Parkinson's Disease Tulip


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Old 06-12-2008, 08:08 AM #1
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Default ?how relaxation decreases inflammation and stress increases it

Nature 405, 458-462 (25 May 2000) | doi:10.1038/35013070


Vagus nerve stimulation attenuates the systemic inflammatory response
to endotoxin


Vertebrates achieve internal homeostasis during infection or injury by
balancing the activities of proinflammatory and anti-inflammatory
pathways. Endotoxin (lipopolysaccharide), produced by all gram-
negative bacteria, activates macrophages to release cytokines that are
potentially lethal1, 2, 3, 4. The central nervous system regulates
systemic inflammatory responses to endotoxin through humoral
mechanisms5, 6, 7, 8. Activation of afferent vagus nerve fibres by
endotoxin or cytokines stimulates hypothalamic–pituitary–adrenal anti-
inflammatory responses9, 10, 11. However, comparatively little is
known about the role of efferent vagus nerve signalling in modulating
inflammation. Here, we describe a previously unrecognized,
parasympathetic anti-inflammatory pathway by which the brain modulates
systemic inflammatory responses to endotoxin. Acetylcholine, the
principle vagal neurotransmitter, significantly attenuated the release
of cytokines (tumour necrosis factor (TNF), interleukin (IL)-1, IL-6
and IL-18), but not the anti-inflammatory cytokine IL-10, in
lipopolysaccharide-stimulated human macrophage cultures. Direct
electrical stimulation of the peripheral vagus nerve in vivo during
lethal endotoxaemia in rats inhibited TNF synthesis in liver,
attenuated peak serum TNF amounts, and prevented the development of
shock.


http://www.nature.com/nature/journal.../405458a0.html
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Old 06-12-2008, 08:09 AM #2
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Default cytolines and sickness

(cound not decide for which topic this was most suited--so I posted the following in 2 posts)
http://psychcentral.com/news/2008/06...sick/2434.html


Why Mental Lethargy When Sick
By: Rick Nauert, Ph.D.
Senior News Editor

Reviewed by: John M. Grohol, Psy.D.
on June 10, 2008

Tuesday, Jun 10 (Psych Central) -- A recent study examines why it is hard to concentrate when you feel sick. This problem very likely reflects the effects of substances that are released by immune cells in the brain.


The research, published in Biological Psychiatry, describes how the immune cells, called inflammatory cytokines, help your body cope with infection.

During an infection, humans typically experience a set of physiological and psychological symptoms, including fever, confusion, decreased motivation, depression and anxiety that are accompanied by a slowing of movements.

These changes, collectively known as “sickness behavior,” are the body’s way of conserving energy during illness so that an effective immune response can be launched. This new study helps researchers further understand how cytokines communicate between the immune system and the brain to promote sickness behavior.

Brydon and colleagues utilized brain imaging to assess the impact of a typhoid vaccine, which prompts a low-grade immune response, on cognitive performance and brain activity in healthy young men. The scientists found that men with larger inflammatory cytokine responses to the vaccine had significantly slower reaction time responses during performance of a cognitive task and perturbed neural activity within a brain region facilitating movement known as the substantia nigra.

The substantia nigra is an important part of the motor system, releasing a chemical called dopamine to other brain regions to facilitate movement and motivate behavior.

The findings of this important study provide a valuable insight into the mechanisms by which infection and inflammation change the way we act and feel, specifically indicating

that chemical messengers released in the blood stream to combat infection can influence motivational centers in the brain leading to ‘psychomotor’ features of sickness.

John H. Krystal, M.D., Editor of Biological Psychiatry and affiliated with both Yale University School of Medicine and the VA Connecticut Healthcare System, comments on the value of this study: “The findings add to our growing knowledge of the intimate involvement of the brain, and by implication our patterns of thought and behavior, in the biology of the body.”

