Tuesday, 14 March 2017

Sniffing salt water the next big treatment?

Nebulization of RNS60, a Physically-Modified Saline, Attenuates the Adoptive Transfer of Experimental Allergic Encephalomyelitis in Mice: Implications for Multiple Sclerosis Therapy.
Mondal S, Rangasamy SB, Ghosh S, Watson RL, Pahan K.
Neurochem Res. 2017 Mar 7. doi: 10.1007/s11064-017-2214-z. [Epub ahead of print]

Developing a new and effective therapeutic approach against multiple sclerosis (MS) is always an important area of research. RNS60 is a bioactive aqueous solution generated by subjecting normal saline to Taylor-Couette-Poiseuille flow under elevated oxygen pressure. Recently we have demonstrated that RNS60, administered through intraperitoneal injection, ameliorated clinical symptoms and disease progression of experimental allergic encephalomyelitis (EAE), an animal model of MS. Since the intravenous route is not preferred for treating a chronic condition, we tested if nebulization of RNS60 could attenuate the disease process of adoptively-transferred EAE in mice. Although we could not directly image RNS60 after nebulization, nebulized Alexa680 reached spleen, spinal cord and different parts of the brain. Nebulization of RNS60 starting from the acute phase attenuated clinical symptoms of relapsing-remitting EAE in female SJL/J mice. RNS60 nebulization also inhibited perivascular cuffing, maintained the integrity of blood-brain and blood-spinal cord barriers, suppressed inflammation, normalized the expression of myelin genes, and blocked demyelination in the CNS of EAE mice. On the immunomodulatory front, nebulization of RNS60 to EAE mice led to the enrichment of anti-autoimmune regulatory T cells (Tregs) and suppression of autoimmune Th17 cells. Together, these results suggest that nebulization of RNS60 may be used to control aberrant immune responses in MS and other autoimmune disorders.


We showed many years ago that if you give too large a volume of salt solution you could inhibit EAE as well or better than many commercial drugs. 

It was the building site effect..the animals were being stressed by the osmotic imbalance causing immunosuppression, just like  noise stresses the animals and stops them getting disease (the building site effect). 

We have the Yale group telling us that saline gives us autoimmunity, yet this current study goes the other way and says that a modified salt solution does the trick to inhibit disease. The use taylor coutte Poiseuilleois flow method with oxygen pressure and made it into an aerosol and it largely stopped EAE and it inhibited Th17 and T reg cells..Salt here we come.

How's it inhibit them T regs/Th17?

41 comments:

  1. "Sniffing salt water the next big treatment?"

    If only. i think i'd start sniffing if only to help people with ms. You can see that sniffing salt water would be a lot less cheaper - personally and financially - then the last MS treatment you seem to have accepted works but we don't know for how long and if only there were some bio-markers to say how long.

    I hope you see where this is going. It's easy to feel superior and have a holly attitude when you are trying to convince desperate people they are throwing away money for no good evidence. But when you can't answer questions about evidence with real answers, then it's time to keep studying instead of sounding smug on account of your scientific knowledge.


    I'm begging you figure out the real stuff more and be sarcastic less about the less real stuff. otherwise, you are just having me on like the rest of 'em.

    sincerely yours,

    impatient black kettle atheist who is tired of religious medical decisions.

    imagine if you could have quelled ccsvi accusations with real knowledge before wasting (what you lament) are inexcusable amounts of money for research that went nowhere...................

    i say that with all the enthusiasm of a partner of an ms person who never had and never really considered ccsvi...

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    1. MD merely points out that the implications of this study are in direct contradiction to previous assertions that elevated salt intake increases the risk of autoimmunity. Personally, I don't think either hypothesis translates to MS, a problem with many animal studies that we do our best to point out. if we sound smug, then sorry about that. Bemused amusement is more accurate.
      Our focus is on the "real stuff", we comment on the "less real" primarily as an educational example to encourage critical examination of published research. It's important that this is done because I'll bet a pound to a penny that bogus groups will be springing up to offer "physically modified saline" as a miraculous cure for MS at an exorbitant fee. So maybe we're providing a public service too.
      I'm not sure how the claims for CCSVI could have been countered, except for doing clinical studies providing hard data, which costs money but was necessary to stop pwMS wasting theirs. Even with the undeniable refutation of the hypothesis the true believers are still not and I suspect never will be convinced in common with conspiracy theorists in general, so maybe it was a waste of money but it had to be done. Now we can move on.

