I would like to propose that the cause of an intensification of
symptoms in PD is a leaky or defective Blood Brain Barrier
I believe that we all have toxins circulating in our blood stream.
In a normal person, they circulate harmlessly, since the BBB is
doing its job. In a person with PD, the barrier is defective, and
toxins are allowed to leak into the brain, where they interfere with
the dopamine production and transfer to the receptors.
Indeed,the BBB has been found to be defective in PD
patients. See

2. Blood-brain barrier dysfunction in Parkinson's disease
KL Leenders, R Kortekaas, AL Bartels, J Oostrom, A Willemsen, J Bart
S77, P257

The blood-brain barrier is defective in PD patients, according to
this study. PET imaging of verapamil was used to measure activity of
the P-glycoprotein system, which transports unwanted substances out
of the endothelium back into the blood. Comparing five PD patients
to five controls, the authors found significant differences in the
brain penetration of verapamil (18% higher for PD patients, p=0.02)
only in the midbrain region. All patient values were higher than all
controls. The authors suggest, "A faulty BBB function on the basis
of genetic predisposition might in the course of years allow toxic
compounds—or compounds normally circulating in the blood but not
passing the BBB—to enter the brain in certain regions and damage
vulnerable cells."

Anything that widens the pores of the BBB, causes an
intensification of symptoms. For example stress is known to do
this, and has been shown to widen the pores.See
http://www.sciencenews.org/pages/pdf...4/15024-10.pdf
"After receiving a drug to protect them against chemical weapons,
many Israeli soldiers serving
in the Persian Gulf War suffered adverse side effects from the
inoculation. These reactions
puzzled physicians, who had expected the blood-brain barrier to keep
this drug—like many
other chemicals circulating in the blood—out of the brain.
Now, an Israeli study suggests that stress may have temporarily
opened the blood-brain barrier.
"It was surprising—we saw quite large amounts of brain penetration,"
says Hermona Soreq of
the Hebrew University in Jerusalem, a coauthor of the report in the
December NATURE MEDICINE."

Other processes or compounds that are known to intensify the
symptons of PD, and widen the BBB are:
Nitric oxide is a compound associated with casusing a worsening of
the symptoms.
Nitric oxide is a well known compound causing neuro damage. It is
reported that nitric oxide "promotes BBB dysfunction"
http://64.233.161.104/search?q=cacheXmHa4nUQ-
sJ:http://www.pharm.stonybrook.edu/facu...irka/lab/2006-
parathath_etal.pdf+Blood+brain+barrier+manganese+n itric+oxide&hl=en&g
l=uk&ct=clnk&cd=1

Another known toxin to cause PD, carbon monoxide also opens up the
BBB.
"CONCLUSIONS: Carbon monoxide, involving in the occurrence of
hypotension and the increase of blood-brain barrier permeability,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=PubMed&list_uids=11983134&dopt=Abs tract

Organic phosphates are another chemical in this class
http://www.foresight-preconception.o...oklet_agro.htm
Chronic exposure to OPs has been found to result in a gradual loss
of brain stem cholinergic muscarinic and nicotinic (97-101) and
serotonergic (102,103) receptors, as well as to an increased
permeability of blood-brain barrier (104).
Note that OP's (organic phosphates) are implicated in causing PD.

PD people have been shown to have abnormally high levels of iron in
their blood
In http://www.medicinenet.com/script/ma...ticlekey=62531
where it is shown that if a baby has an underdeveloped BBB, it can
absorb high levels of iron, leading to PD in adulthood. If we have a
leaky BBB since birth, it would account for the high levels of iron

Old age is known to increase chances of getting PD. Our BBB's
gradually lose their effectiveness with older age, explaining the
greater risk to older people.See
http://www.nootropic.com/smartdrugs/index.html

"Loss of permeability of cell membranes with aging is correlated
with dehydration, declining enzyme activity and increasing
lipofuscin accumulation."



Of the compounds known to improve symptons of PD, I have found
without exception that they all decrease the porosity of the BBB.

GDNF

http://www.ihop-net.org/UniPub/iHOP/gs/88604.html

we previously reported that GDNF reduced the endothelial
permeability of the blood-brain barrier (BBB).





