plant species elicited feeding and supported growth up to fifth instar. The range of acceptability suggested that plants be divided into hosts, acceptable non-hosts, and unacceptable non-hosts. Using the two-choice feeding preference test we found that the initial preference for hosts was preserved when larvae were reared on hosts, but was less strong or absent for larvae reared on acceptable non-hosts. Thus oligophagy in the tobacco hornworm is not induced, but must be inherited. Newly-hatched first instar larvae and fifth instar larvae showed a preference hierarchy among both hosts and non-hosts. Fifth instar larvae reared separately on two different host species showed slightly different preference hierarchies among hosts. The preference for the rearing plant was increased and also two other host species changed positions in hierarchies. Feeding preferences of larvae reared on hosts or acceptable non-hosts were determined using plant combinations of host vs. host, host vs. acceptable non-host, and acceptable non-host vs. acceptable non-host. Induction of feeding preference was found in all three of these categories. This shows that induction of feeding preference in the tobacco hornworm is not restricted to host plant species. The degree to which feeding preferences were induced ranged from very strong to undetectable and dependend on the plant species paired. The strength of induction in the tobacco hornworm was found to correlate inversely with taxonomic relatedness of the plant species paired. Analysis of induction data from the literature revealed a similar correlation for other lepidopteran species.
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  • 15
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    Entomologia experimentalis et applicata 35 (1984), S. 255-261 
    ISSN: 1570-7458
    Keywords: method ; dry matter ; budget ; Lepidoptera ; phytophagous ; gravimetry ; area ; accuracy ; precision
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Résumé Les budgets en matière sèche consommée par des lépidoptères ont été comparés par les méthodes gravimétrique et planimétrique. La méthode gravimétrique est basée sur le rapport poids sec/poids frais de feuilles consommées par les chenilles. Avec la méthode planimétrique, la quantité d'aliment proposée aux chenilles est déterminée par les tracés de la surface des feuilles et le contenu de matière sèche par unité de surface des feuilles. La méthode de planimétrie permet l'utilisation de plus grands rameaux de feuilles et de cages d'élevage extérieures en gaze. Il n'y avait pas de différence appréciable dans les éléments du budget (croissance, ingestion et déjection), ni aucune différence dans la variabilité observée des données attribuable à la méthode utilisée. Cependant, la variabilité attendue d'après la précision des mesures avec la méthode gravimétrique est inférieure à celle de la méthode planimétrique. est inférieure à celle de la méthode planimétrique. Des éléments expérimentaux, inhérents à la méthode gravimétrique, introduisent une variabilité dans les mesures que l'on n'a pas avec la méthode planimétrique. 30–60% de la variabilité dans la consommation ont été attribués à des paramètres internes à la chenille, même quand elles provenaient toutes de la même ooplaque.
    Notes: Abstract Gravimetric and a combination areal-gravimetric methods for determining dry matter budgets for leaf eating Lepidoptera were compared. The gravimetric method is based on dry weight/live weight ratios of the leaves fed to the larvae. In the areal-gravimetric method, the quantity of food offered to the larvae is determined from the area of leaf tracings and the dry matter content per unit area of the leaves. The areal-gravimetric method permits the use of larger leaf sprays and an open, gauze enclosed rearing chamber. There were no consistent differences in budget factors (growth, ingestion or egestion), nor were there any differences in the observed variability of the data attributable to the method used. However, the expected variability based on instrument precision for the gravimetric method is less than for the areal-gravimetric method. Experimental factors inherent in the gravimetric method introduce variability to the measurements that are not present in the areal method. Thirty to 60% of the variability in budget factors was attributed to intrinsic properties of the larvae, even though the larvae were taken from the same egg masses.
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  • 16
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    Entomologia experimentalis et applicata 34 (1983), S. 121-122 
    ISSN: 1570-7458
    Keywords: Lepidoptera ; Noctuidae ; Earias insulana ; Bollworm ; Artificial diets ; Insect fecundity
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  • 17
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    Calcified tissue international 33 (1981), S. 409-416 
    ISSN: 1432-0827
    Keywords: Bone Cells ; Cyclic AMP ; Calcium ; Parathyroid hormone ; Prostaglandin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary We have examined the influence of extracellular Ca2+ on cyclic AMP metabolism in an osteoblast-enriched population of bone cells isolated from the calvaria of rat fetuses. The cyclic AMP1 response to stimulators of cyclic AMP formation (PTH and PGE2), but not basal cyclic AMP levels, increased progressively as the extracellular Ca2+ concentration was raised from 0.2 to 4.0 mM. The response to changes in extracellular Ca2+ were rapid (within 3.5 min), and the level of responsivity that characterized each Ca2+ concentration persisted for at least 6 h when the Ca2+ concentration was kept constant. The effect of Ca2+ spanned the entire time course of PTH action, was not accompanied by altered excretion of cyclic AMP from the cells, and was evident at low as well as at high hormone concentrations. Ca2+ augmented the action of PTH in the presence as well as in the absence of cyclic AMP phosphodiesterase inhibitors, and failed to decrease cyclic AMP phosphodiesterase activity in the short term. Mn2+ and, to a smaller degree, Ba2+ substituted for Ca2+ in promoting the cyclic AMP response to PTH. Verapamil, an inhibitor of Ca2+ penetration, blunted the Ca2+-mediated increments in the cyclic AMP response, and the divalent cation ionophore A23187 enhanced these increments. These results indicate that Ca2+ and other cations are positive effectors of the stimulated cyclic AMP response in isolated bone cells. Accumulation into an as yet unknown cellular compartment may be required for the cation effect. The data are most consistent with enhancement of adenylate cyclase reactivity as the mode of cation action.
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  • 18
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    Calcified tissue international 3 (1969), S. 103-105 
    ISSN: 1432-0827
    Keywords: Mitochondrion ; Calcium ; Excretion ; Bone
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  • 19
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    Calcified tissue international 2 (1968), S. 296-298 
    ISSN: 1432-0827
    Keywords: Calcium ; Lipid ; Bacteria ; Calcification
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé On a fait ce travail pour determiner si le facteur responsable pour la liaison de calcium par un calcifableBacterionema matruchotii est dans la fraction lipide de la cellule. Des cellules congelees et sechees ont ete extraites par le chloroform-methanol. La fraction de chloroform-methanol, les cellules extraites et les cellules non traitees ont ete examinees pour la liaison de calcium. La fraction du chloroform-methanol et les cellules non traitees avaient la liaison de calcium. Les cellules extraites n'en avaient pas.
    Abstract: Zusammenfassung Diese Arbeit wurde durchgeführt um festzustellen, ob sich der Faktor für die Calcium-bindung, durch das calcifizierendeBacterionema matruchotii, in der Lipoidfraktion befindet. Die lyophiilisierten Zellen wurden mit Chloroform-Methanol extrahiert. Die Chloroform-Methanol-Fraktion, die extrahierten Zellen, sowie die nicht behandelten Zellen wurden auf eine Calciumbindung hin untersucht. Die Chloroform-Methanol-Fraktion und die nicht behandelten Zellen demonstrierten eine Calciumbindung. Die extrahierten Zellen hingegen nicht.
    Notes: Abstract This work was done to determine whether the factor responsible for calcium binding by a calcifiableBacterionema matruchotii is in the lipid fraction of the cell. Freeze-dried cells were extracted with chloroform-methanol. The chloroform-methanol fraction, the extracted cells and untreated cells were examined for calcium binding. The chloroform-methanol fraction and the untreated cells bound calcium. The extracted cells did not.
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  • 20
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    Calcified tissue international 3 (1969), S. 340-347 
    ISSN: 1432-0827
    Keywords: Bone ; Calcium ; Fluoride ; Ingestion ; compatibility
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Des expériences ont été faites sur le rat afin de tester les possiblités d'ingestion perorale simultanée de fluor (F) et de calcium (Ca) en proportions calculées pour traitement de certaines ostéopénies humaines. F sous forme de Na2PO3F et Ca sous forme de gluconate de calcium (CaGluc) n'influençaient pas l'un l'autre quant à l'utilisation par le squelette (fémur). Une viscosité élevée, produite par l'addition d'amidon ou de cellulose carboxyméthylée (CMC) à la solution ou dilution ingérée, augmentait l'utilisation du F même si CaGluc était remplacé par citrate de calcium, qui en soi avait un effet réducteur modéré sur l'utilisation du F. Le glycérophosphate de calcium réduisait fortement l'utilisation du F même en présence de CMC. L'utilisation du F comme NaF était fortement réduite par CaGluc, même en présence de CMC. Les concentrations testées de Na2PO3F, NaF ou CMC n'influençaient pas l'utilisation squelettique de Ca comme CaGluc.
    Abstract: Zusammenfassung Es wurden Rattenexperimente mit markierten Substanzen durchgeführt, um die Auswirkung simultaner peroraler Gaben von Fluor (F) und von Calcium (Ca) zu prüfen, und zwar in einem Verhältnis, das für die Behandlung gewisser menschlicher Osteopenien berechnet wurde. Fluor in Form von Na2PO3F und Ca in Form von Calciumgluconat (CaGluc) interferieren gegenseitig nicht bei der Verwertung durch das Skelet (Femur). Eine hohe Viscosität der eingegebenen Lösung oder der Aufschlämmung, die durch Zusatz von Stärke oder Carboxymethylcellulose (CMC) erzielt wurde, erhöhte die Verwertbarkeit von F sogar wenn CaGluc durch Calciumcitrat ersetzt wurde, welches die F-Verwertung leicht reduzierte. Calcium-glyzerophosphat verminderte die Fluoraufnahme in den Knochen stark, sogar in Anwesenheit von CMC. Die Verwertung von F als NaF war stark herabgesetzt durch CaGluc, selbst beim Vorhandensein von CMC. Die untersuchten Konzentrationen von Na2PO3F, NaF oder CMC hatten keinen Einfluß auf die Calciumaufnahme im Skelet in Form von CaGluc.
    Notes: Abstract Rat experiments with labelled compounds were carried out in order to test the possibilities of simultaneous peroral supply of fluorine (F) and calcium (Ca) in proportions calculated for treatment of certain human osteopenias. F in the form of Na2PO3F and Ca in the form of calcium gluconate (CaGluc) did not interfere with each other's utilisation by the skeleton (femur). A high viscosity produced by adding starch or carboxymethyl cellulose (CMC) to the ingested solution or slurry increased the utilisation of F even when CaGluc was replaced by calcium citrate, which moderately reduced F utilisation. Calcium glycerophosphate strongly reduced F utilisation even in the presence of CMC. The utilisation of F as NaF was strongly reduced by CaGluc, even in the presence of CMC. The tested concentrations of Na2PO3F, NaF or CMC did not influence the skeletal utilisation of Ca as CaGluc.
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    Calcified tissue international 30 (1980), S. 209-216 
    ISSN: 1432-0827
    Keywords: Calvarium ; cAMP ; Vitamin D3 metabolites ; Calcium ; Parathyroid hormone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Results from in vitro works suggest that 1,25- and 24,25-dihydroxyvitamin D3 (1,25-(OH)2D3 and 24,25-(OH)2D3) act on bone via different mechanisms. The present investigation was performed to study the effect of these two metabolites and of their precursor 25-hyxdroxyvitamin D3 (25-(OH)D3) on bone cAMP content in vitro. Rats' paired half calvaria were incubated under sterile conditions with one vitamin D3 derivative (10−13 to 10−9 M) or with ethanol (0.005 ml for 15 min to 24 h in 1 ml medium containing 0, 0.2, 1, 2, or 3 mM calcium. In some experiments: (a) cycloheximide (10−5M) was added simultaneously with the vitamin D3 metabolites; (b) 1–84 bPTH (5 × 10−8 M) was added for 5 or 15 min at the end of the 24 h incubation. Calvaria were immersed in 1 ml TCA 5% 4°C and homogenized. The cAMP was extracted with diethylether and measured by a competitive protein binding assay. Results bring further evidence for a particular effect of low doses of 24,25-(OH)2D3 (10−9 to 10−12M) and of 25-(OH)D3 (10−9 to 10−11M) on bone, different from that of 1,25-(OH)2D3: cAMP content was higher in 24,25-(OH)2D3- or 25-(OH)D3-treated and lower in 1,25-(OH)2D3-treated calvaria than in ethanol-treated ones with 1 mM calcium. The 1,25-(OH)2D3 effect persisted in calcium-free medium whereas 25-(OH)D3 and 24,25-(OH)2D3 effects could not be observed with 0 mM nor with 3 mM calcium. The required duration of the preincubation (over 1 h) as well as the inhibitory action of cycloheximide may suggest an involvement of protein synthesis in the vitamin D3 metabolites effects. Neither 1,25-(OH)2D3 nor 24,25-(OH)2D3 affected the PTH-induced increase in bone cAMP content.
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    Calcified tissue international 32 (1980), S. 201-206 
    ISSN: 1432-0827
    Keywords: Magnesium ; Parathyroid hormone ; Secretion ; In vitro ; Calcium
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    Topics: Biology , Medicine , Physics
    Notes: Summary In a well-defined in vitro perifusion system, the effects of extracellular magnesium concentration (Mg) on parathyroid hormone (PTH) secretion by bovine parathyroid tissue were examined. At Mg less than 0.8 mM, the ability of the glands to secrete hormone maximally in response to low calcium (Ca) stimulation was progressively impaired. Low Mg also impaired the ability of isoproterenol, dibutyryl cyclic AMP and theophylline to stimulate hormone release. The defect in hormone release at low Mg observed in vitro was analogous to the well-documented inhibition of secretion observed in vivo. Increases in Mg from 0 to 0.8 mM rapidly repaired the defect in hormone secretion. At Mg above 1.0 mM there was a Ca-like effect on hormone release, with a progressive decrease in secretion at increased Mg. Although its mechanism is not yet clear, the low Mg effect appears to impair principally the process of hormone release rather than its biosynthesis or storage.
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    Calcified tissue international 36 (1984), S. 139-144 
    ISSN: 1432-0827
    Keywords: 1,25(OH)2-vitamin D ; Weight loss ; Phosphate ; Calcium
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    Topics: Biology , Medicine , Physics
    Notes: Summary During a review of 42 metabolic studies in healthy women and men we observed that serum 1,25-(OH)2-D concentrations were directly correlated to the observed daily changes in body weight (r=0.68;P〈0.001) and to caloric intake/kg/day (r=0.39;P=0.01). These relationships could not be accounted for by related and physiologically expected changes in serum Ca or iPTH concentrations. However, serum 1,25-(OH)2-D concentrations were observed to be inversely correlated to serum PO4 levels (r=−0.44;P=0.004). In addition, serum PO4 levels were inversely correlated to the daily changes in body weight (r=−0.40;P=0.009). Since dietary sodium intake averaged 142 mmol/day, it is unlikely that the observed changes in weight were the result of changes in salt and water balance. Thus it seems reasonable to speculate that serum 1,25-(OH)2-D concentrations may vary directly with energy balance, as reflected by changes in body weight. This effect may be mediated by alterations in PO4 metabolism. The accurate assessment of serum 1,25-(OH)2-D levels thus appears to require several measurements over time periods during which body weight is stable.
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  • 24
    ISSN: 1432-0827
    Keywords: Electromagnetic field ; Bicarbonate ; Phosphate ; Calcium ; Fluoride ; Osteogenesis
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    Notes: Summary The present studies are aimed at establishing molecular correlations in the interaction of very low frequency electromagnetic fields with biological systems. Ca-uptake by chick embryo tibia rudiment in short-term culture was a useful model. Tibiae of 8- to 10-day-old chick embryos were incubated 60 min in simplified culture media in the presence of45Ca at 37.5±0.5°C either inside or outside pulsating electromagnetic fields. Radioactivity count in the medium was the most accurate method for determining Ca-uptake by the rudiment. The effect of the fields on the Ca-uptake depended markedly on the chemical composition of the culture medium: bicarbonate was indispensable; glucose or sucrose was important; phosphate was potentiating; ethanol, Mg2+, and NaF were stimulating. The field had no effect in (a) blank medium without tibia, (b) tibiae that had been altered by fixation with aqueous glutaraldehyde, (c) nonliving artificial systems endowed with great or small ion sorption capacity. The unique bicarbonate effect with living systems and the passive behavior of nonliving ion sorbing systems prompt the suggestion that the electromagnetic field probably couples with specific processes, such as a bicarbonate-dependent Ca2+ ATPase and the active ion transport, at the cell membrane level. The molecular mechanisms remain to be established.
