Parkinson's Disease Tulip


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Old 01-31-2007, 11:43 AM #1
michael7733 michael7733 is offline
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Default Initiation, Potentiation and Facilitation

Have you ever wondered why you seem to have a slightly different "brand" of Parkinson's disease than many of the people on this board or at your local support group? It almost makes you wonder sometimes if you really have Parkinson's diaease or something altogether different. Also there are those nagging symptoms that lie outside the symptoms that define Parkinson's disease, as if Parkinson's isn't bad enough. When first dianosed my neurologist (bless her little pea-pickin' heart) told me that I was lucky that I picked a disease that has little pain associated with it. I agreed, because I had nearly no pain at all. Well, that was then...this is now. Sometimes the pain is down right severe on my individual pain tolerance scale. My pain tolerance scale is something like this: 1) oo, 2)oh, 3)ow, 4)ouch, 5)oo ow, 6)owee, 7)ahhhhh, 8)uhhhhhhh, 9)uhh uhhh uhhhhhhh uhhhhhhhhh O' God, 10) AAAAHHH HHHHHEEEEE EEEEEEEEEEE!!!!!!!!!!!!!!!!!! where 1 is the least and 10 is the most. I can only recall two # 10's in my life thus far and that was when I had kidney stones and when I poured straight vinegar onto a severe concrete burn. The last one caused my ears to ring...oh maybe that was me screaming.

Anyway, enough of my history...let's get to the title of this somewhat lengthy post, "Initiation, Potentiation and Facilitation." That kind of sounds like something I would make up. Hmmm, I guess I did. How does it relate to Parkinson's disease? I hope we find out soon before you stop reading.

Some way, some how and by something an initial insult was made against our body. This was the Initiation Phase. We have seen that this could have been in the form of a virus, bacterial infection, toxic chemical (s), trauma or genetic transfer at birth, any or all of which probably had to be accompanied by some extremely stressful time in our life that might have weakened our immune system and caused a second or third insult called inflammation, which might have caused a breech in the blood brain barrier at just the right point to allow it to gain entrance to the substantia nigra. This was the Potentiation Phase. Upon gaining entrance to the substantia nigra it began it's invasion and subsequent destruction of our dopaminergic neurons. This is the Facilitation Phase during which we developed Parkinson's disease. And now, there IT is, destroying us one cell at a time, or two or three or nth depending on how many IT's there are.

Are you getting the picture? The question is, which IT GOT YOU, AND WHICH ONE GOT ME, AND WHERE WAS THEIR POINT OF ENTRY INTO OUR BRAINS? I think it was somewhere along the vagus nerve, but we will disccuss that further after I stop shaking.

michael b.

Last edited by michael7733; 01-31-2007 at 11:52 AM.
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Old 01-31-2007, 03:40 PM #2
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Good post Michael...........Mine all started with my neck. I went to my GP (primary physician) told him I was feeling all disoriented and weird. I asked him if there was anyway my neck DDD (degenerative disc disease) could be slowing the flow of blood to my brain. He replied saying no, that the brain has no blood in it. He said I probably had the flu. And gave me antibiotic to take for 5 days. I knew that that I didn't have the flu. From that incident, was the beginning of some serious change in me? The neck problem I think was the beginning of my problems and I feel it had something to do with bringing on my PD so fast. My cervical DDD of the neck/head area has been just as much of a problem for me as the shaking of having PD. Maybe this is the breach in the blood brain barrier you mention. Anyway I think you’re on to something.
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Old 01-31-2007, 06:35 PM #3
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Default Now, let's get serious.

Much of this has already been posted elsewhere, but for this to make sense, all of the significant parts should be together. This will not, however concentrate on the role of the Blood-Brain Barrier nor the role of specific agents of inflammation. It will concentrate, however, on the role of the Vagus Nerve and its function as a conduit for the transfer of such substances from their point of insult to the Substantia Nigra. It will also cite the role of the Vagus nerve in presenting other symptoms that are outside of the symptoms that have come to define Parkinson's disease.

