In the International Herald Tribune of Feb. 12, 2004 there is a news
story titled "Gene's Toxins and Parkinsons".  In this story is the
implication that toxins, like rotenone, are linked to mutations in two
genes that influence how the body handes proteins.  In effect, toxins
appear to be the root cauise of PD or so I deduce.  I am 81 years old
, in excellent health, and with a recent diagnosis of PD.  To the best
of my knowledge there has never been any PD in any family member.  We
Norwegians are a healthy group of people.  My queston goes like this: 
In 1951 I worked in a Laboratoy and for a while used pyridine (C5H5N)
in certain experiments we were doing.  We were not too careful about
using it and I would after a while get stomach aches which went away
when we stopped using it.  Is there a link between my activity then
and my recent diagnosis of PD?  I would also like some references to
papers cited so I can go to the original source myself.  Also, as a
group, is there much incidence of PD in people of Norwegian descent?

---

Request for Question Clarification by pafalafa-ga on 10 Feb 2005 20:04 PST

Hello hank22-ga,

I am looking into your question, and hope to be able to provide an
answer that will clarify the relation between PD and exposures to
pyridine and associated chemicals.

In brief, pyridine itself has not be linked to PD, as far as I know,
although the simple fact is that there is very little toxicological
information on pyridine.

However, some pyridine compounds are very strongly linked to PD, and
in fact, are known to unambigously cause PD-like symptoms and damage.

The most well-documented such chemical is MPTP
(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine).  I haven't seen
anything, though, that suggests exposures can lead to long-delayed
onset of PD...ordinarily the health effects manifest fairly soon after
exposure.


My question to you is, were you handling pyridine in the lab as a
simple solvent, or were you using it chemically in a fashion that
might have led to the production of pyridine compounds, such as MPTP?

This may be a hard question to shed light on fifty years after the
fact, but if you can provide a bit more detail about the type of work
you were involved with when you were handling pyridine, it might be
relevant to the research I'll be conducting.

Let me know what you can...and best of luck to you.

pafalafa-ga

---

Clarification of Question by hank22-ga on 10 Feb 2005 22:17 PST

Relative to your question, we did not use the pyridine in any chemical
reaction.  We used it only because the index of refraction was such
that it was sufficiently differnt enough from the background index
that we could watch the mixing process of two clear liquids.  So we
started with "pure" pyridine and when we were all finished, the
pyridine did not undergo any chemical change so we ended up with
"pure" pyridine.  Only the final volume changed because we spilled
some on our hands. We were looking for a clear liquid with a certain
index of refraction and pyridine fit the goal--so it was selected for
our use for reasons other than its chemical properties, it was
selected for its non-chemical properties!!

---

Request for Question Clarification by pafalafa-ga on 11 Feb 2005 18:33 PST

Hello again Hank.


Thanks for giving me some of the history of your use of pyridine.

I'm not quite sure how to go ahead with your question.  The bottom
line seems to be that there is no information connecting pyridine
itself to Parkinson's.  On the other hand, there is a definite
connection between pyridine-compounds and PD.

Beyond that, though, it's hard to know how to provide any perspective
on your past experiences, or summarize the current literature beyond
the summaries that are readily available.

For instance, here is a comprehensive overview of the toxicology of
pyridine prepared by the US government:


http://www.atsdr.cdc.gov/tfacts52.html
Toxicological Profile for Pyridine 

(The link above is to a summary profile, and the page contains links
to the full toxicology report, if you are interested in seeing it.)

The bottom line on the tox information is that there is no mention in
the profile of PD, and there is actually very little known about
pyridine toxicology in general:

-----

"How can pyridine affect my health?"
 
"Very little information is available on the health effects of pyridine." 

-----

The full report is basically a litany of statements along the lines
of:  "No studies are available in people or animals on the
carcinogenic effects of pyridine..."

It's worth pointing out that there is certainly nothing to suggest
that exposures from decades past would lead to current symptoms, but
again, so little is known about this chemical that the possibility
can't be discounted either.
 