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    Calcified tissue international 36 (1984), S. 194-199 
    ISSN: 1432-0827
    Keywords: Benzo(B)Thiophene-2-Carboxylic Acid ; Bone cells ; Calcium ; Cyclic AMP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The purpose of the present study was to investigate the mechanism of action on bone of Benzo(B)Thiophene-2-Carboxylic Acid (BL-5583). BL-5583, at a dose range of 0.01–100 µg/ml, inhibited spontaneous as well as A23187 and PTH-induced bone resorption in tissue culture. This compound also decreased calcium uptake in both osteoclastic and osteoblastic enriched bone cell populations obtained by sequential collagenase digestion of 1–2 day newborn rat calvariae. The decrease occurred after a 5 min. incubation with45Ca and BL-5583. The effective dose range was 0.01–100 µg/ml. No effect on leucine incorporation or lactic acid production by bone cells was observed. BL-5583 also induced a transient decrease in calcium uptake in skin cells isolated from fetal rats by collagenase digestion, suggesting a lack of tissue specificity for this compound. No effect on cyclic AMP in isolated bone cells was observed with the same dose range that produced a calcium effect.
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    Calcified tissue international 4 (1969), S. 224-230 
    ISSN: 1432-0827
    Keywords: Calcinosis ; Calcium ; Iron ; Phosphate ; Collagen
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    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé La calcification de la peau (calciphylaxie) provoquée par l'administration sous-cutanée de chlorure de fer chez des rats sensibilisés par le dihydrotachystérol (DHT) est précédée par une déposition sélective de fer (décelable à la microscopie électronique) à la surface des fibres collagènes. Les analyses à la microsonde prouvent que les taux de calcium et de phosphore sont augmentés à l'endroit de l'injection du chlorure de fer même sans l'administration préalable de DHT; cependant, l'apatite ne se forme que chez les animaux prétraités par le DHT. La quantité et le degré de cristallinité de la matière inorganique sont presque identiques au sixième et au trentième jour de l'expérience.
    Abstract: Zusammenfassung Durch elektronenmikroskopische Untersuchungen wurde festgestellt, daß die durch subcutane Verabreichung von Eisenchlorid bei Dihydrotachysterin-sensibilisierten Ratten herbeigeführte Hautverkalkung durch eine selektive Eisenablagerung auf der Oberfläche der Kollagenfibrillen eingeleitet wird. Die Röntgenmikroanalyse zeigt an, daß die lokale Calciumund Phosphorkonzentration bereits nach Eiseninjektion allein ansteigt, während Apatitbildung nur in den mit DHT vorbehandelten Tieren erfolgt. Ausmaß und Menge der Kristallisation sind am 6. und 30. Tage nach Versuchsbeginn fast gleich.
    Notes: Abstract Calcification of the skin (calciphylaxis) induced by the subcutaneous administration of iron chloride to dihydrotachysterol (DHT)-sensitized rats is preceded by the selective deposition of iron (visible with electron microscopic techniques) on the surface of collagen fibrils. Electron probe X-ray microanalysis indicates that the injectionof iron alone suffices to increase local concentrations of calcium and phosphorus; however, apatite formation occurs only in animals pretreated with DHT. The amount and degree of crystallinity of the inorganic material is very similar on the sixth and thirtieth day after the beginning of the experiment.
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  • 27
    ISSN: 1432-0827
    Keywords: Saliva ; Calcium ; Phosphate ; Ion-binding ; Supersaturation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Previous ultrafiltration studies indicated that up to one-half of the calcium and two-thirds of the phosphate in human salivary secretions may be bound by salivary proteins. Since this binding is an important variable in determining the extent of salivary supersaturation with respect to calcium phosphate salts, and since the amount of binding reported is surprisingly large, calcium and phosphate ion-binding by salivary macromolecules has been reexamined. From experiments using equilibrium dialysis, it was found that (1) the fraction of salivary calcium involved in macromolecular complexes ranges from a few percent for unstimulated secretions, to no more than about 10% for stimulated glandular salivas, and (2) salivary proteins do not bind phosphate ions to any significant extent. These findings, and experiments using an improved ultrafiltration membrane, indicate that the earlier results were artifacts of the ultrafiltration technique. Fractionation of salivary proteins, followed by equilibrium dialysis measurements, showed that the anionic proline-rich proteins and a basic proline-rich glycoprotein are responsible for most of the calcium binding now observed. The finding that macromolecular complexes of salivary calcium and phosphate have been overestimated in the past, leads to the conclusion that salivary calcium and phosphate ion activities in stimulated salivary secretions may be up to 50 to 100% higher than previously thought. Revised values were therefore used to recalculate the degree of salivary supersaturation with respect to calcium phosphate salts. The results indicate that stimulated salivary secretions are supersaturated with respect to dicalcium phosphate dihydrate; this is a substantially greater degree of supersaturation than previously reported.
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  • 28
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    Calcified tissue international 3 (1969), S. 184-193 
    ISSN: 1432-0827
    Keywords: Mitochondria ; Calcification ; Calcium ; Chondrocytes ; Growth plate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Des cultures d'épiphyse prélevées sur des rats et des souris ont été étudiées sous le microscope électronique. Un profile de granules mitochondriques de densité électronique a été trouvé. Les chondrocytes dans la zone proliférative avaint peu de granules, alors que ceux des zones successives ont montré une augmentation progressive de leur nombre et densité jusqu'à ce que la zone de calcification provisoire ait été atteinte. Cette zone a montré une distribution périphérique de mitochondries et une réduction du nombre et de la densité des granules mitochondriques. Du calcium isotopique 47 a été utilisé autoradiographiquement pour déterminer la location de calcium dans ces cellules. Des grains ont été trouvés sur les membranes R.E. et sur la plupart des mitochondries. La preuve d'un profile de ces granules et de leur rapport spatial avec la face de minéralisation indique une action éventuelle de mitochondries dès le début de la calcification de la matrice.
    Abstract: Zusammenfassung Epiphysekulturen von Ratten und Mäusen wurden unter dem Elektronenmikroskop untersucht. Ein Profil von mitochondrischen Körnchen mit elektronischer Dichte wurde gefunden. Chondrozyten in der Proliferationszone wiesen wenig Körnchen auf, während die der nachfolgenden Zonen allmählich an Zahl und Dichte zunahmen, bis die Zone der provisorischen Verkalkung erreicht wurde. Diese Zone zeigte eine periphere Verteilung der Mitochondrien und eine Abnahme in Zahl und Dichte der mitochondrischen Körnchen. Isotopes Kalzium 47 wurde autoradiographisch verwendet, um die Lage des Kalziums in diesen Zellen zu bestimmen. Körnchen wurden auf den E.R.-Membranen und auf einem Großteil der Mitochondrien gefunden. Der Nachweis eines Profils dieser Körnchen und ihres räumlichen Verhältnisses zur Mineralisierungsfläche weist auf einen möglich Einfluß der Mitochondrien mit Beginn der Matrixverkalkung hin.
    Notes: Abstract Rat and mice epiphyseal growth plates were studied with the electron microscope. A gradient of mitochondrial electron-dense granules was found. Chondrocytes in the proliferative zone had few granules, while those of the succeeding zones showed a gradual increase in number and density until the zone of provisional calcification was reached. This zone showed a peripheral distribution of mitochondria and a decrease in the number and density of mitochondrial granules. Isotopic47calcium was used autoradiographically to determine the location of calcium in these cells. Grains were found over the endoplasmic reticulum membranes and over most mitochondria. The demonstration of a gradient of these granules and their spatial relation to the mineralization front suggests a possible involvement of mitochondria in the onset of matrix calcification.
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  • 29
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    Calcified tissue international 32 (1980), S. 229-236 
    ISSN: 1432-0827
    Keywords: Bone ; Ion influxes ; Calcium ; Phosphate ; Exchange
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    Topics: Biology , Medicine , Physics
    Notes: Summary Quantitative measurements were made of the ion fluxes of calcium and phosphate into and from calvaria (mouse or rat) when clamped in specially designed micro-Ussing chambers. The effects of varying concentrations of calcium were examined on the influx and efflux of calcium and of its counterion, phosphate. A comparable series of experiments was performed with varying phosphate concentrations. Both ions, as their concentrations increased, depressed their own influx, increased their own efflux, and significantly increased the equilibrium concentration, E/K, supported by the calvaria. Similarly, both ions, as their concentrations increased, affected the influx or efflux of their counterion only slightly but did depress the counterion's equilibrium level, E/K, significantly. In spite of these changes it was shown that calvaria effectively buffered the medium at physiological concentrations of calcium and phosphate. The buffering capacity, however, was small, and the balance, E/K, was modified by small uptake or loss of either ion. The small size of the interacting mineral pool was confirmed by direct measurement of the rapidly exchanging fractions of both calcium or phosphate. They were only ∼1% of the total ions present. The significance of these findings is discussed.
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  • 30
    ISSN: 1432-0827
    Keywords: Calcium ; Vitamin D deficiency ; 1,25(OH)2D3 ; Parathyroidectomy ; Parathyroid hormone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Studies presented here were designed to investigate further the basis for an impaired cAMP response to parathyroid hormone (PTH) in osteoblastlike calvarial bone cells isolated from vitamin D-deficient rat pups. The goal was to perturb Ca, PTH, and vitamin Din vivo in order to see which factors might be responsible for the impairedin vitro bone cell cAMP response. Pups either were parathyroidectomized (PTX) 3–5 days, implanted with osmotic minipumps delivering high doses of PTH, given repeated, high doses of 1,25(OH)2D3, or were D-deficient (-D, i.e., born and suckled by D-deficient mothers). Osteoblastlike bone cells, isolated by sequential enzyme digestion and centrifugation, were exposed to PTH for 5 min in the presence of a phosphodiesterase inhibitor. In bone cells isolated from -D rat pups, both basal and PTH-induced cAMP accumulation were significantly lower than in +D bone cells. Earlier, we had shown that two daily injections of -D pups with 50 ng 1,25(OH)2D3 restores this reduced bone cAMP response of -D pups toward normal. In the present study, neither basal nor PTH-induced bone cell cAMP accumulation was affected by subjecting D-replete pups to PTX, PTH infusion, or repeated high doses of 1,25(OH)2D3 despite the fact that each treatment markedly changed serum Ca or serum immunoreactive PTH. The results indicate that the impaired bone cell cAMP response seen in -D pups is not a direct result of chronic hypocalcemia and that the “heterologous desensitization” seenin vitro with added 1,25(OH)2D3 could not be duplicated byin vivo treatment of +D pups with supraphysiologic doses of 1,25(OH)2D3. Finally the lack of alteration in the bone cell cAMP response to PTHin vitro after chronic PTH infusionin vivo fails to support the notion that the impaired response in -D bone cells can be explained entirely by “homologous desensitization” induced by high circulating levels of PTH in the hypocalcemic, -D rat pup.
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  • 31
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    Calcified tissue international 4 (1969), S. 174-179 
    ISSN: 1432-0827
    Keywords: Calcium ; Strontium ; Bone ; Mineral
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé La proportion Sr/Ca dans l'os est à peu près la même que dans le sérum tandis que les poudres d'hydroxyapatite suspendues dans des solution physiologiques font une distinction contre le strontium. On trouva que la proportion Sr/Ca des fractions de différentes densités d'os compact de tibia de rat en forme de poudre augmentait avec augmentation de la densité jusqu'à une valeur un peu supérieure à celle observée dans le sérum. L'explication pourrait être qu'une barrière cellulaire ôte le calcium par préférence au strontium du fluide d'os ou bien qu'une accentuation précoce de la proportion Sr/Ca dans l'os se réfléchit dans les fractions de densité supérieure.
    Abstract: Zusammenfassung Das Verhältnis Sr/Ca im Knochen ist annähernd dasselbe wie es im Serum vorliegt, während in einer physiologischen Lösung von pulverisiertem Hydroxyapatit das Sr zugunsten des Ca benachteiligt wird. Es wurde festgestellt, daß das Sr/Ca-Verhältnis von Fraktionen verschiedener Dichte von pulverisierten Rattentibiae mit zunehmender Dichte anstieg, und zwar bis zu einem Wert, der etwas höher lag als der im Serum beobachtete. Dies ließe sich so erklären, daß eine Zellbarriere beim Entzug aus der Knochenflüssigkeit Ca dem Sr vorzieht; oder aber daß sich eine frühzeitige Betonung des für den Knochen typischen Sr/Ca-Verhältnisses in den Fraktionen höherer Dichte widerspiegelt.
    Notes: Abstract The Sr/Ca ration in bone is approximately the same as in serum, whereas hydroxyapatite powders suspended in physiological solutions discriminate against strontium. It was found that the Sr/Ca ratio of various density fractions of powdered compact bone of rat tibia increased with increasing density to a value slightly higher than that observed in the serum. The explanation could be that a cellular barrier removes calcium preferentially to strontium from the bone fluid, or that early accentuation of the bone Sr/Ca ration is reflected in the higher density fractions.
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  • 32
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    Calcified tissue international 4 (1969), S. 188-192 
    ISSN: 1432-0827
    Keywords: Serum ; Calcium ; Phosphate ; Calcitonin ; Thyroidectomy ; Metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Après ablation des glandes thyroïdes de chiens, sans lèser les glandes parathyroïdiennes supérieurs, les taux en calcium et phosphate sériques et la gravité spécifique sont comparées avec des valeurs d'un groupe de chiens, chez lesquels une intervention simulée est réalisée. Immédiatement après thyroïdectomie, le taux de phosphate est plus élevé que le taux de calcium. Ce taux de phosphate se maintient plus longtemps à un niveau élevé que le taux de calcium, après thyroïdectomie. Le rapport entre l'augmentation du phosphate et le taux initial de phosphate sérique chez chaque animal indique des variations normales de la calcitonine d'un animal à l'autre.
    Abstract: Zusammenfassung Bei Hunden wurde die Thyreoidea entfernt, ohne die Parathyreoidea zu verletzen. Der Gehalt des Serums an Calcium und Phosphat sowie sein spezifisches Gewicht wurden mit den Werten verglichen, welche nach einer Scheinoperation bei einer Kontrollgruppe von Hunden bestimmt wurden. Unmittelbar nach der Thyreoidektomie war der Phosphatspiegel höher als jener des Calciums. Der Phosphatspiegel blieb nach der Thyreoidektomie länger hoch als der Calciumspiegel. Das Verhältnis zwischen dem Phosphatanstieg und dem Ausgangswert des Serumphosphates bei jedem Tier wies auf normale Variationen der Calcitonin-Konzentration bei verschiedenen Tieren hin.
    Notes: Abstract The thyroid glands were removed from dogs without interfering with the superior parathyroid glands. Levels of serum calcium, phosphate, and specific gravity were measured subsequently for 24 hours, and these values were compared with values obtained from a control group of dogs in which a mock operation was done. Immediately after thyroidectomy, the level of phosphate was greater than the calcium level. The phosphate level remained high longer after thyroidectomy than did the calcium level. The relationship between the increase in phosphate level and the initial serum phosphate value in each animal indicated normal variations in calcitonin levels in different animals.
