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I agree regarding ALSUT Carlos...I'm thinking I may need a colonoscopy soon ;)
 
More scientific evidence of why Propofol could be of help to PALS:

Propofol Inhibits Superoxide Production, Elastase Release, and Chemotaxis in Formyl Peptide–Activated Human Neutrophils by Blocking Formyl Peptide Receptor 1

Abstract
Neutrophils play a critical role in acute and chronic inflammatory processes, including myocardial ischemia/reperfusion injury, sepsis, and adult respiratory distress syndrome.
Binding of formyl peptide receptor 1 (FPR1) by N-formyl peptides can activate neutrophils and may represent a new therapeutic target in either sterile or septic inflammation.

Propofol, a widely used i.v. anesthetic, has been shown to modulate immunoinflammatory responses.

However, the mechanism of propofol remains to be established.

In this study, we showed that propofol significantly reduced superoxide generation, elastase release, and chemotaxis in human neutrophils activated by fMLF.

Propofol did not alter superoxide generation or elastase release in a cell-free system.
Neither inhibitors of γ-aminobutyric acid receptors nor an inhibitor of protein kinase A reversed the inhibitory effects of propofol.

In addition, propofol showed less inhibitory effects in non-FPR1–induced cell responses.

The signaling pathways downstream from FPR1, involving calcium, AKT, and ERK1/2, were also competitively inhibited by propofol.

These results show that propofol selectively and competitively inhibits the FPR1-induced human neutrophil activation.

Consistent with the hypothesis, propofol inhibited the binding of N-formyl-Nle-Leu-Phe-Nle-Tyr-Lys-fluorescein, a fluorescent analog of fMLF, to FPR1 in human neutrophils, differentiated THP-1 cells, and FPR1-transfected human embryonic kidney-293 cells.

To our knowledge, our results identify, for the first time, a novel anti-inflammatory mechanism of propofol by competitively blocking FPR1 in human neutrophils.

Considering the importance of N-formyl peptides in inflammatory processes, our data indicate that propofol may have therapeutic potential to attenuate neutrophil-mediated inflammatory diseases by blocking FPR1.

Sorry if some of you couldn't understand this quote. It was taken from a scientific paper.

Regards,


Carlos
 
Yet another scientific paper that suggests that Propofol might be of help to PALS:

See below:


A general anesthetic propofol inhibits aquaporin-4 in the presence of Zn2+

Aquaporin-4 (AQP4), a water channel protein that is predominantly expressed in astrocyte end-feet, plays an important role in the brain edema formation, thereby considered to be a potential therapeutic target.

Using a stopped-flow analysis, we showed that propofol (2,6-diisopropylphenol), a general anesthetic drug, profoundly inhibited the osmotic water permeability of AQP4 proteoliposomes in the presence of Zn2+.

This propofol inhibition was not observed in AQP1, suggesting the specificity for AQP4.

In addition, the inhibitory effects of propofol could be reversed by the removal of Zn2+ ion.

Other lipid membrane fluidizers also similarly inhibited AQP4, suggesting that the modulation of protein-lipid interactions plays an essential role in the propofol-induced inhibition of AQP4.

Accordingly, we used Blue-Native PAGE and showed that the profound inhibition caused by propofol in the presence of Zn2+ is coupled with the reversible clustering of AQP4 tetramers.

Site-directed mutagenesis identified that Cys253, located at the membrane interface connecting to the C-terminal tail, is responsible for Zn2+-mediated propofol inhibition.

Overall, we discovered that propofol specifically and reversibly inhibits AQP4 through the interaction between Zn2+ and Cys253.

These findings provide new insight into the functional regulation of AQP4 and may facilitate the identification of novel AQP4-specific inhibitors.


Carlos
 
Cross-posted from ALS-TDI Forums from the ongoing thread "Propofol" back there:


Cross-posted from the main propofol thread:

Based on the reports from PALS who have tried it, here's what we know so far about propofol's effect on ALS symptoms:

1. It works and the improvements begin to occur within hours after anesthesia.
2. Low doses (less than 200 mg) are not very effective.
3. High doses (800-1200 mg or more) can result in spectacular reversals of symptoms within a day.
4. The degree of improvement is dose-dependent.
5. Improvements can last up to 4 weeks or more.
6. Low doses can eliminate anxiety levels for about 24 hours (1 patient).
7. It seems to be effective against both limb-onset and bulbar ALS.

If you can think of anything else I may have missed, post it here and I'll revise the list.

Louis

PS. If you or your loved ones have ALS, it's time to get off the fence and join this fight.