===========

On the other hand, a pyridine-related chemical known as MPTP is known
to produce PD-like damage:


http://www.mydr.com.au/default.asp?Article=3299

-----
MPTP AND DRUG-INDUCED PARKINSON'S DISEASE

MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)

It has been known for more than 60 years that idiopathic Parkinson's
disease (PD) is characterised pathologically by the death of neurones
in the substantia nigra area of the brain. While this is not the only
feature of the disease, it is the most obvious and this kind of damage
has been shown to be present with all clinical findings seen in the
disease. It is not known why these cells die in PD, or what it is that
causes them to die. An answer may lie in the research being undertaken
with the recently described neurotoxin, MPTP. This compound appears to
be selectively toxic to the cells in the substantia nigra, and is
capable of producing virtually all the signs and symptoms of
idiopathic PD.

MPTP was first tested for its possible therapeutic use in 1947, but
the primates that were given the drug became rigid and unable to move,
eventually dying. The compound was being tested as a possible
anti-parkinsonian agent. After 6 humans were given the drug and
developed PD symptoms and 2 died, the drug was abandoned.

However, after the production of another compound, MPPP (an illicit
narcotic compound), the importance of MPTP to PD was discovered.

The first case of MPTP causing parkinsonism occurred in 1976 when a
young college student who manufactured and abused MPPP made a mistake
in his synthesis and produced MPTP. Within 3 days he was severely
parkinsonian and his family thought he was schizophrenic. Eventually
he was placed on and responded to Sinemet. Two years later he
committed suicide and the autopsy showed cell destruction in the
substantia nigra, and the damage was, in fact, the same as that seen
in PD patients.

In 1982 MPPP was again manufactured and sold in the street as
synthetic heroin. It was not long before contaminated batches
containing MPTP hit the streets, which dealt a devastating blow to the
young users. Hospitals began admitting patients as young as 19 with
severe end stage parkinsonian symptoms. The source was tracked down to
MPTP and its effect was found to be permanent damage to the neurones
of the substantia nigra. This left patients with what was clinically
idiopathic PD.

============================


Given the nature of the above information, is there anything in
particular you would like me to focus on in the way of providing more
detailed information on pyridine and PD.

Any guidance you can offer at this point would be much appreciated, as
I want to provide the best possible answer to meet your needs.


Looking forward to hearing from you,


pafalafa-ga

---

Request for Question Clarification by pafalafa-ga on 16 Feb 2005 19:55 PST

Hello Hank,

Just checking in.  Was the information above any use to you, or is it
too far off the mark.

Let me know if there's anything I can still do for you at this point.

pafalafa-ga

---

Clarification of Question by hank22-ga on 19 Feb 2005 16:12 PST

Hi--I think you answered my basic question about any latent, long term
impact from pyridine.  Thank you--you have eased my mind.  I did have
a secondary question (last sentence in my original paragraph)about
people like myself of norwegian descent relative to how much PD
occurred with us?  Or is this type of info simply not available?  
Hank

Hello Hank,

Thanks for getting back to me with your clarification...I'm glad the
information I provided earlier has helped to ease some concerns you
had.

I've looked into the information that's available on the prevalence of
PD in Norwegians relative to other populations.  In a nutshell, not
very much is known about the distribution of PD in different parts of
the world, or among different groups of people.  PD is a difficult
condition to diagnose, and statistics about it are notriously
unreliable, making any meaningful comparisons quite difficult.

A good overview of what is known about the epidemiology of PD can be found here:


http://www.wpda.org/articles/intro/epidemiology.php
EPIDEMIOLOGY OF PARKINSON'S DESEASE


In particular, one section discusses comparisons among populations,
but makes no reference to differences among industrialized countries:

-----
Does Parkinson's disease occur equally in all races of the world? 