Bilberry extract

http://www.lef.org/magazine/mag2000/mar00-cover1a.html

In addition, bilberry extract has been shown to enhance the blood-
brain barrier, which tends to become impaired with aging, showing a
decrease in vascular density, increased permeability and other
abnormalities. The normal functioning of blood-brain barrier is
important not only for keeping out toxins and undesirable compounds,
but also for glucose transport to the brain. Anthocyanins and
related compounds seem able to decrease capillary permeability
(possibly by stabilizing membrane phospholipids). Animal studies
have also shown that if the blood-brain barrier becomes damaged and
too permeable, anthocyanins help restore normal permeability



Curcumin, a favourite supplement with many PD people.

. The yellow ingredient turmeric, found in curry, has been shown to
strengthen the blood-brain barrier to resist attacks"

http://en.wikipedia.org/wiki/Blood-brain_barrier



High blood pressure will weaken the BBB, and it is
associated with a high incidence of PD

Parkinson's in general does not cause highblood pressure, although
many people withParkinson's, particularly if they are elderly,
mayalso have high blood pressure, Parkinson's in general does not
cause highblood pressure, although many people withParkinson's,
particularly if they are elderly, mayalso have high blood pressure,
Parkinson's in general does not cause highblood pressure, although
many people withParkinson's, particularly if they are elderly,
mayalso have high blood pressure, though See
http://64.233.161.104/search?
q=cache:4mku3awcc8gJ:www.parkinsons.org.uk/Shared_ASP_Files/UploadedF
iles/68168C8E-F404-44E9-91B7-
841B814616F1_Lowbloodpressureinformationsheet.pdf+ %
22High+blood+pressure%22+Parkinson%27s&hl=en&gl=uk &ct=clnk&cd=23



Conclusion.

Substances which increase the porosity of the BBB make PD
symtoms worse, whilst those that decrease porosity improve symptons.
Research should investigate the effect on PD sufferers of other
known compounds which decrease the porosity of the BBB



Ron Hutton

Another thing which increases the permeability of the BBB is inflammation. Further, it does the same thing in the intestine.

One of the effects of H pylori is inflammation of and increased permeability of both these membranes. This allows more toxins to leech into the bloodstream and to pass into the brain.

Further, endotoxins from similar bacteria are always in the blood from the steady die off that is normal. Infections, periodontal disease, etc. add to the load.

I think Ron's BBB idea is definitely worth talking through.

Rick

The theory is based on the study concerning "Blood-brain barrier dysfunction". The full original reference is not given above, and appears to be Annals of Neurology [2005] 57 (2) : 176-179 (Kortekaas R, Leenders KL, van Oostrom JC, Vaalburg W, Bart J, Willemsen AT, Hendrikse NH.)

The decrease in blood barrier function is quite small (about 18%), and due to the statistical error allowed for may be less than 10%. This would not explain the as much as 90% reduction in function of the enzymes involved in dopamine biosynthesis that is known to occur in Parkinson's Disease.

The study compares the results of people with Parkinson's Disease against a control group. However, there is no indication in the study that the control group was age controlled. Given that the average age of people with Parkinson's Disease is above average, the study may merely indicate that blood brain barrier function deteriorates with age.

This was subsequently proven in another study that has been published since then : Clinical Pharmacological Therapeutics [2006] 79 (6) : 540-54 (Toornvliet R, van Berckel BN, Luurtsema G, Lubberink M, Geldof AA, Bosch TM, Oerlemans R, Lammertsma AA, Franssen EJ). They used exactly the same methods using verapamil, and demonstrated the age related deterioration in function of the blood brain barrier.

The suggestion that the blood brain barrier function deteriorates with age and thereby increases the likelihood of Parkinson's Disease is inconsistent with the known prevalence of Parkinsons' Disease.

In the following newly published study it was found that virtually none of the people between the ages of 110-119 had Parkinson's Disease : Journal of American Geriatric Society [2006] 54 (8] : 1237-1240 (Schoenhofen EA, Wyszynski DF, Andersen S, Pennington J, Young R, Terry DF, Perls TT.)

At the age of nearly 120, their blood brain barrier function should have greatly deteriorated. and if the theory was correct, thereby make them most prone to Parkinson's Disease, yet in the oldest of people Parkinson's Disease is virtually unknown.

Of the dozen or so toxins that are known to be able to cause Parkinson's Disease, most of them are not commonly encountered. The only exception is carbon monoxide which has never been shown to result in Parkison's Disease unless the carbon monoxide poisoning has resulted in a coma.