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    2. thanks mousedoctor2.

      but if it "had to be done", then why am i reading this http://multiple-sclerosis-research.blogspot.com/search?q=ccsvi&max-results=20&by-date=true?

      why are you bemusedly amused (sorry for misinterpreting that for smugness, but you can surely see how i would be confused by reading entries like the one just posted - and that's not the only one, nor is mousedoc the only author).

      my wild proposition is that you will convince more people by being right about what you say than by proving what others said was wrong... my point was to focus on what you say is right rather than this 'us' and 'ccsvi community' war melodrama that seems to be taking place some 10 years after 'the ccsvi community' 'forced' the medical community to 'waste' many hundreds of thousands dollars (if not millions and billions) trying to disprove them...

      yes, you say (and i prolly believe) that you are providing an educational service.

      but how do you teach people by calling people names?

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    3. P.S. The physically modified saline is being developed as a commercial entity...I could have written inhaled drug.

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    4. It takes a number of studies from a number of independent groups for consensus to be achieved. I think with the latest one to be announced, which is yet to be published (it was announced at a meeting) we can say that consensus has been achieved. Replication is the key in science.

      We're amused/bemused/angry even that results that common sense tells you are ridiculous get published. This is one.
      I wonder if the mice sitting in nebulisers get so stressed they don't get EAE? Stress being an immunosuppressive factor in mice as we have stated over and over again.
      You convince people by being right, sometimes this entails proving something is wrong. Karl Popper's idea about doing science is that you formulate a hypothesis, try to prove it wrong, and, from your results, formulate a new hypothesis. Why not try to prove it right? Because you can't; you never know if there isn't one more experiment that will prove it wrong. Scientists have forgotten this, if they ever learned it in the first place.
      Sometimes groups need to be called out on the realism of their results. It should be the job of those that referee the papers but very frequently, this doesn't happen. All other blogs will say everything's great and blandly report everything that comes out. We don't and we're proud of that but we're all after the same thing, a cure for MS.
      There's a joke which I've modified to fit the situation.

      Q. What's the difference between some scientists and a computer?
      A. It's a lot quicker to punch the information into a computer ;-)

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    5. I've done a little digging on the company that has made the miraculous RNS60. Another of the company's products is;
      "Revalesio has developed and marketed a functional consumer beverage that allows faster recovery from strenuous exercise. Branded as Recovery Water by Reliant Hydration, a Revalesio subsidiary, this beverage is available in a growing number of stores throughout the US."
      An examination of the incredible "Recovery water" may be found here,
      http://doubtfulnews.com/2015/08/russell-wilson-says-recovery-water-healed-his-head-injury-from-nfc-title-game-bleacher-report/
      Suffice to say it's not an enthusiastic endorsement and I have to wonder whether RSN60 is in a similar vein?

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    6. or nano-vectors and semi-conductors in the salty environment.

      But seriously now, our so called knowledge is not that impressive either. Read about how Lemtrada works. Hmmm... we know from clinical studies that it seems to work... by changing the proportions of different lymphocytes ... but why are we doing exactly that and what are we trying to modify and why and how does it work?

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    7. I think our "so called" knowledge is sufficient to determine the above paper has certain causes for concern.
      MD will hopefully be publishing soon on what he's found out about Lemtrada, which will answer some of your questions.

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    8. Waiting for the reviewer green light... and then all can be revealed or is that reviled:-)

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    9. I cannot wait, can you whisper in my ear? or at least hint?

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    10. Oh well then, I shall sit patiently and wait for the effect of this "miracle cure" that may give me other autoimmune diseases and not treat the disease it was prescribed for. Kind of encouraging, isn't it?
      A the moment I am having crazy reactions to mouse ( no offence, MD, dosn't take it personally). Never seen urticaria like that and coming so quick.

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    11. OK then..its about ships, submarines, robots, calculators, toys..confused you won't be:-).

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    12. Best stay away from the mice and hopefully it doesn't go to your lungs. Animal allergies, as with all allergies, can be very scary.

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    13. I got the mouse injected (alemtuzumab), cannot just walk away from it, you see :-)

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    14. Read: I have some foreign protein(not fully humanized alemtuzumab) in me and my body does not like it. (not: I experimented on a mouse by giving it alemtuzumab).

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    15. Alemtuzumab was made in a rat not a mouse and be warned most(90percent) people make an anti globulin response to alemtuzumab. This increases with number of doses . It is more than a problem of humanisation which we will show.

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    16. In addition to the potential for anaphylactoid reactions most people also get infusion reaction as the cells being killed are liberating their contents. Ocrelizumab also causes infusion reactions but not the level of anti globulin responses. Data not sufficiently disclosed to the public

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    17. At the moment it subsides with antihistamines ( I also admit to popping some prednisolone tablets as needed). I shall survive (or so I hope). Cannot controll + undo it.

