I thot that Mn had been ruled out as  being a cause of PD.  or does it
produce effects that mimic PD.???????
Bob A.
----- Original Message -----
From: "Jorge A Romero MD" <[log in to unmask]>
To: <[log in to unmask]>
Sent: Sunday, September 24, 2000 2:35 PM
Subject: Re: PMID: 10864903: Manganese increases L-DOPA auto-oxidation in
rat: implications for PD


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