ALS-Untangled has nearly completed its review of Propofol and should be out in about 1-2 weeks from now.
Let's hope it's not a biased review as some of the ALSU Board of Directors have known ties to big drug companies. Although, I'm not holding my breath. We'll see.


Carlos
 
An UPDATE from Jason (the PALS at ALS-TDI Forums, who very recently underwent a non-ALS related endoscopy and experienced some improvements on his ALS symptoms which apparently are still holding on for him).


jchexpress Posted: Friday, July 05, 2013 5:04:42 PM

Rank: Advanced Member

Groups: Member

Joined: 3/3/2007
Posts: 869
Location: USA


Still have kept all my gains Louis even laying in a hospital bed basically 24/7 (I left you a message in the other thread). As I stated in that one, since Propofol is a short acting drug (noted by ENV), then I would guess "it did some repairs" while in me and those repairs are now lasting for a certain amount of time. That's the only theory I can come up with because the improvements I continue to experience are far from placebo. They're real trust me. I haven't choked on any food or drinks since my procedure vs doing both at every meal. My hand doesn't shake anymore from weakness either. There is no doubt in my mind that Propofol does wonder for ALS (at least mine and I would think most other people too but we need that clinical trial asap to find out).

The best thing PALS can do right now if you are not in too too bad shape
(ie... feeding tube, vent, etc.) is go to a gastroenterologist and complain of either heartburn or say you saw blood in your stool and have pain back there). Those two procedures (endoscopy and colonoscopy) are very safe overall (especially for PALS who aren't yet that advanced). I'm sure even the advanced patients would come out fine too, but obviously it's a bit more risky at that point.

Jason


Let's hope his improvements last long enough to warrant some investigation by ALS Researchers of the potential of this drug to treat PALS in the foreseeable future.


Carlos
 
Another very interesting post by one of the PALS at ALS-TDI Forums who underwent recently a non-ALS related endoscopy and was sedated with Propofol and now, his opinion about the effects of this drug on PALS has changed from skeptic to believer.

See quote below:



Hi Daisy,

Thanks for your concerns. I can only answer one question of yours and that is the one about long term usage of anesthetics. My uncle, who is now 70, had a head on motorcycle accident when he was 23. He has had over 50 surgeries from age 23 to age 70 (all with general anesthesia). He still lives a perfectly normal life without any major medical conditions at age 70. So, I would guess one could throw out the bad long term effect theory real quick with anesthetics if science was based on his account alone (but unfortunately it's not - it would take more patients).

I'm not concerned with the long term effects of Propofol anyway considering the death rate is usually 3-5 years with ALS. I'm concerned about getting a quick trial with HUMANS and not MICE as quick as possible so there can be some immediate well deserved relief for one of the worst diseases of mankind. It happened with AIDS and all the gay activists. AIDS is pretty much a cured disease at the moment.

I don't know why this can't happen for ALS patients.

Propofol is a very safe drug in a controlled environment. I also agree with Louis... one should try to get at least 400mg or more of Propofol to clearly see remarkable benefits if they go in for a procedure.

Guys and gals... I will make the bold prediction based on two personal experiences now with Propofol. It has the potential to SIGNIFICANTLY slow or even halt ALS. This is not BS or small news. It is extremely important that we somehow ensure there is a trial done on HUMANS as soon as possible. I am unsure of how we can make this happen, but it needs to happen if any of you PALS want to see daylight for a awhile. FDA has its Fast Track drug program but I am unaware of what is required to fast track an already existing drug. It would be the absolute fastest way to see if Propofol will work and work fast on a subset of ALS patients. Everything else in the works you should just consider yourself already six feet under simply from the wait and FDA process for new drugs.

It's funny. I have never been a believer in anything in the past (from China stem cell therapies, to lithium to sodium chlorite, etc.) but I had to have a needle lung biopsy and was given 150mg Propofol incidentally without even knowing about the propofol thread and immediately noticed a difference shortly thereafter which lasted about a month. So, I scheduled an endoscopy to see if it was really the Propofol or maybe just a fluke in the disease process. Sure enough, I am now experiencing the same (and even better) benefits than before. So, I undeniably believe that ALS patients can benefit from Propofol. As to how many, that can ONLY be answered by a trial.

Jason



Carlos
 
A petition can be started on Change.org, then people should share the page on FB, with friends and family, post it on the MDA FB page, etc. FB is a remarkable tool for causes. It's shameful how little is being done to fight ALS.
 
I am a molecular biologist diagnosed with ALS. This is a fascinating discussion for me.

