The 12th Invest in ME Conference, Part 1
OverTheHills presents the first article in a series of three about the recent 12th Invest In ME international Conference (IIMEC12) in London.
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Rituximab sub study: assessment of Flow-Mediated Dilation and skin microcirculation

Discussion in 'General ME/CFS News' started by deleder2k, Sep 13, 2014.

  1. deleder2k

    deleder2k Senior Member

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    B-lymphocyte Depletion Using Rituximab in Chronic Fatigue Syndrome/ Myalgic Encephalopathy (CFS/ME). A Randomized Phase-III Study. (RituxME)

    Sub study: assessment of Flow-Mediated Dilation and skin microcirculation
    study info: http://clinicaltrials.gov/show/NCT02229942

    The researchers at Haukeland are doing a sub study along with the Rituximab study which is underway as of now:

    Endothelial function: assessment of Flow-Mediated Dilation and skin microcirculation at baseline and repeated during the time interval 17-21 months.

    FMD: The researchers want to measure the degree of impaired FMD with respect to the severity of the disease. The patient will be given nitroglycerin to measure change in the FMD.
    It should be examined whether FMD changes after Rituximab.

    At Haukeland University Hospital they also will conduct an investigation of the microcirculation of the skin on the forearm, using laser measurement.



    Anyone tried nitroglycerin here? It widens the blood vessels. I believe the issue is that one develops tolerance rather quickly.
     
    Last edited: Sep 13, 2014
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  2. DanME

    DanME Senior Member

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    Hi. Very interesting. I think, they ve build in this study protocol from the university of Dundee. Here you can read the layman explanation.

    http://www.meresearch.org.uk/our-research/completed-studies/endo-function/

    Tolerance to nitroglycerin is a very common phenomenon. It is usually used with agina pectoris to prevent heart attackes. And the patients become tolerant to Nitro very fast.

    To pin down, why the endothelium is dysfunctional is very hard. I think, it has nothing to do with the normal process of endothelial dysfunction due to age, oxadative stress, low grade inflammation and high cholesterol.

    If the the endothelium becomes functional again after Rituximab treatment, I think, the damage would be rather caused by an autoimmune process, directly hitting endothelial enzymes like the eNOS or hitting neurones, which control the vessels.
     
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  3. deleder2k

    deleder2k Senior Member

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    Thank you, @DanielBR. It looks like they already have tried this on some patients, and I imagine they've also read the study your referring to.

    Sublingual tablets: 0.25 mg and 0.25. Effect should last for 30-60 minutes. If one develop tolerance rather quickly I guess they have to come up with something clever.

    Are their other medicines that widens the blood vessels? As I have mentioned before on this forum; I get better from alcohol. Maybe PWME's who do tolerate alcohol can benefit from the fact that it widenes the blood vessels? I feel alot better if I drink 6+ beers. My OI is better, feel lezz dizzy, less muscle pain.

    And what about drugs like Viagra/Cialis? They have the same effect, dont they? I wonder if flow mediated dilation increases.
     
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  4. Gijs

    Gijs Senior Member

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    deleder3k, hi, you feel better with alcohol? Don't you have tachycardia and pots? I feel much worse after drinking alcohol like the most ME and pots patients. Strange that we react so different. But i believe that bloodflow problems are the main problems in ME. This hypothese is very interesting.
     
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  5. deleder2k

    deleder2k Senior Member

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    I'm certain I have POTS, and I use 20mg propranolol to get my pulse down. Yes, I do feel better. If I drink way too much I get a hangover like everyone else, but something happens in my body after a six pack.
     
    Last edited: Sep 14, 2014
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  6. aimossy

    aimossy Senior Member

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    LOL
     
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  7. lnester7

    lnester7 Seven

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    I don't understand why they say dilation if most of us are treated with constrictors like midodrine.
     
  8. deleder2k

    deleder2k Senior Member

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    I am sure @DanielBR have some input regarding this.
     
