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Metal chelation / tuberculosis / Parkinsons' cure ?
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PostPosted: Tue Jun 06, 2006 9:34 pm    Post subject: Metal chelation / tuberculosis / Parkinsons' cure ? Reply with quote

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Source: Purdue University Released: Tue 06-Jun-2006, 17:00 ET

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Tuberculosis Drug May Cure Parkinson's-like Illness
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Medical News Keywords
PARKINSON'S-DISEASE OCCUPATIONAL-MANGANESE-PARKINSONISM
SODIUM-PARA-AMINOSALICYLIC-ACID MANGANESE-INTOXICATION
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Description

Researchers have discovered that a drug used to treat tuberculosis
apparently cures patients of a Parkinson's-like illness suffered by
thousands of mineworkers, welders and others exposed to high levels of
the metal manganese.



Newswise - Researchers have discovered that a drug used to treat
tuberculosis apparently cures patients of a Parkinson's-like illness
suffered by thousands of mineworkers, welders and others exposed to
high levels of the metal manganese.

Manganese is used to produce steel alloys and as a coating on welding
rods, among other industrial applications. It replaced lead decades ago
as a component in unleaded gasoline, increasing the risks of manganese
intoxication for the general public, said one of the researchers, Wei
Zheng, a professor and University Faculty Scholar in Purdue's School of
Health Sciences.

When manganese builds up in toxic levels in the body, people suffer
from "occupational manganese parkinsonism," which causes symptoms
similar to Parkinson's disease. Victims experience hand tremors, poor
coordination, unsteady gait and a masklike inability to show facial
expressions, Zheng said.

Manganese contained in the coating of welding rods is released in
fumes. Welders involved in manufacturing vehicles, tanks and ships are
especially prone to manganese intoxication because they work in close
quarters, increasing their exposure to the metal, Zheng said.

"There are about 430,000 welders in the United States alone, and even
more in China, so manganese intoxication likely affects many people,
including workers involved in manganese mining and steel production,"
he said. "In Beijing, we found a high percentage of welders have these
symptoms."

While the condition's symptoms are similar to those of Parkinson's
disease, the standard treatments for Parkinson's disease, including the
drug levodopa, are not effective for manganese intoxication. A chemical
compound called EDTA has been used to help patients eliminate manganese
in the urine. The drug's effectiveness, however, is limited because it
is water-soluble, preventing it from readily passing through membranes
in the "blood-brain barrier," layers of cells surrounding blood vessels
that block substances from traveling from the blood into brain tissue.

Ten researchers from institutions around the world - including Purdue -
conducted a 17-year medical follow-up study on a manganese-poisoned
worker and about 80 other patients. The researchers learned that an
aspirinlike drug called sodium para-aminosalicylic acid, or PAS,
dramatically reduces symptoms on a long-term basis.

"The amazing thing is that this drug reverses Parkinson-type symptoms
of manganese intoxication," Zheng said. "We see remarkable improvement
after treatment with this drug even 17 years later."

PAS has been used for decades to treat tuberculosis and apparently can
cross the blood-brain barrier because it is fat-soluble, or lipophilic.
That's because the drug contains a structure known as a benzene ring,
which enables it to penetrate the membranes.

Findings will appear in the June issue of the Journal of Occupational
Environmental Medicine. The paper was written by Yue-Ming Jiang, Xue-An
Mo, Feng-Qi Du, Xue Fu and Xia-Yan Zhu, from Guangxi Medical University
in China; Hong-Yu Gao and Feng-Ling Liao, from Wuzhou Center for
Disease Prevention and Control in China; Jin-Lan Xie from the Wuzhou
Worker's Hospital in China; Enrico Pira from the University of Turin in
Italy; and Zheng.

The research has focused on China because that country is a major
manganese ore producer and provides one-third of the world's supply of
steel alloys.

The paper includes data from research involving a female Chinese
mineworker who suffered debilitating symptoms, including lack of
coordination, trouble walking and writing, and a masklike appearance
caused by tense facial muscles. The woman's symptoms nearly disappeared
after treatment with PAS in 1987, and she remained free of symptoms
when re-examined during a follow-up study in 2004.

The researchers suggest several possible mechanisms that enable the
drug to reverse symptoms of the illness. One is that the drug may
contain "chelating arms" that grab manganese.

"However, we are not just looking at this drug as a chelating compound,
but also as an anti-inflammatory, like aspirin," Zheng said.
"Historically, we have believed that neurodegeneration is permanent and
cannot be reversed, but PAS appears to shed light on a reversal
mechanism.

"It may possibly repair neurons. If this is true, this would be a major
finding, but further research will be needed to study this possibility.
We think the bigger picture is that the drug might also be used as a
treatment for Parkinson's disease, but much more work is needed to
confirm this theory."

Zheng's research has been funded by the National Institute of
Environmental Health Sciences, the U.S. Department of Defense and the
Purdue Research Foundation.

Related Web site:

Wei Zheng: http://people.healthsciences.purdue.edu/~wzheng/

Abstract on the research in this release is available at:
http://news.uns.purdue.edu/UNS/html3month/2006/060606.Zheng.manganese.html



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2006 Newswise. All Rights Reserved.
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