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08-27-2006, 12:39 AM | #1 | |||
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In Remembrance
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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 |
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