1. Patients launch a $1.27 million crowdfunding campaign for ME/CFS gut microbiome study.
    Check out the website, Facebook and Twitter. Join in donate and spread the word!
The Lipkin Microbiome Crowdfunding Campaign Launches!
An ambitious $1.27m international, patient-led fundraising campaign storms into action. Sasha invites you to join it!
Discuss the article on the Forums.

Rituximab study in norway. An application to The Research Council of Norway

Discussion in 'Rituximab: News and Research' started by deleder2k, Jul 5, 2014.

  1. deleder2k

    deleder2k

    Messages:
    75
    Likes:
    218
    Oslo, Norway
    Hi. This is the application for funding of the phase 3 Rituximab study in Norway.
    I translated some of the content for you. It is a mess, but I thought you would be interested. I have dropped to translate some of it, as I am having trouble translating medical terms from Norwegian to English.

    All the information translated by me is on your own risk. I am not qualified health personnel nor a certified translator. The slides (in Norwegian) are publicly available through The Research Council of Norway's website.

    Please ask questions about my mess! :)
    Last edited: Jul 7, 2014
    Helen, beaker, rosie26 and 6 others like this.
  2. deleder2k

    deleder2k

    Messages:
    75
    Likes:
    218
    Oslo, Norway
    Last edited: Jul 6, 2014
    Helen, Sidereal, beaker and 7 others like this.
  3. Denise

    Denise Senior Member

    Messages:
    161
    Likes:
    213
    Thank you very much for sharing this! I look forward to reading it.
  4. Mark

    Mark Acting CEO

    Messages:
    4,460
    Likes:
    1,838
    Sofa, UK
    Thanks very much for posting this.

    The 'hypothesis' slide, 6 from the end, is what was presented at IiME in 2013 as their tentative working hypothesis. I believe that it was stated as embargoed at that time; I haven't seen any real discussion of it before now. It appears that with the funding application posted here, this is now public domain, I hope I've got that all correct...:D

    Anyway to my understanding the hypothesis is that an autoimmune attack that affected the endothelium could cause all the symptoms indicated on that slide, via disturbance of NO synthesis. Hence the last slide of the PDF, focusing on the NO synthesis process in endothelial cells. On this last slide some regulators of the process are detailed. HSP90 is an interesting one, as Blomberg found a subset of ME/CFS patients with antibody reactions to an HSP60 region earlier this year (see the end of my IiME report here), so perhaps that finding might join up with this hypothesis eventually. If another result or two from a separate group were to confirm a link in ME/CFS to antibodies that target receptors present in the endothelium, I think I'd be getting very excited...
  5. IreneF

    IreneF Senior Member

    Messages:
    347
    Likes:
    308
    Endothelium where?
  6. deleder2k

    deleder2k

    Messages:
    75
    Likes:
    218
    Oslo, Norway
    If we just think for a case that we suffer from endothelium dysfunction, how can one treat it? Or at least alleviate the symptoms? "Association of testosterone levels with endothelial function in men: results from a population-based study." from 2012 states that low testosterone levels are linked with endothelial function. My testosterone level is measured to 10 nmol/L or 280 ng/dl. I am 24 years old, and it seems like 99.5% of 25 year olds have a higher value of testo than I do. May be i should head to my GP.

    I am also starting on pranolol to help ease problems. Not sure if this can help the blood flow or not.
    What about Cialis/Viagra? Some say that helps the blood flow.

    Isn't endothelium dysfunction the step before you get atherosclerosis? It feels like I have atherosclerosis in my legs sometimes. Hurts like hell to walk. Pain eases when resting.
  7. alex3619

    alex3619 Senior Member

    Messages:
    6,639
    Likes:
    9,719
    Logan, Queensland, Australia
    Its not an unreasonable hypothesis about B cell interaction with endothelial layers, giving rise to NOS irregularities. Indeed the Tenth Paradigm stuff from Martin L. Pall is about this kind of thing, though he emphases feedback loops.

    Every large blood vessel, though not I think capillaries, has an endothelial layer that can produce nitric oxide on demand. We have known from the work by Vance Spence in the UK since about 2000 that we have a prolonged and abnormal acetylcholine response. This all ties together. It also ties in with the methylation hypotheses, and probably various pathogens that have affinity for both endothelial cells and B cells (I think enteroviruses do but I could be wrong, its been so very long since I read this stuff).

    I would like to stress though that just because this makes sense does not mean its right. That for the science, not speculation. However I really don't care what the reason is, if Rituximab can restore most of my function that's enough for me even if the theory its based on ultimately turns out to be as reliable as Tooth Fairy Science. Empirical results trump theory. In time it will get figured out, because if Rituximab becomes widely used it will generate a lot of research interest.

    It is not clear that this leads to cardiovascular disease as commonly known. What does seem possible is it may predispose to heart failure eventually. From Jason's study we know heart failure is common in us in our late 50s, decades before the general population get it.
    Last edited: Jul 7, 2014
    melihtas, rosie26, Sidereal and 3 others like this.
  8. optimist

    optimist

    Messages:
    74
    Likes:
    50
    Norway
    I think there was something in the news on this just last week, that many people here in Norway were too low on testosterone. And today friend brought testosterone back up suggesting I should have the levels checked. So, I was just planning to ask my doctor on my appointment with him this week. It was interesting seeing you mention it too. Now I am pretty interested in finding out about it.