The other inconsistency with the theory is that if toxins via reduced blood brain barrier function resulted in Parkinson's Disease, then why doesn't it result in all other potential neurological disorders, because there are dozens of cell types in the nervous system. The dopaminergic neuron is only one of them. Many people with Parkinson's Disease suffer additional problems that could be a result of the dysfunction of certain nerve cell types, such as dementia. However, many people with Parkinson's Disease do not. Thisis obviousy inconsistent with the theory of Parkinson's Disease resulting from a general toxicity that would affect the nervous system generally.

Hi Keith,
Another alias, The Godfather!!
I can't remember the all the aliases you used when you were banned from Braintalk 1. Still, nice to hear from you again.
Best wishes
Ron

http://forums.braintalk2.org/showthr...p?t=165&page=7

Yes, thanks Thelma, I did not realise Keith Bridgeman's pseudo science had done so much damage. His style is unmistakeable, yet he never has the sense to alter it. He spent months trying to convince me we had met, in the hope I would worry when etc., only to admit months later it was a lie.
I get quite a laugh over his musings,
Ron

At least be honest Ron. You wrote a long time ago how you had been winding me up. For a short while (not for months) I returned the favour as a joke.

If my knowledge of biochemistry is inferior to yours, how come you can't rebut any of my criticisms of your theory on this Thread ?

Keith,
I wouldn't spend any time rebutting your "arguments", it was a waste of time in the past. You never took any notice of anything put forward.
I am very busy at the moment, organising fund raising for esential research, while you spend your time being mischievous. You don't even have PD.
I won't reply any further.
Ron

Ron, as you're raising funds for the Parkinson's Disease Society, then you're also raising them for me, because the Parkinson's Disease Society want to support what we are doing. Isn't that ironic. So thank you for your efforts.

You didn't rebut my scientific arguments because you can't. You never could. You put up your theory for scrutiny. It was something I had not previously considered and so it grabbed my interest. My response was entirely scientific and respectful. That is not being mishievous. Would you have preferred that everybody just ignored you - because everybody else but me did just that.

You claim that I never took any notice of what you put forward scientifically in the past. However, I was usually the only person that really did. I took the time to provide relevant scientific evidence. Because a critical evaluation of what you had written did not result in total agreement with your theories is not my fault. Just as now, your theories were contradicted by established scientific fact. You studied chemistry NOT biochemistry. Chemistry does not teach anything at all about human biochemistry. So you are very limited as to the scientific evidence that you could consider. I studied biochemistry NOT chemistry. I've written over twenty volumes on the subject. I spent over three years of my life solely on Parkinson's Disease biochemistry. So I've always had a massive scientific advantage over you. If somebody sees glaring inconsistencies and weaknesses in what you have written do you want them to not mention it ? Is it solely positive feedback that you want ? Do you want to be right, or merely feel that you are right ?

I've heard of people being prejudiced against somebody because they have a medical disorder. That's really disgraceful. But for you to be prejudiced against somebody for NOT having a medical disorder is equally bad. I didn't know that sort of thing went on. If you actually checked what people wrote on BT1's PD Forum you would have known that as many as a third of the people there didn't have Parkinson's Disease. There are over six Billion people guilty of not having Parkinson's Disease. That's a lot of people you're prejudiced against Ron.

....than to step into ancient battles between ageing warriors, but isn't it kind of dumb to waste resources when there is a clock running on us - or at least the ones with PD? And Mr. Bridgeman, as a total stranger, let me suggest that you reinvent yourself once again. You are obviously intelligent and have an excellent command of the language and you really could be a help to your family.

Are you by any chance a science fiction fan? If so, run (do not walk) out and buy Julian May's wonderful cycle that begins with "The Many-Colored Land" set 6,000,000 years ago and running twelve volumes into 3000 AD. You will especially like the character Marc Remillard (aka The Adversary). He IS the persona you seem to project. You'll love it.

But back to business. The BBB is bound to be a factor and, once suggested, an obvious one. It particularly ties in with my own pet theory of endotoxin involvement. Endotoxins (LPS) trigger inflammation which opens the BBB as well as the equivalent at the gut. This allows LPS to enter the brain triggering the activation of the microglia. Thus begins the "slow burn".