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  • 1
    Electronic Resource
    Electronic Resource
    Distribution of 125I-tetanus toxin and 125I-toxoid in rats with generalized tetanus, as influenced by antitoxin (1973)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 276 (1973), S. 327-340 
    Details
    ISSN: 1432-1912
    Keywords: Tetanus Toxin ; Pharmacokinetics ; Central Nervous System ; Iodine Labelling ; Receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00499887
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  • 2
    Electronic Resource
    Electronic Resource
    Histoautoradiographic localisation of 125I-labeled tetanus toxin in rat spinal cord (1973)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 280 (1973), S. 177-182 
    Details
    ISSN: 1432-1912
    Keywords: Tetanus Toxin ; Iodine Labeling ; Spinal Cord ; Histoautoradiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 125I-labeled tetanus toxin was injected intravenously and intramuscularly in rats. Specific localisation within the spinal cord was obtained by histoautoradiography. 1. In generalized tetanus grain density was maximal in the ventral grey matter of spinal cord. The grains were closely correlated to the motoneurons and their neuropil. Other areas showed background activity only. 2. In local tetanus the injected side was labeled selectively. High grain density regularly covered a distinct group of motoneurons and their neuropil. 3. There is some evidence for intracellular accumulation of the toxin since the maximum of grain density was found over the perikarya whilst the nucleus corresponded to a minimum. 4. Cells yielding high grain density were less intensively stained with toluidine blue than neighbouring unlabeled cells. It is concluded from these experiments that tetanus toxin develops its action within or around selected motoneurons and that it induces morphological alterations there.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00499178
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  • 3
    Electronic Resource
    Electronic Resource
    Distribution of 125I-tetanus toxin and 125I-toxoid in rats with local tetanus, as influenced by antitoxin (1972)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 272 (1972), S. 75-88 
    Details
    ISSN: 1432-1912
    Keywords: Tetanus Toxin ; Tetanus Antitoxin ; Local Tetanus ; Spinal Cord
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 0 1. Local tetanus was produced in rats by application of sublethal doses of 125I-tetanus toxin into the right m. gastrocnemius. Radioactivity was found in the lumbar part of the spinal cord for at least 24 days which is indicative of a long-lasting binding of toxin to its target organ. Radioactivity appears in the lumbar region before local tetanus becomes manifest. 2. The influence of antitoxin on both local tetanus and radioactivity of the lumbar cord heavily depends on the time of its application. When it is injected simultaneously into a foreleg, it prevents the symptoms and the spinal concentration process. When given ten hours after toxin, it does not change appreciably the severity of local tetanus; it diminishes, however, the radioactivity accumulating in the spinal cord. Antitoxin, given 48 hours after toxin, is ineffective in both respects. 3. 22 hours after application, about 9% of the initial radioactivity still persists in the injected leg; 50 hours after application, only 1–2% are still present. 4. Plasma radioactivity is measurable for between 50 and 96 hours in animals given 125I-toxin i.m. It is higher in animals having received antitoxin 10 hours after the toxin or simultaneously with toxin. 5. Labelled toxoid was prepared by formol treatment of labelled toxin. Following i.m. injection, toxoid was bound to a lesser degree and for a shorter time by the lumbar cord than was toxin. Like toxin, toxoid was found in the ipsilateral sciatic nerve, and simultaneous application of antitoxin prevented its appearance there as wells as in the lumbar cord. As with toxin, plasma radioactivity after injection of labelled toxoid was increased by simultaneous application of antitoxin into another leg. 6. It is concluded that antitoxin prevents the entrance of toxin into the spinal cord, but does neither remove nor detoxify appreciable amounts of radioactive material once fixed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00498795
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  • 4
    Electronic Resource
    Electronic Resource
    125I-labelled tetanus toxin as a neuronal marker in tissue cultures derived from embryonic CNS (1975)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 290 (1975), S. 329-333 
    Details
    ISSN: 1432-1912
    Keywords: Tetanus Toxin ; Iodine Labelling ; Neurones ; Tissue Culture ; Autoradiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Primary cultures derived from embryonic mouse brain and spinal cord were exposed to 125I-labelled tetanus toxin and subjected to autoradiography. Cells with neuronal, but not glial, morphology selectively accumulated the toxin. The distribution of the grains over these cells and their processes was not uniform, discrete processes showing heavier labelling.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00510562
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  • 5
    Electronic Resource
    Electronic Resource
    Direct evidence for the specific fixation of Cl. Botulinum A neurotoxin to brain matter (1975)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 287 (1975), S. 97-106 
    Details
    ISSN: 1432-1912
    Keywords: Tetanus Toxin ; Botulinum A Toxin ; Synaptosomes ; Neuraminic Acid ; Fixation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. Rat brain homogenate and synaptosomes from rat brain bind botulinum toxin. The binding is accompanied by partial inactivation. The binding decreases with increasing ionic strength. A considerable fixation of tetanus toxin can still be demonstrated under conditions which prevent the fixation of botulinum toxin. 2. Only the grey substance, not the white substance from bovine brain is able to bind the toxin. 3. Upon pretreatment with neuraminidase, synaptosomes lose nearly all of their binding capacity. However, neither gangliosides nor ganglioside-cerebroside mixtures nor brain extracts could replace the synaptosomes. Thus botulinum A toxin closely resembles tetanus toxin in its ability to react with (a) neuraminidase-sensitive site(s) of the grey matter of the CNS. It differs from tetanus toxin by its stronger sensitivity against ionic forces and by its failure to react with certain gangliosides.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00632641
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  • 6
    Electronic Resource
    Electronic Resource
    Interaction of labelled tetanus toxin with substructures of rat spinal cord in vivo (1973)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 276 (1973), S. 361-373 
    Details
    ISSN: 1432-1912
    Keywords: Tetanus Toxin ; Iodine Labelling ; Spinal Cord ; Autoradiography ; Antitoxin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The in vivo interaction of 125I-labelled toxin with substructures of rat spinal cord has been studied. The rats were poisoned by i.v. injection about 40–50 h before sacrifice. 1. The labelled material accumulates in the grey substance, which is, on microdissection, about 6 times more active than the white. Autoradiography reveals that the toxin is particularly enriched in the ventrolateral part of the grey substance. 2. On ultracentrifugation of the homogenates, the label is preferentially fixed to the dense fractions known to contain the synaptosomes. However, a considerable part of the toxin is fixed to the lighter fractions too. 3. Upon gel filtration, the labelled material in SDS-homogenates from spinal cords poisoned in vivo is indistinguishable from toxin added to the homogenates already prepared. The same is true for the bulk of radioactivity when subjected to disc gel electrophoresis. 4. The labelled material is degraded by enzymes from spinal cord at pH 3.5, but not at pH 7.5. 5. The labelled material is relatively firmly bound to structures of spinal cord. The bonding is fairly resistant against washing, even in the presence of an excess of cold toxin, but it can be partially released by treatment with antitoxin. According to these findings, the labelled material is firmly but not irreversibly bound in vivo to discrete structures, corresponding preferentially to the synaptosomal fractions in the homogenates and the ventrolateral grey in the slices. No evidence has been found for its degradation in vivo. So far, the bulk of labelled material in the spinal cord is indistinguishable from tetanus toxin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00499889
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  • 7
    Electronic Resource
    Electronic Resource
    Interaction of labelled tetanus toxin and toxoid with substructures of rat brain and spinal cord in vitro (1973)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 276 (1973), S. 341-359 
    Details
    ISSN: 1432-1912
    Keywords: Tetanus Toxin ; Iodine Labelling ; Central Nervous System ; Receptors ; Antitoxin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00499888
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