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  • Articles: DFG German National Licenses  (10)
  • Botulinum A toxin  (4)
  • Spinal Cord  (4)
  • Antitoxin  (3)
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  • Articles: DFG German National Licenses  (10)
Material
Years
Keywords
  • 1
    ISSN: 0014-5793
    Keywords: Botulinum A toxin ; Chain, heavy ; Chain, light ; Chromaffin cell, permeabilized ; Exocytosis
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 267 (1970), S. 1-19 
    ISSN: 1432-1912
    Keywords: Tetanus Toxin-Labelled Protein ; Spinal Cord ; Pharmaco-kinetics ; Radioimmunassay ; Tetanustoxin ; Markierte Proteine ; Rückenmark ; Phar-makokinetik ; Radioimmunassay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. The preparation and properties of125I-labelled tetanus toxin are described. 2. After intravenous injection there is a short phase when the labelled toxin is rapidly removed from the blood plasma. This initial period is followed by a slow second phase of decay which has a longer duration. The first phase in very pronounced in rabbits, but not in rats. Unlabelled toxin is removed equally fast from rabbit plasma, as has been revealed by measuring the immunological reactivity (so-called “junction test”) and toxicity. 3. Thirty minutes after i.v. administration torabbits about 2/3 of the radioactive label are found in the liver. The highest concentration is attained in the spleen. 24 hours later, the bulk of the label has been excreted in the urine and faeces, which indicates catabolism of the toxin. In therat, the concentration in the liver is much less prominent, and the excretion of the label is slower. In both species, the central nervous system does not accumulate more than just measurable quantities of the label, even if the animals are given large toxic doses. 4. After injection into the left gastrocnemius muscle of the rat, the labelled tetanus toxin is absorbed very slowly from the site of administration. It is taken up by the corresponding N. ischiadicus and the lumbar region of the spinal cord. The injection of toxin into the anterior leg leads to concentration of radioactivity in the cervical area of the medulla. The arrival of the label in the spinal cord coincides approximately with the appearance of local tetanus. Sectioning of the N. ischiadicus prevents the appearance of the local tetanus of the lower extremity. The enrichment of the toxin in the lumbar cord is prevented in operated, but not in sham-operated rats. 5. When the spinal cord was subdivided into four sectors, the label was found to be greatly concentrated in the ipsilateral ventral sector of the segment corresponding with the injected extremity. This indicates transport into the ventral roots. 6. 131I-labelled tetanus antitoxin also disappears very slowly from the rat gastrocnemius. In contrast to labelled tetanus toxin, however, it is not concentrated in the spinal cord.
    Type of Medium: Electronic Resource
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  • 3
    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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  • 4
    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.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 316 (1981), S. 135-142 
    ISSN: 1432-1912
    Keywords: Tetanus toxin ; Botulinum A toxin ; Choline ; Gangliosides ; Fixation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Tetanus toxin and, to a lesser degree, botulinum A toxin inhibit partially and noncompetitively the uptake of [3H]choline into a crude synaptosomal fraction from rat brain cortex. Botulinum toxin acts by its neurotoxin content. The effect is not due to nonspecific synaptosomal damage by the toxins as shown by the lactate dehydrogenase occlusion test, by the absence of swelling and by the preservation of choline stores. The ratio between [3H]acetylcholine and [3H]choline was decreased by both toxins. Inhibition by either toxin depends strongly on the temperature and duration of incubation, and is preceded by an initial latency period. The effect of tetanus toxin, once manifest, is largely resistant against antitoxin. It is not significantly diminished by pretreatment of the synaptosomes with V. cholerae