Lipkin's Monster ME/CFS Study: Microbes, Immunity & Big Data
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Ampicillin increases GLT-1 expression

Discussion in 'Antivirals, Antibiotics and Immune Modulators' started by physicsstudent13, Mar 5, 2015.

  1. physicsstudent13

    physicsstudent13 Senior Member

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    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2788649/
    http://www.ncbi.nlm.nih.gov/pubmed/15635412

    it does increase GLT-1 expression by 200%, I just took an injection I feel a bit less foggy

    it does seem a lot safer than rocephin which destroys the gallbladder in many patients it seems, but rocephin may better for increasing glutamate transport and rocephin may have been developed to treat the neuroinflammation with Lyme's disease
    Ceftriaxone may precipitate in bile, causing biliary sludge, biliary pseudolithiasis, and gallstones
     
    Last edited: Mar 6, 2015
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  2. physicsstudent13

    physicsstudent13 Senior Member

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    Last edited: Mar 6, 2015
  3. cafe

    cafe

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    I do not know the answer- but I am highly interested in this topic!
    I seem to have a glutamate receptor variant which is quite uncommon (according to 23andme and SNPedia; something like 1 in a million if I remember correctly). This also could explain why I experience this "spacey" feeling if I had a meal with excess of glutamate. The world feels "unreal" and like I am not myself at all.... well this is difficult to explain :confused:

    But how quickly would amoxicillin change the gene expression ? I experience usually some effect after one day ... wouldn´t it take more time than 24 h ? I do have some experience with eucaryotic cell cultures as I am a biologist by training - but of course not with GLT-1 expression ;)
     
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  4. physicsstudent13

    physicsstudent13 Senior Member

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    I have terrible horrific asthma and can't exhale with a calcified granuloma. I'm ready to start empirical treatment of tuberculosis with rifampacin and isoniazid and biofilm busters like nitroxoline.

    glutamate excitotoxicity leads to Alzheimer's and ALS or Lou Gerig's disease. glutamate can destroy neurons. I also noticed severe fog and tiredness after eating one muffin. On the measures of GLT-1 activity I think rocephin and penicillin were the highest.
    http://www.msgfacts.com/nutrition/what_foods_are_glutamate-rich.aspx
    so if we only ate beef and chicken for a while then would our glutamate levels fall, I'm not sure there is a vegetable under 100 units of glutamate?
     
  5. physicsstudent13

    physicsstudent13 Senior Member

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    http://bergleslab.com/pdf/Rothstein_et_al_2005.pdf

    You can see NB in figure 2a the human GLT1 promoter fragment was much more activated by ceftriaxone than the other chemicals.
    Figure 3d seems to be especially significant-

    'Glutamate transporters are preferntially localized to astroglial membranes although in some cases increased protein expression is not mirrored by concommitant membrane localization and functional activity. However cephalasporin activity did increase glutamate transport as measured by LH3 glutamate uptake into cortical membrane and spinal cord homogenates'
    Similarly after 7 day treatment ceftriaxone increased LH3 transport in cultured spinal cord slices'
    Is this a test that is more important since it measures actual glutamate transport and not just GLT-1 expression?

    Yes I was wondering about the differences in 2 or 4 fold expression with ampicillin. I did take a break in my rocephin 10 day course and the main benefit was the improvement in cardiac problems and disease which lead me to think that I had some bacterial infection of the heart affecting my heart function and causing tachycardia. I did not have lasting improvement in fog that I have really noticed.
     
  6. nandixon

    nandixon Senior Member

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    What is the rs# for the rare SNP you found?

    I'm pretty sure that depending on the gene and the stimulus, that a (noticeable) change in expression could occur anywhere from several hours to several weeks later. So 24 hours is definitely within the realm of possibility, I would think.
     
    Last edited: Mar 7, 2015
  7. cafe

    cafe

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    @nandixon it is rs1114620 (GG) and I thought I had another one somehow linked to "glutamate" which I can not find / remember at the moment.

    @physicsstudent13 I also feel a lot better if I adjust my diet- although it is not a cure. My "ideal" diet so far is close to paleo although potatoes and whole grains is also fine for me but on the other hand some types of vegetable not e.g. cabbage.

    Thanks for the article! This looks interesting! I need some more time to read it in detail- what I have just seen: they say "Increased expression could be seen as early as 48h after drug treatment"...??
     
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  8. physicsstudent13

    physicsstudent13 Senior Member

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    wow I feel really weak losing my grip strength, nerves in my right arm felt warm under cold water

    so changing the expression of this gene can result in increased glutamate transport?
    I really need to try the paleo, I'm dying of asthma and there is JD Moyer online who said that he was cured of asthma by the paleo diet.
    1. The diet improves the Omega-3/Omega-6 ratio, which is effective against inflammatory conditions.
    2. The diet is high in vitamin D. Vitamin D levels are inversely correlated with asthma symptoms.
    3. The diet is low in lectins, gluten, and casein a1, all of which which are associated with “leaky gut syndrome.” Whole, undigested proteins (as opposed to amino acids) directly entering your bloodstream via your intestines can trick your immune system into attacking its own tissues (resulting in chronic inflammation).
    4. The diet is relatively low in carbohydrates, which helps keep plasma serotonin levels from getting too high (which can trigger bronchoconstriction).
    5. The diet is very high in phytonutrients, many of which have anti-inflammatory effects
    http://jdmoyer.com/2010/07/17/how-i-cured-my-asthma-with-one-simple-lifestyle-change/
     
    Last edited: Mar 7, 2015
  9. Valentijn

    Valentijn Senior Member

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    2% of people are GG for rs1114620, and it's not on any gene, so it's very unlikely to be impacting the function of any gene.
     
