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(HOME) Subject: myelin/multiple sclerosis/Guillain-Barre Brain Pathol 1999 Jan;9(1):69-92 Demyelination: the role of reactive oxygen and nitrogen species. Smith KJ, Kapoor R, Felts PA Department of Clinical Neurological Sciences, Guy's, King's and St. Thomas' School of Medicine, London. k.smith@umds.ac.uk This review summarises the role that reactive oxygen and nitrogen species play in demyelination, such as that occurring in the inflammatory demyelinating disorders multiple sclerosis and Guillain-Barre syndrome. The concentrations of reactive oxygen and nitrogen species (e.g. superoxide, nitric oxide and peroxynitrite) can increase dramatically under conditions such as inflammation, and this can overwhelm the inherent antioxidant defences within lesions. Such oxidative and/or nitrative stress can damage the lipids, proteins and nucleic acids of cells and mitochondria, potentially causing cell death. Oligodendrocytes are more sensitive to oxidative and nitrative stress in vitro than are astrocytes and microglia, seemingly due to a diminished capacity for antioxidant defence, and the presence of raised risk factors, including a high iron content. Oxidative and nitrative stress might therefore result in vivo in selective oligodendrocyte death, and thereby demyelination. The reactive species may also damage the myelin sheath, promoting its attack by macrophages. Damage can occur directly by lipid peroxidation, and indirectly by the activation of proteases and phospholipase A2. Evidence for the existence of oxidative and nitrative stress within inflammatory demyelinating lesions includes the presence of both lipid and protein peroxides, and nitrotyrosine (a marker for peroxynitrite formation). The neurological deficit resulting from experimental autoimmune demyelinating disease has generally been reduced by trial therapies intended to diminish the concentration of reactive oxygen species. However, therapies aimed at diminishing reactive nitrogen species have had a more variable outcome, sometimes exacerbating disease. Publication Types: * Review * Review, academic PMID: 9989453, UI: 99142559 ___________________________________ (HOME) ______________________________ Subject: multiple sclerosis/iron Neuroreport 2000 Jan 17;11(1):15-21 MRI T2 shortening ('black T2') in multiple sclerosis: frequency, location, and clinical correlation. Bakshi R, Shaikh ZA, Janardhan V Imaging Services-Kaleida Health, State University of New York, Buffalo 14203, USA. [Medline record in process] Abnormal iron deposition occurs in the brains of patients with multiple sclerosis (MS) and may cause MRI T2 shortening ('black T2'; BT2). The frequency, distribution and clinical significance of BT2 in MS is unknown. Analysis of brain MRI scans of 114 MS patients showed BT2 in thalamus (n = 65; 57%), putamen (n = 48; 42%), caudate (n = 27; 24%) and Rolandic cortex (n = 9; 8%). BT2 was significantly related to longer disease duration and advancing neurological disability. Wheelchair-bound patients had worse BT2 in thalamus (p < 0.05), putamen (p < 0.001) and Rolandic cortex (p < 0.05). Patients with secondary progressive disease (n = 34) had worse BT2 in thalamus, putamen and caudate (all p < 0.05) than those with relapsing remitting disease (n = 80). BT2 is proposed as a clinically relevant finding relating to neuronal degeneration in MS. PMID: 10683822, UI: 20147446 _________________________________________________________________ Save the above report in [Macintosh] [Text] format Order documents on this page through Loansome Doc _________________________________________________________________ (HOME) Subject: multiple sclerosis/antioxidants Ukr Biokhim Zh 1999 May-Jun;71(3):112-5 Oxidative stress in patients with multiple sclerosis. Syburra C, Passi S Dermatological Institute, Rome, Italy. thsyburr@studi.unizh.ch [Medline record in process] It is well known that brain and nervous system cells are prone to oxidative damage because of their relatively low content of antioxidants, especially enzymatic ones, and of the high levels of both membrane polyunsaturated fatty acids (PUFA) and iron easily released from injured cells. We have investigated the oxidative stress in the blood (plasma, erytrocytes and lymphocytes) of 28 patients affected with multiple sclerosis (MS) and of 30 healthy age matched controls, by performing a multiparameter analysis of non-enzymatic and enzymatic antioxidants--Vitamin E (Vit. E), ubiquinone (UBI), reduced and oxidized glutathione (GSH, GS-SG), superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT) and fatty acid patterns of phospholipids (PL-FA). PL-FA and Vit. E were assayed by GC-MS; UBI and GSH/GS-SG by HPLC; SOD, GPX and CAT by spectrophotometry. In comparison to controls, patients with MS showed significantly reduced levels of plasma UBI (0.21 +/- 0.10 vs. 0.78 +/- 0.08 mg/ml, p < 0.001), plasma Vit. E (7.4 +/- 2.1 vs. 11.4 +/- 1.8 mg/ml, p < 0.01), lymphocyte UBI (8.1 +/- 4.0 vs. 30.3 +/- 7.2 ng/ml blood, p < 0.001) and erythrocyte GPX (22.6 +/- 5.7 vs. 36.3 +/- 6.4 U/g Hb, p < 0.001). This blood antioxidant deficiency was associated with plasma levels of PL-PUFA--especially C20:3 n-6 and C20:4 n-6--significantly higher than controls. In conclusion, the blood of patients with MS shows the signs of a significant oxidative stress. The possibility of counteracting it by antioxidant administration plus an appropriate diet, might represent a promising way of inhibiting the progression of the disease. Antioxidant supplements should include not only GSH repleting agents, but also Vit. E, ubiquinol, and selenium. PMID: 10609336, UI: 20077336 _________________________________________________________________ Save the above report in [Macintosh] [Text] format Order documents on this page through Loansome Doc _________________________________________________________________ (HOME) Subject: multiple sclerosis/chelator Cell Mol Biol (Noisy-Le-Grand) 2000 Jun;46(4):865-9 A multiple course trial of desferrioxamine in chronic progressive multiple sclerosis. Lynch SG, Fonseca T, Levine SM Department of Neurology, University of Kansas Medical Center, Kansas City 66160, USA. slynch@kumc.edu [Medline record in process] Chronic progressive multiple sclerosis (MS) is a debilitating disease that is often refractory to treatment. We have previously published a pilot study using a single 2-week course of the iron chelating drug, desferrioxamine (DFO), as a candidate drug for treatment of this form of MS. In this study, we gave 9 patients up to 8 courses of this regimen over 2 years. The patients tolerated the medication well. During the study, 1 patient improved, 3 remained stable, and 5 worsened by 0.5 on the Kurtzke expanded disability status scale (EDSS). These results suggest that, while the drug is well tolerated, no effect on disease progression can be identified at this dosage level. A more continuous dosage schedule could be studied as a candidate for treatment in this disease process. PMID: 10875447, UI: 20331702 _________________________________________________________________ _________________________________________________________________ (HOME)