Possible cause and treatment for MS discovered

[MSUK]

Researchers have found evidence that an environmental pollutant may play an important role in causing multiple sclerosis and that a hypertension drug might be used to treat the disease.

The toxin acrolein was elevated by about 60 percent in the spinal cord tissues of mice with a disease similar to multiple sclerosis, said Riyi Shi, a medical doctor and a professor of neuroscience and biomedical engineering in Purdue University's Department of Basic Medical Sciences, School of Veterinary Medicine, Center for Paralysis Research and Weldon School of Biomedical Engineering.... Read More - http://www.msrc.co.uk/index.cfm/fuseact ... ageid/1850

[BioDocFL]

The acrolein could be coming from elevated polyamines, and the polyamines are elevated because of over-expression of X-linked polyamine genes, spermine synthase and spermidine/spermine-N1-acetyltransferase, at Xp22.1 when X chromosome inactivation is lost in a few cells. This is what I was talking about 6 years ago. There is also elevated acrolein in Sjogren's syndrome.
I am going to start writing an article on my latest version of the polyamine hypothesis because there is so much to incorporate now and it all fits together. I think I need to quit my day job so I can focus on writing.

A link between polyamines and acrolein has been shown by others:


Biochemical Society Transactions (2003) 31, (371–374) Abstract
Acrolein produced from polyamines as one of the uraemic toxins
K. Sakata, K. Kashiwagi, S. Sharmin, S. Ueda and K. Igarashi1
Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan

--------------------------------------------------------------------------------

It is well known that the addition of spermine or spermidine to culture medium containing ruminant serum inhibits cellular proliferation. This effect is caused by the products of oxidation of polyamines that are generated by serum amine oxidase. Among the products, we found that acrolein is a major toxic compound produced from spermine and spermidine by amine oxidase. We then analysed the level of polyamines (putrescine, spermidine and spermine) and amine oxidase activity in plasma of patients with chronic renal failure. It was found that the levels of putrescine and the amine oxidase activity were increased, whereas spermidine and spermine were decreased in plasma of patients with chronic renal failure. The levels of free and protein-conjugated acrolein were also increased in plasma of patients with chronic renal failure. An increase in putrescine, amine oxidase and acrolein in plasma was observed in all cases such as diabetic nephropathy, chronic glomerulonephritis and nephrosclerosis. These results suggest that acrolein is produced during the early stage of nephritis through kidney damage and also during uraemia through accumulation of polyamines in blood due to the decrease in their excretion into urine.


Wesley

[HarryZ]

Researchers have found evidence that an environmental pollutant may play an important role in causing multiple sclerosis and that a hypertension drug might be used to treat the disease.

Squiffy,

Thanks for that note and I don't want to sound skeptical, but there has never been any decent results for a treatment that came from work on that poor MS mouse. I sure hope this is different but I won't hold my breath

Take care.

Harry

[cheerleader]

acrolein is also found in cigarettes-linked to the progression of MS and a known endothelial disrupter and inflammatory agent. Acrolein would certainly exacerbate venous stenosis

Endothelial dysfunction by proinflammatory stimuli represents an important link between risk factors and the pathologic mechanisms underlying atherosclerosis. Thus, control of the inflammatory status of endothelial cells is crucial to limiting the disease. Tobacco smoking induces inflammatory reactions and promotes atherosclerosis; however, the mechanism that links cigarette smoking to an increased incidence of atherosclerosis is poorly understood. Our study demonstrates that acrolein, a known toxin in tobacco smoke, elevates oxidative stress via inactivation of thioredoxin reductase and stimulates expression of cyclooxygenase-2 through activation of the protein kinase C, p38 mitogen-activated protein kinase, and cAMP response element-binding protein pathway in endothelial cells. Our finding suggests that acrolein may play a role in the progression of atherosclerosis.

