[paula_w]

http://tinyurl.com/2lmozt


Blood-brain Barrier Damage Could Affect MS Severity 04/09/07 -- Immunology researchers at the Kimmel Cancer Center at Jefferson studying a multiple sclerosis (MS)-like disease in mice have shown that the amount of ?damage? to the central nervous system?s protective blood-brain barrier ? in essence, opening it ? almost always correlates to the severity of the disease. The findings, reported online in the Proceedings of the National Academy of Sciences, can be used for testing potential MS therapies and for better understanding the role of the blood-brain barrier in disease processes.


Scientists led by D. Craig Hooper, Ph.D., associate professor of cancer biology at Jefferson Medical College of Thomas Jefferson University in Philadelphia, and Hilary Koprowski, M.D., professor of cancer biology at Jefferson Medical College and director of Jefferson?s Center for Neurovirology and the Biotechnology Foundation Laboratories, wanted to find out what factors might affect the onset and severity of EAE (experimental allergic encephalomyelitis), an MS-like autoimmune disease often used as a model. They studied various strains of mice, each lacking some genes associated with inflammation and immunity, and looked at what happened to the blood-brain barrier.
They discovered that the amount of blood-brain barrier damage and subsequent permeability increase correlated to the severity of disease, and surprisingly, in nearly every case, the mouse?s genetic make-up didn?t matter. The mice developed EAE even without supposedly crucial factors in inflammation and autoimmunity ? and disease.
?We?ve now shown in all of these mice missing certain components of the immune system that, as expected, opening the blood-brain barrier and letting cells and factors in from the circulation is critical to the development of disease,? Dr. Hooper says. ?The fact that the extent of the permeability change correlates with the severity of clinical disease signs shows that this is an important element in determining how sick these animals can get.
?This puts an emphasis on the fact that blood brain permeability changes are an important aspect of the development of a CNS inflammatory disease like EAE, an animal model of MS,? he says.
According to Dr. Hooper, previous studies by his group and other researchers have shown that blood-brain barrier permeability is critical in the development of MS. To study this permeability, he and his co-workers looked at a range of mice lacking certain genes for various types of immune system and inflammatory cells such as NF kappaB, TNF-alpha, and interferon alpha, beta and gamma that contribute to disease. The researchers established EAE in each mouse strain and examined what was common to all of the animals when they developed disease.
?What?s astounding is that mice that wouldn?t be expected to develop EAE because they have major defects in their immune system are still able to develop disease,? though at different rates, he notes.
However, mice missing the immune protein TNF-alpha often did not show disease, despite the increase in brain barrier permeability, causing the scientists to speculate about its role in the disease. ?This is the first proof that there are permeability changes in all of these animals and the first hint that permeability doesn?t always equal disease,? he says. Dr. Hooper notes that the work is part of the long-range goal of determining the exact role of blood-brain barrier permeability in disease. ?These results tell us a great deal about the mechanisms that damage the blood-brain barrier,? he says. ?All of these factors that are missing in the mice aren?t essential to opening the blood brain barrier.? Source: Thomas Jefferson University

[lou_lou]

now this one was at Dr. John's reading room?

This is really not the best advise?




what's the dope on smoking - from NOVA

http://www.pbs.org/wgbh/nova/cigarette/nicotine.html














Smoking and Caffeine May Protect Against Parkinson's Disease

In families affected by Parkinson's disease, the people who smoked cigarettes and drank a lot of coffee were less likely to develop the disease, say researchers at Duke University Medical Center.

The findings suggest that both genetic and environmental factors may influence the development of Parkinson's, a progressive neurodegenerative disease marked by trembling of the arms and legs, stiffness and rigidity of the muscles and slowness of movement.

Previous studies have suggested that smokers and coffee drinkers have a lower risk of developing Parkinson's disease. However, this is the first study to look specifically at cigarette smoking and caffeine consumption within families affected by the disease, the researchers said.

Smoking cigarettes and consuming copious amounts of caffeine carry their own risks and should not be taken up in an attempt to avoid developing Parkinson's disease, cautions study investigator Burton L. Scott, M.D., Ph.D., associate professor of medicine.

The findings were published in the April 2007 issue of the journal Archives of Neurology. The research was funded by the National Institute of Neurological Disorders and Stroke.