neuraminidase. Fixation of 125I-tetanus toxin proceeds fast, is largely independent of temperature and is diminished by pretreatment of the synaptosomes with neuraminidase. Thus only some of the fixation sites, and not the long-chain gangliosides, are required for the effects of tetanus toxin. A slow, temperature-sensitive process links the fixation with the action. In contrast to rat synaptosomes the chicken preparation is more sensitive to botulinum A than to tetanus toxin, which reflects the differences in sensitivity between live birds and rodents. Our data underline the similarities between the effects of tetanus and those of botulinum A toxin. Their dependence on time and temperature, the time dependence of efficacy of antitoxin, and the concordance in species specificity indicate that the in vitro system mirros some crucial features of poisoning of isolated organs and live animals.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 318 (1981), S. 105-111 
    ISSN: 1432-1912
    Keywords: Tetanus toxin ; Botulinum A toxin ; Noradrenaline outflow ; Gangliosides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Tetanus toxin and, to a lesser degree, botulinum A toxin partially depress the basal and the potassium evoked outflow of [3H]noradrenaline from preloaded particulate rat forebrain cortex. The effect is due to the toxins and not to any contaminant, as shown by dialysis, heating and antitoxin treatment, and also by replacement of crystalline botulinum A toxin with purified neurotoxin. Tetanus toxin also depresses the outflow due to sea anemone toxin II, 4-aminopyridine and d-amphetamine. The effect of the toxins proceeds with time and strongly depends on temperature. Once manifest the tetanus toxin effect is not reversed by antitoxin. Pretreatment with V. cholerae neuraminidase degrades the long-chain gangliosides quantitatively to GM1. Tetanus toxin, applied subsequently remains fully active. High concentrations of tetanus toxin and botulinum A neurotoxin promote the outflow of small amounts of tritium within short incubation times. It is concluded: a) Tetanus toxin is a broad range neurotoxin which acts on processes subsequent to the depolarization step. b) Long-chain gangliosides are only binding sites, but not receptors of tetanus toxin. c) Botulinum A toxin is less potent but resembles tetanus toxin in both promoting and depressing the outflow of noradrenaline.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 52 (1974), S. 255-265 
    ISSN: 1432-1440
    Keywords: Tetanus toxin ; Antitoxin ; 125Iodine ; Spinal cord ; Nerves ; Tetanustoxin ; Antitoxin ; 125Jod ; Rückenmark ; Nerven
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Unsere Kenntnis der Pathogenese des Wundstarrkrampfes hat sich durch Anwendung neuer biochemischer und neurophysiologischer Techniken innerhalb der letzten Jahre erheblich erweitert. Radioaktiv markiertes Tetanustoxin wurde innerhalb verschiedener Nerven bis zu den Vorderhörnern des Rückenmarks verfolgt; dort wurde das Toxin z.T. noch auf cellulärer Ebene nachgewiesen. Die Verteilung des Toxins ist zeitabhängig und wird durch Antitoxin beeinflußt. Je weiter der Zeitpunkt der Vergiftung zurückliegt, desto geringer ist der Effekt des Antitoxins auf die Symptomatologie und die spinale Anreicherung des Toxins. Die neurale Wanderung des Toxins wird durch Erregung des toxinhaltigen Nerven gefördert. Neben den motorischen Anteilen sind auch rein sensibel-sensorische und vegetative Nerven zur Weiterleitung des Toxins imstande. Der generalisierte Tetanus kann als eine Sonderform des lokalen Tetanus betrachtet werden. Während bisher das klassische α-motorische System des Rückenmarks im Vordergrund der Untersuchungen stand, weisen neuere Arbeiten auf eine gleichzeitige, vielleicht sogar vorwiegende Enthemmung des γ-motorischen Systems hin. Außerdem werden vegetative Spinalreflexe enthemmt, was auch bei der Therapie bedacht werden sollte. Die Hemmwirkung des Tetanustoxins auf periphere Synapsen weist auf große Ähnlichkeiten mit Botulinumtoxin hin, obwohl die Symptome am vergifteten Tier so verschieden sind. Künftige Untersuchungen werden sich voraussichtlich mit der Wirkungsweise des Toxins auf molekularer und cellulärer Ebene befassen.
