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We should not forget the fact that chronic manganese poisoning is one of the causes of parkinsonism. Indeed, the original work on the efficacy of L-dopa in the treatment of Parkinsonism was done by Dr. George Cotzias, and involved trials of l-dopa in manganese miners in Chile. Jorge Romero, MD ----- Original Message ----- From: "janet paterson" <[log in to unmask]> To: <[log in to unmask]> Sent: Sunday, September 24, 2000 10:54 AM Subject: PMID: 10864903: Manganese increases L-DOPA auto-oxidation in rat: implications for PD > Manganese increases L-DOPA auto-oxidation in the striatum of the freely > moving rat: > potential implications to L-DOPA long-term therapy of Parkinson's disease. > > We have previously shown that manganese enhances L-dihydroxyphenylanine > (L-DOPA) toxicity to PC12 cells in vitro. > > The supposed mechanism of manganese enhancing effect [an increase in L-DOPA > and dopamine (DA) auto-oxidation] was studied using microdialysis in the > striatum of freely moving rats. > > Systemic L-DOPA [25 mg kg(-1) intraperitoneally (i.p.) twice in a 12 h > interval] significantly increased baseline dialysate concentrations of > L-DOPA, dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and > uric acid, compared to controls. > > Conversely, DA and ascorbic acid concentrations were significantly > decreased. A L-DOPA oxidation product, presumptively identified as L-DOPA > semiquinone, was detected in the dialysate. > > The L-DOPA semiquinone was detected also following intrastriatal infusion > of L-DOPA. > > In rats given L-DOPA i.p. , intrastriatal infusion of N-acetylcysteine > (NAC) significantly increased DA and L-DOPA dialysate concentrations and > lowered those of L-DOPA semiquinone; in addition, NAC decreased DOPAC+HVA > and uric acid dialysate concentrations. > > In rats given L-DOPA either systemically or intrastriatally, intrastriatal > infusion of manganese decreased L-DOPA dialysate concentrations and greatly > increased those of L-DOPA semiquinone. > > These changes were inhibited by NAC infusion. > > These findings demonstrate that auto-oxidation of exogenous L-DOPA occurs > in vivo in the rat striatum. > > The consequent reactive oxygen species generation may account for the > decrease in dialysate DA and ascorbic acid concentrations and increase in > enzymatic oxidation of xanthine and DA. > > L-DOPA auto-oxidation is inhibited by NAC and enhanced by manganese. > > These results may be of relevance to the L-DOPA long-term therapy of > Parkinson's disease. > > > Br J Pharmacol 2000 Jun;130(4):937-45 > Serra PA, Esposito G, Enrico P, Mura MA, Migheli R, > Delogu MR, Miele M, Desole MS, Grella G, Miele E > Department of Pharmacology, University of Sassari, 07100 Sassari, Italy. > PMID: 10864903, UI: 20325006 > > http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list > _uids=10864903&dopt=Abstract > > > janet paterson > 53 now / 44 dx cd / 43 onset cd / 41 dx pd / 37 onset pd > TEL: 613 256 8340 URL: http://www.geocities.com/janet313/ > EMAIL: [log in to unmask] SMAIL: PO Box 171 Almonte Ontario K0A 1A0 Canada