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  • Tetanus Toxin  (7)
  • Ouabain  (4)
  • Antitoxin  (3)
  • Permeability  (3)
  • 1
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochimica et Biophysica Acta (BBA)/Biomembranes 861 (1986), S. 165-176 
    ISSN: 0005-2736
    Keywords: (Erythrocyte membrane) ; (Na^+ + K^+)-ATPase ; Ligand binding ; Membrane permeability ; Ouabain ; Palytoxin
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochimica et Biophysica Acta (BBA)/Biomembranes 688 (1982), S. 486-494 
    ISSN: 0005-2736
    Keywords: (Erythrocyte) ; Amphotericin B ; Palytoxin ; Permeability
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
    Type of Medium: Electronic Resource
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  • 3
    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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  • 4
    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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  • 5
    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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  • 6
    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.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 319 (1982), S. 101-107 
    ISSN: 1432-1912
    Keywords: Palytoxin ; Ouabain ; Erythrocytes ; Permeability ; ATPase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. Palytoxin in concentrations as low as 1 pM raises the potassium permeability of rat, human and sheep erythrocytes, and the sodium permeability of human erythrocytes. The release of potassium or sodium from human cells also occurs when extracellular sodium is replaced by choline. 2. Ouabain inhibits the release due to palytoxin of potassium ions from human, sheep and rat erythrocytes, and also the release of sodium ions from human cells. The glycoside effect is specific since a) it is already prominent with 5×10−8 M ouabain b) rat erythrocytes are less sensitive than human cells to ouabain c) potassium release due to amphotericin B or the Ca2+ ionophore A23187 is not influenced by ouabain and d) dog erythrocytes are resistant to palytoxin as well as to ouabain. 3. Palytoxin has no direct influence on the Na+, K+-ATPase. It inhibits the binding of [3H]ouabain to erythrocyte membranes within the same concentration range as unlabelled ouabain. It partially displaces bound [3H]ouabain, and partially inhibits the inactivation of erythrocyte ATPase by the glycoside. Depletion of ATP or of external Ca2+ renders the cells less sensitive to palytoxin. Nevertheless inhibition by ouabain can be still demonstrated with human cells whose ATP stores had been largely exhausted, and also in the absence of external Ca2+. 4. Palytoxin decreases the surface tension at the air-water interface. We assume that the formation of nonspecific pores by palytoxin is linked with its surface activity. Further experiments should demonstrate whether ouabain prevents the binding of palytoxin to erythrocytes (“receptor hypothesis”), or whether an ouabain-sensitive hydrolysis of trace amounts of ATP (“metabolic hypothesis”) promotes the palytoxin effect.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 325 (1984), S. 85-87 
    ISSN: 1432-1912
    Keywords: Na+, K+-ATPase ; Palytoxin ; Ouabain ; Kidney ; Erythrocyte
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Hog kidney Na+, K+-ATPase, purified to the microsomal stage and activated with detergent, binds palytoxin, as shown by the nearly complete competition of the toxin with 3H-ouabain. The K i-values of palytoxin, but not of ouabain, depend on the protein concentration; this indicates additional binding sites for the toxin on kidney membranes. — Palytoxin inhibits the enzymatic activity of the detergent-activated preparation nearly completely (IC50 8·10−7 mol/l). Inhibition of ATPase activity and of ouabain binding are promoted by borate, a known activator of palytoxin. — Palytoxin also inhibits the Na+, K+-ATPase of erythrocyte ghosts in the same dose range. The data are discussed in context with the hypothesis (Chhatwal et al. 1983) that palytoxin raises the cellular permeability by altering the state of Na+, K+-ATPase or its environment.
    Type of Medium: Electronic Resource
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  • 9
    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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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 264 (1969), S. 476-493 
    ISSN: 1432-1912
    Keywords: Kinins ; Permeability ; Heat ; Inflammation ; Kinine ; Permeabilität ; Hitze ; Entzündung
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. The suboutis of rat paws heated (46,5° C) in situ has been perfused. Kinin activity could be demonstrated regularly in the fluid which was collected in ice. When the solutions were tested immediately after having passed the tissue, only some of the experiments yielded positive results. Native and125Jlabelled kininogen as well as kininogenase and kininase activities passed into the perfusates. The sensitivity to dextran and the kinin release on heating were, in contrast to recent reports, not correlated. 2. The release of the components of the kinin system approximately paralleled that of labelled human albumin. Their concentration rose until about 1 hour after the start of the heating. There was no priority of the components of the kinin system when compared with human albumin which can be regarded as permeability indicator. 3. Intravenously injected carboxypeptidase B, because of its lower molecular weight, entered the interstitial fluid more easily than did the plasma carboxypeptidase N. Its blood level decreased rapidly; but sufficient tissue concentrations could be maintained by intravenous infusions. Neither the volume nor the time dependence of the thermic edema changed during carboxypeptidase B-infusions. The same was true for infusions of trasylol, whereas phenylbutazone inhibited the edema significantly. Edema formed by short heating (30 sec, 55° C) was equally resistant to carboxypeptidase B. 4. In the skin and muscles of the heated rat paw, carbon particles mainly stained the capillary walls. This finding argues against a considerable involvement of “classical” mediators which should induce venular lesions. 5. Infusion of large amounts of bradykinin into the arterial supply did not imitate the thermic edema; neither has bradykinin been found in the perfusate of the subcutis. 6. In the light of these findings, a significant role of the kinin system in the thermic edema of the rat paw is to be doubted.
    Type of Medium: Electronic Resource
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