    Notes: Summary Due to the use of advanced biochemical and neurophysiological techniques, our knowledge of the pathogenesis of tetanus has considerably improved during the past years. Radio-labelled tetanus toxin has been traced within different nerves up to the anterior horn of the spinal cord where its localization down to the cellular level has been achieved. The distribution of labelled toxin depends on time and is influenced by antitoxin. The longer the duration of poisoning, the smaller the effect of antitoxin on the spinal enrichment of toxin and on the onset of toxic symptoms. The neural ascent of toxin into a spinal cord segment is enhanced by stimulation of the segmental nerves. Not only the motor nerves, but also sensory and vegetative nerves are able to serve as guide-rails for the toxin. The generalized tetanus has been understood as a special kind of local tetanus. For a long time, disinhibition of the alpha motor system was considered to be the characteristic action of tetanus toxin, but recent evidence is in favour of an additional disinhibition of the gamma motor system (perhaps even preceding the alpha disinhibition) and also of the sympathetic spinal reflexes. This finding should have therapeutic implications. The detection of inhibitory effects of tetanus toxin on peripheral cholinergic synapses points again to the close similarity between tetanus toxin and botulinum A toxin. The trends of future research will presumably lead to the elementary processes at the molecular and cellular level which are the basis of the clinical picture of tetanus.
    Type of Medium: Electronic Resource
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  • 8
    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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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 276 (1973), S. 361-373 
    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
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  • 10
    ISSN: 1432-1912
    Keywords: Tetanus toxin ; Botulinum A toxin ; Neurotransmitter ; Uptake ; Release
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of tetanus toxin and botulinum A toxin on the uptake and evoked release of various neurotransmitters were studied using particles from rat forebrain, corpus striatum and spinal cord. 1. Uptake. Tetanus toxin partially inhibits the uptake of glycine and choline into spinal cord synaptosomes. The effect on glycine uptake becomes statistically significant after a lag period of 60\2-120 min. It is no longer present when the toxin is heated, antitoxin-treated or toxoided. The inhibition by botulinum A toxin of choline uptake into spinal cord synaptosomes is weak but measurable, that of glycine uptake is at the borderline of detection. The uptake of GABA into forebrain cortex synaptosomes is slightly inhibited by tetanus toxin but hardly by botulinum A toxin. The effects of tetanus toxin and botulinum A toxin on the uptake of noradrenaline into striatal synaptosomes are negligible. 2. Release. Tetanus toxin inhibits the potassium (25 mM) evoked release of radioactivity from rat forebrain cortex particles preloaded with labelled neurotransmitters. The sensitivity decreases in the following order: Glycine 〉 GABA \2〉 acetylcholine. The toxin also inhibits the release of radioactivity from striatal particles preloaded with labelled noradrenaline. It is always 10\2-50 times more potent on spinal cord than on brain particles. The sensitivity of the evoked release from the spinal cord decreases in the order glycine 〉 GABA 〉 acetylcholine 〉 noradrenaline. The toxin is identical with the causative agent because toxin-antitoxin complexes, toxoid and heated toxin do not influence the release from particles preloaded with glycine (spinal cord), GABA (forebrain) and noradrenaline (striatum). Botulinum toxin resembles tetanus toxin by its ability to diminish the release of radioactivity from preloaded forebrain (acetylcholine 〉 GABA), striatal (noradrenaline), or spinal cord (glycine) particles. The botulinum toxin effect on the striatum (noradrenaline) and on the spinal cord (glycine) is due to its neurotoxin content. The identity of the toxin and the causative agent has been established by preheating and preincubation with antitoxin. It is proposed that a) tetanus and, however to a much lesser degree, botulinum A toxin act in a basically similar manner on a process underlying the function of synapses in general, and b) the pronounced sensitivity of glycine and GABA release from spinal cord, together with the axonal ascent of tetanus toxin, may be crucial in the pathogenesis of tetanus.
    Type of Medium: Electronic Resource
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