The increasing toxicity of our planet should be a much more pressing subject of our concern than it seems to be. This should be the most important health issue before congress, and it should be placed on the very top of the items being considered for funding. Every day, the mountain of compiled information grows. It grows at an alarming rate. So why hasn't the alarm been sounded more loudly? Epidemiologists are beginning to see more and more evidence that indicates that all life on this planet could soon be in danger of extinction if a new course of action is not set and adhered to. We are talking about the possibility of a major catastrophe in the annals of human history. Obviously, it's not going to conclude tomorrow or the next day, but conclude it will if we don't stop polluting our planet.

http://lansbury.bwh.harvard.edu/pd_reviews_2003.htm

Quote:
Braak, H., U. Rub, et al. (2003). "Idiopathic Parkinson's disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen." J Neural Transm 110(5): 517-36.
The progressive, neurodegenerative process underlying idiopathic Parkinson's disease is associated with the formation of proteinaceous inclusion bodies that involve a few susceptible neuronal types of the human nervous system. In the lower brain stem, the process begins in the dorsal motor nucleus of the vagus nerve and advances from there essentially upwards through susceptible regions of the medulla oblongata, pontine tegmentum, midbrain, and basal forebrain until it reaches the cerebral cortex. With time, multiple components of the autonomic, limbic, and motor systems become severely impaired. All of the vulnerable subcortical grays and cortical areas are closely interconnected. Incidental cases of idiopathic Parkinson's disease may show involvement of both the enteric nervous system and the dorsal motor nucleus of the vagus nerve. This observation, combined with the working hypothesis that the stereotypic topographic expansion pattern of the lesions may resemble that of a falling row of dominos, prompts the question whether the disorder might originate outside of the central nervous system, caused by a yet unidentified pathogen that is capable of passing the mucosal barrier of the gastrointestinal tract and, via postganglionic enteric neurons, entering the central nervous system along unmyelinated praeganglionic fibers generated from the visceromotor projection cells of the vagus nerve. By way of retrograde axonal and transneuronal transport, such a causative pathogen could reach selectively vulnerable subcortical nuclei and, unimpeded, gain access to the cerebral cortex. The here hypothesized mechanism offers one possible explanation for the sequential and apparently uninterrupted manner in which vulnerable brain regions, subcortical grays and cortical areas become involved in idiopathic Parkinson's disease.

http://psychiatrictimes.com/p0104vagus.html

Quote:
George et al. cited evidence that VNS prompts changes in norepinephrine and serotonin, the neurotransmitters most closely associated with mood regulation, as well as GABA and glutamate. They noted that VNS can activate the locus ceruleus, the main source of central nervous system norepinephrine-containing neuronal cell bodies, and is associated with increased cerebrospinal fluid levels of 5-hydroxyindoleacetic acid, a serotonin metabolite.

The researchers also observed that there has been a historical association of autonomic nervous system dysfunction mediated by the vagus, including heart rate variability, in patients with depression. They speculated, "If depressed patients have abnormalities in brain regions that control the vagus nerve (top-down regulation), then stimulating the vagus nerve might theoretically engage this dysfunctional circuit (a bottom-up approach
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Old 01-31-2007, 09:04 PM #4
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Default Now we're cooking

I'm glad you found Braak. I had started to talk about him in the bacterial thread before I realized that you had this one going and I apologize for scattering the subject. But Braak is a key component. Here is his latest from last year:

1: Mov Disord. 2006 Dec;21(12):2042-51.

Stanley Fahn Lecture 2005: The staging procedure for the inclusion body
pathology associated with sporadic Parkinson's disease reconsidered.

Braak H, Bohl JR, Muller CM, Rub U, de Vos RA, Del Tredici K.

Institute for Clinical Neuroanatomy, JW Goethe University, Frankfurt/Main,
Germany. braak@em.uni-frankfurt.de