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  • 33
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    Calcified tissue international 4 (1969), S. 245-256 
    ISSN: 1432-0827
    Keywords: Bone ; Densitometry ; X-ray ; Diet ; Calcium ; Osteoporosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé L'ingestion quotidienne de calcium of été déterminée en interrogeant 398 individus, âgés de 15 à 90 ans. Le rapport entre l'ingestion de calcium et la minéralisation vertébrale, mesurée par densitométrie radiographique quantitative, est fiable mais cependant significatif. Chez 53 personnes, atteintes d'ostéoporose, comparées à un nombre égal d'individus, d'âges similaires, les valeurs de la minéralisation vertébrale sont 60 pour cent plus faibles que celles du groupe témoin. L'ingestion totale moyenne de calcium est plus faible de 21 per cent chez les ostéoporotiques. Chez les sujets, à ingestion unique de calcium, les patients du groupe témoin ingèrent preque le double de calcium que le groupe des ostéoporotiques. Une diminution moyenne de l'ingestion calcique est notée avec l'âge. Il semble qu'il existe une diminution de l'absorption calcique avec l'âge, l'ostéoporose ou les deux, ainsi qu'un besoin plus grand en calcium chez les sujets âgés pour assurer l'équilibre en calcium. Indépendamment de l'homéostase calcique, un équilibre négatif en calcium augmente la résorption osseuse, et diminue l'ostéogenèse. De nombreux facteurs interviennent dans l'étiologie et la pathogénie de l'ostéoporose: les résultats de cette étude indique que la présence de calcium alimentaire est l'un de ces facteurs.
    Abstract: Zusammenfassung Die tägliche Calciumeinnahme wurde anhand einer Befragung von 398 Personen im Alter von 15–90 Jahren geschätzt. Die Korrelation der Calciumeinnahme und der Mineralisation der Wirbelsäule, wie sie röntgenologisch durch quantitative Messung der Dichte festgestellt wurde, war niedrig, aber durchwegs signifikant. Bei 53 Osteoporose-Patienten, die mit 53 Kontrollpersonen gleichen Alters verglichen wurden, waren die Mineralisationswerte der Wirbelsäule um 60% niedriger als jene der Kontrollgruppe, und die durchschnittlich geschätzte Gesamt-Calciumeinnahme der Osteoporotiker war um 21% tiefer. Von den Exploranden, die Angaben über eine gleichmäßige Calciumaufnahme machten, nahmen die Kontrollpersonen beinahe doppelt so viel Calcium ein als diejenigen mit Osteoporose. Im Durchschnitt wurde eine Verminderung der Calciumeinnahme mit fortschreitendem Alter festgestellt. Es ergibt sich deutlich, daß die Calciumabsorption mit dem Alter, bei Osteoporose oder in der Kombination dieser beiden Faktoren abnimmt, und daß eine größere Calciumeinnahme bei älteren Personen nötig wäre, um eine positive Calciumbilanz aufrechtzuerhalten. Ungeachtet der Komplexität der Calciumhomöostase, kann eine negative Calciumbilanz schließlich dazu führen, daß mehr Knochen resorbiert als gebildet wird. Demzufolge sollte bei erkanntem Bedürfnis eine adäquate Calciumeinnahme gesichert sein. Es ist eine Tatsache, daß viele Faktoren an der Ätiologie und Pathogenese der Osteoporose beteiligt sind; die Resultate dieses Berichtes unterstützen die Wahrscheinlichkeit, daß das Calciumangebot in der Nahrung einer dieser Faktoren ist.
    Notes: Abstract Lifetime daily calcium intake was estimated through interview of 398 individuals from 15 to 90 years of age. The correlation of calcium intake with vertebral mineralization as determined by quantitative radiographic densitometry was low but persistently significant. In 53 persons with osteoporosis matched by age with 53 individuals from the control group, vertebral mineralization values were 60% lower than those of the control group, and the mean estimated total calcium intake in osteoporotics was 21% lower. In those persons reporting a single lifetime calcium intake, the control patients ingested almost twice as much calcium as those with osteoporosis. A mean decrease in calcium intake with advancing years has been shown. Evidence points to a decrease in calcium absorption with age, osteoporosis, or both, as well as a greater need for calcium intake in the elderly to maintain a positive calcium balance. Regardless of the intricacies of calcium homeostasis, a negative calcium balance leads eventually to greater bone resorption than formation, hence the rationality of insuring an adequate calcium intake with recognized nutritional needs. Evidence suggests that many factors are involved in the etiology and pathogenesis of osteoporosis; the data in this report support the likelihood that availability of calcium in the diet is one of them.
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  • 34
    ISSN: 1432-0827
    Keywords: Calcitonin ; Parathyroid hormone ; Calcium ; Newborn ; Fracture
    Source: Springer Online Journal Archives 1860-2000
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    Notes: Summary Determinations of serum calcium (Ca), phosphorus (P), calcitonin (CT), and parathyroid hormone (PTH) were carried out in 36 full-term newborn infants with fracture of the clavicle (CF) and in 46 normal neonates (N). At the 6th hour of life the CF neonates demonstrated lower serum Ca and higher serum CT in comparison with normal infants. In the hours following, no significant differences between the two groups for the Ca levels were found, whereas serum CT remained significantly higher in the CF newborns at the 24th, 48th, and 72nd hour of life. Significant differences between normal and CF infants in the PTH serum levels were detected only at the 48th hour, when PTH was lower in the CF newborns. The results of this investigation indicate that the fracture of the clavicle is a significant and peculiar factor in stimulating CT secretion. Serum Ca level appeared to be controlled by CT rather than auto-regulating the secretion of the hormone.
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  • 35
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    Calcified tissue international 33 (1981), S. 365-368 
    ISSN: 1432-0827
    Keywords: Absorptiometry ; Osteoporosis ; Spinal bone ; Bone mineral content ; Neutron activation ; Calcium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Dual-photon absorptiometry using153Gd (44 and 100 keV) was used to measure the bone mineral content (BMC) of the trunk and of the total body (TBBM) in 7 volunteers with no overt bone disease. These values were compared to those obtained with partial-body neutron activation of calcium (trunk Ca). The trunk Ca seemed to represent best a 60 × 30 cm area; the correlation coefficient with the corresponding BMC in that area was 0.97 (SEE ⋍ 7%). Trunk Ca was also highly correlated with TBBM (r=0.96; SEE=8%) and with radius BMC (r=0.92; SEE=11%), but the correlations with the BMC of smaller subareas of the trunk were lower (r⋍0.9; SEE ∼ 12%). The BMC of the lumbar spine was only moderately correlated with trunk Ca, radius BMC and TBBM (r ∼ 0.82; SEE ∼ 18%), and only slightly more associated with trunk BMC (r ∼ 0.88; SEE ∼ 14%). The BMC of the combined lumbar-thoracic spine showed higher correlations with trunk Ca, radius BMC and TBBM (r ∼ 0.87; SEE ∼ 13%), and trunk BMC (r=0.93; SEE ∼ 10%). An accurate and sensitive measure of spinal status requires a direct measurement of that area.
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  • 36
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    Calcified tissue international 3 (1969), S. 100-102 
    ISSN: 1432-0827
    Keywords: Mitochondria ; Calcium ; Mineralisation
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  • 37
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    Calcified tissue international 2 (1968), S. 67-76 
    ISSN: 1432-0827
    Keywords: Calcergy ; Calciphylaxis ; Calcium ; Metals
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    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Chez le rat, des expériences ont montré que, sauf de rares exceptions, les calcifications produites au site d'injection d'acétate de plomb, de chlorure de cérium, chlorure de calcium ou de permanganate de potassium sont complètement prévenues ou fortement inhibées par l'application locale simultanée de provocateurs calciphylactiques, mais non par des agents non provocateurs. Malgré quelques exceptions (attribuées à des interrelations chimiques spécifiques entre certaines des substances utilisées), cette curieuse corrélation entre l'efficacité calciphylactique provocatrice et le pouvoir anticalcergique est, d'après le test χ2, hautement significative (P〈0,001).
    Abstract: Zusammenfassung Nach subcutaner Injektion von Bleiacetat, Ceriumchlorid, Calciumchlorid oder Kaliumpermanganat tritt an der Injektionsstelle eine starke Verkalkung auf. Bis auf sehr wenige Ausnahmen kann diese durch gleichzeitige lokale Anwendung von calciphylaktischen Provokatoren verhütet oder weitgehend unterdrückt werden. In dieser Beziehung sind nicht provolatorisch wirkende Stoffe inaktiv. Trotz der wenigen Ausnahmen (die wahrscheinlich auf spezifische, chemische Wechselwirkungen zwischen manchen der untersuchten Substanzen beruhen) ist dieser merkwürdige Zusammenhang zwischen calciphylaktisch provozierender und anticalcergischer Aktivität, nach dem χ2-Test berechnet, statistisch hochsignifikant (P〈0,001).
    Notes: Abstract Experiments on rats indicate that, with very few exceptions, the calcification which occurs at subcutaneous sites of treatment with lead acetate, cerium chloride, calcium chloride or potassium permanganate is completely blocked or severely inhibited by simultaneous topical application of calciphylactic challengers but not of non-challengers. Despite the few exceptions (which are thought to depend upon specific chemical interactions between some of the compounds tested) this singular correlation between calciphylactic challenging and anticalcergic potency, is highly significant by the Chi-square-test (P〈0.001).
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  • 38
    ISSN: 1432-0827
    Keywords: Bone cells ; Cyclic AMP ; Calcium ; Ascites fluid resorptive protein
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    Notes: Summary The effects of a bone resorptive protein isolated from human cancer ascites fluid on bone cell calcium and cyclic AMP were studied with fetal rat cells. The osteoclast-activating factor increased bone cell calcium uptake at 37°C and 4°C with no direct effects on calcium efflux. Concentrations of the resorptive factor that increased in vitro bone resorption and cell calcium uptake had no effect on cyclic AMP. The effects of the protein on calcium uptake were not specific for bone cells, and large increases were also observed in isolated fetal rat skin cells. These studies suggest that increases in the permeability of the cell membrane to calcium are involved in the mechanism of action of the ascites fluid resorptive protein.
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  • 39
    ISSN: 1432-0827
    Keywords: Hydroxyapatite ; Dissolution ; Pyrophosphate, Diphosphonates ; Calcium ; Phosphate
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    Notes: Summary Pyrophosphate and diphosphonate ions have been said to diminish the dissolution of hydroxyapatite crystals, because they lower the equilibrium concentrations of calcium and phosphate ions in the bulk solution around hydroxyapatite crystals in a closed system. However, in a closed system these effects are not necessarily due to an effect on dissolution alone. In this paper we have used a continuous flow system to study the effects of pyrophosphate and two diphosphonates, ethane-1-hydroxy-1,1-diphosphonate and dichloromethane diphosphonate, on the dissolution of hydroxyapatite. All three compounds decreased markedly the rate of dissolution of hydroxyapatite as well as the exchangeable pools of calcium and phosphate ions around the cystals.
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  • 40
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    Calcified tissue international 31 (1980), S. 231-238 
    ISSN: 1432-0827
    Keywords: Magnesium ; Bone ; Calcium ; Parathyroid gland
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    Notes: Summary Calcium homeostasis and bone pathology were studied in weanling rats fed a low (70 ppm) magnesium diet for 2–21 days. The rats developed significant, progressive hypercalcemia after 6 days on the diet. The increase in blood calcium was accompanied by progressive hypoactivity of the parathyroid gland (PTG), as determined by histologic and morphometric analyses. Thus hyperactivity of the PTG could not have been responsible for the hypercalcemia observed. Histologic examination of femora and humeri from magnesium-deficient rats showed progressive subperiosteal hyperplasia, consisting of undifferentiated osteoprogenitor cells and fibrous tissue, after 7 days of deficiency. The presence of unmineralized osteoid tissue in the metaphyses indicated that mineralization was not proceeding normally. The alterations in differentiation of osteoprogenitor cells, together with the failure of mineralization, resulted in significantly lower rates of bone formation (as measured by fluorochrome labeling) in the magnesium-deficient rats. Basophilic cementing lines and inactive osteocytes in the cortices of bones from magnesium-deficient rats indicated that bone resorption was also severely reduced in magnesium deficiency. We postulate that bone magnesium depletion (66% by day 21) has a direct negative effect on osteoblastic and osteocytic activity, and may explain, in part, the decreased responsiveness of bone to parathyroid hormone (PTH) that has been observed in magnesium-deficient animals.
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    Calcified tissue international 32 (1980), S. 45-53 
    ISSN: 1432-0827
    Keywords: Dentin ; Periodicity ; Allometry ; Calcium ; Sulfur
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    Notes: Summary We have described differences in the aspects of biological rhythms for calcium and sulfur deposition on the labial and lingual sides of the growing rabbit incisor, where growth occurs along a spiral axis. The calcium oscillations appear to be smoother on the labial side than on the lingual side. The lingual side is characterized by high-frequency rhythms with high amplitudes which possess the greatest percent of the power (Fourier analysis). These observations also reflect a difference in behavior of the mean Ca concentration across the labial and lingual sides. Sulfur rhythms on the labial side have higher amplitudes than those on the lingual side, but systematic differences in distribution of power between high and low frequencies is not as pronounced as in the case of Ca. The differences in Ca rhythms reflect differences in the growth rates of incisors on either side of the spiral axis. The labial side grows slightly faster than the lingual side, and its odontoblasts secrete Ca along the spiral axis and toward the pulp cavity at the same time. Thus the resultant direction of growth is more nearly opposite the extension of the occlusal end on the labial side, and Ca is consequently deposited over a wider area relative to that on the lingual surfaces. On the lingual side, Ca is deposited within a more limited area, and growth must therefore be continuous at high frequencies. The distribution of Ca on both sides of the tooth reflects these differences in growth rate and periodicity in two ways. First, given a unit area of tooth, the calcium concentration on the labial side is less than that of the lingual side. Second, whereas the calcium concentration on the labial side declines rapidly from the enamel-dentin junction to the pulp cavity, it is uniformly high across the lingual side because its growth is more continuous at high frequencies.
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  • 42
    ISSN: 1432-0827
    Keywords: 1α-Hydroxy vitamin D3 ; 1,25-Dihydroxyvitamin D3 ; Calcium ; Transport ; Intestine
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    Notes: Summary The timed sequence of events following the oral administration of 1α-hydroxy vitamin D3 (1αOHD3) to rachitic chicks was compared to that following a comparable dose of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3). RNA polymerase activity was maximally increased 20% by 1αOHD3 within 1 to 2 h and returned to control values after 8 h. Alkaline phosphatase activity was stimulated by 4 h and was maximal (3- to 5-fold increase) at 24 h. Calcium binding protein (CaBP) was detected initially within epithelial cells at the proximal end of the villus (just above the crypt) 6 to 8 h after 1αOHD3 administration, in epithelial cells lining the proximal half of the villus by 24 h, and in epithelial cells along nearly the entire villus by 48 h. At no time did goblet cells contain CaBP. Serum calcium concentrations were significantly elevated in 2 h and maximal by 12 h (an increase of 3.6 mg/dl). Calcium accumulation by the intestinal mucosa in vitro was increased by 6 to 8 h and maximal (60% increase over controls) at 24 h. Phosphate accumulation by the intestinal mucosa in vitro was increased by 6 h and maximal (105% increase over controls) between 8 and 24 h. 1,25(OH)2D3 increased CaBP and calcium accumulation by 4 h, 2 h sooner than did 1αOHD3. 1,25(OH)2D3 decreased serum calcium levels and increased serum phosphate levels at 2 h unlike 1αOHD3. No difference in the effects of these compounds on alkaline phosphatase activity, RNA polymerase activity, and phosphate accumulation could be demonstrated. These results are consistent with the possibility that 1αOHD3 may not require conversion to 1,25(OH)2D3 for all of its biological effects.
