Rick,
The paper is interesting, but I can't connect it with the concept of the BBB widening as we age or through chemical insult, causing leakage out of dopamine and leakage in of carbidopa and toxins, which are normally kept out.
Every time I see something that improves PD, I do a search to see if I can find a reference showing it reduces BBB permeability. However, this week, I did searches on NSAIDS and also osteopontin, but could not find anything.
Ron

how about iv glutathione? there is evidennce that it improves symptoms and is neuroprotective. not being patentable, iv glutathione hasn't generated much n the way of research money.

Oyster,
To see how glutathione fits in with the concept that anything that reduces BBB dysfunction is good news for PD symptoms, you need to do a search to find what effect glutathione has on BBB permeability. Glutathione is well known for its positive effect in improving symptoms, so we would expect it reduces permeability.
I did a quick search and sure enough, found that it does reduce dysfunction of the BBB.

http://www.springerlink.com/content/n6166473240wr556/

"It was also shown that observed BBB permeability dysfunction was associated with brain GSH depletion."

Also see

http://www.meao-cfs.on.ca/about_me/res_bloodbrain.shtml
"Certain deficiencies such as glutathione and essential fatty acids can lead to the barrier becoming more permeable, as can acute and chronic stress."
meaning as your level of glutathione drops, the BBB becomes more permeable.

Ron

A paper proposing permeability of the BBB is the cause of many CNS disorders. Why are these papers ignored by big pharma.?
A. Because they have 5 million captive customers for life, that they don't want cured.
Ron

Med Hypotheses. 2001 Aug;57(2):231-7.

Chronic fatigue syndrome: neurological findings may be related to blood--brain
barrier permeability.

Bested AC, Saunders PR, Logan AC.

Environmental Health Clinic, Sunnybrook and Women's College, Health Sciences
Centre, Toronto, Canada.

Despite volumes of international research, the etiology of chronic fatigue
syndrome (CFS) remains elusive. There is, however, considerable evidence that CFS
is a disorder involving the central nervous system (CNS). It is our hypothesis
that altered permeability of the blood-brain barrier (BBB) may contribute to
ongoing signs and symptoms found in CFS. To support this hypothesis we have
examined agents that can increase the blood-brain barrier permeability (BBBP) and
those that may be involved in CFS. The factors which can compromise the normal
BBBP in CFS include viruses, cytokines, 5-hydroxytryptamine, peroxynitrite,
nitric oxide, stress, glutathione depletion, essential fatty acid deficiency, and
N-methyl-D-aspartate overactivity. It is possible that breakdown of normal BBBP
leads to CNS cellular dysfunction and disruptions of neuronal transmission in
CFS. Abnormal changes in BBBP have been linked to a number of disorders involving
the CNS; based on review of the literature we conclude that the BBB integrity in
CFS warrants investigation.

PMID: 11461179

------------------------------------------------------------------------

study published in Brain Research shows that rats drinking only 1 part per million fluoride (NaF) in water had histologic lesions in their brain similar to Alzheimer's disease and dementia. In addition, evidence was seen pointing to possible damage to the blood brain barrier from extended fluoride exposure. This study was the third in a series of papers published by Varner et al. Brain Research Vol. 784 No. 12 p 284-298 (1998). Results of this recent study and other studies showing significant dangers from low-level fluoride exposure were presented at a recent scientific symposium.

In the paper above on "chronic fatigue syndrome," you can substitute PD for CFS totally, and you get exactly what I have been proposing for PD. Fatigue is commonly associated with PD, does this mean that we all have CFS as well as PD???
However, this set me thinking (again)!
No-one would listen to BArry Marshall's assertions on helicobacter pilori and ulcers, so he infected himself with HP, got ulcers then erradicated the HP with antibiotics. Then they listened and gave him the Nobel prize!!
So what if we find a volunteer, give him some of the substances in the CSF reference above that damages the BBB, and show that he gets PD!!!
Then all we have to do to cure him, is find out how to repair his BBB such that the permeability is back to that of a healthy person. Easy Eh....
Ron

Chronic fatigue may be a gluten related immune disorder in the narcolepsy spectrum. I believe fibromyalgia is related too, an inordinate amount of people with narcolepsy have fibro. I believe they probably incur more peripheral lewy bodies thus the muscle fatigue/pain vs sleep or motor symptoms. I wrote to the leading Lewy body researcher in the UK asking her to consider looking for LB in fibro patients.

