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Ron Davis latest: more evidence of "something in the blood" (Simon M blog)

Discussion in 'BioMedical ME/CFS News' started by Simon M, Dec 10, 2019.

  1. alex3619

    alex3619 Senior Member (Voting Rights)

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    The evidence is moderately strong that something in the blood is large molecule size, which might include vesicles, and mediates cellular energy deficit. It may or may not be the whole problem, but it must indeed be caused by something. As a possible mediating mechanism its a target for treatment. If its not causal then it probably wont directly lead to a cure, but it might point the way.
     
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  2. Mij

    Mij Senior Member (Voting Rights)

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    I read a study (can't find it right now) that increased lactate impairs the coagulation system. I had an ISAC panel done years ago from HEMEX labs, and one particular marker indicated 'something in the blood'- interestingly enough. My doctor travelled down to a workshop in Arizona to meet with physicians and David Berg (lab owner) and he was very insistent that it was a virus. The virologist and head haematologist disagreed.

    I don't know whether I should have posted this on the lactate thread or this one.
     
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  3. MeSci

    MeSci Senior Member (Voting Rights)

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    I did an internet search for "increased lactate impairs coagulation" and got this:

    https://journals.lww.com/jnsa/Abstr..._Lactate_Levels_Impair_the_Coagulation.7.aspx

    and several others.
     
  4. Simon M

    Simon M Senior Member (Voting Rights)

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    Not an answer for ME/CFS, but here's an example of (non-nanoneedle) bioimpedance being used to measure changes in cells for studying the effect of candidate drugs in fibrotic disease.

    https://pubs.acs.org/doi/full/10.1021/acssensors.7b00442?src=recsys#

    Crucially, the study identified what was happening at the cellular level as bioimpedance changed.
    Hopefully, one day we will have similar for mecfs.
     
    Last edited: Dec 13, 2019
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  5. Andy

    Andy Committee Member & Outreach

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    http://www.virology.ws/2019/12/16/t...grath-on-ron-davis-on-something-in-the-blood/
     
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  6. Barry

    Barry Senior Member (Voting Rights)

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    upload_2019-12-17_7-9-2.png
    Surely there is something else significant about this graph, other than the very high value reached by the "ME/CFS Cells in CFS Plasma" line. The shape of the lines.

    "Healthy Cells in Healthy Plasma" is the only line that is almost straight. The others have the same characteristic drop in impedance before then rising again, even though the timings and amplitudes are different. So any ME/CFS association would seem to be influencing healthy cells or healthy plasma. Is that dip not significant?
     
    Last edited: Dec 17, 2019
  7. Amw66

    Amw66 Senior Member (Voting Rights)

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    I have not had much sleep, so this may not be relevant at all.
    Did healthy controls have IDO mutations ?
    Graphs in CFS plasma remind me of the bistability " kick in "
    Did experiment continue longer ( do we know of CFS in healthy plasma ever got to the same impedance level as HC?)

    ETA what happens if data is logged?
     
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  8. lansbergen

    lansbergen Senior Member (Voting Rights)

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    https://en.wikipedia.org/wiki/Bistability

    In biological and chemical system
    Bistability is key for understanding basic phenomena of cellular functioning, such as decision-making processes in cell cycle progression, cellular differentiation,[5] and apoptosis. It is also involved in loss of cellular homeostasis associated with early events in cancer onset and in prion diseases as well as in the origin of new species (speciation).[6]
     
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  9. Amw66

    Amw66 Senior Member (Voting Rights)

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    Thanks. I feel a bucket load of coffee is needed to get any brain function today!
     
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  10. Snow Leopard

    Snow Leopard Senior Member (Voting Rights)

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    A simple hypothetical explanation for the cellular response to the salt challenge (in the nanoneedle study) is inhibited Na+/K+-ATPase activity (which is in turn upregulated by cAMP activity). Suggesting altered G protein coupled receptor activity, downregulation of Gs activity or upregulated Gi activity.
     
  11. alex3619

    alex3619 Senior Member (Voting Rights)

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    I have had an interest in this area for a long time, largely because of the cAMP/Ca++ axis, and resveratrol. One of the drugs under invesigation by RonDavis' group has a resveratrol version.
     
  12. FMMM1

    FMMM1 Senior Member (Voting Rights)

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    I don't have specialist knowledge; however, Ron mentioned that it should be possible to:
    • identify what the "something in the blood" is; and
    • work back/upstream from the something in the blood i.e. to find where it is coming from (parent cells).

    Potentially this requires separating plasma into fractions (nano-needle) and testing these. E.g. at it's simplest filtering out exosomes and testing these on a relatively high resolution mass spectrometer - to find candidates for "something in the blood" and possible sources for the exosomes - protein signature.


    It may simply be a resource issues not a knowledge/technology issue.
     
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  13. FMMM1

    FMMM1 Senior Member (Voting Rights)

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    I gather there's been some comment on-line regarding "positive" results from Carmen Scheibenbogen's group --- "Immunoadsorption is an apheresis procedure to remove specific proteins from a patient’s plasma" [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5854315/]
    Theory was they may have accidentally removed the "something in the blood". All conjecture of course!
     
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  14. FMMM1

    FMMM1 Senior Member (Voting Rights)

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    I think Karl's really concerned to ensure they don't artificially create this effect. Remember how Ron's red blood cell deformability work de-railed temporarily, due to using buffer rather than plasma from people with ME --- So Karl want's to repeat his experiments in a way that replicates the real world scenario --- all very complex to me, so my explanation is poor!
     
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  15. FMMM1

    FMMM1 Senior Member (Voting Rights)

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    You and Derya Unutmaz?
     
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  16. Badpack

    Badpack Established Member (Voting Rights)

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    @FMMM1 they did an Immunoadsorption which just removes the igG. So even if they wanted, i highly doubt they accidentally removed the something in the blood. Also i talked with some ppl from this study. Lets say it this way, the study seems not to reflect what they told me.

    I got a cycle of 7 plasma exchanges in 10 days. Thats the most you can do in such a short time. And it did nothing.
     
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  17. Forbin

    Forbin Senior Member (Voting Rights)

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    The general idea of CFS-like symptoms being created by the overgrowth of a toxin-producing microbe in the gut goes back at least to the early 1980's, with the "hangover" toxin acetaldehyde being thought overproduced by too much "candida albicans" in the gut.

    The media played this up in the 1980's and "candida overgrowth" in the gut became considered a "fad" diagnosis by mainstream medicine. It would be pretty ironic if something along these lines turned out to be part of the puzzle.
     
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  18. Sly Saint

    Sly Saint Senior Member (Voting Rights)

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    It might also be interesting if they could see whether the concentration of the 'something' changes up or down pre and post stressing; ie if there is a connection with PEM.
     
  19. strategist

    strategist Senior Member (Voting Rights)

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    :D I wonder how many such fads originated from ME/CFS.

    Dysbiosis could be quite plausibly be an exacerbating factor in the illness in some subgroup of patients.
     
    Last edited: Dec 22, 2019
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  20. Badpack

    Badpack Established Member (Voting Rights)

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