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  • 43
    ISSN: 1432-0827
    Keywords: Perifusion ; Parathyroid hormone ; In vitro ; Calcium ; Beta regulation
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    Notes: Summary An in vitro perifusion system was used to study parathyroid hormone (PTH) secretion in response to calcium (Ca) and beta-adrenergic agents. Perifused parathyroid tissue responded to changes in Ca within the physiologic range during experiments up to 5 h. There was rapid secretory stimulation after exposure to low Ca, with the maximum response being observed at 20 min. Normal bovine glands showed a Ca-independent nonsuppressible component of PTH release at concentrations of Ca above physiologic. 1-isoproterenol produced rapid stimulation of PTH release, the response being blocked by a beta antagonist. The maximum secretory response to either low Ca (0.5 mM) or 1-isoproterenol (10−5 M) was enhanced when the two stimuli were applied simultaneously. The response to isoproterenol was blocked by raising Ca to 2.5 mM. Although d,l-propranolol (10−4 M) caused mild suppression of PTH release at a Ca of 1.25 mM, it did not cause additional suppression at 2.5 mM Ca nor did it decrease the response to 0.5 mM Ca stimulation. The secretory response of the gland to low Ca was sustained at a level more than double the baseline rate. The response to isoproterenol was more transient, with a return to or toward baseline secretion within 60 min. These results suggest that beta agonists and low Ca have separate but related mechanisms for stimulating PTH release and may affect different pools of hormone. The perifusion system described is a relatively simple technique for assessing the kinetics and interactions of various stimulators of PTH secretion.
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  • 44
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    Calcified tissue international 32 (1980), S. 29-44 
    ISSN: 1432-0827
    Keywords: Rabbit ; Dentin ; Calcium ; Sulfur ; Periodicity ; Circadian ; Ultradian
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary We have identified a variety of biological rhythms involved in the apposition and mineralization of dentin in the rabbit incisor. Animals were injected during the day or night with lead acetate at 2-week intervals—to provide biological time markers in forming dentin—and transverse undecalcified sections of the lower incisors were prepared for electron microprobe analysis. The positions of the lead markers were identified, and the continuous distribution of calcium and sulfur was measured at 1 µm intervals between the markers. In thin sections stained with hematoxylin after decalcification, the widths of a series of structural increments (bands) were measured with an ocular micrometer. Fourier analysis of the data revealed spectra of structural and compositional rhythms with a range of periodicities which extended from a matter of hours [ultradian (〈24 h)] to days [infradian (〉24 h) and circadian (approximately 24 h)]. The structural and compositional rhythms appeared to be independent to the extent that they did not necessarily have the same periods, or amplitudes. Nor were there simple phase relationships between all of the rhythms. At some times, Ca and S fluctuations are inversely proportional (180° out of phase), but in other cases they are directly proportional or out of phase by varying degrees other than 180°. The analyses thus suggest that calcium and sulfur deposition (representing mineral and glycosaminoglycan deposition, respectively) are not simply inversely proportional, and that the hematoxylin-stained structural increments did not solely reflect differences in the distribution of the mineral components in dentin.
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  • 45
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    Calcified tissue international 34 (1982), S. 253-257 
    ISSN: 1432-0827
    Keywords: Prednisolone ; Calcium ; Bone ; Corticoid osteopenia ; Vitamin D metabolites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Adult male rats were fed a diet containing 0.15% calcium, 0.3% phosphorus, and either 100, 50, or 20 mg of prednisolone per kg of diet. All these levels of prednisolone led to osteopenia, decreased intestinal absorption of calcium, slightly lower serum calcium and phosphorus, and a decreased level of serum 1,25-dihydroxyvitamin D3. Exogenous parenteral 1,25-dihydroxyvitamin D3 corrected steroid-induced changes in serum calcium and phosphorus, but could not completely correct the low intestinal calcium transport; nor did it prevent the development of osteopenia. The prednisolone-induced osteopenia seems at least in part to be caused by impaired intestinal calcium transport. The impaired calcium transport may be the result of low levels of 1,25-dihydroxyvitamin D3 and a direct effect of presnisolone on the intestine.
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  • 46
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    Calcified tissue international 36 (1984), S. 596-603 
    ISSN: 1432-0827
    Keywords: Calcium ; Ameloblasts ; X-ray microanalysis ; Transport ; Frozen
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    Topics: Biology , Medicine , Physics
    Notes: Summary Energy dispersive X-ray microanalysis was applied to freeze-dried blocks of enamel organ tissue to determine levels of calcium in various celular regions. The tissue blocks were dissected free from adjacent forming enamel following injection of cobalt or fluoride ions, both of which temporarily inhibit enamel mineralization. In all control and experimental specimens there was an increasing gradient of calcium from the stratum intermedium cells to the distal ends of the ameloblasts. Calcium levels were significantly reduced near the distal ends of the ameloblasts following cobalt or fluoride injection as compared with controls. It is suggested that evidence of an intercellular buildup of calcium near the distal ends of the ameloblast supports a controlling function of these cells. The changes in calcium levels are correlated with alterations in mineralization known to occur in the adjacent enamel of the model systems employed.
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  • 47
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    Calcified tissue international 4 (1969), S. 180-184 
    ISSN: 1432-0827
    Keywords: Strontium ; Calcium ; Bone ; Shell
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    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Des poules ont été nourries avec une alimentation riche en strontium stable. Des concentrations de strontium de 3000 p.p. m. à 50000 p.p.m. montre une augmentation nette en strontium du tibia, alors que le contenu en calcium n'est pas modifié. Les concentrations en calcium sérique diminue, lorsque le strontium alimentaire augmente. Le calcium des coquilles d'oeufs diminue progressivement avec l'augmentation du strontium alimentaire, alors que le contenu en strontium des coquilles présente une augmentation correspondante. Des analyses de diffraction par rayons X des os et des coquilles ne permettent pas de déterminer sous quelle forme le strontium est déposé.
    Abstract: Zusammenfassung Die Resultate einer Verfütterung von hohen stabilen Strontiumdosen an Hühnern werden erläutert. Strontiumzusätze zur Nahrung in der Höhe von 3000–50000 p.p.m. führten zu einer signifikanten Zunahme des Strontiumgehaltes der Tibia und verursachten keine wesentlichen Änderungen des Calciumgehaltes. Die Calciumkonzentration im Plasma verminderte sich, wenn der Nahrung ansteigende Strontiummengen zugegeben wurden. Mit zunehmendem Strontiumzusatz zur Nahrung zeigte der Calciumgehalt der Eischale eine fortlaufende Abnahme, während sich der Strontiumgehalt entsprechend erhöhte. Durch Röntgendiffraktionsanalysen der stark Strontium-haltigen Knochen und Eischalen konnte nicht festgestellt werden, in welcher Form das Strontium abgelagert wurde.
    Notes: Abstract The results of feeding high dietary levels of stable strontium to hens are reported. Dietary levels of strontium from 3,000 p.p.m. to 50,000 p.p.m. showed a significant increase in strontium content of the tibia bone and essentially no change in the calcium content. Plasma calcium concentration was shown to decrease with increasing dietary strontium treatment. Egg shell calcium showed a progressive decrease with increasing dietary strontium treatment, whereas the strontium content has a corresponding increase. X-ray diffraction analyses of bones and shells containing large amounts of strontium were unsuccessful in evaluating the from in which strontium was deposited.
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    Calcified tissue international 4 (1969), S. 193-201 
    ISSN: 1432-0827
    Keywords: Calcium ; Carbonate ; Gland ; Ultrastructure ; Spherolith
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Les cellules activement sécrétantes des glandes riches en calcium deLumbricus terrestris ont une forme en dôme. La partie basale de la cellule présente de nombreux prolongements ramifiés. Ces prolongements contiennent de nombreuses mitochondries, ainsi que des invaginations de la membrane formant des vésicules qui migrent dans diverses parties de la cellule. Le noyau irrégulier est en position centrale. La région supranucléaire contient surtout de l'ergastoplasme, plusieurs appareils de Golgi et de nombreuses granules provenant de l'appareil de Golgi. Ces granules augmentent de taille et sont rejetées dans le sinus de la glande, où elles se modifient et se calcifient pour donner des sphérolithes. Des radioautographics glandulaires, obtenues 1/2 heure après injection de Ca45, montrent une localisation isotopique, située presque exclusivement dans les cellules; 4–24 heures après, l'isotope se localise dans les sphérolithes de la cavité glandulaire. Ces cellules semblent assurer deux fonctions liées à la production de sphérolithes: 1. absorption et transport de calcium de la région basale vers la surface cellulaire et 2. formation d'une matrice protéique qui se calcifiera.
    Abstract: Zusammenfassung Die aktivsezernierenden Zellen der calcifizierenden Drüsen vonLumbricus terrestris sind annähernd kuppelförmig gestaltet. Der untere Teil dieser Zellen besteht aus unzähligen ineinandergreifenden Zellfortsätzen. Diese Fortsätze enthalten zahlreiche Mitochondrien und membranöse Einstülpungen, welche Bläschen bilden, die zu den verschiedenen Regionen der Zelle wandern. Der Zellkern ist unregelmäßig und zentral angeordnet. Die supranukleäre Region ist zu einem großen Teil mit grobem endoplasmatischem Reticulum und mehreren Golgi-Komplexen sowie zahlreichen Granula, die von den Golgi-Komplexen stammen, ausgefüllt. Diese Granula vergrößern sich und werden in den Drüseninus ausgestoßen, wo sie schließlich reorganisiert und mineralisiert werden, um Sphärolithen zu bilden. 1/2 Std nach Injektion von Ca45 wurde die Drüse entfernt; eine Radioautographie zeigte, daß das Isotop beinahe ausschließlich in den Zellen lokalisiert war; 4–24 Std später befand sich das Isotopin den Sphärolithen der Drüsenhöhlung. Diese Zellen sind anscheinend an zwei für die Bildung von mineralisierten Sphärolithen notwendigen Funktionen beteiligt: 1. an der Calcium-Absorption und deren Transport von der Basalregion bis zur Zelloberfläche; 2. an der Bildung einer Proteinmatrix, in welcher die Mineralisation stattfindet.
    Notes: Abstract The actively-secreting cells of the calciferous glands ofLumbricus terrestris are roughly dome shaped. The basal part of the cell consists of numerous interdigitating cell processes. These processes contain numerous mitochondria and membranous infoldings, forming vesicles which migrate to various regions of the cell. The nucleus is irregular and centrally located. The supranuclear region is occupied to a great extent by the rough endoplasmic reticulum, several Golgi complexes and numerous granules derived from the Golgi complexes. These granules enlarge and are extruded into the gland sinus, where they eventually become reorganized and mineralized to give rise to spheroliths. Radioautographs of glands removed 30 min following injection of45Ca showed uptake of the isotope located almost exclusively in the cells; 4–24 h later the isotope was located in the spheroliths in the gland cavity. These cells apparently perform two functions necessary for the production of mineralized spheroliths, 1, absorption and transport of calcium from the basal region to the cell surface and 2, the elaboration of a protein matrix in which mineralization occurs.
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    Calcified tissue international 4 (1969), S. 291-304 
    ISSN: 1432-0827
    Keywords: Bone ; Fluorescence ; Resorption ; Deposition ; Calcium ; Microradiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Divers agents chimiques, colorés, fluorescents et se localisant dans les os, à savoir la tétracycline, l'alazazine rouge S et le DCAF, ont été administré en série à des rats sevrés et on a mesuré le taux de la formation et de la résorption osseuse sur les coupes transversales du tiers supérieur de la diaphyse. Ici la formation osseuse périostale s'effectue progressivement avec peu de changement endostéal. Avec alimentation carnée, la croissance des rats est significativement restreinte pendant la première semaine, mais se rétablit ensuite. Bien qu'il y ait croissance des os, ceux-ci ne se minéralisent pas normalement et ils deviennent rapidement fragiles et amincis. La résorption osseuse est lente d'abord, puis s'accelère pendant 2–3 semaines pour atteindre un taux de 15μ par jour, après quoi elle se ralentit de nouveau. Bien que le taux de formation osseuse soit réduit, en comparaison avec celui des os normaux, la résorption s'effectue environ deux à trois fois plus rapidement que la croissance osseuse. Des études microradiographiques sur des rats à régime carné mais carencés en calcium ont permis la constatation suivante: tandis que la résorption s'effectue à la marge endostéale et que la formation osseuse a lieu sur l'aspect périostéal, la matière osseuse nouvellement formée est moins calcifiéc que chez les témoins.
    Abstract: Zusammenfassung Einige farbige, fluoreszierende, knochensuchende Chemikalien, z. B. Tetracyclin, Alazarin-Rot S und CDAF, wurden nacheinander an entwöhnten Ratten verabreicht, worauf man die Knochenbildungs- und Knochenresorptionswerte an hartgeschliffenen Schnitten des oberen Drittels der Diaphyse gemessen hat. Hier findet fortschreitend periostale Knochenbildung statt, mit geringer Veränderung des Endosteums. Bei Fleischdiät wird das Körperwachstum während der ersten Woche erheblich beschränkt; danach aber normalisiert es sich wieder. Obwohl die Knochen noch wachsen, zeigen sie keine normale Mineralisierung und werden schnell zerbrechlich und dünn. Die Knochenresorption ist anfangs langsam, dann beschleunigt sie sich während einer Zeitspanne von 2–3 Wochen bis auf 15 μ pro Tag, um sich dann wieder zu verlangsamen. Während die Knochenbildungsgeschwindigkeit relativ zum Normalwert heruntergesetzt wird, verläuft die Resorption ungefähr 2–3mal so schnell wie die Knochenbildung. Mikroradiographische Untersuchungen an mit Fleisch ernährten Ca-armen Ratten haben bestätigt, daß während die Resorption am Endosteumrande stattfindet und sich die Knochenbildung an der Periostenfläche fortsetzt, die neugebildete Knochensubstanz weniger kalzifiziert ist, als die der Kontrolltiere.
    Notes: Abstract Different coloured, fluorescent bone-seeking chemicals, viz., tetracycline, Alizarin Red S, and DCAF, have been administered sequentially to weanling rats and the rate of formation and resorption of bone measured from hard-ground cross sections of the upper third of the diaphysis of the femur. On a meat diet, bodily growth is significantly restricted for the first week and then recovery occurs. While bones grow they fail to mineralize normally and rapidly become fragile and rarefied. Resorption of bone is at first slow, then accelerates for a period of 2–3 weeks to about 15μ/day and then slows again. While the rate of bone formation is reduced relative to normal bone, resorption proceeds at approximately two to three times the rate of bone growth. Microradiographic studies confirm tht while resorption occurs on the endosteal margin and formation proceeds on the periosteal aspect of meat fed Ca-deficient rats, new bone is less calcified than that in control animals.
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    Calcified tissue international 33 (1981), S. 477-484 
    ISSN: 1432-0827
    Keywords: 1,25-(OH)2-D ; Calcium ; Phosphorus ; Sex ; Age
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Dietary phosphate deprivation in women, but not men, is accompanied by a fall in plasma PO4 and a rise in plasma 1,25-(OH)2-vitamin D concentrations. In contrast, young male rats exhibit a fall in plasma PO4 and a rise in plasma 1,25-(OH)2-D concentrations in response to PO4 deprivation. To evaluate whether age and sex influence basal plasma 1,25-(OH)2-D levels and their regulation by PO4 deprivation, plasma 1,25-(OH)2-D, PO4, and Ca levels were measured in male and female rats ranging in age from 6 weeks to 6 months while they were eating normal or low PO4 diets for 1 to 16 days. Similar observations were also made in 6-week-old castrated male and female rats, males replaced with testosterone, and females replaced with estradiol. Basal plasma 1,25-(OH)2-D levels were higher in 6-week-old males (228±76 pmol/l) than in 6-week-old females (148±62 pmol/l;P〈0.01) and declined by age 11 weeks to stable levels averaging about 100 pmol/l without sex difference. Dietary PO4 deprivation resulted in a three-to fourfold increase in plasma 1,25-(OH)2-D concentrations regardless of age and sex, accompanied by a correlated rise in serum Ca concentrations. Castration of 6-week-old males and females eliminated the sex difference in basal plasma 1,25-(OH)2-D levels and appeared to enhance the elevation of plasma 1,25-(OH)2-D concentrations in response to PO4 deprivation in females. Although gonadal hormones may modify basal plasma 1,25-(OH)2-D levels, they are not required for the augmentation of plasma 1,25-(OH)2-D levels in response to PO4 deprivation.
