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   Vol. 5, No. 6, 1998
   
   Review
   Oxidative Stress and Neurodegenerative Disorders
   Albert Y. Sun, Yong-Mei Chen
   Department of Pharmacology, University of Missouri, Columbia, Mo., USA
   Journal of Biomedical Science 5:6:1998, 401-414.
   Abstract
   
   Oxidative insults, whether over-excitation, excessive release of
   glutamate or ATP caused by stroke, ischemia or inflammation, exposure
   to ionizing radiation, heavy-metal ions or oxidized lipoproteins may
   initiate various signaling cascades leading to apoptotic cell death
   and neurodegenerative disorders. Among the various reactive oxygen
   species (ROS) generated in the living organism, hydroxyl and
   peroxynitrite are the most potent and can damage proteins, lipids and
   nucleic acids. It appears that some natural antioxidants (tocopherol,
   ascorbic acid and glutathione) and defense enzyme systems (superoxide
   dismutase, catalase and glutathione peroxidase) may provide some
   protection against oxidative damage. Recent findings indicate several
   polyphenols and antioxidant drugs (probucol, seligilline) are
   effective in protecting the cells from ROS attack. Further development
   of these antioxidant molecules may be of value in preventing the
   development of neurodegenerative diseases.


Subject: iron/chorea/schizophrenia

   
   Eur Neurol 1999;42(3):157-62
   
A case of hereditary ceruloplasmin deficiency with iron deposition in the brain
associated with chorea, dementia, diabetes mellitus and retinal pigmentation:
administration of fresh-frozen human plasma.

    Yonekawa M, Okabe T, Asamoto Y, Ohta M
    
   Department of Neurology, Hiroshima Kosei Hospital, Hiroshima, Japan.
   
   We report a familial case of hereditary ceruloplasmin deficiency (HCD)
   showing an A-G transition in intron 6 of the ceruloplasmin gene.
   Clinical features consisted of chorea, cerebellar ataxia, dementia,
   diabetes mellitus, retinal pigmentation and iron deposition in the
   liver and brain without copper overload in those organs. The patient's
   children and siblings had similar laboratory results, but did not show
   any neurological abnormalities. She was medicated for diabetes
   mellitus at 43 years of age, and neurological signs appeared when she
   was 52 years old. The laboratory findings were anemia, low
   concentrations of iron and copper in serum and of copper in urine.
   Ceruloplasmin was not detected in the serum. The iron and copper
   contents in the liver were 3,580 and 10 microg/g wet tissue,
   respectively. MRI of the brain showed iron deposition in the basal
   ganglia, dentate nucleus and thalamus. This case did not show any
   abnormal increase in copper in the blood and urine following
   CuSO(4)5H(2)O oral overloading test. Following the intravenous
   administration of commercially available fresh-frozen human plasma
   (FFP) containing ceruloplasmin, the serum iron content increased for
   several hours due to ferroxidase activity of ceruloplasmin. In the
   liver, the iron content decreased more with the combined intravenous
   administration of FFP and deferoxamine than with FFP administration
   alone. Her neurological symptoms improved following repetitive FFP
   treatment.
   
   Publication Types:
     * Review
     * Review of reported cases
       
   PMID: 10529542, UI: 20002496
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Subject: propofol/trolox/iron/brain

   
   Eur J Pharmacol 2000 Sep 15;404(1-2):21-27
   
Propofol protects cultured brain cells from iron ion-induced death: comparison
with trolox.

    Boland A, Delapierre D, Mossay D, Hans P, Dresse A
    
   Laboratory of Pharmacology, Institute of Pathology B23, University of
   Liege, B-4000, Liege, Belgium
   
   [Record supplied by publisher]
   
   The anesthetic propofol (PPF) has been shown to be an antioxidant in
   acellular experiments. This study was designed to assess the ability
   of PPF to protect primary-cultured brain cells against iron-mediated
   toxicity. A comparison with trolox (TX), a hydrosoluble vitamin E
   analogue, was performed. Rat cortical cells were exposed to 10 muM
   FeSO(4), PPF and/or TX. After a 4-h incubation, PPF and TX improved
   cell survival (lactate dehydrogenase measurements) in a
   concentration-dependent manner. The respective EC(50s) of each
   substance were 4 and 4.6 muM. The maximal effect was obtained at a
   25-muM concentration which is similar to concentrations of PPF used
   clinically. The combination of both drugs at certain concentrations
   showed a complete protection of the cells, a significant decrease in
   intracellular peroxide production (dichloro-fluorescein diacetate
   (DCF-DA) fluorescence, 4-h incubation), in lipoperoxidation
   (thiobarbituric acid reactive substances fluorescence, PPF 6.25 muM+TX
   12.5 muM) and an additive protective effect. This was true after 4-
   and 16-h incubation. These data suggest that PPF is neuroprotective.
   Moreover, the combination with a vitamin E analogue confers long
   duration protection against oxidative stress.
   
   PMID: 10980259
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