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  • Tetanus Toxin  (7)
  • Tetanus  (6)
  • Botulinum toxin  (3)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 276 (1973), S. 327-340 
    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
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 280 (1973), S. 177-182 
    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
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 272 (1972), S. 75-88 
    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.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 287 (1975), S. 97-106 
    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.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 303 (1978), S. 133-138 
    ISSN: 1432-1912
    Keywords: Tetanus ; Botulism ; Acetylcholine ; Nerve tissue ; Cell cultures
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Primary nerve cell cultures derived from embryonic rat central nervous system form [3H]ACh from exogenous [3H]Ch, and release it upon potassium depolarization. Pretreatment of the cultures with botulinum-A toxin or tetanus toxin diminishes the cellular accumulation of [3H]ACh. Poisoning the cultures during the period of [3H]Ch uptake fails to lower [3H]ACh formation. Dependent on dosage, both toxins suppress the release of [3H]ACh upon potassium depolarization. Heat-denaturated toxins as well as tetanus toxin preincubated with tetanus antitoxin were without effect.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 311 (1980), S. 33-40 
    ISSN: 1432-1912
    Keywords: Tetanus toxin ; Botulinum toxin ; Neuromuscular junction ; Calcium ; Neuraminidase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. The blocking effect of tetanus toxin on the neuromuscular junction of the mouse phrenic nervehemidiaphragm preparation exposed to the toxin (0.05–20 μg/ml) in the organ bath was studied and compared with the action of botulinum A toxin. 2. The time course of the paralysis of the diaphragm could be divided into a latent and a manifest period. Still during the latent period the effect of the toxin became progressively resistant to washing and, with some delay, to antitoxin. 3. Between 25 and 41°C the time until paralysis strongly depended on temperature with Q 10 of about 2.7. 4. Procedures increasing the transmitter release shortened, and procedures depressing it prolonged the time until paralysis. 5. 4-Aminopyridine and guanidine temporarily restored the contraction of the partially paralyzed diaphragm, indicating the persistence of activatable calcium and acetylcholine pools. Raising the external Ca2+-concentration and application of the Ca-Ionophore A 23187 were ineffective in the doses applied. 6. About 80 min after exposure to the toxin (10 μg/ml), the m.e.p.p. activity decreased by a factor of 30. Parallel to this, paralysis of nerve evoked muscle contraction developed. 7. Neuraminidase treatment did not prevent tetanus toxin poisoning. 8. The paralysis is produced by tetanus toxin itself and not by contaminants as shown by the parallel decrease of toxicity and paralysis following treatment with either antitoxin or brain homogenate, or by the use of spontaneously inactivated toxin. 9. Tetanus toxin was compared with botulinum A toxin as to the shape of its dose-response curve, time course of paralysis, temporary reversal by 4-aminopyridine and behaviour against Ca-ionophore. In any case, both toxins were indistinguishable, albeit botulinum A neurotoxin was calculated to be about 2000 times more potent than tetanus toxin.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 312 (1980), S. 255-263 
    ISSN: 1432-1912
    Keywords: Acetylcholine ; Tetanus toxin ; Botulinum toxin ; Myenteric plexus ; Transmitter release
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of tetanus and botulinum A toxin were studied on the electrically stimulated myenteric plexus-ileum strip of the guinea pig. The concentrations used were in the range of 104–106 mouse LD50/ml. 1. Tetanus and botulinu, A toxin slowly decrease the amplitude of the contractile response to field stimulation in a dose-dependent manner without influencing the sensitivity to acetylcholine of the smooth muscle. 2. Development of paralysis is preceded by a latent period. Washing and antitoxin slow the paralytic process only when applied during the latent period. 3. The time course of development of paralysis depends on the activity of the strip. It can be slowed by rest, high [Mg2+], or low [Ca2+], and accelerated by raising the stimulation frequency. 4. Substances like 4-aminopyridine, sea anemone toxin II and scorpion toxin which prolong the membrane depolarization restore temporarily the contraction of partially paralysed muscle strips. 5. Poisoned preparations do not differ from controls in their total acetylcholine contents, whereas formation as well as release of [3H]-acetylcholine are decreased by either toxin. It is concluded that a) tetanus toxin and botulinum A toxin are qualitatively indistinguishable with respect to their actions on the postganglionic cholinergic neurons in the ileum, botulinum A toxin being 5 times more potent than tetanus toxin, b) the effects of the toxins at postganglionic cholinergic neurons in the ileum and at motor nerve endings are qualitatively similar, botulinum A toxin being about 500 times more potent than tetanus toxin at the latter preparation (see Habermann et al., 1980b, c) both toxins influence the turnover of acetylcholine but not its tissue concentration.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 301 (1977), S. 135-138 
    ISSN: 1432-1912
    Keywords: Tetanus ; Toxin ; Axonal transport ; Autoradiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rats were injected i.v. with 125I-tetanus toxin. In autoradiographs of the spinal cord radioactivity was found over the pericarya and in the surroundings of the motoneurones whereas grain density was less over their nuclear region. In addition, pericarya in the lateral horn of the thoracic region and also the bipolar cells of the spinal ganglia contained radioactivity. The central part and the dorsal horns of spinal cord, and the white substance did not show any appreciable radioactivity. Within the medulla oblongata, clusters of large cells representing motor nuclei, as well as some fibre tracts close to them, contained 125I. Forebrain and cerebellum remained free. According to its histoautoradiographic appearance, generalized tetanus can be described best as a combination of multiple local tetani.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 276 (1973), S. 341-359 
    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
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 276 (1973), S. 321-326 
    ISSN: 1432-1912
    Keywords: Tetanus ; Antibodies ; Radioimmunological Measurement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A radioimmunological assay procedure allows the measurement of small amounts of tetanus antibodies; it should also be applicable to antibodies against other soluble antigens. It is based on the competition between dissolved and solid phase antibodies for labelled antigen. In the range of experimental error, the same antibody titers are found with the radioimmunological and with the mouse protection test. The detection limit is in the range of 0.001 IU/ml. The reaction conditions allow the determination of antibodies in multiple samples.
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