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  • 1
    Digitale Medien
    Digitale Medien
    Possible evidence for secondary degeneration of central nervous system in the pathogenesis of anencephaly and brain dysraphia (1979)
    Springer
    Virchows Archiv 384 (1979), S. 285-294 
    Details
    ISSN: 1432-2307
    Schlagwort(e): Anencephalus ; Amyelia ; Secondary degeneration ; Central nervous system: abnormalities
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary In an attempt to help elucidate pathogenetically those human cases exemplifying secondary degeneration of the neural tube causing brain dysraphia, macroscopic and histologic observations of two young human fetuses are described. A nine-week-old anencephalic fetus exhibited an absence of spinal cord (amyelia) with retention of neural crest derivatives (dorsal root ganglion cells and their processes, and sympathetic ganglia) implying the presence of a neural tube in early gestation. The second, ten-week-old exencephalic case exhibited restricted brain hemorrhage and necrosis of the telencephalon and brain stem amongst otherwise normal brain and spinal cord tissue. These two young fetal cases may represent examples of a previously normal neural tube which has undergone degeneration at a stage where neural crest has already undergone differentiation, and thus distinguishes them from cases of complete dysraphism which probably results from primary degeneration during neurulation.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00428230
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  • 2
    Digitale Medien
    Digitale Medien
    Synthesis and Preclinical Pharmacology of 2-(2-Aminopyrimidinio) Ethylidene-1,1-Bisphosphonic Acid Betaine (ISA-13-1)-A Novel Bisphosphonate (1999)
    Springer
    Pharmaceutical research 16 (1999), S. 1399-1406 
    Details
    ISSN: 1573-904X
    Schlagwort(e): bisphosphonates (diphosphonates) ; calcium-related disorders ; bone-related disorders ; drug administration ; drug absorption tight junctions ; mannitol
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. To validate our hypothesis that a bisphosphonate (BP) having a nitrogen-containing heterocyclic ring on the side chain, and with no hydroxyl on the geminal carbon would possess increased activity, and better oral bioavailability due to enhanced solubility of its calcium complexes/salts and weaker Ca chelating properties. Methods. A novel BP, 2-(2-aminopyrimidinio)ethylidene-l,l-bisphosphonic acid betaine (ISA-13-1) was synthesized. The physicochemical properties and permeability were studied in vitro. The effects on macrophages, bone resorption (young growing rat model), and tumor-induced osteolysis (Walker carcinosarcoma) were studied in comparison to clinically used BPs. Results. The solubility of the Ca salt of ISA-13-1 was higher, and the log βCa: BP stability constant and the affinity to hydroxyapatite were lower than those of alendronate and pamidronate. ISA-13-1 exhibited effects similar to those of alendronate on bone volume, on bone osteolysis, and on macrophages, following delivery by liposomes. ISA-13-1 was shown to have 1.5−1.7 times better oral absorption than the other BPs with no deleterious effects on the tight junctions of intestinal tissue. Conclusions. The similar potency to clinically used BPs, the increased oral absorption as well as the lack of effect on tissue tight junction of ISA-13-1 warrant its further consideration as a potential drug for bone diseases.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1018951025493
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  • 3
    Digitale Medien
    Digitale Medien
    Bisphosphonates and Tetracycline: Experimental Models for Their Evaluation in Calcium-Related Disorders (1998)
    Springer
    Pharmaceutical research 15 (1998), S. 606-613 
    Details
    ISSN: 1573-904X
    Schlagwort(e): bisphosphonates ; tetracycline ; calcification ; hydroxyapatite ; bone resorption ; synthesis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. This work was aimed at synthesizing novel bisphosphonates (BPs) and examining them in comparison to clinically used BPs such as pamidronate and alendronate, and to tetracycline, in order to evaluate their potential as anticalcification and antiresorption agents. The correlation between the various models was examined in order to establish facile experimental models for pre-screening of potential compounds. Methods. Nitrogen-containing heterocyclic, novel BPs such as 2-(3-methylimidazolio) ethylidene-l,l-bisphosphonic acid betaine (VS-5b), 2-(2-dimethylamino-4-pyrazinio)ethylidene-1,1 -bisphosphonic acid betaine (VS-6b), and 2-(2-α-pyridylethylthio) ethylidene-1,1-bisphosphonic acid (ISA-225), were synthesized and evaluated in comparison to clinically used BPs, in various experimental models of resorption and calcification. Results. The physicochemical properties of the novel compounds are slightly different than the BPs in clinical use: the pKa values are lower, the affinity for hydroxyapatite is lower and the solubilities of the calcium salts are higher. The anticalcification potencies of the novel compounds were high and ranked as follows: alendronate = pamidronate 〉 VS-6b = VS-5b = ISA-225 〉 tetracycline. The in vivo antiresorption activity of VS-5b and VS-6b in comparison to that of the clinically employed, pamidronate, was shown to be similar and higher, respectively. Conclusions. The anticalcification activity of the novel compounds as well as that of tetracycline was lower than that of alendronate. The antiresorption activity of VS-6b was similar to that of pamidronate. A good correlation between the different models was found, enabling the facile screening of novel compounds. The activities of tetracycline and EDTA highlight the distinct behavior of BPs as "crystal poison”. In addition, tetracycline was found to be a potent anticalcification agent in the ectopic calcification model.