Dr. Lena Brydon, corresponding author on this article, agrees, adding that “understanding the link between the body’s immune defenses and the brain mechanisms responsible for sickness-related behavior may assist the development of novel interventions to control the depressive symptoms that accompany a wide range of inflammatory diseases.”

As the authors note, these mechanistic findings are critical to the development of interventions to control symptoms in inflammatory diseases as varied as obesity and cancer, or even neurodegenerative disorders such as Parkinson’s.

Source: Elsevier
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Old 06-12-2008, 07:27 PM #3
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"Inflammatory" Cytokines: Neuromodulators in Normal Brain?

Short Reviews
Journal of Neurochemistry. 74(2):457, February 2000.
Vitkovic, Ljubisa; Bockaert, Joel *; Jacque, Claude

Abstract:
If cytokines are constitutively expressed by and act on neurons in normal adult brain, then we may have to modify our current view that they are predominantly inflammatory mediators. We critically reviewed the literature to determine whether we could find experimental basis for such a modification. We focused on two "proinflammatory" cytokines, interleukin (IL)-1 and tumor necrosis factor-[alpha] (TNF[alpha]) because they have been most thoroughly investigated in shaping our current thinking. Evidence, although equivocal, indicates that the genes coding for these cytokines and their accessory proteins are expressed by neurons, in addition to glial cells, in normal brain. Their expression is region- and cell type-specific. Furthermore, bioactive cytokines have been extracted from various regions of normal brain. The cytokines' receptors selectively are present on all neural cell types, rendering them responsive to cytokine signaling. Blocking their action modifies multiple neural "housekeeping" functions. For example, blocking IL-1 or TNF[alpha] by several independent means alters regulation of sleep. This indicates that these cytokines likely modulate in the brain behavior of a normal organism. In addition, these cytokines are likely involved in synaptic plasticity, neural transmission, and Ca2+ signaling. Thus, the evidence strongly suggests that these cytokines perform neural functions in normal brain. We therefore propose that they should be thought of as neuromodulators in addition to inflammatory mediators.

http://pt.wkhealth.com/pt/re/jneu/ab...195628!8091!-1



(C) 2000 International Society for Neurochemistry
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Old 06-12-2008, 09:13 PM #4
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Default closer and closer

Yes, indeed, cytokines are neuroactive. So, the immune system affects our brain.

That's half the picture. Hormones are neuroactive, too. So, the endocrine system affects our brain.

But why don't we all have PD?

If, as an embryo, we encounter our mother's cytokines at the right time, then as adults our immune systems react more extremely to less stimulus. More cytokines than the other guy.

If, as an embryo, we encounter our mother's stress hormone's at the right time, then as adults we are hypersensitive to our own hormones and the control systems associated with them get out of whack which leads to a permanent low-level fight or flight state. Chronic stress increases inflammation and leads to more cytokines. It also blocks our innate repair capabilities.

These two blocks are the cornerstone of PD. There are additional factors - none essential but each one contributory. For example, pesticides synergize with the inflammogen/endotoxin LPS to kill neurons. So does mercury.

That's why we lose neurons - a relentless rain of causic hormones and cytokines. That's why a bad infection sets us back - increased cytokines do damage AND disrupt brain function. That's why stress KOs us - hormones acting as neurotransmitters.

That is the gist of what Anne Frobert and I have built up over the last few years. There are a thousand details to be worked out, but that is the heart.

If you want to work on the model, visit
http://www.parkinsonsonline.org/PD_Outline_Index.html
and look around.
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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 06-12-2008, 09:22 PM #5
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Great info. I always thought that. When I am tired I always feel worse.
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Old 06-12-2008, 10:18 PM #6
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Default sharing big

OK this thread is soooo close to home that I am going to share what I am going through right now. I've lived with my daughter and grandson for the last four years and it was time for her to face some of the world's greatness???harsh reality??