I'd like to add my own home-grown therapies: ozone treatments (weekly) and daily liquid lipids (e.g. Vitamin E). I won't get too far into the science of it, but I personally believe ALS is caused by improper protein folding of one or more cytokines (TNF) due to a high concentration of Hydrogen in the immediate environment. I started treating myself last week with ozone and lipids (to correct the pH) and I feel better but it is too early to report on symptoms.

I live in San Diego and will be having my first Propofol treatment at a medical clinic in Mexico. If you live on the east coast, there is at least one good option in Bermuda. But it'll be years before Americans can be treated regularly with Propofol for ALS in their hometown. If you decide to travel abroad, MAKE SURE you have your procedure done in a world-class hospital. Remember, Michael Jackson died from Propofol. It is SAFE when administered in a modern hospital, but stay clear from places like small medical clinics and certainly not dentists. Hell no.

You're going to pay out of pocket because your insurance is not going to cover this. I am having mine done for $1500 for one treatment, and I am negotiating an annual membership which you should ask for because some of you may need to have two procedures done each month, while many should be OK with one thorough one.

I doubt I'll get a response on this, but if anyone is interested in going to Mexico next week for Propofol, I was given a discount voucher for a friend and I don't have any friends with ALS that can go. PM me if interested, I know there are some folks with ALS who are struggling financially, so if this is you, please PM me and let me know I'd love to help.
 
More scientific evidence backing up why Propofol could alleviate the symptoms of ALS/MND on PALS.

Read below:



Propofol is a very short acting drug: an anesthetized patient usually recovers within minutes after infusion. Some (e.g., Eric Valor) have insinuated that this means that its beneficial effects will be just as ephemeral as its sedative effects. However, this is not observed. What is observed is that the improvements can last up to four weeks or more. How can this be? Since propofol is rapidly eliminated by the body, it's obvious that it does something positive to the brain and spinal cord that survives sedation.

This begs two questions, why do the improvements survive sedation and why do they return after a few weeks? In my opinion, it has to do with two things: neurotransmitter receptors and inflammation. Previous studies have shown that ALS patients have deficient GABA-A alpha-1 and glycine alpha-1 receptors. 'Deficient' simply means that the effectors have a high threshold of activation. Obviously, not all the receptors are deficient at the same time. There is disease progression but why is that? The only thing that can explain the spreading nature of ALS is the inflammation. ALS seems to be a self-propagating disease whereby the inflammation that is caused by the disease is also what causes it to spread. In other words, the genetically imperfect receptors are sensitive to inflammation and new receptors continually turn deficient when subjected to the stress of inflammatory molecules. Inflammation begets more inflammation and thus progression.

Assuming the above is correct, we can surmise that the reason that symptoms return days or weeks after propofol anesthesia is that the inflammation in the brain and spinal cord of the patient is not completely eradicated. This hypothesis explains why ALS afflicts mostly middle aged patients. This is the time that a person's immune system begins to malfunction. This creates all sorts of inflammatory problems such as arthritis and other autoimmune diseases. This is what triggers the start of ALS symptoms, in my opinion.

This hypothesis is a scientific hypothesis because it makes a falsifiable prediction. It predicts that a comprehensive treatment with Propofol can fully eliminate the ALS-induced inflammation and cause a full remission of symptoms that can last for a long time, possibly years.



Carlos
 
I don't understand why this hasn't been investigated more thoroughly since there seems to be treatments available outside the US. I have an appt at the MGH als clinic this week and I will ask the doctor and see what he says.
 
PLEASE READ...

VERY IMPORTANT NOTICE:

Don't attempt Propofol with an existing infection.
If you have an infection try first to clear it up with antibiotics for several days (even weeks) before undergoing any procedure where anesthetics are involved (either Propofol or else).


READ THIS PAPER BELOW:


1. Title: Anaesthetic impairment of immune function is mediated via GABA(A) receptors. Read the title a number of times! Hint: It is not just about GABA receptors.
2. BACKGROUND: We are interested in how and why anaesthetics increase infections in intensive care patients; a serious problem as more than 50% of patients with severe sepsis will die.
3. SIGNIFICANCE: Our results show that functional GABA(A) receptors are present on monocytes with properties similar to CNS GABA(A) receptors. The functional data provide a possible explanation as to why chronic propofol and thiopental administration can increase the risk of infection in critically ill patients: their action on GABA(A) receptors inhibits normal monocyte behaviour. "See the words chronic administration and the increased risk"!
4. The data also suggest a potential solution: monocyte GABA(A) receptors are insensitive to diazepam, thus the use of benzodiazepines as an alternative anesthetising agent may be advantageous where infection is a life threatening problem.


