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  • 1
    ISSN: 1432-0533
    Keywords: Intoxication ; Dog ; Clioquinol ; 2,5-hexanedione ; Distal axonopathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The central distal axonopathy induced in dogs by the administration of high doses of clioquinol is contrasted with the central-peripheral distal axonopathy precipitated by intoxication with 2,5-hexanedione. Mature, pure-bred Beagle dogs received a daily oral dose of 400 mg/kg of clioquinol for up to 7 months, or 1 ml per animal (approximately corresponding to 110 mg/kg) of 2,5-hexanedione for up to 5 months. Intoxicated and control animals were killed and perfused at monthly intervals, so that the spatial-temporal development of the lesion could be followed and correlated with clinical symptoms. During the treatment, dogs intoxicated with 2,5-hexanedione developed symptoms of peripheral neuropathy consisting of flaccid weakness, muscle atrophy, hind-limb foot-drop and areflexia. By contrast, the dogs surviving clioquinol intoxication exhibited a stiff-legged gait, hyperreflexia but no muscle atrophy. Light and electron microscope examination of central and peripheral nervous tissue from dogs intoxicated with 2,5-hexanedione revealed giant axonal swelling and distal axonal degeneration. By contrast, dogs receiving clioquinol showed a distal axonal degeneration confined to the optic tract and the long spinal cord tracts, without any visible involvement of peripheral nerves.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 32 (1979), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract— Neurotoxic hexacarbon compounds 2,5-hexanedione (2,5-HD) and methyl n-butyl ketone (MnBK) inhibit crystalline and endogenous CNS and PNS glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Preincubation of the enzyme with the toxin was necessary for inhibition. The enzyme activity of GAPDH was preserved by the addition of dithiothreitol in the presence of either neurotoxin. By contrast, lactate dehydrogenase (LDH) activity was not inhibited by these neurotoxic chemicals. Neurologically inactive compounds 1,6-hexanediol and acetone failed to inhibit GAPDH. The present data indicate that 2,5-HD and M “BK block energy metabolism by inhibiting glycolysis at the site of GAPDH. These observations may account for the known failure of GAPDH-dependent axonal transport and the axonal degeneration which occurs in hexacarbon neuropathy.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2072
    Keywords: Narcotic Agonists/Partial Agonists ; Intracerebroventricular Injection ; Noradrenaline ; 5-Hydroxytryptamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Using a tail immersion technique in mice, the anti-nociceptive activity of some narcotic agonists (diamorphine, etorphine, morphine and pethidine), partial agonists (cyclazocine, nalorphine and pentazocine) and naloxone have been determined alone, and after the intracerebroventricular (ICV) injection of 5-hydroxytryptamine (5-HT) or noradrenaline (NA). In common with morphine, the anti-nociceptive effects of each agonist and partial agonist studied were significantly increased by ICV 5-HT, and significantly attenuated by ICV NA. The marginal anti-nociceptive activity of naloxone was not significantly affected by the ICV injection ot either amine. It is concluded that the anti-nociceptive effects of all narcotic agonist and partial agonist agents are determined by the balance within the brain of the activities of the two amines, 5-HT and NA.
    Type of Medium: Electronic Resource
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