http://onlinelibrary.wiley.com/doi/10.1 ... 4/abstract

oh, and I agree with Harry. EAE is never going to solve MS....but it had a good run. And blood pressure medicine isn't going to help many people with MS, either. Neither is studying one isolated compound. Dr. John Cooke's book, The Cardiovascular Cure, is where I learned about endothelial dysfunction, vascular disease and nitric oxide in humans. Highly recommended reading.

cheer

[patientx]

acrolein is also found in cigarettes-linked to the progression of MS and a known endothelial disrupter and inflammatory agent. Acrolein would certainly exacerbate venous stenosis

Endothelial dysfunction by proinflammatory stimuli represents an important link between risk factors and the pathologic mechanisms underlying atherosclerosis. Thus, control of the inflammatory status of endothelial cells is crucial to limiting the disease. Tobacco smoking induces inflammatory reactions and promotes atherosclerosis; however, the mechanism that links cigarette smoking to an increased incidence of atherosclerosis is poorly understood. Our study demonstrates that acrolein, a known toxin in tobacco smoke, elevates oxidative stress via inactivation of thioredoxin reductase and stimulates expression of cyclooxygenase-2 through activation of the protein kinase C, p38 mitogen-activated protein kinase, and cAMP response element-binding protein pathway in endothelial cells. Our finding suggests that acrolein may play a role in the progression of atherosclerosis.

http://onlinelibrary.wiley.com/doi/10.1 ... 4/abstract

oh, and I agree with Harry. EAE is never going to solve MS....but it had a good run. And blood pressure medicine isn't going to help many people with MS, either. Neither is studying one isolated compound. Dr. John Cooke's book, The Cardiovascular Cure, is where I learned about endothelial dysfunction, vascular disease and nitric oxide in humans. Highly recommended reading.

cheer

The study you linked was about acrolein possibly worsening atherosclerosis, a disease of the arteries. It doesn't mention venous disease, and certainly doesn't support the statement that "acrolein would certainly exacerbate venous stenosis."

[cheerleader]

patient-
the mechanism of endothelial disfunction is the same in all blood vessel walls...arteries or veins. I've discussed this with Dr. Cooke. Most studies are done on arteries, But here's a study which included the saphenous vein and acrolein. Hypercontraction will affect stenosis.

Isolated human CABG blood vessels (internal mammary artery, radial artery, saphenous vein) were used to determine: (1) vessel responses and sensitivity to acrolein, allylamine, and H2O2 exposure (1 μM–1 mM), (2) SSAO dependence of allylamine-induced effects using SSAO inhibitors (semicarbazide, 1 mM; MDL 72274-E, active isomer; MDL 72274-Z, inactive isomer; 100 μM), (3) the vasoactive effects of two other SSAO amine substrates, benzylamine and methylamine, and (4) the contribution of extracellular Ca2+ to hypercontraction. Acrolein or allylamine but not H2O2, benzylamine, or methylamine stimulated spontaneous and pharmacologically intractable hypercontraction in CABG blood vessels that was similar to clinical vasospasm. Allylamine-induced hypercontraction and blood vessel SSAO activity were abolished by pretreatment with semicarbazide or MDL 72274-E but not by MDL 72274-Z. Allylamine-induced hypercontraction also was significantly attenuated in Ca2+-free buffer. In isolated aorta of spontaneously hypertensive rat, allylamine-induced an SSAO-dependent contraction and enhanced norepinephrine sensitivity but not in Sprague–Dawley rat aorta. We conclude that acrolein generation in the blood vessel wall increases human susceptibility to vasospasm, an event that is enhanced in hypertension.

link

Hope this clarifies a bit more....but honestly, Dr. Cooke's book is the place to go. I'm not a doctor...and he explains it better than I ever could.

[elliberato]

ok so now what????? we all start taking antihypertensives and we get are mobility back?

[concerned]

http://www.sourcewatch.org/index.php?ti ... n_P._Cooke

Probably totally irrelevant, but I thought this was sort of interesting.

