Intracellular calcium and viruses

pamojja

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S-VV

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@Iritu1021

I was perusing a printed copy I have of Naviaux's latest study, and came across this:


Metabolic features and regulation of the healing cycle—A new model for chronic disease pathogenesis and treatment

[...]
The dauer-like energy conservation program in mammals may also involve a ligand-receptor desensitization process, decreasing the ability of cells to release intracellular calcium when needed. Calcium stimulates mitochondrial oxidative phosphorylation. When stimulated by ATP and related nucleotides, IP3-gated calcium release is decreased (Schmunk et al., 2017), and mitochondrial and whole cell reserve capacity is reduced
[...]

I had already underlined it in September, but forgot about it :D:D
 

Sidny

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@Iritu1021

What else could I possibly do to lower intracellular calcium?
Vitamin K perhaps?
Vitamin K is a fat-soluble vitamin important in blood coagulation and bone metabolism. One of its functions is to keep calcium in the bones and out of soft tissues, blood vessels, and the nervous system



• Vitamin K regulates calcium in the body through osteocalcin and the matrix G1A protein.3 Both bone proteins are active only after undergoing carboxylation, a process in which Vitamin K is a required cofactor. Carboxylated bone proteins have a strong affinity for calcium and control its movement, directing it to the bones and teeth and preventing its deposition in soft tissues.

Calcium management appears to be dysregulated in people with the E4 form of Apolipoprotein.4,5,6 Osteocalcin is found in the brain; in its absence, it appears that brain cells become more vulnerable to the effects of calcium



• Vitamin K inhibits production of Interleukin-6, an inflammatory cytokine.11



• Vitamin K, an anti-oxidant that is more powerful than Vitamin E or CoQ10, is able to potently inhibit glutathione depletion-mediated oxidative cell death.9,10


http://discoveringschizophrenia.blogspot.com/2010/11/vitamin-k-deficiency-linked-to-autism.html?m=1
 

Iritu1021

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That's a great find, @S-VV ! It's amazing how everything is so inter-related. Maybe if you spend a lot of time in dauer state, you develop long term genetic adaptations, so when you raise it suddenly (with T3 or stress hormones or stimulants), you no longer have the ability to regulate calcium and you end up with calcium toxicity symptoms?

And @pattismith brought up in another article about how puringergic receptors that bind ATP might be affected by the latent viral genome replication and that lithium treatment might exert its action through these receptors. It's interesting how ATP and Ca2+ appear to be inversely related.

@pamojja - very interesting. A lot of people here do respond to magnesium. Magnesium is also apparently a co-factor for CaATP-ase enzyme, I've seen it referred in my calcium book is MgCa-ATPase. But also interesting how ATP and Ca2+ appear to be inversely related.[/USER]
 

Iritu1021

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And it looks like thyroid hormone also affects Akt so I'm taking two drugs that increase Akt. What does it mean besides better cytoprotection?

 

pattismith

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Learner1

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Though I know I take magnesium for good reasons, my adrenergic antibodies seem to override any vasodilation properties, keeping my BP up. The only thing that has helped is a beta blocker, propranolol.

It does sound like nimlodipine may be helpful for those of us with MCAS given the article you posted, however I am extremely gunshy after amlodipine almost killed me a few months ago, by destroying all my red and white blood cells and platelets (pancytopenia).

Why would nimlodipine help when amlodipine was an aggressive disaster - it attacked so fast, and exhausted me so badly, I was prone on the couch and stopped taking it long before my labs came back with the glaring problem.

I still am not understanding why a CCB would do so much damage to my blood cells so fast, does anyone know why?
 

pattismith

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@Iritu1021

What else could I possibly do to lower intracellular calcium?
Macrolides antibiotics lower intracellular calcium via purinergic receptor inhibition, although the exact receptor type is not known. Also each macrolide has it's own affinity to different pruinergic receptor.

I do myself experience muscle weakness from any macrolides, so I have a special interest into this.

I wonder if the intracellular target could be P2Y2 inhibition...

https://forums.phoenixrising.me/ind...-macrolides-effect-on-intracel-calcium.61553/

...
 

Wonkmonk

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@Wonkmonk you asked me about Akt. I found that it's also involved in lithium response - it's under BDNF and TrkB.
But as I understand the drawing, it raises Akt activity, so it would raise intracellular calcium and help herpes simplex virus (HSV upregulates Akt activity for cell entry and replication).
 

Wonkmonk

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And it looks like thyroid hormone also affects Akt so I'm taking two drugs that increase Akt.
This is very interesting because after I had thyroid surgery there is a several day waiting period before starting thyroid hormones (not sure exactly why it is needed). I didn't get much worse during that period, but I got much worse in a matter of days after starting thyroid hormone replacement and I am permanently worse (and worsening) since then.

I was always convinced that thyroid hormones played a role for my condition getting so bad. I definitely was sick before, but I could work, manage my own household, felt not too bad. After starting thyroid hormones, it all went downhill very fast.

Maybe Akt activation is the reason.
 

Iritu1021

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This is very interesting because after I had thyroid surgery there is a several day waiting period before starting thyroid hormones (not sure exactly why it is needed). I didn't get much worse during that period, but I got much worse in a matter of days after starting thyroid hormone replacement and I am permanently worse (and worsening) since then.

I was always convinced that thyroid hormones played a role for my condition getting so bad. I definitely was sick before, but I could work, manage my own household, felt not too bad. After starting thyroid hormones, it all went downhill very fast.

Maybe Akt activation is the reason.
Thyroid hormone definitely played a role in my condition. I crashed within a month after being started on low dose Armour thyroid.