The synucleinopathy known as sporadic Parkinson's disease (PD) is a multisystem
disorder that severely damages predisposed nerve cell types in circumscribed
regions of the human nervous system. A recent staging procedure for the
inclusion body pathology associated with PD proposes that, in the brain, the
pathological process (formation of proteinaceous intraneuronal Lewy bodies and
Lewy neurites) begins at two sites and continues in a topographically
predictable sequence in six stages, during which components of the olfactory,
autonomic, limbic, and somatomotor systems become progressively involved. In
stages 1 to 2, the Lewy body pathology is confined to the medulla
oblongata/pontine tegmentum and anterior olfactory structures. In stages 3 to 4,
the substantia nigra and other nuclei of the basal mid- and forebrain become the
focus of initially subtle and, then, severe changes. During this phase, the
illness probably becomes clinically manifest. In the final stages 5 to 6, the
lesions appear in the neocortex. This cross-sectional study originally was
performed on 168 autopsy cases using material from 69 incidental cases and 41
clinically diagnosed PD patients as well as 58 age- and gender-matched controls.
Here, the staging hypothesis is critically reconsidered and discussed. Copyright
2006 Movement Disorder Society.

PMID: 17078043 [PubMed - in process]
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Born in 1953, 1st symptoms and misdiagnosed as essential tremor in 1992. Dx with PD in 2000.
Currently (2011) taking 200/50 Sinemet CR 8 times a day + 10/100 Sinemet 3 times a day. Functional 90% of waking day but fragile. Failure at exercise but still trying. Constantly experimenting. Beta blocker and ACE inhibitor at present. Currently (01/2013) taking ldopa/carbadopa 200/50 CR six times a day + 10/100 form 3 times daily. Functional 90% of day. Update 04/2013: L/C 200/50 8x; Beta Blocker; ACE Inhib; Ginger; Turmeric; Creatine; Magnesium; Potassium. Doing well.
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Old 01-31-2007, 09:55 PM #5
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Default Genetic causes must be a part of the mix

Do not overlook genetics as being a risk factor. My sister and I both have young onset Parkinson's disease which has different symptoms than idiopathic parkinson's disease. My sister will not get a Parkin gene test. I have had the test.

Genes are made up of exxons which, when triggered by other neurons and proteins, produce proteins. If triggered too much it will create more protein than needed, if not triggered enough, then lack of protein produced will affect the job of the protein that is supposed to be produced. I am missing 2 exxons. This makes my brain overproduce synuclein protein strands because whatever exxon 3 and 5 produce is missing. The protein strands attach themselves to the walls of the delivery system of dopamine to the nerves that control movement. Eventually the delivery system becomes so clogged with these protein strands that the dopamine produced by the neurons in the substantia niagra end up basically committing suicide.

The result is not the traditional tremors, although they are a part of my symptoms. The worst of my symptoms is ridgidity, and slowness of movement as well as gait disturbances. Study is being attempted to discover what exxons produce what products. Once this is understood, then serious work can begin to replace whatever isn't there too stop my brain from over producing the protein strands.

There may be a bacterium, virus, or environmental toxin that destroys the same product missing in my brain. Or it could be a completely different exxon in the Parkin gene that has been destroyed in other idiopathic parkinsonian brains. Whichever exxon is missing or overproducing would cause slightly different variations on patients symptoms. This could explain why no one Parkinson's disease patient is exactly like another. Genetic research is in its infancy. Right now the government has formed a genome project and is making the rules on how research is to be conducted. Private companies have already discovered and copyrighted gene lines which could cause several different types of neurological disease disorders. No research can be done on these disorders without paying for the rights to the holder of the copyrighted DNA strand.

DO NOT GIVE AWAY YOUR RIGHT TO KNOW YOUR DNA INFORMATION TO ANY RESEARCH PROGRAMS WHICH MAKE YOU SIGN A DOCUMENT PROMISING NOT TO EXPECT TO KNOW THE RESULTS OF THE DNA TESTING. THERE IS NO REASON YOU SHOULD NOT KNOW YOUR DNA. WHICHEVER RESEARCH COMPANY OR AGENCY IS COLLECTING OUR PERSONAL INFORMATION AND REORGANIZING THE INFORMATION INTO USABLE FREE INFORMATION FOR CREATION OF PRODUCTS THAT COULD HELP YOU. IF YOU DON'T KNOW WHAT YOUR MUTATION IS, YOU WILL NOT BE ABLE TO CHOOSE THE RESEARCH PRODUCTS WHICH HAVE THE BEST CHANCE TO HELP YOU. BE AN AWARE CONSUMER.

Knowing your personal information does not hurt the research being done in any way. The information stays the same if you know or don't know.