The researchers studied the associations between smoking, caffeine and Parkinson's disease in 356 Parkinson's disease patients and 317 family members without the disease.

Individuals with Parkinson's disease were half as likely to report ever smoking and a third as likely to report current smoking compared with unaffected relatives, the researchers found.

Individuals with Parkinson's disease were also less likely to drink large amounts of coffee, the researchers found.

The biological mechanisms through which smoking and caffeine might work in individuals at risk of Parkinson's disease are still not clear, said study co-investigator Mark A. Stacy, M.D., associate professor of medicine and director of the Duke Movement Disorders Center.

"Smoking and caffeine may modify underlying genetic susceptibilities that exist in families with Parkinson's disease, but further work is needed to see how this interaction ultimately plays out," Stacy said.

Source: Duke University Medical Center

This news is brought to you by PhysOrg.com

[Ronhutton]

Paula,
Very many thanks for posting this. It confirms that the severity of the disease, be it PD, ALS, AD or MS, follows the level of permeability of the BBB.

Quote:
"They discovered that the amount of blood-brain barrier damage and subsequent permeability increase correlated to the severity of disease, and surprisingly, in nearly every case, the mouse?s genetic make-up didn?t matter."

I had only today started to see if I could add to my summary,
http://neurotalk.psychcentral.com/sh...ad.php?p=77531
but I ran out of time. (Little sleep last night when our neighbour, a lady whose husband had left her, tried to kill herself. My wife, Margaret, went in the ambulance with her, and stayed with her at the hospital until the early hours, so far, she has survived.) I noticed that I had given evidence that the nerve gas Sarin, widens the BBB, but had not shown it's effect on PD.

In
http://www.cnn.com/2003/US/01/17/gulf.war.illness/
it states,
"The Pentagon acknowledges that more than 100,000 troops were exposed to low levels of sarin when the Iraqi chemical depot at Khamisiyah was destroyed shortly after the war."

and

This resulted in Gulf War Syndrome, of Parkinson like symptons,
" "The symptoms that we see are characteristic of well known diseases of the brain, for example in the basal ganglia, Huntington's disease and Parkinson's disease," Haley says.

There are several other cases of Sarin causing PD or PD like symptons. The record is intact, every substance or treatment I have found which is instrumental in widening the porosity, of the BBB, either causes PD or exacerbates the symptons of an existing PD disease. Conversely, everything which closes down the BBB pores, improves the PDer. I have found no exceptions.
Treatments which widen the BBB (cause PD or worsen sypmtons)
Stress
Nitric Oxide
Carbon monoxide
Sarin
Organophosphates, (pesticides)
Old age
Treatments which close down pores, (Reduce symptons)
Curcumin
Alpha LIpoic Acid,
Citicholine (CPD choline)
GNDF
BIlberry extract
Also, Prof Leenders of Holland has shown PDers do indeed have defective BBB's.

I believe there are fast test methods for determining the effect of a substance on the BBB. We need a relatively inexpensive project to measure the reduction in permeability of a series of test materials, and select several which reduce the permeability of a PD BBB to that of a normal person. Then do live testing to see the effect on symptons. How do we interest a research group to do it???
Ron

[reverett123]

Ron-

A couple of things I wonder about-

First, do you suppose that something that affects the BBB has a similar effect upon the barriers around the GI tract? They are both endothelial tissue serving similar functions (actually both are linings of the capillaries I think) and would seem to respond similarly to various substances.

If both linings get leaky at the same time then you have a major problem. The toxins in the bowel wind their way into the brain unimpeded. Add in a slow GI tract such as in PD and it would get toxic real quick.

Second, you mentioned sarin causing neurological problems and that got me to thinking about our old friend H pylori and its toxin LPS. When I inadvertently poisoned myself with a massive kill of H pylori last fall, the effects were very much like a neurotoxin. It was unlike anything I had ever experienced. That makes me wonder if LPS itself is capable of opening the tight junctions at either end - bowel or brain.

Finally, you mentioned a possible test program approach and wondered who might manage it.Tom Isaacs some time ago was telling me of similar dreams. You might discuss it with him.

Sorry to hear of your neighbor.

-Rick

[vlhperry]

Try writing up your findings in the form of a grant research project and send it to the Michael J. Fox Foundation. I believe his foundation would give the idea a fair hearing.