After publishing a paper on nicotine and angiogenesis (the growth of new blood vessels) in 2001 in Nature Medicine, Cooke applied for and received funding from PMERP.
In May of 2000, a tobacco industry publication, the Tobacco Reporter, ran an article titled "Healing Weed: New research shows that certain tobacco compounds have therapeutic qualities." The article described supposed health benefits derived from tobacco. It cites work done by Cooke at Stanford University on this count and cites him as stating in a media release:

We went into our research suspecting strongly that nicotine might play a negative role, that it would prevent the growth of new blood vessels. In doing our experiments, we were surprised to find that nicotine, which is usually considered harmful, did the opposite... It actually had a potent therapeutic effect on the enhancement and growth of new blood vessels in cases of ischemic (oxygen-starved) vessels. The paradoxical results caused a shift in our thinking. [9]

[ikulo]

Thanks for posting this. I continue to be amazed and surprised how industry money finds its way into every piece of medical research.

Cooke also stated: "All my career, I've been telling people to stop smoking," Cooke said. "But for me, the moral issue is that whatever accelerates our understanding of disease is good. And whatever impedes our ability to do research is bad."

Translation: 'But for me, the moral issue is that my vacation home isn't gonna pay for itself.'

http://www.sourcewatch.org/index.php?ti ... n_P._Cooke

Probably totally irrelevant, but I thought this was sort of interesting.

After publishing a paper on nicotine and angiogenesis (the growth of new blood vessels) in 2001 in Nature Medicine, Cooke applied for and received funding from PMERP.
In May of 2000, a tobacco industry publication, the Tobacco Reporter, ran an article titled "Healing Weed: New research shows that certain tobacco compounds have therapeutic qualities." The article described supposed health benefits derived from tobacco. It cites work done by Cooke at Stanford University on this count and cites him as stating in a media release:

We went into our research suspecting strongly that nicotine might play a negative role, that it would prevent the growth of new blood vessels. In doing our experiments, we were surprised to find that nicotine, which is usually considered harmful, did the opposite... It actually had a potent therapeutic effect on the enhancement and growth of new blood vessels in cases of ischemic (oxygen-starved) vessels. The paradoxical results caused a shift in our thinking. [9]

[patientx]

patient-
the mechanism of endothelial disfunction is the same in all blood vessel walls...arteries or veins.

Veins do not experience atherosclerosis, so in that respect the mechanisms are very different.

I don't see the relevance of this, anyway. The study that Squiffy linked dealt with the effects of acrolein in the nervous system of mice who had been treated to develop EAE. The researchers showed that acrolein was elevated in the EAE mice (but not controls), and they presented evidence that it might be responsible for demyelination seen in the spinal cord. These mice didn't have venous insufficiency, and their veins weren't blocked, so I'm not sure why you are trying to link this to CCSVI.

[cheerleader]

guys...whoa. Angiogenesis is not always a "good" thing. It accelerates cancer. Look it up. Oh, the heck with it. I'll look it up for you....

http://www.cancer.gov/cancertopics/unde ... giogenesis

So, it is a double-edged sword.

But the larger point is that Dr. Cooke was looking at in this tobacco study is different than the studies and book this thread BEGAN WITH. We weren't discussing angiogenesis.

We were talking about acrolein, and I brought up endothelial dysfunction, because that is how I met Dr. Cooke, met Dr. Dake and started the investigation into CCSVI at Stanford. And they continue to study endothelial dysfunction in MS. These doctors are brilliant, and help people everyday. I still do not understand all of the animosity.

The toxin, acrolein, is found in air pollutants like auto exhaust and tobacco smoke. It is also created inside the body when nerve cells are damaged.

patient is right...in the original study cited by Squiffy, acrolein is created in this instance due to nerve degeneration.

Nerve cells are insulated with myelin, and when a person has MS, the myelin is dismantled and the nerve fibers are damaged. Researchers believe acrolein is responsible for the dismantling of the myelin as well as inducing the creation of free radicals, which are compounds that cause further injury to tissues that are already damaged due to trauma or disease.