Nonetheless, I'm still with you on the leaky membrane Ron!

I got my parents to donate some money, I'm going to the conference tomorrow armed with enough for 20 blood tests. Wish me luck in finding a researcher willing to do a preliminary study... H.

Ron and others,

I’ve been puzzled for a while by the correlation between Parkinson’s disease, low levels of B12 vitamin and high levels of Homocysteine.

There is for example a clinical trial going on by the American institute of health to investigate the effect of b12 supplementation in PD on homocysteine levels.

Levodopa is metabolized by COMT to 3-O-methyldopa. This conversion requires the methyl-donor S-adenosylmethionine. After S-adenosylmethionine donates its methyl- group, it is converted to S-adenosylhomocysteine and then to homocysteine.

There is research going on at the American Society of Hematology about elevated levels of homocysteine being responsible for damage to the blood-brain barrier integrity in mice

Elevated levels of plasma homocysteine are known to correlate with increased risk of cardiovascular and Alzheimer diseases.

On a hyperhomocysteinemic diet, cystathionine beta-synthase (Cbs)–heterozygous mice develop hyperhomocysteinemia. BBB permeability was measured and was found to be 25% greater.

Joop Oele (Netherlands)

Hi Joopoele,
Hoe gaat U?
"Homocysteine increases the BBB permeability", see
http://bloodjournal.hematologylibrar.../107/2/591.pdf
and "Elevated levels of homocysteine have been observed in Parkinson's disease (PD) patients treated with levodopa." see

http://www.sciencedirect.com/science...eca28b1d018ad2

Isn't this what we would expect, accoding to the theory. It is yet another example of substances that increase the BBB permeability, are associted with PD.
"Vitamin B12-B6-folate. treatment improves blood-brain barrier function"
so low levels would be expected to worsen PD symptoms.
You can only do a literature search and you will find ever more examples of the 2 classes of substance, those that widen the pores of the BBB cause worsening of symptoms. whilst those that reduce the porosity
improve symptoms.
Ron

Dank je Ron, het gaat best lekker. Ik wist niet dat je zo goed nederlands sprak, maar als ik er niet meer uit kom in het engels is het goed dat te weten.

But you really have an interesting theory Ron. I wish there was something to put this theory to a test. This may all well be true, but still there are so many things I cannot explain. For example homocysteine, which is supposed to injure the BBB is associated with Parkinson’s disease, Alzheimer, Addison Biermer, restless legs and many other brain disorders, so far so good, but also with heart disease and other cardiovascular conditions. Further heavy metals are known to interfere with the BBB. They are also associated with lots of neurological disorders. There are theories that methylisation has something to do with that. Methyl groups seem to play a crucial role.

What do you think the mechanism is that widens the BBB? Do you have a theory why some people have a damaged BBB and others do not. Why is it that b12 shortage causes homocysteine levels to raise which in turn damages the BBB. How is this damage done. Does the damage consist of one big opening or many smaller holes. Do you have a picture of the size of the molecules that once couldn’t pass, and now can. For example levodopa can pass any BBB but carbidopa normally cannot.

Carbidopa, has a molecular weight of 244.3. It is designated chemically as (---)-L-a-hydrazino-a-methyl-ß-(3,4-dihydroxybenzene) propanoic acid monohydrate. Its empirical formula is C10H14N2O4•H2O,
Levodopa, has a molecular weight of 197.2. It is designated chemically as (---)-L-a-amino-ß-(3,4-dihydroxybenzene) propanoic acid. Its empirical formula is C9H11NO4.

The difference doesn’t seem too big to me.

Joop