Take this into account as it's very, very important.
Let's say if you have Pneumonia, Propofol may worsen the infection.
Clear it up first (thr infection) before even attempting to be administered Propofol.


Carlos
 
I am a molecular biologist diagnosed with ALS. This is a fascinating discussion for me.

I'd like to add my own home-grown therapies: ozone treatments (weekly) and daily liquid lipids (e.g. Vitamin E). I won't get too far into the science of it, but I personally believe ALS is caused by improper protein folding of one or more cytokines (TNF) due to a high concentration of Hydrogen in the immediate environment. I started treating myself last week with ozone and lipids (to correct the pH) and I feel better but it is too early to report on symptoms.

I live in San Diego and will be having my first Propofol treatment at a medical clinic in Mexico. If you live on the east coast, there is at least one good option in Bermuda. But it'll be years before Americans can be treated regularly with Propofol for ALS in their hometown. If you decide to travel abroad, MAKE SURE you have your procedure done in a world-class hospital. Remember, Michael Jackson died from Propofol. It is SAFE when administered in a modern hospital, but stay clear from places like small medical clinics and certainly not dentists. Hell no.

You're going to pay out of pocket because your insurance is not going to cover this. I am having mine done for $1500 for one treatment, and I am negotiating an annual membership which you should ask for because some of you may need to have two procedures done each month, while many should be OK with one thorough one.

I doubt I'll get a response on this, but if anyone is interested in going to Mexico next week for Propofol, I was given a discount voucher for a friend and I don't have any friends with ALS that can go. PM me if interested, I know there are some folks with ALS who are struggling financially, so if this is you, please PM me and let me know I'd love to help.

Jerry,
Please let us know how the propofol works for you. I would love to know what kind of results you get. Have a safe trip.
 
Jerry,
Please let us know how the propofol works for you. I would love to know what kind of results you get. Have a safe trip.

There is also an ongoing thread about this Jerry mentions on his post (Mexico + Propofol) at ALS-TDI Forums, in case you'd like to read about it.


Carlos
 
I don't understand why this hasn't been investigated more thoroughly since there seems to be treatments available outside the US. I have an appt at the MGH als clinic this week and I will ask the doctor and see what he says.

Don't waste your time. He will just tell you that there is no scientific proof so he will not recommend it. My neuro will not discuss anything beyond approved drugs and treatments.
 
Here's an example of how propofol targets the types of inflammation that are known to wreak havoc in PALS. p38 mitogen activated protein kinase is known to be strongly associated with the inflammatory response in both familial and sporadic ALS.



Propofol inhibits the activation of p38 through up-regulating the expression of annexin A1 to exert its anti-inflammation effect.
Tang J, Chen X, Tu W, Guo Y, Zhao Z, Xue Q, Lin C, Xiao J, Sun X, Tao T, Gu M, Liu Y.

Department of Anesthesia, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.

Abstract

Inflammatory response is a kind of nonspecific immune response, with the central link of vascular response, which is mainly manifested by changes in neutrophils and vascular endothelial cells. In recent years, the in vivo and in vitro role of intravenous anesthetic propofol in inhibiting inflammatory response has been attracting more and more attention, but the anti-inflammatory mechanisms of propofol for mononuclear cells still remain undefined. In this study, proteomics analysis was applied to investigate protein expression profile changes in serum mononuclear cells following intervention of rats with endotoxemia using propofol. After two-dimensional electrophoresis and mass spectrometric identification, it has been found that the protein Annexin A1 was up-regulated in the propofol intervention group. Annexin A1 is a glucocorticoid-dependent anti-inflammatory protein. After detection using ELISA and Western blot assays, it has also been found that propofol can not only promote the expression of Annexin A1, but also inhibit the phosphorylation level of p38 and release of inflammatory factors (IL-1β, IL-6 and TNF-α) in rats with endotoxemia. In order to further determine the role of up-regulated expression of Annexin A1 in anti-inflammation of propofol, this gene was silenced in vitro in human THP-1 cells, to detect the phosphorylation status of p38 and release of inflammatory factors. The results show that Annexin A1 can negatively regulate phosphorylation of p38 and release of IL-1β, IL-6 and TNF-α in THP-1 cells following propofol intervention and lipopolysaccharide (LPS) stimulation. Our results clearly indicate that propofol can up-regulate Annexin A1 to inhibit the phosphorylation level of p38 and release of IL-1β, IL-6 and TNF-α, so as to inhibit inflammatory response. Therefore, it can be speculated that Annexin A1 might be the key signaling protein in the in vivo and in vitro anti-inflammatory mechanisms of propofol.



Carlos
 
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