My two cents for what its worth.

Vicky
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Old 02-27-2007, 02:22 PM #6
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Default Let's put it all together now.

So...what causes Parkinson's disease, and can it be cured? I am glad you asked. Since most of the technical explanation has already been stated above, I will attempt to keep the rest brief and simple. What follows will be my OPINION based on what I have read and what I have observed.

Parkinson's disease, in a majority of cases, begins outside the body and in our soils and waterways which have been both polluted with environmental toxins and stripped of vital nutrients. This is the same soil that is used to grow produce for our consumption. Much of what we consume is deficient in what humans need to sustain health. Then, in order to keep it from going bad on the shelf, we irradiate it to destroy certain enzymes that would cause it to oxidize and spoil.

Without intact enzymes, our digestive system is no longer able to process the 'food' we eat. It begins to spoil inside of us and causes inflammation and leakage from the gut to the vagus nerve which serves as a conduit through the Blood Brain Barrier and then on to the various areas in the brain that are in close proximity to the vagus. How these substances affect the brain is determined by their mode of action. Some of them might be Oxidative Phosphorylation inhibitors. Some might interfere with the proton pumps or the electron transport system, or the voltage gated ion pumps, etc. Any or all of these are capable, eventually, of interferring with the production of ATP as it relates to carbohydrates and oxygen and hydrogen. Inevitably, the mitochondria will become useless without ATP, the cell will cease to function, and it will lie dormant or die, no longer producing dipamine or anything else for that matter.

In the meantime, continuing on along the vagus nerve, these same toxins begin to affect the afferent and efferent nerve responses in the limbs and other extremities. Movement becomes impaired and impoverished. We have full blown Parkinson's disease.

michael b.
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Old 02-27-2007, 02:40 PM #7
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Default Is there a cure?

I believe that for most of us there IS a cure that already exists. It could be as simple as keeping our pH levels in the normal range for an extended length of time, so that the body has a chance to heal itself. Mitochondria need both negatively charged Hydrogen and well as positive charged Hydrogen in order to carry out all of the manufacturing and dispersal processes of vital substances the assist our body in running smoothly. I do believe that Hydrogen will be a key element in the cure when it is found.

michael b.
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Old 03-01-2007, 01:31 PM #8
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Default So, what does all that mean?

Well, it actually means that we need to rethink the entire Parkinson's model...well, not in its entirety. The way we have been looking at Parkinson's disease has caused us to look toward the brain as the point where the cure has to take place. Let's take another look and focus on another area .

Instead of looking at the brain first, let's look at the stomach. Most of us are familiar with that old saying, "The way to a man's heart is through his stomach." Well, I am sure it wasn't meant like I am going to use it, but here goes. In actuality, there IS a connection between the stomach and the heart. Yes, it is the Vagus Nerve. The vagus nerve receives information from the Enteric Nervous System. Inflammation, due to infection (viral, bacterial or from dehydration) and stress occur due to the presence oftoxins. Inflammation causes an over production of acetylcholine and cytokines. An imbalance between acetylcholine and dopamine occurs as well as a powerful immune response. The afferent and efferent nerves of the muscle tissue ensues, causing tremor and motility problems. And it goes on from there..........

What we need to be addressing is our diet, our lifestyles and the inflammation. The rest should take care of itself in time. Can it possibly be that easy?

What is your opinion on this?

michael b.
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Old 03-01-2007, 03:09 PM #9
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Default Hi Mike

I believe your thesis is right on. Those who have it at a much younger age, though must be prooven to:

1. Have an unusual amount of inflamation from likely exposure to toxin(s), or,
2. Have an unusual of stress in their lives, or,
3. One of the above plus genetic mutations.

I was exposed to tremendous stress due to child abuse, exposed to nitric oxide on a regular basis by being forced to inhale it via a plastic bag held over my neck. Plus 2 genetic mutations in the Parkin gene.

Just finished my second snow shoveling of the day. Am in the middle of a blizzard in Minnesota. Am worried about my husband making the 30 mile drive home from the school he teaches at in St. Paul. His dad lives in St. Paul. Think I will call Dave and suggest he stay with his dad tonite.

Love,
Vicky
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