It is clear that PD has a worldwide occurrence. Available data
suggests that the prevalence (frequency) of PD is lower in Orientals
(studies done in Japan and China) and in black Africans (studies done
in Nigeria). There is controversy as to whether PD occurs less
frequently in black Americans since several, but not all studies have
found a low prevalence among them. Studies performed in northern
Europe are simiiar to that in the United States.
-----


That said, there is a bit of research available that suggests the some
cases of PD *may* have a genetic component, and that some people of
Norse descent may have a higher incidence of certain genes related to
PD.  This isn't definitive work, by any means, but it is certainly
suggestive.  The authors of one study hold out the hope that the
understanding of the genetic component may lead to improved treatment
strategies.

I've included some information about this, along with some other
studies about Norwegian populations, or by Norwegian researchers,
along with brief excerpts from the abstracts (I can't reproduce them
in full as they are copyright):


Tidsskr Nor Laegeforen. 2004 Apr 1;124(7):922-4.
The genetics of Parkinson disease
Toft M, Aasly J.
Institutt for nevromedisin, Det medisinske fakultet, Norges
teknisk-naturvitenskapelige universitet.

...A genetic component in Parkinson's disease was long thought to be
unlikely, but recent genetic studies have identified several genes
associated with the disease.

...a locus on chromosome 1 was linked to common late-onset PD in the
Icelandic population. Iceland's population is primarily of Norse
descent. This locus may be of significant importance to Norwegian PD
patients.

...The genes and loci identified have improved our understanding of
the pathogenesis in PD significantly. This knowledge may help to
create new treatment strategies for PD.


=====


Neurology. 2004 Mar 23;62(6):937-42. 
Mortality and Parkinson disease: A community based study.
Herlofson K, Lie SA, Arsland D, Larsen JP.
Departments of Neurology (Drs. Herlofson and Larsen) and Psychiatry (Dr.
Arsland), Central Hospital of Rogaland, Stavanger.

[This study did not compare rates of PD in Norway and elsewhere, but
these researchers are experts in the incidence of PD in Norway...you
may want to contact them]


=====

[This study again makes an association between PD and a gene present
in Norwegian populations]

Neurosci Lett. 2002 Apr 5;322(2):83-6. 
The tau H1 haplotype is associated with Parkinson's disease in the
Norwegian population.
Farrer M, Skipper L, Berg M, Bisceglio G, Hanson M, Hardy J, Adam A, Gwinn-Hardy
K, Aasly J.
Laboratory of Familial Movement Disorders, Mayo Clinic, Jacksonville, FL, USA.

We investigated the association of Parkinson's disease (PD) with tau gene H1
haplotypes in the Norwegian population...Findings provide evidence
that tau participates in the PD pathogenic process and demonstrate the
value of isolated populations in mapping complex traits.


=====

[This study mentions a treatment approach that appeared to slow the
onset of PD in Scandanavian patients]

Eur J Neurol. 1999 Sep;6(5):539-47. 
Does selegiline modify the progression of early Parkinson's disease? Results
from a five-year study. The Norwegian-Danish Study Group.
Larsen JP, Boas J, Erdal JE.
Department of Neurology, Central Hospital of Rogaland, Stavanger, Norway.


The objective of this study was to examine the effect of long-term treatment
with selegiline on the progression of Parkinson's disease (PD)...Results 
indicated that patients treated with the combination of selegiline 
and levodopa developed markedly less severe parkinsonism and required
lower doses of levodopa during the five-year study period than patients treated
with levodopa and placebo....


=====


Lastly, I want to mention the existence of this site, which you are
probably aware of already, but just in case:


http://www.parkinson.no/
Norges Parkinsonforbunds


If you speak/read Norwegian, you may want to check it out.



I trust this answer provides the information you were looking for. 
But before rating the answer, please let me know if there's anything
else that you need.  Just post a Request for Clarification to let me
know how I can assist you further, and I'm at your service.

All the best to you,

pafalafa-ga


search strategy  -- Google searches on:

parkinson's

parkinson's norway

parkinson's epidemiology