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  9. NK17

    NK17 Senior Member

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    Let's not forget that some types of beers are called isotonic, in the sense that they have similar amount/concentration of salt and sugar to the human body and are also naturally rich in B vitamins ;).

    There's a german brand that is alcohol free, for many PWME who can't tolerate alcohol, that might be a good option.
    An alcohol and gluten free version, would be a godsend for many of us on restricted diets.

    Not all alcoholic beverages are created equal ;).

    And yes I'm sure that @DanielBR can probably have some suggestions to make on this apparently more mundane topic ;).
     
    Last edited: Sep 14, 2014
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  10. MeSci

    MeSci ME/CFS since 1995; activity level 6?

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    That would seem a bad idea if this thread is correct.

    But I guess the midodrine is for POTS, and some threads on nitric oxide talk about high NO levels in POTS, so it's very confusing!
     
  11. DanME

    DanME Senior Member

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    I am confused as well. But the study from the Dundee University showed an impaired vessel response to increased blood flow. All vessels, especially the middle sized ones, have the ability to widen or constrict and so to change their diameter. They are regulated by the autonomic nervous system and are in addition capable of auto regulation, depending on the amount of blood flow coming through.

    The body changes the amount of blood flow to all organs, muscles and tissues constantly. If you go swimming, the blood flow to the muscles can increase by around 60% and the blood flow to the gastrointestinal system decreases by around 20%.

    Here is a good picture of this.

    http://s1251.photobucket.com/user/vladimirzec/media/Fiziologija/img332.jpg.html

    I think the arteries are not just stiff (like in arteriosclerosis), but have lost their ability to regulate blood flow and blood perfusion. If this this the case, it would have huge consequences. It could be, you have low blood pressure and the blood sinks to the legs and the lower abdomen and causes sever OI. Midodrine would counter that by constricting the vessels in general and increasing the pressure. Increasing blood volume would counter this as well. But the vessels would still not be able to control and regulate the right amount of blood flow. The flexibility is lost. Regulating this system happens to a large amount by NO release (but a lot of other substances are involved).

    You can imagine, this lost ability of flexible blood regulation, could lead to exercise inability. It could lead to muscle weakness, fatigue, exhaustion and in impaired brain perfusion.

    I think it is not about open or closed vessels in general, but about loosing the ability to close the right vessels at the right time and open the right vessels at the right time.
     
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  12. deleder2k

    deleder2k Senior Member

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    @DanielBR but are there other drugs that open vessels? We do got nitroglycerin, but apparently tolerance is an issue.
     
  13. NK17

    NK17 Senior Member

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    I propose that we look into Niacin (Vit B3) again.
     
  14. deleder2k

    deleder2k Senior Member

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  15. MeSci

    MeSci ME/CFS since 1995; activity level 6?

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    But that guy said that eliminating niacin was what did it.
     
  16. deleder2k

    deleder2k Senior Member

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    Oh... I should really learn to read. Silly me. :rofl:

    Tomorrow I am doing a 5 day test with Cialis to check if it helps my OI and blood flow. It is severe now as I cant stand on my feet for more than seconds before I get dizzy.
     
  17. MeSci

    MeSci ME/CFS since 1995; activity level 6?

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    I'll leave any smutty remarks to someone else..:D

    Good luck anyway!
     
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  18. deleder2k

    deleder2k Senior Member

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    Haha! Don't be cheesy, maybe this will be the standard treatment for OI after this! lol
     
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  19. deleder2k

    deleder2k Senior Member

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    Vodka does the same job :) hehe
     
  20. NK17

    NK17 Senior Member

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    If I remember correctly alcohol in general depletes glutathione, so if the theory that PWME are low in glutathione is correct, drinking alcohol might not be the right solution ;).

    Also alcohol metabolism differs greatly between males and females, in part due to liver enzymes as well as body size/weight.

    But you guys up there in the long cold northern winters might give it a try, always with moderation ;).
     
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