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  2. Dear ********* (not you? If not you have a soul sister:-)

    If this approach works then it will be no cheaper than any current MS drug!

    Whilst having a pop at me

    If you read our recent paper on B cells then there is indeed a suggestion of a biomarker. Is there evidence to support this claim...maybe there is. But sorry I hold my hands up. I do not know how long any drug will work for. No one does.

    Sorry I hold up my hands too, I don't have a grant to study this (if someone offers, we would love to do this). I did this be reading in my spare time. Simplest way forward, until we get support, is to ask companies who already have the data you want, to get the data.

    As to content of posts...we are always looking for content and can only talk about smoking vitamin D, HSCT so many times. Biomarkers is not my thang. Clinical stuff is not my thang. If I am spending my time reading this stuff, I figure I may as well do the posts as the same time, e.g what is taylor coutte Poiseuilleois flow?

    I am just a stocking filler for the main clinical show:-(On other sites you get "EAE cure of the Week" This one of them.

    However, saline and autoimmunity had one of the biggest almetrics (massive media coverage) of all time, within the top 5% of papers and so is topical. Has this made people stop taking salt?.

    The CCSVI FAD was before my time and yes it has wasted millions of dollars.
    However, you cannot respond with real data quickly. It may take 6 months to get the ethics even if you have funding to do this.

    Faecal transplants are another one. I don't have the evidence that people should not be wasting their money....but I believe they are? I do not have enough minutes of a day, or the resource, or the interest to work on this at the moment.

    I have other things to do that interest me.

    Call me a whinging Pom...which you may...because that is the MD persona. If you do not want it, we can kill the mouse off. You'll miss me when I'm gone:-0 (OK maybe some of you you won't).

    Is it the same anonymous having a gripe or is anonymous is not just the same person.

    As MD2 says be a mensch and use a handle so we and other know if it is the same Anon being Mr or Ms Angry:-)

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    1. MD, what you are doing is much needed! Do you know Neuroskeptic blog? Bad science has to be debunked, so that real science can be appreciated
      And when I see nanobubbles, I don't need to read any further...

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    2. The more I dig, the more alarmed I get :-(

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    3. Do I know of NeuroSkeptic blog...I think I met the author once, but interesting...and look thirty copied papers and only three get cut, leaving 27 out there, with journals unwilling to do anything. Sounds like the case we reported about J Exp Med. That one ended up in house arrest.

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    4. p.s. Not saying this is bad science...but it is hard to understand the logic of the science.

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  3. A few years ago my wife thought I was stupid spending $40 on a bottle of Japanese sea salt spray to style my hair. But this is unbelievably dumb, who pays for this 'research'? If you had published this on April 1st I would have thought it was an April fool joke.

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    1. Hi Aidan
      It was paid for by the company concerned (Revalesio). I too thought this had come out 3 weeks too early but there are other studies too by the same group.Here's another take-down (Alzheimer's this time).
      http://blogs.sciencemag.org/pipeline/archives/2014/10/21/oxygenated_nanobubbles_for_real

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    2. I'm beginning to get a strong whiff of week-old non-refrigerated haddock ;-)

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    3. I'm with your wife on that one Aidan ;-) and can't quite believe I've read all the way to the end of these posts!

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    4. But now I'm here, reminds me of a recent experience at a well known restaurant in Glastonbury (where I live, UK) sat down with delicious healthy vegan meal (love that kinda food) and asked for tap water only to be told they don't do it but we could have a carafe of activated water for £1. So my husband told them to deactivate it before bringing it over for free. Needless to say have never been back ;-)

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    5. That's a great story Judy. Will be using in future ;-)
      Do you get to hear the festival for free?

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    6. Festival is actually at Pilton, a few miles away. Pilton residents get free village tickets, other locals often get Sunday day tickets which involve travelling on one of a fleet of ancient double deckers that look like they were last used in the miners strike. Or you volunteer as a steward, but am told that's hard work ;-) Haven't been in for a few years, happy memories :-)

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    7. :-D giggle giggle at the activated water

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    8. How much for the water with nano bubbles..:-)

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  4. Davines sea salt spray, to be honest Judy; I still use this spray everyday- it's really good.

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    1. Must be good stuff for $40, you should at least have a blog photo Aidan, your hairstyle must be worth sharing ;-)

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    2. My hair always feel like rubbish when I've been in the sea

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    3. Yep, mine too. Not to mention all the bits of seaweed and occasional crustacean ;-)

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    4. This comment has been removed by the author.

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