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    Calcified tissue international 33 (1981), S. 575-581 
    ISSN: 1432-0827
    Keywords: Osteoporosis ; Vitamin D ; Bone mineral ; Estrogen ; Aging ; Thiazide ; Fluoride ; Calcium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Bone mineral content (BMC) was measured by125I photon absorptiometry every 3 months in 264 normal females (45–54 years) over a 2-year period together with serum samples for calcium, phosphate, magnesium, creatinine, alkaline phosphatases, potassium, and protein. A 48-h urinary calcium and creatinine measurement was obtained. The subjects were divided into 7 treatment groups and 3 placebo groups. Five of the treatments (thiazide, vitamin D3, fluoride + vitamin D3, fluoride, and 1αD3) were ineffective at the doses used; the annual loss of compact bone was 1.5–2.2% (-X=1.8%), similar to the loss seen with placebos. Estrogen and estrogen + thiazide, in contrast, produced a 1.34% annual increase of BMC. The subjects were divided into groups with low, medium, and high initial BMC. Also, individual regressions for bone change were calculated and the subjects were divided into groups of responders, maintainers, and losers (annual change of 〉0%, 0 to −1%, and 〉−1%, respectively). The initial BMC status did not consistently affect bone or biochemical responses to the therapeutic agents. Estrogen was effective even in subjects with high BMC, whereas the other agents did not inhibit bone loss even in subjects with low initial BMC. Virtually all subjects responded to estrogen positively; in contrast we could not identify a subset of “responders” with any of the other treatments. Time since menopause appeared to influence the bone changes, although it was not a significant effect given the sample size. Bone loss in groups not treated with estrogens was 2%/year at 20 months after menopause with a decline to 1.3%/year at 45 months post-menopause. There was no apparent decline in the bone response to estrogen during the first 4 years after menopause, and in fact bone response tended to increase with time.
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    Calcified tissue international 33 (1981), S. 485-488 
    ISSN: 1432-0827
    Keywords: 1,25-(OH)2-D ; Hypophysectomy ; Calcium ; Phosphorus
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    Notes: Summary The mechanism by which dietary phosphate deprivation elevates plasma 1,25-(OH)2-D levels is not known. To evaluate the role of the pituitary in regulating plasma 1,25-(OH)2-D concentrations, the responses of plasma 1,25-(OH)2-D to dietary phosphate deprivation and, separately, to dietary calcium deprivation were evaluated in intact and hypophysectomized male rats. Among intact and hypophysectomized rats eating normal diets, plasma 1,25-(OH)2-D levels averaged 228±76 and 148±62 pmol/1, respectively (P〈0.01). During dietary phosphate deprivation, plasma 1,25-(OH)2-D levels rose to 1160±260 in intact rats and fell to 90±26 pmol/l in hypophysectomized rats (P〈0.001). By contrast, during dietary calcium deprivation, plasma 1,25-(OH)2-D levels rose in both intact and hypophysectomized animals to 856±107 and 742±279 pmol/l, respectively (NS). In response to dietary phosphate deprivation, serum calcium concentrations rose as 1,25-(OH)2-D concentrations rose in intact rats but remained at control levels in hypophysectomized rats. These results support the hypothesis that a pituitary hormone acting either directly or indirectly on the kidney mediates the increase in plasma 1,25-(OH)2-D during dietary phosphate deprivation. The hypercalcemia that occurs in rats during dietary phosphate deprivation appears to depend on the elevation of plasma 1,25-(OH)2-D.
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    Calcified tissue international 2 (1968), S. 253-261 
    ISSN: 1432-0827
    Keywords: Calcium ; Ion ; Binding ; Chondroitin ; Cartilage
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    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé La liaison du calcium par le sulfate de chondroitin C a été étudiée en utilisant des méthodes biologiques et physicochimiques pour la détermination quantitative du calcium ionique. Les valeurs moyennes pour logK j, le logarithme de la constante de formation non corrigée d'un complexe calcium-sulfate de chondroitin C, sont 1,64 par la technique de cœur de grenouille, 1,55 par la méthode de murexide, 1,39 par l'ultrafiltration et 1,04 par l'électrode sélective du calcium. L'ordre de grandeur de ces valeurs suggèrent que le sulfate de chondroitin C a une capacité de liaison pour calcium relativement élevée, mais les valeurs calculées pour un paramètre d'échangeK p indiquent que le calcium a une affinité faible pour le polysaccharide.
    Abstract: Zusammenfassung Die Bindung von Calcium mit Chondroitinsulfat C wurde untersucht mittels biologischer und physikalisch-chemischer Methoden für die quantitative Bestimmung des ionischen Calciums. Im Durchschnitt ergab logK j, der Logarithmus der unkorrigierten Formationskonstante für einen Calciumchondroitinsulfatkomplex, 1,64 mit der Technik des Froschherzens, 1,55 mit der Murexidmethode, 1,39 mittels Ultrafiltration und 1,04 mit den Calciumselektiven Elektroden. Die Größe dieser Werte zeigt, daß Chondroitinsulfat eine relativ hohe Bindungskapazität für Calcium hat, die berechneten Werte für einen AustauschparameterK p jedoch, daß Calcium eine kleine Affinität für Polysaccharide hat.
    Notes: Abstract The binding of calcium by chondroitin sulfate C was studied by employing biological and physicochemical methods for the quantitative determination of ionic calcium. Mean values for logK j, the logarithm of the uncorrected formation constant for a calcium-chondroitin sulfate complex, were 1.64 with the frog heart technique, 1.55 with the murexide method, 1.39 with ultrafiltration and 1.04 with the calcium selective electrode. The magnitude of these values suggests that chondroitin sulfate has a relatively high binding capacity for calcium, but calculated values for an exchange parameterK p indicate that calcium has a low affinity for the polysaccharide.
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    Calcified tissue international 2 (1968), S. 301-313 
    ISSN: 1432-0827
    Keywords: Calcium ; Absorption ; Vitamin D
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    Calcified tissue international 2 (1968), S. 20-29 
    ISSN: 1432-0827
    Keywords: Bone Atrophy ; Bone Resorption ; Calcium ; Collagen ; Osteoporosis
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    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Atrophie osseuse d'immobilisation était induite par section de la plexus brachial et/ou désarticulation de la coude. Après 9 bis 12 semaines de désuétude huméri intactes furent examinés par rayons X et leur qualités physiques déterminés. Les humérientiers furent isolés, dégraissés, desséchés au poids constant, et leur teneur en cendre d'os et collagène déterminés. Huit des 10 huméri immobilisés monstrérent radiodensité diminué. La jambe inusitée monstra perte parallèle en poids sec et poids sans gras (−23.2%), en collagène (−25.3%), et en cendre d'os (−26.1%) en comparaison de la jambe normale. Les données monstrèrent que la portion plus grande du tissu osseux perdu en atrophie osseuse d'immobilisation est remplacée par de l'eau, du gras, et des autres matériels organiques inconnus plutôt que par tissu fibreux, et que collagène est perdu en proportion du minéral. La perte proportionellement plus grande du collagène et de la cendre d'os que du poids sec et poids san gras semble dû à une augmentation du matériel organique, non-collagéne, non-lipide, kprobablement protéine.
    Abstract: Zusammenfassung Immobilisations-Knochenatrophie wurde in 10 erwachsenen Hunden herbeigeführt durch Brachialplexusschnitt und/oder Ellenbogenexartikulation. Nach 9–12 Wochen der Immobilisation wurden die intakten Humeri unter Röntgenstrahlen untersucht und ihre physischen Eigenschaften bestimmt. Derintakte Humerus wurde isoliert, entfettet, zu konstantem Gewicht getrocknet und der Knochenaschengehalt und Kollagengehalt bestimmt. Acht der 10 experimentellen (immobilisierten) Humeri demonstrierte Beweis von verringerter Röntgendichte. Die immobilisierte Extremität zeigte ähnlichen Verlust in trockenem, fettfreiem Gewicht (−23,2%) in Kollagen (−25.3%) und Knochenasche (−26,1%) im Vergleich zur normalen Extremität. Die Date deuten an, daß der Hauptanteil des Verlustes des Knochengewebes (bei Immobilisations-Knochenatrophie) von Wasser, Fett und anderen unidentifizierten organischen Substanzen ersetzt wird, als von Faserngewebe und daß Kollagen und Knochenasche im gleichen Verhältnis verloren gehen. Der größere, proportionale Verlust an Kollagen und Knochenasche, eher als der Verlust an fettfreiem Gewicht, scheint in der Zunahme an nicht kollagener, nicht lipoider, organischer Substanz, vermutlich Protein, zu liegen.
    Notes: Abstract Disuse bone atrophy was induced in 10 adult dogs by means of brachial plexus section and/or elbow disarticulation. After 9 to 12 weeks of disuse intact humeri were examined by X-ray, and their physical properties determined. Thewhole humeri were isolated, defatted, dried to constant weight, and their mineral and collagen content determined. Eight out of 10 experimental (non-used) humeri demonstrated evidence of decreased radiodensity. The non-used limb demonstrated parallel loss in dry, fat-free weight (−23.2%), in collagen (−25.3%), and in mineral (−26.1%), as compared to the normal limb. The data indicated that the major portion of the lost bone tissue in disuse osteoporosis is replaced by water, fat, and other unidentified organic materials rather than fibrous tissue, and that collagen is lost in equal proportion to mineral. The proportionatelly greater loss of collagen and mineral than of dry, fat-free weight appears to be due to an increase of non-collagenous, non-lipid organic material, presumably protein.
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    Calcified tissue international 30 (1980), S. 27-34 
    ISSN: 1432-0827
    Keywords: Ultrastructure ; Calcium ; Cartilage ; Vesicles
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The potassium pyroantimonate technique was utilized for the selective subcellular localization of calcium in the mandibular condylar cartilage of 1-day-old rats. Electron dense calcium pyroantimonate precipitates were localized principally in mitochondria and at the cell membrane of the chondrocytes. In addition, small intracellular vesicles 0.1–0.2µm in diameter were observed in proximity to the cell membrane of chondrocytes of the mid-hypertrophic zone. The results suggest that these vesicles were being extruded from the cell into the extracellular matrix. Energy-dispersive analysis by X-rays confirmed that calcium is the principal cation of the electron-dense precipitates.
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  • 57
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    Calcified tissue international 34 (1982), S. 43-48 
    ISSN: 1432-0827
    Keywords: Calcium ; Phosphate ; Phosphatidylserine ; Transport ; Mineralization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Experiments were performed to study the effect of inorganic phosphate (Pi) on phosphatidylserine-mediated Ca2+ transport utilizing two- and three-compartment lipid-aqueous phase model systems. When the three-compartment model was used, the rate of Ca2+ transport from an aqueous donor compartment to an aqueous receiver compartment, separated by a nonaqueous phospholipid phase, was determined. This experiment showed that the rate of Ca2+ transport was proportional to the phosphatidylserine concentration and the pH. Pi modulated the rate of Ca2+ transport; even when the Pi concentration of the donor aqueous phase was low, there was a marked enhancement of transport. To determine whether the Pi-mediated rise in the Ca2+ transport rate was due to an increase in the uptake of Ca2+ into the lipid phase, or to an increase in the ability of the lipid phase to release Ca2+, a two-compartment model was used. It was found that the ability of the phosphatidylserine phase to take up Ca2+ increased as the Pi concentration of the aqueous donor phase was raised. With the increase in Ca2+ uptake there was a concomitant elevation in the rate of Ca2+ transport into an aqueous receiver phase. However, Pi did not stimulate Ca2+ release from the phosphatide. Thus it was concluded that Pi enhanced the interaction between Ca2+ and phosphatidylserine, possibly by forming a Ca-phospholipid-Pi complex. Once this interaction had taken place, Ca2+ release into the aqueous receiver compartment was independent of the Pi concentration.
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    Calcified tissue international 36 (1984), S. 77-82 
    ISSN: 1432-0827
    Keywords: Osteogenesis ; Diffusion chambers ; Alkaline phosphatase ; Calcium ; Phosphorus
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    Topics: Biology , Medicine , Physics
    Notes: Summary The alkaline phosphatase activity and the calcium and phosphorus content of osteogenic tissue formedin vivo following the implantation of diffusion chambers loaded with rabbit bone marrow cells is reported. (In this study the term osteogenic includes osteoblastic and chondroblastic.) Chambers examined 14–70 days after implantation revealed progressive accumulation of mineral. Alkaline phosphatase activity increased until day 30 and declined thereafter. The osteogenic potential of the marrow cells decreased with increasing weight (age) of the cell donor rabbit when measured either as the percentage of chambers containing osteogenic tissue or as the amount of calcium, phosphorus, or alkaline phosphatase activity within the chambers. The results confirm that measurements of these parameters in tissue formed by cells incubated in diffusion chambersin vivo may be used as a method for assay of osteogenesis.
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    Calcified tissue international 36 (1984), S. 269-273 
    ISSN: 1432-0827
    Keywords: Bone loss (osteopenia) ; Calcium ; Corticosteroids (glucocorticosteroids) ; Fluoride ; Vitamin D
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary To evaluate the effect of prednisone and triple treatment (sodium fluoride, calcium, and vitamin D) on trabecular and cortical bone serial bone mineral content (BMC) measurements were made at a metaphyseal (BMCD) and diaphyseal (BMCP) site on the forearm on 31 consecutive and previously bone-healthy patients scheduled for at least 24 weeks high-dose prednisone treatment. The patients were randomized into two further treatment groups: group I (n=16) received prednisone plus triple treatment and group II (n=15) received only prednisone. The two groups were similar with regard to age, sex, prednisone dose, and initial BMC. During 24 weeks treatment, BMCD (partially representing trabecular bone) and BMCP (mainly representing cortical bone) fell significantly and similarly, demonstrating that there is no preventive effect on bone mineral loss on the triple regimen. The BMC fall after 12 weeks was significantly more pronounced for metaphyseal (partially trabecular) than for diaphyseal (cortical) bone, whereas the values did not differ significantly after 24 weeks; this indicates a greater sensitivity to the hormone treatment of trabecular bone. In the entire group, the fall in BMC correlated positively with individual prednisone dose, significant at the diaphyseal site (r=0.39,P〈0.05), but not at the metaphyseal site (r=0.31, P=0.08). It is concluded that corticosteroid-induced osteopenia is a diffuse bone disease which affects trabecular as well as cortical bone, suggesting that BMC measured on the forearm reflects changes in bone mineral at other locations.
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    Calcified tissue international 36 (1984), S. 392-400 
    ISSN: 1432-0827
    Keywords: Vitamin D ; Chick embryo ; Bone ; Calcium ; Phosphate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Chick embryos were injected in the yolk sac at various ages with various doses of different vitamin D3 metabolites. Serum concentrations of total calcium and inorganic phosphate were determined 24 h after the injection and histological and electron microscopic studies of the tibiae were conducted 3–6 days after. Confirming previous results, the injection of 1,25(OH)2D3 was found to produce significant hypercalcemia and hypophosphatemia. The dose required to produce these effects decreased with age: 100 ng on the 9th day, 50 ng on the 11th, and 10 ng on the 15th. This finding is interpreted as resulting from the fact that the specialized cells in the chorionic epithelium which are considered to be involved in mineral resorption from the shell differentiate between the 11th and 13th days. Although no bone changes were observed in embryos injected before the 11th day, a rim of unmineralized trabeculae (osteoid) was observed at the periphery of the cortex of the tibial diaphysis in the embryos which had been injected after that age. Thus, in embryos injected on the 11th day with 100 ng 1,25(OH)2D3, the trabeculae formed between the 11th and 14th day remained unmineralized until the 15th or 16th day at which time they completed their mineralization. In the embryos injected on the 14th day, the alterations were more severe and could be produced with doses 10 times smaller than those required when the injections were made on the 11th day. At all ages, the doses that produced an osteoid rim also induced hypercalcemia and hypophosphatemia. The electron microscopical study of the osteoid trabeculae showed that osteoblasts and osteocytes had normal cytological characteristics and that the bone matrix did not present changes other than the reduction in mineral deposition. While the above findings do not exclude a direct action of 1,25(OH)2D3 on bone cells as the mechanism of osteoid formation, they do underline the importance of the humoral changes at least as partial determinants of this phenomenon. The activities of various vitamin D metabolites were compared using as parameter the threshold-dose required to produce a rim of unmineralized trabeculae in the tibia of 14–15 days embryos (T-D). The most active metabolite appeared to be 1,25(OH)2D3 (T-D: 10 ng); it was followed by 1,24,25(OH)3D3 (T-D: 100 ng) and 1,25,26(OH)3D3 (T-D: 100 ng). Vitamin D3 itself (T-D: 100 µg), 25(OH)D3 (T-D: 2.5µg) and 24,25(OH)2D3 (T-D: 5 µg) produced similar responses but only when administered in much larger doses.
