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