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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 16 (1974), S. 145-152 
    ISSN: 1432-0827
    Keywords: EHDP ; Bone ; Chemistry ; Serum ; Rabbits
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract The effects of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) on bone and serum chemistry were investigated in adult rabbits. EHDP was administered by subcutaneous injection at doses of 0.25, 2.5 and 10 mg/kg body weight/day for of 28 days. Blood samples were obtained weekly from each rabbit and serum levels of total calcium, ionized calcium, inorganic phosphate and alkaline phosphatase were determined. At the end of the treatment period all rabbits were sacrificed and the tibiae removed for chemical analysis and histological evaluation. The effect of EHDP administration on serum chemistry was both dose- and time-related. The highest of the three doses, 10 mg/kg/day, resulted in a time-related decrease in total serum calcium. This dose also caused a rapid but transient reduction in serum ionized calcium. The effect of EHDP on serum inorganic phosphate was biphasic. Administration of 2.5 mg/kg/day resulted in a time-related elevation in this parameter, whereas the 10 mg/kg/day dose resulted in a time-related hypophosphatemic response. There were no significant drug-related changes in tibial fat-free dry weight, ash weight, total calcium or total phosphorus values. However, administration of 2.5 and 10 mg/kg/day EHDP resulted in increased osteoid tissue as measured histologically. These results are compared with data from other EHDP studies, and discussed in relation to the maturity and growth-state of the experimental animals.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1435-1463
    Keywords: Pineal ; bovine pineal extracts ; pineal antigonadotropin ; pineal peptides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An antigonadotropic substance was partially purified from aqueous extracts of bovine pineal glands by methods of gel filtration, ultrafiltration and ion exchange chromatography. Two biological tests,viz. inhibition of compensatory ovarian hypertrophy and reduction of ventral prostate weight, were used to guide the purification. The partially purified antigonadotropin was characterized chemically using techniques of UV and fluorescence spectrometry, thin layer and paper chromatography, paper electrophoresis and amino acid analysis. The results reveal a diversity of ninhydrin-positive components present in the preparations, including free and peptide-bound amino acids, as well as other unidentified components, but not including any of the commonly occurring indoles, indoleamines or catecholeamines. One peptide, oxidized glutathione, was identified in the most purified material containing the biologically active principle yet pure, synthetric glutathione has no antigonadotropic activity in the biological tests utilized. Although the chemical nature of the bovine pineal antigonadotropin remains in question it may be purified by the methods described. The activity is thought to reside in the extremely small, perhaps trace quantities of residues derived. It is believed that large scale, preparative studies will be required for structural determination.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 16 (1974), S. 239-250 
    ISSN: 1432-0827
    Keywords: EHDP ; Bone ; Collagen ; Histology ; Bone chemical analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract The purpose of this study was to determine the short-term effects of various systemic doses of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) on bone organic matrix and to relate these effects to the corresponding dose-related changes in bone mineral. EHDP was administered daily by subcutaneous injection at doses of 0.25, 2.5 and 40 mg/kg body weight for periods of one and two weeks. At both time intervals, rat tibiae were quantitatively analyzed for mineral content (ash, calcium and phosphorus) and for organic matrix content (matrix weight, nitrogen and certain amino acids). The latter data were correlated with semiquantitative histological analyses of the tibiae. Results of this study demonstrate that the short term effects of EHDP on bone chemistry and histology are variable and depend on the systemic dose and the duration of treatment. Systemic doses of 0.25 and 2.5 mg/kg EHDP following daily administration for one week resulted in transitory decreases in bone mineral content compared to controls. Following two weeks of treatment, both of these dose levels resulted in increased bone mineral content and, in addition, the 2.5 mg/kg dose resulted in tibiae which contained more organic matrix compared to control bones. In contrast to the low dose effects, a high systemic dose of EHDP—e.g. 40 mg/kg administered daily for 1 or 2 weeks—appears to act solely by inhibiting mineralization of newly-formed matrix.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 23 (1977), S. 151-159 
    ISSN: 1432-0827
    Keywords: Diphosphonate analogs ; Cardiac calciphylaxis ; Rat model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Seven diphosphonate analogs were tested for their effects on myocardial and cardiovascular degeneration and calcification in an experimental model of cardiac calciphylaxis. A single oral dose of dihydrotachysterol (DHT) administered to rats induced myocardial and vascular degeneration, focal myocarditis and vasculitis, and myocardial and vascular mineralization. The results demonstrated a considerable variation among the various diphosphonates in their ability to block the pathological changes observed in this model. Ethane-1-hydroxy-1,1-diphosphonate (EHDP) was the most effetive diphosphonate in reducing myocardial and vascular degeneration and calcification, whereas diphosphonates such as ethane-1-amino-1,1-diphosphonate (EADP) and hydroxymethylene diphosphonate (HMDP) had little or no effect compared to saline controls. For those diphosphonates which were effective, e.g., EHDP, the tissueprotective effects were observed whether the rats were treated with drug prior to the administration of DHT, or whether drug treatment commenced after DHT administration. The results are discussed in terms of the known biological properties of the diphosphonate drugs.
    Type of Medium: Electronic Resource
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