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  • 1990-1994
  • 1970-1974  (2)
  • Receptors  (2)
  • 1
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 276 (1973), S. 327-340 
    ISSN: 1432-1912
    Schlagwort(e): Tetanus Toxin ; Pharmacokinetics ; Central Nervous System ; Iodine Labelling ; Receptors
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary In order to understand the symptomatology of generalized tetanus from the pharmacokinetics of the toxin, 125I-labelled toxin was injected i.v. in rats without and with antitoxin. 1. After a few hours latency, brain stem and spinal cord concentrate radioactive material up to the third day. The decline of radioactivity is very slow, semilogarithmic, and can be followed up to the 24th day after injection. In contrast, forebrain and cerebellum do not bind measurable radioactivity. Less than 1% of the radioactivity injected is found in the CNS. 2. The symptoms of tetanus start some time after the bulk of labelled toxin has been taken up by the CNS. They cease before all radioactivity has left it. 3. Antitoxin, given simultaneously, prevents the onset of symptoms and the uptake of radioactivity by the CNS. When given 10 h after labelled toxin, it nearly abolishes the fixation and still prevents the onset of symptoms. When given 48 h after toxin, it is nearly ineffective in both respects. Antitoxin first delays, then enhances the elimination of labelled toxin from the blood. 4. Labelled antitoxin is not enriched in the CNS. 5. The uptake of radioactivity into various parts of spinal cord corresponds well to their relative content in grey matter. 6. The pharmacokinetic behaviour of 125I-toxoid resembles that of toxin. However, in order to get measurable fixation to the CNS at least 50 times higher amounts are to be applied. It is concluded that the barrier between blood and CNS is practically impermeable to tetanus toxin. The results can be harmonized best with the assumption that generalized tetanus is nothing else than a multiple local tetanus.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 276 (1973), S. 341-359 
    ISSN: 1432-1912
    Schlagwort(e): Tetanus Toxin ; Iodine Labelling ; Central Nervous System ; Receptors ; Antitoxin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary 1. Lyophilized homogenate of rat brain binds 125I-labelled tetanus toxin better than does homogenate from spinal cord. This is in contrast to the in vivo behaviour of the toxin where it is bound only to spinal cord. Liver homogenate does not fix the toxin. 2. Autoradiography of preincubated slices from spinal cord shows that the radioactivity is evenly and nearly exclusively bound to gray matter. 3. Maximally 40% of the labelled material interacts with brain homogenate. The toxicity of the remaining supernatant is much more reduced than is its radio-activity. 125I-toxoid, prepared from labelled toxin by treatment with formol, is bound only very weakly. Thus we assume that our toxin preparation is already partially toxoided, and that binding to CNS matter bears some relevance to toxicity. 4. The fixation of the labelled toxin is reversible. The degree of reversibility depends on the conditions used. Binding can be nearly completely reversed or prevented by treatment with antitoxin, but not more than 50% of the binding is reversed by treatment with unlabelled toxin. Repeated washings also remove the bulk of the initially bound toxin. Thus binding sites with different affinities are to be assumed. 5. A complex between ganglioside and cerebroside binds the labelled toxin more firmly than does brain homogenate. No competition between unlabelled and labelled toxin has been observed for this solid phase. Antitoxin nearly completely prevents and largely reverses the fixation of labelled toxin. 6. On the basis of the selective, competitive reactivity of labelled and unlabelled tetanus toxin with brain matter, a radio receptor assay has been developed. It can be used for the measurement of tetanus toxin down to 5 ng. 7. Gradient centrifugation of sucrose homogenates preincubated with labelled toxin reveals one peak of radioactivity in the fractions where the synaptosomes are to be expected; the larger part of the toxin remains, however, unevenly distributed near the starting volume. 8. Desoxycholate solubilizes the complex between labelled toxin and brain matter with parallel dissolution of brain proteins. 9. Neither brain nor spinal cord homogenates degrade labelled toxin into TCA-soluble fragments at pH 7.5. Partial degradation occurs, however, at pH 3.5.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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