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    Calcified tissue international 36 (1984), S. 702-710 
    ISSN: 1432-0827
    Keywords: Corticosteroids ; Cartilage ; Organ culture ; Calcium ; Matrix vesicles
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    Topics: Biology , Medicine , Physics
    Notes: Summary The present study examined the effects of various corticosteroid and noncorticosteroid hormones upon the ultrastructure of chondroprogenitor cells and chondroblasts in an organ-culture system of late fetal condylar cartilage. Corticosteroids, (triamcinolone acetonide, dexamethasone, corticosterone) at concentrations of 10−6–10−8M stimulated markedly a precocious formation of matrix vesicles by chondroblasts. This stimulation was accompanied by a significant accretion of calcium complexes intra- and extracellularly in both the chondroprogenitor cell population and chondroblastsin vitro, as well as in the newly induced matrix vesicles. Nonglucocorticoid steroids (progesterone, estradiol, testosterone, cortexolone) did not evoke similar effects. Progesterone and testosterone, however, seemed to adversely affect the ultrastructure of the cartilage cells, whereas estradiol appeared to have a favorable effect on the morphology of cultured condylar cartilage.
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    Calcified tissue international 34 (1982), S. 121-124 
    ISSN: 1432-0827
    Keywords: Bone ; Calcium ; Metabolism
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    Notes: Summary Bone Gla protein (BGP) was measured in the plasma by radioimmunoassay (RIA) during treatment of 59 patients with bone diseases including Paget's disease (N=9), primary hyperparathyroidism (N=25), chronic renal failure (N=20), and cancer involving bone (N=5). Plasma BGP was increased above normal in all patients. BGP decreased in the patients with Paget's disease following the acute and chronic administration of salmon calcitonin. Plasma BGP was higher in women then in men with primary hyperparathyroidism. Following parathyroidectomy, BGP decreased in both sexes but the decrease was significant in women only. Plasma BGP was increased in patients with renal osteodystrophy and did not change after hemodialysis. In the patients with bone cancer, plasma BGP decreased during treatment of the attendant hypercalcemia with salmon calcitonin. Although plasma BGP and serum alkaline phosphatase (AP) levels were generally correlated in these studies, there were examples of dissociation between the two. The measurement of plasma BGP appears to provide a specific index of bone metabolism that may in some circumstances be more sensitive than serum alkaline phosphatase measurement. However, further studies are necessary to establish the clinical value of plasma BGP measurement by RIA in the management of patients with bone diseases.
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    Calcified tissue international 35 (1983), S. 107-110 
    ISSN: 1432-0827
    Keywords: Calcium ; Glucocorticoid ; Vitamin D ; Osteoporosis ; Rat
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    Topics: Biology , Medicine , Physics
    Notes: Summary Eighty-eight adult male Sprague-Dawley rats were given a diet with either (a) 0.5% Ca and 0.6% P or (b) 0.01% Ca and 0.6% P. Osteopenia was created by adding prednisolone to the diet. The prophylactic effect of oral 1,25(OH)2D3 on the osteopenia was studied. It was found that prednisolone osteopenia in the rat was associated with defective Ca absorption. By giving an oral dose of 1,25(OH)2D3, it was possible to maintain normal Ca absorption during prednisolone treatment and to prevent the bone loss. No significant hypercalcemia or any kidney calcifications were seen. These results are in contrast to earlier findings, in which subcutaneous administration of 1,25(OH)2D3 failed to prevent prednisolone osteopenia because of its tendency to increase bone resorption.
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  • 64
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    Keywords: 31P NMR spectroscopy ; Phosphoprotein ; Dentin ; Calcium ; Inorganic orthophosphate ; Bovine
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    Topics: Biology , Medicine , Physics
    Notes: Summary The single phosphoprotein of fetal calf dentin, having a molecular weight of approximately 94,000 and a phosphorus content of 8% (w/w), was examined by31P NMR spectroscopy. The single resonance at 3.7 ppm at pH 10 and its chemical shift during acid titration established the phosphomonoester nature of the organic phosphorus moiety. During titration of the phosphoprotein with CaCl2 in the presence of inorganic orthophosphate ions, line broadening for the orthophosphate resonance was both phosphoprotein- and calcium-dependent, indicating ternary complex formation. The data indicate that the phosphoprotein of fetal calf dentin binds both calcium and inorganic orthophosphate ions and therefore has the requisite physical chemical properties necessary for it to facilitate the heterogeneous nucleation of a Ca-PO4 solid phase from solution during tissue mineralization.
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  • 65
    ISSN: 1432-2048
    Keywords: Calcium ; Cation exchange ; Lycopersicon esculentum ; Rhythm ; diurnal Transport (calcium) ; Zea mays
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    Topics: Biology
    Notes: Abstract Tomato (Lycopersicon esculentum Mill. cv. Moneymaker) and maize (Zea mays L. cv. spec.) plants were supplied with 45Ca-labeled nutrient solutions for a period of 8 or 16 h in the dark, in the light, or in a light-dark régime. Plant parts were analyzed for 45Ca content. The partitioning of 45Ca between mature leaves and meristems was shown to be affected by the presence of light. The transport of 45Ca to meristems was higher in a dark period than in a comparable light period. Experiments with excised tomato shoots yielded similar distribution patterns of 45Ca over leaves and meristems, thus excluding root pressure as the main driving force for the enhanced import of 45Ca into the meristems in the dark. Results are discussed in terms of cation-exchange transport and competition between the various calcium sinks.
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    Planta 158 (1983), S. 320-328 
    ISSN: 1432-2048
    Keywords: Calcium ; Egeria ; Fluorescent probe ; Ions, group II ; Symplast
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    Topics: Biology
    Notes: Abstract The hydrophyllic dyes fluorescein glutamic acid, fluorescein glutamylglutamic acid (F(Glu)2), fluorescein hexaglycine, fluorescein leucyldiglutamyl-leucine and 6-carboxyfluorescein are unable to pass the plasmalemma in leaves of E. densa. However, when injected into single cells the dye conjugates of molecular weight 665 dalton or less move freely from cell-to-cell. This intercellular movement presumably occurs via the plant symplast. Movement of F(Glu)2 from the injected cell occurs with greatly reduced frequency when Ca2+, Mg2+ or Sr2+ are injected into the cell immediately prior to the dye. The fraction of dye injections leading to movement declines with increasing group II ion concentration in the electrode tip, up to 10 mM. Sodium and K ions do not affect dye movement. When dye injection is delayed 30 min after Ca2+ injection, dye movement is no longer inhibited. Thus the cells recover from the Ca2+ injection, indicating that the ion does not cause major cell damage. Recovery from Mg2+ injection is not complete within 60 min. Treatment of leaves with chemicals expected to raise the concentration of free intracellular group II ions, notably the mitochondrial uncoupler carbonyl cyanide p-trifluoromethoxyphenyl hydrazone, the inhibitor of mitochondrial Ca2+ uptake trifluralin, or the ionophore A23187 also inhibits dye movement, while the calmodulin inhibitor trifluoperazine does not. Cytoplasmic streaming is inhibited by Ca2+ or Mg2+ injection and by the metabolic inhibitors. However when streaming is stopped by cytochalasin B, dye movement is not inhibited. Hence steaming is not necessary for dye movement. Thus the cytoplasmic concentration of free group II ions may directly regulate the permeability of the plant symplast.
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  • 67
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    Keywords: Bryophyta ; Bud formation (moss) ; Calcium ; Chlorotetracycline ; Cytokinin ; Funaria
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    Topics: Biology
    Notes: Abstract We have investigated the changes in membrane-associated calcium that occur during cytokinin induced bud formation in Funaria hygrometrica Hedw. using the fluorescent Ca2+-chelate probe chlorotetracycline (CTC). In the target caulonema cells a localization of CTC fluorescent material becomes evident at the presumptive bud site 12 h after cytokinin treatment. By the time of the initial asymmetric division this region is four times as fluorescent as the entire caulonema cell. Bright CTC fluorescence remains localized in the dividing cells of the bud. To relate the changes in CTC fluorescence to changes in Ca2+ as opposed to membrane-density changes we employed the general membrane marker N-phenyl-1-naphthylamine (NPN). NPN fluorescence increases only 1.5 times in the initial bud cell. We conclude that the relative amount of Ca2+ per quantity of membrane increases in this localized area and is maintained throughout bud formation. We suggest that these increases in membrane-associated Ca2+ indicate a localized rise in intracellular free Ca2+ concentration brought about by cytokinin action.
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    Planta 152 (1981), S. 450-456 
    ISSN: 1432-2048
    Keywords: Calcium ; Cell elongation ; Gibberellin ; Lactuca ; pH and growth
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    Topics: Biology
    Notes: Abstract The relationship between calcium ions and gibberellic acid (GA3)-induced growth in the excised hypocotyl of lettuce (Lactuca sativa L.) was investigated. The short-term kinetics of growth responses were measured using a linear displacement transducer. Test solutions were added either as drops to the filter paper on which the hypocotyl stood (“non-flow-past”) or by switching solution flowing past the base of hypocotyl (“flow-past”), resulting in differences in growth behavior. Drops of CaCl2 added at a high concentration (10 mM) inhibited growth within a few minutes. This inhibition was reversed by ethylenediaminetetraacetic acid (EDTA). Drops of EDTA or ethyleneglycol-bis(2-aminoethylether)-tetraacetic acid caused a rapid increase in growth rate. Growth induced by EDTA was not further promoted by GA3. A continuous H2O flow resulted in growth rates comparable to those in response to GA3. Addition of CaCl2 to the flow-past medium inhibited growth and this inhibition was reversed by a decrease in CaCl2 concentration. The growth rate was found to be a function of CaCl2 concentration. When a constant CaCl2 concentration was maintained by the flow-past medium, a shift in pH from 5.5 to 4.25 had no obvious effect on hypocotyl elongation. Gibberellic acid was found to reverse the inhibitory effect of CaCl2, causing an increase in growth rate similar to that found previously when GA3 was added to hypocotyls grown in H2O under non-flow-past conditions. We propose that gibberellin controls extension growth in lettuce hypocotyl sections by regulating the uptake of Ca2+ by the hypocotyl cells.
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    European biophysics journal 9 (1982), S. 131-136 
    ISSN: 1432-1017
    Keywords: Chemotaxis ; Calcium ; Oscillation ; Dictyostelium ; Ionophore
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    Topics: Biology , Physics
    Notes: Abstract Migration of differentiated cells to a capillary containing cyclic AMP was enhanced in the presence of 1 mM CaCl2 and was virtually absent in the presence of 1 mM EGTA. Furthermore, the cells contracted and extended pseudopods to a capillary filled with the calcium ionophore A 23187. At short distances, migration to the tip of the capillary was observed. The ionophore also induced transient decreases of the optical density of suspended cells indicating changes of cell shape. These findings support the hypothesis that cyclic AMP-binding to cell surface receptors causes a local influx of calcium ions. These in turn lead to an increase of the cytosolic calcium concentration and subsequently to an activation of cell migration. Perturbing pulses of the ionophore induced permanent phase shifts of free-running light scattering oscillations. This result indicates that cytosolic calcium is an intrinsic component of the oscillatory system.
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    European journal of clinical pharmacology 17 (1980), S. 111-116 
    ISSN: 1432-1041
    Keywords: zimelidine ; norzimelidine ; antidepressants ; pharmacokinetics ; bioavailability
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The systemic availability of a new antidepressant, zimelidine, and of its pharmacologically active metabolite, norzimelidine, was studied in six healthy male volunteers. Three single doses of zimelidine (25 mg and 100 mg orally and 25 mg i.v.) and two single doses of norzimelidine (25 mg orally and i. v.) were given to each volunteer allowing at least seven days between administrations. Plasma concentrations of zimelidine and norzimelidine were determined in serial blood samples by HPLC. Following oral zimelidine peak plasma concentrations of the metabolite were attained about 3 h after dosing. Oral administration of norzimelidine itself resulted in a plasma concentration profile for this compound that was similar to that observed after oral zimelidine. Utilising the plasma concentration data following intravenous infusion of each compound, the elimination half-lives for zimelidine and norzimelidine were calculated to be 5.1 h (range 4.3–6.0) and 15.5 h (range 10.6–22.9) respectively. The total body clearances of the 2 compounds were similar at 0.52 l · min−1 (range 0.26–0.70) for zimelidine and 0.56 l · min−1 (range 0.28–0.83) for norzimelidine. The substantially longer elimination half-life of norzimelidine was apparently the result of a larger volume of distribution (9.4 l · kg−1; range 7.8–11.4) for this metabolite, as compared to zimelidine (3.21 · kg−1; range 1.6–4.9). The calculated bioavailability of zimelidine was 26% (range 9.1–39) after the 25 mg oral dose, and 29% (range 14–46) after the 100 mg dose. The bioavailability of norzimelidine was 66% (range 36–91). However, oral administration of zimelidine resulted in as much or more norzimelidine reaching the systemic circulation, as the oral administration of norzimelidine itself. This is important as a large part of the activity of the drug may be due to the metabolite.
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    European journal of clinical pharmacology 19 (1981), S. 251-258 
    ISSN: 1432-1041
    Keywords: medigoxin ; digoxin ; dissolution rate ; proportionality ; bioavailability ; prediction
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We compared our ability to predict the dose of medigoxin and of digoxin required to achieve a fixed serum concentration (the dose requirement) in 33 outpatients. Preliminary work supported the assumptions that the steady state glycoside concentration achieved was proportional to the daily dose given to an individual, and that the bioavailability of the different tablet presentations was similar for either glycoside. We were not able to predict the dose requirement from patient characteristics with any more certainty for medigoxin than for digoxin. Not only the between-patient variability in dose requirement, but also the within-patient variability, was similar for the two glycosides. However the digoxin used had a dissolution rate of over 90% in 1 h. When comparing medigoxin with digoxin of lower, or more variable dissolution rate, medigoxin may be preferable.
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    European journal of clinical pharmacology 18 (1980), S. 423-428 
    ISSN: 1432-1041
    Keywords: pyridostigmine ; myasthenia gravis ; pharmacokinetics ; bioavailability ; plasma levels
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of pyridostigmine was evaluated after intravenous injection in two healthy male volunteers and after oral administration to five subjects. Plasma concentrations of pyridostigmine were determined after ion pair extraction from plasma and analysis by gas chromatography — mass spectrometry with chemical ionization, using d6-pyridostigmine as internal standard. Degradation of pyridostigmine in vitro was compensated for by use of the deuterated internal standard and by rapid cooling and separation of plasma after blood sampling. After intravenous administration of pyridostigmine 2.5 mg the plasma elimination half-life was 1.52 h, the volume of distribution was 1.43 l/kg and the plasma clearance 0.65 l/kg × h. The pharmacokinetic constants were very similar after oral administration of pyridostigmine 120 mg; the elimination half-life was 1.78±0.24 h, the volume of distribution 1.64±0.29 l/kg and the plasma clearance was 0.66±0.22 l/kg × h. The bioavailability was calculated to be 7.6±2.4%. When pyridostigmine was taken together with food, the time to reach the peak plasma concentration was prolonged from 1.7 to 3.2 h. Bioavailability, however, was not influenced by concomitant food intake. “Steady-state” plasma concentrations of pyridostigmine were measured in myasthenic patients on their ordinary dose schedule of cholinesterase inhibitor drugs. More than a seven-fold difference in steady-state plasma concentration was found between patients taking approximately the same daily dose of pyridostigmine.