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1011990129437
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  • 4
    Digitale Medien
    Digitale Medien
    EHDP-induced rachitic syndrome in rats is not reversed by vitamin D metabolites (1988)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 220 (1988), S. 22-30 
    Details
    ISSN: 0003-276X
    Schlagwort(e): Life and Medical Sciences ; Cell & Developmental Biology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: To examine whether either of the two known active vitamin D metabolites 1,25(OH)2D3 or 24,25(OH)2D3 could reverse the mineralization defect induced by 1-hydroxyethylidene-1,1-bis phosphonate (EHDP), a model of EHDP-induced rickets was used. Rats at the age of 31 days were injected for 10 consecutive days with EHDP (10 mg/kg). Other littermates were treated with a combination of EHDP and either 1,25(OH)2D3 or 24,25(OH)2D3 or were treated following 10 days of EHDP, with either of the vitamin D metabolites for an additional 72 hr. Samples of cartilage fluid (Cfl) and of blood were removed prior to sacrifice for biochemical studies of some parameters of calcification. These parameters were correlated with the results of light and electron microscope studies of growth plate cartilage and bone. EHDP-treated rats revealed signs of typical rickets, manifested by widened growth plates and impaired bone mineralization. Transmission electron microscope (TEM) examination revealed matrix vesicles distributed throughout the growth plate; however, there appeared to be an arrest of the spread of the crystals at the provisional zone of calcification. Treatment with either 1,25(OH)2D3 or 24,25(OH)2D3 failed to reverse the rachitic condition of the animals. Serum calcium blood levels were elevated in the 1,25(OH)2D3 and EHDP-treated group. 1,25(OH)2D3 and 24,25(OH)2D3 further increased the already elevated serum alkaline phosphatase levels observed in EHDP rats, although the increase observed with 1,25(OH)2D3 was not statistically significant. In contrast to this, 24,25(OH)2D3 lowered the Cfl levels of alkaline phosphatase to the normal range despite the absence of apparent morpholoogical healing of the EHDP rachitic condition. It therefore appears that in our animal model pharmacological doses of vitamin D metabolites do not reverse the EHDP-induced mineralization defect.
    Zusätzliches Material: 5 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/ar.1092200104
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  • 5
    Digitale Medien
    Digitale Medien
    Transplacental effects of vitamin A on fetal bones in mice - follow-up studies on postnatal recovery (1988)
    Hoboken, NJ [u.a.] : Wiley-Blackwell
    Journal of Orthopaedic Research 6 (1988), S. 704-712 
    Details
    ISSN: 0736-0266
    Schlagwort(e): Vitamin A ; Growth cartilage ; Calcification ; Matrix vesicles ; Calcium ; Phosphate ; Life and Medical Sciences
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: Pregnant mice were injected with pharmacological doses of vitamin A during days 11-19 of gestation with the purpose of studying the long bones of offspring up to the age of 1 week. Tibiae were collected for routine light microscopic examination and tranmission electron microscopic examination. In addition, biochemical studies were conducted to determine the calcium, phosphorus, and magnesium content as well as the hydroxyproline and protein content of the bones. Treatment with vitamin A resulted in reduced weight and length of the long bones, as well as the presence of excessive calcification throughout the hypertrophic zone of the cartilaginous epiphyses. Matrix vesicles, many of them containing hydroxyapatite crystals, were observed and found to be distributed within the cartilaginous epiphyses in a similar pattern as in untreated control mice offspring, but mineral crystals were also observed unassociated with the matrix vesicles. The calcium, phosphate, magnesium, and hydroxyproline content was reduced in the vitamin A offspring. However, the percentage of these minerals expressed per dry weight bone was higher than in controls, verifying the morphological findings that although vitamin A inhibits bone growth, it enhances calcification in the growth plate.
    Zusätzliches Material: 9 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/jor.1100060513
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