Thyroid hormone also activates immune system, but depressed immune system might also be a part of protective response because if the virus has already established itself in large part of the nervous system, activation of immune system will cause neuroinflammation. The overactive immune system in this case might be causing more harm than a latent virus itself. I know that my ANA skyrocketed after I went on thyroid.

I find that I do much better with T4 than T3 but I still think that exogenous thyroid dosing always results in supra physiological peaks that are probably not good for the body. I'm thinking of trying to dose my levothyroxine twice a day instead of once a day.
 

pattismith

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I had relatively high-dose IV erythromycin for a week a while ago and it didn't do any good.
maybe a week is not enough, or maybe another Macrolide might work better? Macrolides are known to have some antiviral activities (azithromycin), although I'm not sure for Herpes virus.
Did you experienced any bad effect from Erithromycin?

Have you tryed calcium channel blockers?

I just read this article, however I didn't find any clinical trial with calcium channel blockers for HSV.

More over, some calcium channel blockers proposed in this patent are not going through the Brain Blood barrier (but Nimodipine does).

https://patents.google.com/patent/WO2002041893A1/en

Therapy for herpes neurological viral conditions utilizing 1,4-dihydropyridine calcium channel blockers

Abstract

A therapy for Bell's Palsy in mammals is proposed that rests on a causal hypothesis involving both endothelin and the herpes virus, particularly the herpes simplex virus for Bell's Palsy. Similarly, the same therapy would apply to Ramsay Hunt, but in this case the herpes zoster virus would be involved in the causal hypothesis. Other herpes viral related conditions are also suggested to be amenable such as herpes simplex encephalitis. The therapy uses therapeutically effective doses of calcium channel blockers that are of the 1,4-dihydropyridine derivative class, such as felodipine but also including nifedidine, nimodipine, nisodipine or alenodipine. The treatment is proposed as continuing up to the tenth day of progression, but to be started as early as possible. Acyclovir or other herpes antagonists such as famciclovir may also be administered in therapeutically effective dosages.
 

Iritu1021

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But as I understand the drawing, it raises Akt activity, so it would raise intracellular calcium and help herpes simplex virus (HSV upregulates Akt activity for cell entry and replication).
Hmm... Lithium however has been shown to have a protective effect against Herpes viruses. So perhaps the cumulative effect with decrease in IP3 and calpain outweighs the effect on Akt. Also, cell entry is only important during active infection (lytic stage). If the virus mostly exists in the latent stage (as most likely is the case with long standing CFS) and your primary goal is to suppress its genome from being expressed. If it can't express its genome than it won't replicate - unless you abruptly stop the medication that keeps it suppressed, than you will be at a higher risk of a rebound activation.
 

Wonkmonk

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Did you experienced any bad effect from Erithromycin?

Have you tryed calcium channel blockers?
Yes, my tinnitus worsened for a few weeks and I felt generally worse during the AB course.

I in fact tried Nimodipine and it had some positive effect, but it was very limited. I tried both high and low doses (low doses worked better) and I also tried other calcium channel blockers, without success.
 

Wonkmonk

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I find that I do much better with T4 than T3 but I still think that exogenous thyroid dosing always results in supra physiological peaks that are probably not good for the body. I'm thinking of trying to dose my levothyroxine twice a day instead of once a day.
Even tiny doses of T3 (~5 µg) sent me into an instant crash. I couldn't tolerate it at all. I tried splitting the T4 dose to reduce peaks, but it didn't help much. But it's worth trying, although you might get fluctuations in hormone levels if you don't keep every dose 6 hours away from meals.
 

Iritu1021

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Even tiny doses of T3 (~5 µg) sent me into an instant crash. I couldn't tolerate it at all. I tried splitting the T4 dose to reduce peaks, but it didn't help much. But it's worth trying, although you might get fluctuations in hormone levels if you don't keep every dose 6 hours away from meals.
Not sure if it's a really worthy trade-off, I'm super sensitive to the fluctuations. When you say it didn't help much, is it more like it didn't help at all or there was some benefit? I have the same issue with even tiniest doses of T3 (now that I'm on T4 even 1 mcg is too much!).
 

Iritu1021

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I'll put Lithium on my list of drugs I might want to try. How about the risks/possibly adverse effects? Is it a safe drug?
Lithium orotate is sold as the supplement here in the US but I used higher doses than what would be taken as a supplement. Theoretically, there is a very small risk of kidney damage or hypercalcemia, and a more substantial risk of worsening thyroid dysfunction. On the plus side, there's a decreased risk of dementia and mood disorders.

There's no way to sugar coat it - lithium usually makes you feel like shit when you first start it. I think the initial side effects might due to its action on sodium channels which is useful in mania but not useful for our purposes. This seems to get worse within 3-5 days as the channels adjust. Raising thyroid dose higher or using a lot of sodium in your diet might help to get through that. And also starting with really low doses (even in microgram range for some people) to help the body to adjust.

I think it affects thyroid production which is already downregulated in CFS so most people who have borderline thyroid function and not taking thyroid hormone might not be able to tolerate it.

And it will leave you with lower "dopamine levels" (or whatever the good feelings we usually attribute to dopamine) than before you start it - less prone to lows but also, unfortunately, less prone to highs. I still plan on trying some way to offset that effect it by combining it with some agent that raises dopamine.

The benefits begin to unveil only after about 2 weeks, although if you're super sensitive you might pick up on some changes sooner. For me, the really strong effects became apparent when I've reached about 20 mg/day.

You can also check out my blog post Recovering with Lithium orotate.