"Only recently have researchers started to understand the details about what acrolein does to the human body," said Shi. "We are studying its effects on the central nervous system, both in trauma and degenerative diseases such as multiple sclerosis.

link
I tried to bring a tie in to external sources of acrolein as a pollutant and endothelial disrupter. Apologies. I will go back to my corner, heartily chastened
happy thanksgiving, guys!
cheer

[patientx]

...in the original study cited by Squiffy, acrolein is created in this instance due to nerve degeneration.

Actually that's not what the authors of this study are saying. They argue that acrolein damages meylin and possibly leads to axonal degeneration (thanks for the link, but I have a copy of the entire paper). They aren't saying that acrolein is created by by axonal damage.

[cheerleader]

Glad you have the whole paper, patient.
Here's something interesting...the Purdue scientists involved have already been studying acrolein for five years in spinal cord injuries, stroke and other neurodegenertive diseases-that's how they first started. Acrolein doesn't appear to be exclusive to MS in the EAE model.

"When a spinal cord ruptures, not only are the traumatized cells at increased risk of damage from free radicals that oxidize the tissue, but the cells also spill chemicals that actually help the free radicals to launch repeated attacks," said Shi, who is an associate professor of neuroscience and biomedical engineering in Purdue’s School of Veterinary Medicine and Weldon School of Biomedical Engineering. "Our latest research indicates that acrolein may be the primary culprit that enables this vicious cycle. Because acrolein has already been implicated in cancer and neurological diseases, drugs that detoxify it could become important for treating not only spinal cord damage but a host of other conditions as well."

Because a high concentration of acrolein also has been linked to neurodegenerative conditions such as Parkinson’s, Huntington’s and Alzheimer’s diseases – all of which progress slowly and resist treatment – Shi’s team decided to see if the chemical was present in another slow-developing, seemingly untreatable condition: the degeneration of the spinal cord after initial traumatic injury.

When the brain suffers a stroke, for example, it is deprived of oxygen, which is often thought to be the cause of brain damage. But, in fact, you can starve the nervous tissue of oxygen for up to an hour without harm if only you control the acrolein levels," Shi said. "This paper suggests that the body is generally pretty resilient but that acrolein may be something it can’t handle."

link

The level of protein-conjugated acrolein was greatly increased, and levels of spermine and spermidine were decreased at the locus of infarction at 24 hours after the induction of stroke. The size of infarction was significantly decreased by N-acetylcysteine, a scavenger of acrolein. It was also found that the increases in the protein-conjugated acrolein, polyamines, and polyamine oxidases in plasma were observed after the induction of stroke.

link

interesting,
cheer

[Bubba]

WOW...Possibly, I think.... Can ya'll start breaking this down in redneck terms? This sounds interesting, however, I aint edumacted enough for all the technical terms...

[cheerleader]

WOW...Possibly, I think.... Can ya'll start breaking this down in redneck terms? This sounds interesting, however, I aint edumacted enough for all the technical terms...

BUBBA!
How are you doin? Miss you. Not good on the redneck terms, but will try to make it a bit easier to digest....
Basically, scientists found a lot this stuff in spinal fluid pwMS called acrolein. So they make this big announcement and the press says "Acrolein causes MS!" Which isn't really right, but you know how the press is. The body naturally releases acrolein when there is spinal or brain injury, and it's also found in pollution, cigarette smoke, and other toxins. So, it's an external and internal toxin. Bad stuff. It's also found in people with strokes, or Alzheimers or other neurological diseases, and a blood pressure medicine called hydralazine seems to stop acrolein from causing further damage to the brain and spine.
Here's an article that explains it really clearly. The Purdue scientists that discovered this made press releases to all the neurodegenerative foundations....not just MS, since they believe this will help a lot more people than just those with MS.
http://www.canparaplegic.org/en/Researc ... ms/28.html

Honestly...I think it might be better to try and stop the acrolein from releasing in the first place, rather than taking another pill...but that's jut me But if you want to take a cheaper supplement to go after acrolein, it looks like NAC might fit the bill.
Now the guys will pile on and say how wrong I am.
Happy Thanksgiving, Bubba--
cheer