So i got in the car and drove to pittsburgh, where i grew up. it took me three days and I didn't even check the air in the tires until i got to PA from FL. Then, of course I thought wow - you actually did that. But of course, the reasons are slowly being revealed, and one of them is that my father, 84, fell and broke his hip since I got here, a few days ago. And i finally had to take care of an infection that i've had in my gums probably for years as i keep losing teeth. This last one was supposed to be pulled with a few others a year ago, but the dental surgeon didn't think so. That tooth has been going bad ever since.

its spring in PA and the first thing i got was a sinus infection. i went to the doctor's when over the counter didn't help and by then also had an abscess on my gums. he gave me antibiotics. THese didn't help the abscess tho. so i went to a dentist and he said - you have to have two teeth pulled today. i had to drive to the dental surgeon close to Pittsburgh with a very sore mouth. First he had to stick needles all around the abscess to numb it. Then he drained it - which can be exceeded in pain level only by childbirth. Then more needles and cutting out the teeth. We finished with stitches.

The right side of my head and face were screaming in pain, and i had to drive home, after a stop at the pharmacy for the pain medication. Entered the house with zero tolerance and wished for death.

They kept saying, there is so much infection. it was massive.

I have been feeling poorly for a very long time and mentioned dentures on this forum a while back. Lately, I have truly felt like i was dying - i had no energy at all. i was taking a sinemet an hour and going nuts.

For the first time, I feel better. I don't know how much I am going to gain back, but i realize now how much trouble my teeth and gums were causing, including pain. I believed I was approaching the end, seriously.

Don't ignore your teeth and gums. i have lost so much weight. So if I hadn't come up here, I wouldn't have gotten the sinus infection, that either started with or led to the abscess, which led to my feeling better and - best of all - i didn't need as much sinemet today.

i'm a happy and sad camper at the same time. extremely stressful with episodes of revelation.

perfect article Olsen....i guess you are part of my journey. My body has been in serious sickness behaviors for quite some time.

Also thankful for Ron's post about his teeth and Rick's about the dangers. Some things happen in mysterious ways.

paula
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Old 06-13-2008, 06:00 AM #7
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Wow, Paula, that IS a lot to go through.The thing that always amazes me about myself - and I have a feeling the same is true for you - is that I can go through so much scary stuff, and somehow eventually I find myself rebounding. Very strange - trying to figure out how to work with that more directly. But it has been giving me a sense of my life force beneath my condition and its various treatments, the stand of personal energy which is authentically mine. Focusing and meditating on this during perods of crisis or panic attacks has been helpful for me to build on.
hope you feel better, soon....
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Old 06-13-2008, 07:18 AM #8
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Default teeth and balance

Two posts for the price of one-

1) Teeth and gums can kill you. A full blown infection such as Ron and Paula experienced dumps a huge toxin load into your system with the results noted. But there are two more sneaky variants as well. An infection can hide at the root of a tooth and if it finds an outlet so that pressure doesn't build up and cause you pain, it can smoulder there for years dumping toxins in the whole time. The other is periodontal disease when a different bacteria colonizes the space around the roots of the teeth and begins to dissolve the bone and tissues around the tooth. This leads to inflammation and bleeding gums and more toxins. It also acts as a reservoir for bacteria that can end up affecting your heart.

2) While all this thought about what leads to PD is important, it is even more so for us to think about what PD is. All living systems survive by maintaining balance. Things swing back and forth but the forces work to bring things back to a center that is appropriate for the environment the creature finds itself in. All to maximize the odds of survival. This happens in the womb when unusual levels of stress hormones arise. The assumption is that the world outside is a dangerous place and that the fetus will have a better chance if its triggers are set such that the child will be more "alert". That translates into a greater stress response in the adult. Anything which disrupts our balanced systems can have major impact, whether an infection or a confrontation with our boss or just hurrying to get to work. In a normal person there is a control system (the HPA axis) that automatically nudges everything back into place but in PWP the controls have lost their calibration.
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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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