I would encourage you both to try together as both of you have similiar suspicians, and with a great deal of logic to support them.

I was exposed to direct inhalation of nitric oxide as a young teenager and have the gene mutations. I also had ulcers in my early 20's. Perhaps you might also survey persons with a diagnosis of parkinsonism to see if the majority of them have had direct contact with the gases mentioned in your post to support your thesis.

Vicky

[paula_w]

I wonder if a university student studying microbiology or something similar to this stuff would take it on as a thesis? Aren't some of these studies done by lab students or assistants who also need to get published? If we could find someone interested enough in the field to champion it we may have some luck.

Vicky, I wrote to the Fox Foundation and Dr. Todd Sharer did agree that it is an undeveloped area of research and needs more research, along with inflammation. Ron, maybe you should send your entire write up to him again - it can't hurt.

I am sorry to hear about your neighbor too.....hopefully as I write this you are sawing logs as they say over here hope that doesn't mean anything bad on your side of the Atlantic.

There isn't a doubt in my mind that GDNF is a key factor in our welfare. We are reading manuscripts of the book written by Nick Nelsen called 'The Uncured', and will have excerpts on the Pipeline Site hopefully tomorrow. I can't wait for it to be published. And of course there it is on your list, Ron, as one of the good guys.

paula

[Ronhutton]

Rick,
I am sure you are right about the GI tract, the upper intestine also plays a part. Apparently, substances are absorbed very rapidly into the bloodstream from the upper intestine. I don't have much medical knowledge in the area, and will have to do a lot more studying. You could do a search on LPS to find if it has an effect on the BBB.
Paula, Yes, I think this topic would make a marvellous subject for a Ph.D student. There is so much evidence out there to be found, we have only uncovered a small proportion. As a conclusion to the thesis, you could have manipulation techniques of the BBB to remove PD symptoms. When I get time, I want to compare the structural formulae of the "good guys" list and the "bad guys" list, to see if there are any similarities. If there are, then it will help to select the best substance to remove symptons. The paper you posted mentioned encephalomyelitis. People who developed encephalopathy after a 1918 influenza epidemic were later stricken with severe, progressive Parkinson's-like symptoms. See
http://www.ninds.nih.gov/disorders/p...ns_disease.htm
http://www.springerlink.com/content/y2c21r2yx9dnp4ay/
states
"encephalomyelitis of the brain stem and...... breakdown of the blood-brain barrier (BBB) was suggested to be the direct cause ......"

Vicky, It is a good idea to write up the whole story in a clear logical form, with all references documented etc. One problem is I keep finding more evidence and have to rewrite parts again. It is very time consuming. I am not sure whether M.J. Fox is the best group to contact though. They seem to have a preoccupation with curing only the developing world. I wrote to them previously to ask them to support a certain line of research, and they seemed to say they were only supporting projects in developing countries.

Overall, this is a topic where we could all contribute to gather the evidence. I am sure there is a lot more than I have found. It is so time consuming searching and writing it up, and documenting the references. Another problem I find is I get a great lead, only to find you need a subscription to get the article.
Ron

[paula_w]

Ron,

There are some articles that I may be able to get for you from a college librarian who has access. I wouldn't be able to post them, but could email them. There is limited access, but better than average.

paula

[vlhperry]

I am great at research. I can go to the University of Minnesota library and get whatever article you need if they have the journal. You can check online to see if they have the journal, year, no. and pages and send me a list and I would be happy to spend an afternoon or two and look them up, copy them, and snail mail them to you.

Everitt, the same goes for your intestinal tract theory. I would be happy to find articles for you and mail them to you.

I am surprised to hear the the Fox Foundation is interested in funding only underdeveloped country grants. The likelyhood of the cure being found in an economy that is stressed out provideing basic living conditions for its people is slim at best. The United States has been in a slump research wise because of politics. Let's work togeather on this site and contribute what skills each of us has to search for a cure. What a thrill it would be to have the headlines read, "Parkinson patients find the cause of Parkonsionism."
America, what a country!

Vicky

[vlhperry]

Dear Ron,

If the blood brain barrier has been damaged could a sample of spinal fluid show what the foreign matter is that caused the damage?

Vicky

A study which proves your hypothesis:

http://www3.interscience.wiley.com/c...73259/ABSTRACT