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  • Artikel: DFG Deutsche Nationallizenzen  (14)
  • Tetanus  (6)
  • Acetylcholine  (3)
  • Antitoxin  (3)
  • Botulinum toxin  (3)
  • Pharmacokinetics  (3)
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  • Artikel: DFG Deutsche Nationallizenzen  (14)
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  • 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
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 303 (1978), S. 133-138 
    ISSN: 1432-1912
    Schlagwort(e): Tetanus ; Botulism ; Acetylcholine ; Nerve tissue ; Cell cultures
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 311 (1980), S. 33-40 
    ISSN: 1432-1912
    Schlagwort(e): Tetanus toxin ; Botulinum toxin ; Neuromuscular junction ; Calcium ; Neuraminidase
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 312 (1980), S. 255-263 
    ISSN: 1432-1912
    Schlagwort(e): Acetylcholine ; Tetanus toxin ; Botulinum toxin ; Myenteric plexus ; Transmitter release
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    Journal of molecular medicine 52 (1974), S. 255-265 
    ISSN: 1432-1440
    Schlagwort(e): Tetanus toxin ; Antitoxin ; 125Iodine ; Spinal cord ; Nerves ; Tetanustoxin ; Antitoxin ; 125Jod ; Rückenmark ; Nerven
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: 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.
    Notizen: 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.
    Materialart: Digitale Medien
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  • 6
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 301 (1977), S. 135-138 
    ISSN: 1432-1912
    Schlagwort(e): Tetanus ; Toxin ; Axonal transport ; Autoradiography
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 7
    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
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  • 8
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 276 (1973), S. 321-326 
    ISSN: 1432-1912
    Schlagwort(e): Tetanus ; Antibodies ; Radioimmunological Measurement
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 9
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 276 (1973), S. 361-373 
    ISSN: 1432-1912
    Schlagwort(e): Tetanus Toxin ; Iodine Labelling ; Spinal Cord ; Autoradiography ; Antitoxin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 10
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 281 (1974), S. 47-56 
    ISSN: 1432-1912
    Schlagwort(e): Botulinum A ; Tetanus ; Neurotoxin ; Hemagglutinin ; Iodine Labeling
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary 1. Labeling of crystalline botulinum A toxin has been done with 125I by aid of the chloramine T method. The neurotoxic component is well preserved, whereas the hemagglutinin undergoes physicochemical alterations. Neither with labeled nor with unlabeled toxin, hemagglutinating power parallels the main protein peak. 2. Neurotoxin, homogeneous in gel filtration, is bound to synaptosomes from rat brain. Cold toxin competes with labeled toxin, and antitoxin or neuraminidase partially remove the bound neurotoxin. 3. Upon intramuscular injection, some radioactivity is recovered in the respective parts of the spinal cord. Antitoxin prevents the ascent. The similarities between tetanus and botulinum A neurotoxins are stressed.
    Materialart: Digitale Medien
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