    I read that the test has to be done over time to get an accurate result, as the levels fluctuate during the day, so perhaps it is not something that can be done straight away?
  9. daisybell

    daisybell Senior Member

    Messages:
    111
    Likes:
    186
    New Zealand
    This is fascinating reading!
    I have spent the last hour trying to make sense of information on endothelial dysfunction from the internet....
    It does seem to be a very plausible hypothesis. I was interested to see that endothelial cells also make up the blood-brain barrier....
    All the research I found was from cardiology, with a focus on atherosclerosis. Also it seems that measuring endothelial function is not easy, and most of the measures are found in research only, not general medical practice due to their highly technical nature.
    I wish there was some way to speed up time.... I have a vision of myself post-Rituximab.....
    rosie26, Sidereal, taniaaust1 and 3 others like this.
  10. knackers323

    knackers323 Senior Member

    Messages:
    626
    Likes:
    108
    I have had really low test levels my whole illness but just put it down to my body being so unwell in general. Are you suggesting there may be a direct cause for this?
  11. optimist

    optimist

    Messages:
    74
    Likes:
    50
    Norway
    Did you try to take testosterone, and did it help on how you felt?
  12. knackers323

    knackers323 Senior Member

    Messages:
    626
    Likes:
    108
    I only tried it a bit because I was more interested in getting to the root of the problem and taking test from artificial sources will lead to other problems.

    I didn't see much benefit from it though I prob should give it a better try
  13. deleder2k

    deleder2k

    Messages:
    75
    Likes:
    218
    Oslo, Norway
    No, I don't know about the cause, but it is an interesting thought though. 99.50% of men have more testosterone than me. Is that just a coincidence? Or does it have something to do with my M.E?
  14. knackers323

    knackers323 Senior Member

    Messages:
    626
    Likes:
    108
    Nope I would say it's definitely to do with ME. I was told in my twentys that my test level was that of a 80 year old.

    That's not normal and surely CFS related
  15. deleder2k

    deleder2k

    Messages:
    75
    Likes:
    218
    Oslo, Norway
    Must be. Hemoglobin level at 13.0, everything under 13.4 is considered anemia. Seems like you can get values outside of reference range by chronic pain in muscles. Dah.
    NK17 likes this.
  16. NK17

    NK17 Senior Member

    Messages:
    243
    Likes:
    413
    Sorry guys to break the flow of this thread, but what about testosterone levels in females?

    I also remember a doctor once told me that niacin (Vit B5) is a powerful vasodilator and some use it by building the dose up till they tolerate it without the intense flush (aspirin apparently is the antidote); apparently niacin is the cheap viagra.

    Niacin together with Gaba are the active ingredients of Picamilon, a supplements that I'd love to try for migraines.

    @daisybell your tip on the BBB and endothelial cells is very interesting ...

    I'll have to seriously look into all this.
  17. taniaaust1

    taniaaust1 Senior Member

    Messages:
    7,414
    Likes:
    4,152
    Sth Australia
    Lots of us females here have low testosterone levels, this has been talked about at times. One thing thou for us females with ME, we tend to get bad reactions from testosterone (so whatever you do, if you are female dont get a testosterone implant! like my gyno did to me). I think nearly every ME female whos had testosterone for testosterone deficiency that Ive heard from, has had a bad reaction from it. ME guys thou seem to do far better with it.
    NK17 likes this.
  18. alex3619

    alex3619 Senior Member

    Messages:
    6,639
    Likes:
    9,719
    Logan, Queensland, Australia
    I tried boosting herbs, then testosterone cream and then injections. No improvement on energy and symptoms at all, though in the end I wound up with more symptoms - acne and a bad case of agro.
  19. Firestormm

    Firestormm Senior Member

    Messages:
    5,785
    Likes:
    5,868
    Cornwall England
    Low testosterone has been linked to several illnesses and can cause symptoms in its own right. I suggest if your levels are really that low you go and see a doctor - it might account for some of your symptoms - or it could account for something else. A quick search on the internet for low testosterone revealed your levels were at the bottom of the range: and also revealed the debate around the subject. It can be treated - there are other perhaps more noticeable signs of low testosterone e.g. sex drive: but see a doctor. Low levels in and of themselves are linked to 'fatigue' of course. A friend of mine has Type 2 Diabetes and was also low in testosterone which when boosted he felt improved his symptoms enough to return him to work once again. So who knows? But I haven't heard it related to ME/CFS.
  20. deleder2k

    deleder2k

    Messages:
    75
    Likes:
    218
    Oslo, Norway
    Went to my GP and did some bloodwork today. Mye value of 10.00 or 285 ng/dl was when I was 22 years old. That is low. Will get the results in two days, so I am excited to see if they are lower or not. If they are equal or lower testosterone injections may be up for debate.
    Firestormm likes this.

See more popular forum discussions.

Share This Page