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    European journal of clinical pharmacology 21 (1982), S. 343-350 
    ISSN: 1432-1041
    Keywords: orphenadrine ; single dose ; multiple doses ; bioavailability ; pharmacokinetics ; N-demethylorphenadrine ; metabolism ; dog ; man
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations of orphenadrine were measured by a specific gaschromatographic method in 5 healthy male volunteers after a single oral dose of orphenadrine hydrochloride 100mg. The single dose pharmacokinetic profile of orphenadrine was evaluated from these data. The elimination half-life ranged from 13.2–20.1 h after the commercial tablet formulation. Plasma concentrations, determined in volunteers and patients under different conditions of repeated oral administration of the same formulation of orphenadrine hydrochloride exceeded the theoretical values, predicted from the single dose pharmacokinetics, by a factor 2 to 3. The elimination half-lives after discontinuation of treatment showed a 2 to 3-fold increase over the single dose values. This demonstrates a clear discrepancy between the multiple and single dose pharmacokinetics of orphenadrine. Experiments in dogs suggested competition for biotransformation between orphenadrine and its metabolite N-demethylorphenadrine. Product inhibition of this type could explain the observed discrepancy.
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  • 74
    ISSN: 1432-1041
    Keywords: indapamide ; bioavailability ; pharmacokinetics
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    Notes: Summary Two formulations of indapamide tablets (2.5 mg) were given as a 5.0 mg dose and the subsequent blood levels were compared to those obtained after administration of a 5.0 mg solution. The study was conducted as a randomized three-way crossover design using healthy male volunteers. The drug was well tolerated by all the subjects involved. The area under the blood concentration versus time curve, extrapolated to infinity was essentially the same for all three formulations (4.2, 4.7, and 4.4 µg-h/ml). Statistical comparison of the blood levels from the two tablets showed that one tablet had a significantly greater maximum blood concentration (263 vs 231 ng/ml) and a significantly shorter time of maximum blood concentration (2.3 vs 3.5 h). Cmax (333 ng/ml) and tmax (0.7 h) values for the solution were significantly higher than either tablet. The average half-life (β-phase) for all three formulations was 15 h, while the average systemic clearance was 20 ml/min. Indapamide has a low clearance rate and there was no evidence that the drug undergoes a first-pass effect.
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  • 75
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    European journal of clinical pharmacology 23 (1982), S. 59-64 
    ISSN: 1432-1041
    Keywords: morphine ; rectal administration ; i.m. administration ; gas chromatographic mass spectrometric analysis ; bioavailability ; plasma levels
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 21 healthy women undergoing gynaecological operations received rectal premedication with morphine 0.3 mg/kg body weight. Plasma concentrations of morphine were followed for 4 h by a GC/MS technique. In most patients the peak plasma concentration was reached after 30 min; the mean peak plasma level of morphine was 18 ng/ml (range 8.5–57 ng/ml). The bioavailability of rectal morphine was determined in 6 patients, who received an i.m. injection of morphine at a second operation. The mean bioavailability of rectal morphine was 31% (range 12%–61%). None of the patients showed any clinical sign of respiratory depression, and there was no increase in end-tidal carbon dioxide tension measured in 5 patients operated under spinal block.
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  • 76
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    European journal of clinical pharmacology 23 (1982), S. 235-240 
    ISSN: 1432-1041
    Keywords: ergotamine ; pharmacokinetics ; migraine ; plasma drug levels ; i.v. administration ; i.m. administration ; bioavailability
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of ergotamine has been investigated in migrainous patients using a new, specific, sensitive HPLC assay (detection limit 100 pg/ml plasma). 10 patients were given ergotamine tartrate 0.5 mg i.v. and 5 of them received the same dose i.m. 2–3 weeks later. Blood samples were collected for up to 54 h following administration and the plasma concentration were analysed. After intravenous administration the plasma ergotamine declined rapidly, with an initial distribution half-life of 3 min followed by a mean terminal half-life of 1.86 h (range 90–155 min). The mean total plasma clearance was 11.0 ml kg−1 min−1, and the volume of distribution (Vdβ ) was 1847.6 ml kg−1. Individual t1/2β showed a positive linear correlation with the individual Vdβ . The intramuscular absorption of ergotamine was rapid and maximum plasma levels were usually obtained 10 min following administration. The biological availability was incomplete and variable at 46.6% (range 28.3–60.8%).
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  • 77
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    European journal of clinical pharmacology 24 (1983), S. 127-136 
    ISSN: 1432-1041
    Keywords: statistical analysis ; nonparametric statistical methods ; bioavailability ; confidence interval ; ANOVA
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary For a two-way cross-over design, which appears to be the most common experimental design in bioavailability studies, 95%-confidence limits for expected bioavailability can be obtained by classical analysis of variance (ANOVA). If symmetry of the confidence interval is desired about zero (differences) or unity (ratios) rather than about the corresponding point estimator, Westlake's modification can be used. Two nonparametric methods and their adaptations to bioavailability ratios are reviewed, one based on Wilcoxon's signed rank test (Tukey), and the other on Pitman's permutation test. The necessary assumptions and the merits of these procedures are discussed. The methods are illustrated by an example of a comparative bioavailability study. A FORTRAN program facilitating the procedures is available from the authors upon request.
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  • 78
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    European journal of clinical pharmacology 24 (1983), S. 791-796 
    ISSN: 1432-1041
    Keywords: furosemide ; bioavailability ; diuretic effect ; urine sodium ; urine potassium ; power of ANOVA ; tablet formulations ; urinary flow rate ; normal volunteers
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The relative bioavailability and diuretic effect of 2 commercially available tablet preparations of furosemide 40 mg was examined in 10 healthy male volunteers. A close linear relationship between the urinary excretion rate of furosemide and the rate of sodium ion excretion in urine and/or flow rate of urine was demonstrated. There were no significant differences in the urinary excretion of furosemide, sodium and potassium ions or urinary volume following the oral doses. The difference in drug content affected the urinary recovery of furosemide over 24 h but had no effect on the pharmacological response. The analytical power of ANOVA using the various parameters of the responses to furosemide was no lower than when the parameters of urinary excretion of furosemide were used.
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  • 79
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    European journal of clinical pharmacology 25 (1983), S. 237-241 
    ISSN: 1432-1041
    Keywords: triamterene ; bioavailability ; pharmacokinetics ; metabolism ; hydroxy triamterene sulphate ; urinary excretion ; i.v. administration ; first-pass-effect
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary With a new formulation, which made intravenous infusion of triamterene (TA) possible, plasma levels and urinary excretion rates of TA and its main metabolite (OH-TA-ester) were measured in a randomized, cross-over trial in 6 healthy volunteers given triamterene 10 mg i.v. and 50 mg p.o. TA and OH-TA-ester were determined by densitometric measurement of native fluorescence after thin layer chromatography. Distribution volumes of the central compartment of TA and OH-TA-ester were 1.49 l/kg and 0.11 l/kg, respectively. Terminal half-lives were 255 min for TA and 188 min for OH-TA-ester after i.v. administration. For TA total plasma clearance was 4.5 l/min and renal plasma clearance 0.22 l/kg. The formation of OH-TA-ester was very rapid and the concentration of the metabolite exceeded that of TA at all times. After i.v. administration the urinary recovery of TA and OH-TA-ester was 4.4% and 50.9%, respectively. The bioavailability of TA was 52%, corresponding to absorption of 83%. TA is partly eliminated by a first-pass-effect. The main metabolite of TA is OH-TA-ester, which is pharmacologically active.
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  • 80
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    European journal of clinical pharmacology 25 (1983), S. 449-453 
    ISSN: 1432-1041
    Keywords: canrenone ; pharmacokinetics ; plasma level ; bioavailability ; urinary excretion ; spironolactone
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five healthy male volunteers received canrenoate-K 200 mg (Sincomen® pro injectione) by intravenous injection and one week later spironolactone 200 mg (Sincomen®-100) orally. Plasma levels and urinary excretion of unchanged canrenone were determined up to 24 h by a specific HPLC method. Following intravenous administration, the maximum plasma level of 2066±876 ng/ml was found after 29±15 min and thereafter the concentration declined with a half-life of 3.7±1.2 h. Total clearance was 4.2±1.7 ml/min·kg. After oral ingestion, the maximum concentration of 177±33 ng/ml was observed at 4.4±0.9 h. The absolute bioavailability of canrenone was 25±9%. Within 24 h, respectively 0.4 and 0.6 mg, canrenone were excreted by the kidney after intravenous and oral administration. The half-life of elimination was 4.9±1.8 h (i.v.) and 3.9±1.2 h (p.o.).
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  • 81
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    European journal of clinical pharmacology 26 (1984), S. 513-520 
    ISSN: 1432-1041
    Keywords: xipamide ; electrolyte excretion ; bioavailability ; elimination ; extrarenal clearance ; chronic renal failure ; furosemide ; hydrochlorothiazide ; amiloride
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of a single oral dose of 40 mg xipamide on urinary excretion of Na+, K+, Cl−, Ca2+ and Mg2+ in healthy subjects and in patients with varying degrees of renal impairment was compared with various conventional diuretics. Xipamide caused marked excretion of Na+ and Cl−, whereas the diuretic produced only moderate kaliuresis; urinary excretion of Ca2+ was increased in proportion to Na+, like the loop diuretics. Xipamide affected electrolyte excretion even in patients with a creatinine clearance below 30 ml/min, as do the loop diuretics, too. Therefore, the pharmacodynamic characteristics of xipamide are more like those of a loop diuretic than of a thiazide. Xipamide was good bioavailable, its t1/2β was 7 h and urinary recovery of the undegraded drug was 40% of the given dose. In renal insufficiency, t1/2β increased from 7 to only 9 h, yielding a moderate increase in the AUC. Urinary recovery of the drug was reduced in proportion to the reduction in the creatinine clearance of the patient. Therefore, significant extrarenal elimination of the diuretic must be postulated, which suffices to prevent significant drug accumulation in renal failure.
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  • 82
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    European journal of clinical pharmacology 27 (1984), S. 105-110 
    ISSN: 1432-1041
    Keywords: phenytoin ; epileptic women ; pharmacokinetics ; bioavailability ; pregnancy
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five epileptic women needing to commence phenytoin therapy during pregnancy received a single intravenous and a single oral dose of phenytoin several days apart before starting regular intake of the drug. Plasma phenytoin concentration — time data were analysed by three different pharmacokinetic techniques. However assessed, the mean oral bioavailability of the drug proved to be about 90% of the intravenous bioavailability. This finding makes it unlikely that impaired bioavailability accounts for the increase in oral phenytoin dosage necessary in pregnancy to maintain plasma phenytoin concentrations at pre-pregnancy values. Phenytoin clearance in the pregnant subjects was approximately double the published values for phenytoin clearance in nonpregnant persons. This suggests that increased (metabolic) clearance accounts for the increased phenytoin dosage requirement of pregnancy.
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  • 83
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    European journal of clinical pharmacology 27 (1984), S. 595-602 
    ISSN: 1432-1041
    Keywords: furosemide ; bioavailability ; generic tablet formulations ; intrasubject variability
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Intrasubject variation in bioavailability (rate and extent) and disposition of furosemide 40 mg was investigated using a repeated, randomized, double-blind cross-over study in 8 healthy subjects. Two generic tablet formulations (Lasix and Furix) and intravenous furosemide were compared on 6 separate days. Extensive intrasubject variability after oral administration was observed in AUC, mean absorption time (MAT) and urinary excretion. The variability (error variance) within the dosage forms was as large as that between the two generics. These variations most probably depended on the absorption process, since the repeated i.v. doses showed only marginal intrasubject variability. Absolute bioavailability was 56% for Lasix and 55% for Furix (AUC). The range was 20 to 84% between individuals and the maximal range within one individual was 20 to 61%. Confidence interval and Bayesian analysis showed a high probability of non-equivalence not only between but also within the generics when the separate cross-over experiments were analyzed (8 observations). When extending the analysis to 16 observations, bioequivalence was demonstrated for the two generic tablets. Rate of absorption, quantified as MAT, was 128 min for Lasix and 98 min for Furix (16 observations). Since MAT was significantly longer (p〈0.001) than the mean residence time after the i.v. dose (57 min), absorption was evidently the rate-limiting step in the overall kinetics of oral furosemide. Intraindividual variation in absorption is a confounding factor in bioavailability studies of furosemide using limited numbers of subjects. This is important to consider when designing and evaluating bioavailability studies for drugs showing these variations.
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  • 84
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    European journal of clinical pharmacology 18 (1980), S. 415-418 
    ISSN: 1432-1041
    Keywords: diclofenac ; acetyl salicylic acid ; intravenous bolus administration ; oral administration ; interaction ; bioavailability
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Previous studies have shown that aspirin interacts with orally administered diclofenac sodium, causing reduced peak concentrations, lower levels and decreased areas under curves. In this study, diclofenac sodium was administered orally and intravenously with and without aspirin, to 6 healthy female volunteers. After intravenous dosing both plasma levels and areas under curves were significantly reduced although none of the rate constants was affected. The volume of distribution of diclofenac was increased as was the plasma clearance. Oral administration with aspirin also resulted in lower plasma levels, particularly peak levels, and areas under curves. Comparison of AUC's for both modes of administration with and without aspirin suggested that lower levels after oral administration were not due to impaired absorption. These observations are best explained by decreased protein binding and increased biliary excretion of diclofenac in the presence of salicylate.
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  • 85
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    European journal of clinical pharmacology 17 (1980), S. 309-315 
    ISSN: 1432-1041
    Keywords: valproic acid ; sodium valproate ; suppositories ; micro-enemas ; steady-state concentration ; absorption ; bioavailability
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Rectal and oral absorption of valproic acid and its sodium salt by man were compared to explore the possibility of rectal administration of the drug. The plasma concentration of valproic acid was measured by gas chromatography after a single oral dose of sodium valproate 600 mg, and after single rectal doses of sodium valproate 600 mg and valproic acid 520 mg, in a cross-over study in 7 volunteers. The rectal dosage forms included fatty suppositories and aqueous solutions. Compared with oral administration, rectal absorption of sodium valproate from an aqueous micro-enema was fast and complete. The free acid was absorbed more rapidly from fatty suppositories than was the sodium salt. The absorption rate from the rectum increased with the dose of valproic acid. Both findings are consistent with a diffusion — absorption mechanism based on the pH-partition hypothesis. Differences in the chemical composition of the fatty suppository base were not reflected in differences in absorption rate and relative bioavailability. No essential difference in absorption rate was observed if volunteers remained lying or sitting during the experiment. Rectal dosing with valproic acid 520 mg dissolved in 4 ml suppositories, twice a day resulted in steady-state plasma concentrations of 50 to 100 µg · ml−1, within the therapeutic range.
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  • 86
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    European journal of clinical pharmacology 17 (1980), S. 379-384 
    ISSN: 1432-1041
    Keywords: theophylline ; aminophylline ; obstructive lung disease ; microcrystalline ; bioavailability ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Variation in the systemic disposition of theophylline after ingestion of a new microcrystalline product (Theolair®) has been investigated in 7 hospitalized patients with generalized obstructive lung disease. Disposition (absolute bioavailability) was determined by comparing in the same patients the areas under the serum concentration-time curves after a single oral dose of microcrystalline theophylline and after an intravenous infusion of aminophylline. Oral absorption appeared to be fast. The half-life of absorption was 19±9 min (mean±SD). Maximal serum concentrations reached after 100±30 min were found to be in a rather narrow range: 9.8±2.5 mg · 1−1. The absolute bioavailability of the microcrystalline preparation was high and it showed only small variation: 102.7±10.2% of the dose. Relevant pharmacokinetic parameters (half-life of elimination, volume of distribution and total body clearance) were determined after both routes of administration. Individual dosage regimens required to obtain a therapeutic serum concentration were calculated for each individual patient on the basis of the observed pharmacokinetic parameters.