  10. cafe

    cafe

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    I guess I need some more help with this :) Promethease tells me for rs1114620(G;G): "frequency 0.9%" and "GLUTAMATE RECEPTOR, IONOTROPIC, N-METHYL-D-ASPARTATE, SUBUNIT 1; GRIN1"
    @Valentine where did you get the additional information?
     
  11. nandixon

    nandixon Senior Member

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    @cafe
    Promethease has an error there. The SNP associated with GRIN1 is actually rs11146020 aka G1001C (or 1001G>C).

    (Promethease probably has that error due to the same error being made once on the following page which I think was then carried forward to SNPedia and hence to Promethease:
    http://www.omim.org/entry/138249)
     
    Last edited: Mar 7, 2015
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  12. energyoverload

    energyoverload Senior Member

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    Cytokine release (TNF-a etc.) from microglia may inhibit activity of EAAt2/ GLT-1 glutamate transporter on neighboring astrocytes, thus increasing synaptic glutamate availability. Moreover EAAT2 activity is somewhat decreased under conditions of mitochondrial dysfunction.
     
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  13. energyoverload

    energyoverload Senior Member

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    Have you looked into Riluzole at all? This is thought to work in ALS primarily via increased activation of EAAT2 tranpsorter
     
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  14. energyoverload

    energyoverload Senior Member

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    Also TGF-b leading to reduced activity of astrocytic glutamine synthetase, thus leading to accumulation of glutamate. http://www.ncbi.nlm.nih.gov/pubmed/1358919

    I found this interesting, a group who were pioneering new treatments for epilepsy induced by TBI found that blockade of TGF-b yielded quite significant benefit. They used Losartan, which was found to penetrate BBB under conditions of BBB dysruption (such as after TBI) but doesn't reach neurons under normal conditions of BBB integrity.

    See: http://www.ncbi.nlm.nih.gov/pubmed/24659129
     
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  15. Hip

    Hip Senior Member

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    Note that this current thread is on a similar topic to this older thread: Rocephin shots. In that older thread, some ME/CFS patients found a dramatic reduction in brain fog after taking the beta lactam antibiotic Rocephin (ceftriaxone).


    Rocephin greatly increases the gene expression of the glutamate transporter GLT-1 (also called EAAT2). The glutamate transporter GLT-1 pumps glutamate out of the extracellular spaces in the brain, reducing brain glutamate levels. The beta lactam antibiotic ampicillin also increases GLT-1 expression, as indeed do many other beta lactam antibiotics.

    If I understood it correctly, this study (full paper here) found that ampicillin was the most potent booster of GLT-1 expression out of the beta lactam antibiotics tested, increasing the GLT-1 gene promoter by nearly fourfold (see figure 2b).

    In that same study, Rocephin was shown to increase the GLT-1 gene promoter by threefold, so ampicillin seems more effective than Rocephin at boosting GLT-1 expression.

    Plus ampicillin is also cheaper, much safer, and you can take ampicillin orally as a pill (whereas Rocephin requires injections or IV infusions, and these can be painful).
     
    Last edited: Mar 9, 2015
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  16. Hip

    Hip Senior Member

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  17. physicsstudent13

    physicsstudent13 Senior Member

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    My venous O2 was a terrible horrific 33% at the Emergency Room. I really need to increase my oxygen capacity and red blood cells. I have been suffocating for about 5 years on asthma, I cannot even EXHALE anymore and had a traumatic and terrible tracheostomy

    what causes overactivation of the AMPA and NMDA receptors?
    http://www.myelin.org/lorenzosoil/howtogetlorenzosoil.html

    where can I buy rizuole cheaply?
    I have terrible problems speaking, hearing loss and other symptoms related to gabapentin overdose

    My oxygen concentrator is breaking down, I feel much better resting on oxygen.
     
    Last edited: Mar 9, 2015
  18. nandixon

    nandixon Senior Member

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    Additionally, losartan and other "ARBs" have some ability to upregulate GLT-1 in their own right and thus may be useful for glutamate excitotoxicity in that way. See, e.g.:

    Angiotensin receptor type 1 antagonists protect against neuronal injury induced by oxygen-glucose depletion
     
    Last edited: Apr 25, 2015
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  19. Hip

    Hip Senior Member

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    That's very interesting. Though I could not find any quantitative data in the study about how much up-regulation of GLT-1 glutamate transporter these angiotensin II receptor blocker (ARB) drugs were able to achieve.

    They used the ARB drugs losartan and telmisartan in the study.
     
    Last edited: Apr 26, 2015
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  20. nandixon

    nandixon Senior Member

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    From Fig. 5A of the full text, it looks like telmisartan (at 1uM) increased the level of GLT-1 protein by roughly 70% or so after 48 hrs. And they said it was even "more profoundly up-regulated" after 4 to 6 days. So, just guessing, but maybe at least 100%? (Not sure about losartan.)

    I started looking at losartan a few days ago after seeing it might have some potential to improve tetrahydrobiopterin (BH4) and nitric oxide levels in relation to problems with GTP cyclohydrolase 1 (GCH1). Then I noticed that it not only had the ability to increase GLT-1 but also to activate AMPK, among other potentially useful properties. It's pretty interesting all the good things it can do - in theory.

    If ME/CFS people with lower blood pressure were to try to use an ARB, it may be necessary to also use fludrocortisone (Florinef). (That combination has sometimes been used in people who have both orthostatic hypotension and supine hypertension.)

    The most famous use of an ARB in ME/CFS is, of course, olmesartan (Benicar) in the controversial Marshall Protocol. Losartan seems better to me on paper, but then Marshall was wanting a VDR agonist effect that he thought his computer modeling showed Benicar capable of - for people with relatively high calcitriol levels. I might end up trying both out of curiosity since I unfortunately fall into that category.
     
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