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  • 87
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    European journal of clinical pharmacology 19 (1981), S. 53-55 
    ISSN: 1432-1041
    Keywords: digoxin ; bioavailability ; dose-dependency ; urinary excretion ; healthy volunteers
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nine healthy volunteers received single 0.25, 0.5, 1.0, 1.5, and 2.0 mg doses of oral digoxin tablets in random sequence on five occasions separated by at least 4 weeks. Urinary excretion of immunoassayable digoxin was determined from 8 consecutive 24 h urine samples collected after each dose. Mean values of cumulative urinary excretion of digoxin at the 5 doses were: 40.9, 35.6, 36.4, 34.1, and 33.5% of the dose (F=0.64; d. f.=4.32; N. S.). Mean values of urinary excretion half-life were: 2.48, 2.03, 2.20, 2.07, and 1.87 days (F=2.87; d. f.=4.32;p=0.05). Thus, the bioavailability of orally administered digoxin tablets in healthy volunteers is dose-independent over an 8-fold range of doses.
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  • 88
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    European journal of clinical pharmacology 19 (1981), S. 287-292 
    ISSN: 1432-1041
    Keywords: diacetolol ; acebutolol ; bioavailability ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and bioavailability of diacetolol, the principal metabolite of acebutolol, were studied in 6 healthy subjects. Plasma concentrations were determined following a single intravenous injection of diacetolol 100 mg and three oral doses of diacetolol 100, 400 and 800 mg, in random order. The average oral bioavailability of diacetolol was F: 0.302±0.052 (100 mg), 0.363±0.052 (400 mg) and 0.426±0.068 (800 mg); the differences are not significant. The mean plasma half-life of the terminal phase, 7.94±0.26 h after intravenous administration, was significantly higher than after oral administration 12.27±1.00 h (100 mg), 12.82±1.59 h (400 mg) and 13.05±1.22 h (800 mg) (p〈0.02 to 0.05); the mean urine half-lives of the terminal phase were not significantly different. Renal clearance of diacetolol 10.2±0.81·h−1 represented about two-thirds of total body clearance 15.9±1.21·h−1. The results suggest either a first-pass effect or incomplete absorption of diacetolol after oral administration.
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  • 89
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    European journal of clinical pharmacology 19 (1981), S. 305-307 
    ISSN: 1432-1041
    Keywords: ketoprofen ; aluminium phosphate ; bioavailability ; antacid ; pharmacokinetics ; interaction study
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The purpose of this study was to determine whether a concomitant single dose of antacid (aluminium phosphate), or multiple doses of this antacid, administered prior to and with ketoprofen would alter the bioavailability of this non steroidal anti-inflammatory agent. The possible effects of aluminium phosphate were evaluated following administration of ketoprofen alone (Phase I), co-administration of antacid and ketoprofen (Phase II), and antacid for four days before administration of ketoprofen with co-administration on the day of the study (Phase III). There were no significant differences between treatment means for peak plasma concentration, time to peak plasma concentration, and area under the plasma concentration-time curve. The observed differences were due only to individual effects. The results indicate a lack of interaction between ketoprofen and the antacid aluminium phosphate (Phosphalugel)
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  • 90
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    European journal of clinical pharmacology 19 (1981), S. 359-365 
    ISSN: 1432-1041
    Keywords: tolfenamic acid ; anti-inflammatory agent ; human pharmacokinetics ; bioavailability ; intravenous administration
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of tolfenamic acid, a new anti-inflammatory agent was studied in six healthy volunteers after an intravenous dose of 100 mg and oral doses of 100, 200, 400 and 800 mg. The disposition of intravenous tolfenamic acid could be described by two-compartment open model, with a central compartment volume (Vdc) of 5.6±0.31 (mean±SE), volume during β-phase (Vdβ) of 31±21, and a total elimination rate constant (k10) 1.6±0.1 h−1. The terminal elimination half-life was 2.5±0.6 h and the total plasma clearance 155±15 ml/min. The elimination occured principally by extrarenal mechanisms, the recovery of unchanged drug together with is glucuronide in urine averaging only 8.8% of the intravenous dose. The binding of tolfenamic acid to plasma proteins averaged 99.7%. The gastrointestinal absorption had a mean half-life of 1.7±0.1 h. Based on comparison of areas under the plasma concentration time-curves after intravenous and oral administration, the biovailability of tolfenamic acid capsules averaged 60%. The rate and extent of absorption and the rate of elimination of tolfenamic acid were independent of dose.
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  • 91
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    European journal of clinical pharmacology 21 (1982), S. 293-301 
    ISSN: 1432-1041
    Keywords: metipranolol ; deacetyl metipranolol ; pharmacokinetics ; bioavailability ; healthy volunteers
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic parameters of deacetyl metipranolol were determined after i.v. infusion of increasing doses (6–25 mg) in 17 normal volunteers. In a second cross-over trial, deacetyl metipranolol 10 and 20 mg were infused in a further 10 subjects, and in a third trial another 20 volunteers received metipranolol 40 mg orally. Metipranolol is very rapidly and completely deacetylated in man, so all pharmacokinetic data refer to deacetyl metipranolol, which was assayed by gas chromatography-mass spectrometry. The pharmacokinetic analysis was performed using a recently developed model, using a volume of distribution which is variable with time. The following data were obtained after oral administration: (mean values); lag-time 7.3 min; tmax 50 min, invasion half-life 6.3 min; elimination half-life 3 h; urinary excretion of unchanged drug approximately 4% of the dose. The experiments with infusion of increasing doses, as well as the cross-over study with 10 and 20 mg i.v., showed dose-linearity of the kinetics. The respective mean half-lives of elimination were 2.6, 2.9 and 2.8 h. The mean total, renal and extra-renal clearances amounted to 1237 ml/min, 149 ml/min and 1068 ml/min, respectively. The distribution coefficient was 3.5 l/kg, and protein binding amounted to 70% within the range of therapeutic concentrations. Absolute bioavailability was found to be approximately 50% by several different evaluation procedures. Thus, the pharmacokinetic profile of metipranolol shares features of both the lipophilic and the hydrophilic groups of β-blocking agents.
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  • 92
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    European journal of clinical pharmacology 20 (1981), S. 65-72 
    ISSN: 1432-1041
    Keywords: tranexamic acid ; pharmacokinetics ; bioavailability ; oral absorption ; influence of food ; plasma clearance
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Tranexamic acid 1 g was given intravenously to three healthy volunteers. Plasma concentrations decayed in three monoexponential phases. Most elimination took place during the first eight hours, giving an apparent elimination half-life of approximately two hours. Plasma clearance ranged between 110–116 ml/min. The urinary recovery of tranexamic acid exceeded 95% of the dose. Ten healthy volunteers were given tranexamic acid 2 g orally on an empty stomach, and together with a meal. Food had no influence on the absorption of tranexamic acid, as judged by comparison of the peak plasma concentration, the time required to reach the peak, the AUC from zero to six hours, and the urinary excretion data. The oral bioavailability of tranexamic acid, calculated from 24 h urinary excretion after oral and intravenous administration, was 34% of the dose.
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  • 93
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    European journal of clinical pharmacology 22 (1982), S. 171-173 
    ISSN: 1432-1041
    Keywords: theophylline ; neonates ; bioavailability ; food intake ; premature infants
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 16 premature infants suffering from neonatal apnoea received orally an aqueous solution of theophylline 5 mg/kg bodyweight under fasting conditions and immediately before a milk feed. Bioavailability up to 7 h after administration was determined from the serum concentration-time course. The rate of absorption was significantly decreased if the drug was given with food; mean maximum serum concentrations were reached after 4.7 h instead of 1.6 h under fasting conditions. The area under the curve did not differ between the two patient groups which indicates that only the rate but not the amount of absorption was affected by food intake. The influence of feeding on the rate of absorption of theophylline by premature infants, which is more pronounced than in adults, can be related to particular functional factors in the gastrointestinal tract during the neonatal period.
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  • 94
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    European journal of clinical pharmacology 22 (1982), S. 309-314 
    ISSN: 1432-1041
    Keywords: acetylsalicylic acid ; salicylic acid ; dipyridamol ; bioavailability ; kinetics ; rapid- and slow-release formulations
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Acetylsalicylic acid (ASA) is a strong, irreversible inhibitor of platelet aggregation, but loses this activity following first-pass deacetylation to salicylic acid (SA). In order to compare the bioavailability of unchanged ASA from rapid- and slow-release formulations, the single-dose concentration profiles of ASA and SA were studied in healthy volunteers following intake of two different rapid-release (conventional and effervescent tablets) and three different slow-release (microencapsulated ASA in tablets and in capsules, and enteric-coated tablets) formulations of ASA, and of one slow-release formulation of sodium salicylate. Since anti-platelet therapy with ASA is often combined with dipyridamol, the influence of this drug was also examined. The concentrations of ASA and SA were measured by high-pressure liquid chromatography. While the bioavailability of SA from the 5 ASA formulations was essentially equal and similar to that of the salicylate formulation, the bioavailability and peak concentrations of ASA appeared to be the much greater after rapid-release than after slow-release formulations. Indeed, ASA was only rarely detected in systemic blood following intake of slow-release ASA. Co-administered dipyridamol did not significantly influence the kinetics of ASA or SA. It appears that rapid-release formulations of ASA should be prefered in anti-platelet therapy, either alone or in combination with dipyridamol.
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  • 95
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    European journal of clinical pharmacology 20 (1981), S. 277-282 
    ISSN: 1432-1041
    Keywords: dexamethasone phosphate ; dexamethasone sulphate ; intravenous injection ; bioavailability ; pituitary-adreno-cortical suppression ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The metabolic fate and ACTH-supressant activity of two injectable dexamethasone esters, 21-phosphate and 21-sulphate, were studied in healthy men. After i.v. injection of 20 mg free steroid alcohol, dexamethasone phosphate was efficiently hydrolyzed to free dexamethasone, reaching its peak plasma concentration within 5 min. About 9% of the administered dose appeared in the urine as free dexamethasone. By contrast, virtually no free dexamethasone was found in plasma and urine after injection of dexamethasone sulphate. Pharmacokinetic analysis showed that dexamethasone sulphate had a shorter plasma half-life and a higher metabolic clearance rate than free dexamethasone. A larger fraction (60%) of dexamethasone sulphate was rapidly excreted unmetabolized in urine. The plasma cortisol level was significantly suppressed for more than 24 h after dexamethasone phosphate, while the plasma cortisol profile after dexamethasone sulphate merely showed physiological circadian variations. When the steroid esters were injected after pretreatment with metyrapone, a definite suppression of plasma ACTH was noted after dexamethasone phosphate, but again, dexamethasone sulphate was ineffective. These results cast serious doubt on the clinical value of dexamethasone sulphate as an injectable glucocorticoid, and critical reevaluation of this preparation is needed.
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  • 96
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 24 (1983), S. 103-108 
    ISSN: 1432-1041
    Keywords: dexamethasone ; bioavailability ; pharmacokinetics ; ‘first-pass’ effect ; pre-systemic elimination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and oral biovailability of dexamethasone were studied in 6 patients with neurological disease being treated with high dosages of the drug. A specific high performance liquid chromatographic assay was used to measure dexamethasone concentrations. Unlike the previously published mean figure of 0.78 for the oral bioavailability of the drug given in single doses to healthy volunteers, the mean bioavailability of dexamethasone in the patients studied was 0.53±SD 0.40. It appeared more likely that this incomplete bioavailability was due to presystemic elimination than to poor absorption. The intravenous clearance of the drug was relatively high (0.4902±SD 2291 l kg−1, approximately 65% of expected hepatic plasma flow), the oral clearance higher (2.5804±SD 3.2181 l kg−1 h−1) while the absorption rate constant (4.8729±8.4998 h−1), suggested rapid absorption after oral administration. Prior phenytoin and possibly prior dexamethasone therapy is likely to have contributed to the higher clearance values of the drug in these patients than the values reported in healthy volunteers after single dose studies.
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  • 97
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 20 (1981), S. 465-471 
    ISSN: 1432-1041
    Keywords: metoclopramide ; pharmacokinetics ; bioavailability ; first-pass effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The time courses of plasma metoclopramide concentrations were followed in six subjects after oral and intravenous single dose administration. Plasma concentration-time data following i.v. administration in each subject were found to fit a two compartment model with a mean terminal half-life of 4.55 h±0.80 h and a mean distribution half-time of 0.35 h±0.09 h. Volumes of distribution were high (3.43±1.181 · kg−1), and clearances (0.53±0.191 · kg−1h−1) approached liver plasma flow. This suggests that metoclopramide occurs at higher concentrations in tissues than in plasma, and that its clearance is probably limited by liver blood flow rather than liver metabolic capacity. The post-absorption decline in metoclopramide plasma levels after oral administration was also biexponential in each subject. The terminal half-life was 5.17 h±0.98 h. Mean volume of distribution and mean clearance were similar to intravenous values (after adjustment for bioavailability). Oral absorption was rapid with peak plasma concentrations being reached at a mean time of 0.93 h. A mean bioavailability of 0.77 was calculated for the six subjects, and it was postulated that this incomplete availability is due to a first-pass effect. The inter-individual variation in the degree of ‘first-pass’ was considerable (0.47–1.14).
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  • 98
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 20 (1981), S. 473-478 
    ISSN: 1432-1041
    Keywords: methadone ; bioavailability ; pharmacokinetics ; single dose ; stable isotope technique ; two compartment model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of methadone was studied in eight opiate dependent subjects during detoxification. Plasma concentrations were determined by mass fragmentography for 48 hours after administration of methadone 20 mg as tablets and simultaneous intravenous injection of deuterium-labelled methadone 20 mg. Pharmacokinetic parameters were calculated for the intravenous dose assuming a two compartment open model. Bioavailability was determined by comparing the areas under the plasma concentration versus time curves of unlabelled and labelled methadone. The beta-phase plasma half-lives varied five-fold, with a range from 8.5 to 47 h. The apparent volumes of distribution varied from 2.1 to 5.61/kg. Five patients had a bioavailability exceeding 90%, and three had lower bioavailabilities of between 41 and 76%. The unlabelled and labelled drug appeared to be pharmacokinetically equivalent. The data show that for a majority of these subjects the bioavailability was higher than 45%, the previously reported value. The marked individual variation in methadone pharmacodynamics and kinetics, and the possibilities both of cellular and methabolic tolerance, require an individually optimized dosage regimen.
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  • 99
    ISSN: 1432-1041
    Keywords: oxmetidine ; pharmacokinetics ; bioavailability ; plasma half-life ; clearance ; oral dose ; i.v. dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma concentration curves and urinary excretion of oxmetidine after administration of single i.v. (100 mg) and oral (200 mg) doses have been studied in 11 patients with peptic ulcer disease. The mean bioavailability of the drug was 70% (range 53–91%). After intravenous administration, the mean plasmat 1/2β was 3.0 h, the mean apparent volume of distribution 0.7 l/kg, the mean total plasma clearance 12.3 l/h and the mean plasma renal clearance was 0.7 l/h. Following intravenous and oral administration an average of 6% and 3%, respectively, of unchanged drug was found in the urine. The plasma concentration curve after oral administration in most patients exhibited two maxima, with peak concentrations appearing between 45 and 210 min after dosing.
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  • 100
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 22 (1982), S. 85-90 
    ISSN: 1432-1041
    Keywords: lignocaine ; verapamil ; propranolol ; bioavailability ; predictions ; first pass effect ; oral clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary For drugs with a high hepatic clearance, bioavailability is low due to the so-called “first pass effect”. Prediction of the bioavailability for these drugs has been only lossely tested. It is proposed that by plotting the reciprocal of bioavailability versus the oral clearance, a straight line with intercept of unity and slope of reciprocal of hepatic blood flow should ensue. For lignocaine and verapamil, this relationship was found to be strong and gave good predictability, whereas for propranolol this relationship was weak and gave poor predictability. The proposed method may be of value in determining whether the low bioavailability of a drug is due to hepatic first pass metabolism.
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