Intracellular calcium and viruses

[Iritu1021]

yes, very difficult to study all this in vivo but you might be able to deduce it through self -experimentation. have you experimented with how substances that act on IP (such as inositol or lithium) affect you?

I think there is definitely some sort of secondary messaging underneath a lot of CFS cases, whether its IP3, cAMP or Ca2+ which leads to multiple neurotransmitter abnormalities.

 

[Inara]

I don't want to experiment. These pathways are intelligently orchestrated, and I don't understand them completely. I don't want to cause damage. But re. caffeine, I am waiting for feedback by someone who tested it (by drinking coffee ).

Supplemented inositol won't influence the IP3R I think. Lithium is an IP3R inhibitor (if I remember correctly), and I think in contrast to caffeine, it doesn't influence the ryanidine receptors.

 

[pattismith]

I don't want to experiment. These pathways are intelligently orchestrated, and I don't understand them completely. I don't want to cause damage. But re. caffeine, I am waiting for feedback by someone who tested it (by drinking coffee ).

Supplemented inositol won't influence the IP3R I think. Lithium is an IP3R inhibitor (if I remember correctly), and I think in contrast to caffeine, it doesn't influence the ryanidine receptors.

Do you think that your mutation in the IP3R is blocking your receptors?

you may be interested in this study about IP3R KO mice cells, it shows an increase in inosine (cf table1):

https://www.sciencedirect.com/science/article/pii/S0167488915002578

Fig. 4. Metabolic alterations and schematic representation of ROS-related pathways in IP3R KO DT40 cells.
The changes in ROS, antioxidant enzyme, and metabolite levels in IP3R KO DT40 cells, compared to the WT cells, are indicated on cellular energy metabolic pathways and cellular redox pathways. The increased metabolites in IP3R KO DT40 cells are colored in red, decreased ones in blue, and those without significant changes in green. The levels of ROS species (O2−, ONOO−and H2O2) were deduced from the flow cytometry results and the levels of SOD2 and catalase (see text). The abbreviations are as follows: ALA, alanine; ARG, arginine; ASN, asparagine; ASP, aspartate; GLU, glutamate; GLN, glutamine; ILE, isoleucine; LAC, lactate; LEU, leucine; OAA, oxaloacetate; PRO, proline; SUC, succinate; VAL, valine; G6P, glucose 6-phosphate; R5P, ribulose 5-phosphate; F6P, fructose 6-phosphate; PYR, pyruvate; CIT, citrate; ACA, acetyl-CoA; AKG, α-ketoglutarate; NAD+/NADH, oxidized/reduced nicotinamide adenine dinucleotide; NADP+/NADPH, oxidized/reduced nicotinamide adenine dinucleotide phosphate; GSH/GSSG, reduced/oxidized glutathione; ATP/ADP/AMP, adenosine triphosphate/diphosphate/monophosphate; O2−, superoxide anion; ONOO−, peroxynitrite; H2O2, hydrogen peroxide; SOD2, superoxide dismutase 2; CATA, catalase; GPx, glutathione peroxidase; GR, glutathione reductase.

 

[Inara]

Do you think that your mutation in the IP3R is blocking your receptors?

I don't know. My feeling is the Ca signal may be altered; sometimes I think the receptor may leak too much Ca.

The study is very interesting, and I will read it. Thank you!

I see these were mice completely devoid of any IP3R. (Funny they survived...) That makes it difficult to draw comparisons to single IP3R1, IP3R2 or IP3R3.

 

[Archie]

Dont know if someone already write about the connection between : EMF radiation------Intracellular calcium--------Elevated Peroxynitrite & CFS


This spotted on mercola.com

Reduce EMF Exposure
January 08, 2018

https://articles.mercola.com/sites/articles/archive/2018/01/08/reduce-emf-exposure.aspx


"
Martin Pall, Ph.D., Professor Emeritus of biochemistry and basic medical sciences at Washington State University, has identified and published several papers describing the molecular mechanisms of how EMFs from cellphones and wireless technologies damage humans, animals and plants.2,3,4,5,6 Many studies indicate your intracellular calcium increases with exposure to EMFs.


Pall also discovered a number of studies showing that you can block or greatly reduce the effects of EMFs using calcium channel blockers — medication commonly prescribed to patients with heart disease. Notably, it is the excess calcium in the cell and increased calcium signaling that are responsible for a vast majority of the biological effects of EMFs.


Pall discovered no less than 26 bodies of research asserting that EMFs work by activating voltage-gated calcium channels (VGCCs), which are located in the outer membrane of your cells. Once activated, they allow a tremendous influx of calcium into the cell — about 1 million calcium ions per second per VGCC.


When there's excess calcium in the cell, it increases levels of both nitric oxide (NO) and superoxide. While NO has many beneficial health effects, massively excessive amounts of it react with superoxide, forming peroxynitrite, which is an extremely potent oxidant stressor.


Peroxynitrites, in turn, break down to form reactive free radicals, both reactive nitrogen species and reactive oxygen species, including hydroxyl radicals, carbonate radicals and NO2 radicals — all three of which do damage. Peroxynitrites also do their own damage. All this to say EMFs are not having a thermal influence; they are not "cooking" your cells as some suggest. Rather, EMF radiation activates the VGCCs in the outer cell membrane, triggering a chain reaction of devastating events that, ultimately:

• Decimates your mitochondrial function, cell membranes and cellular proteins
• Causes severe cellular damage
• Results in DNA breaks
• Dramatically accelerates your aging process
• Puts you at higher risk for chronic disease

Peroxynitrites, Cellphones and Spikes in Chronic Disease

Once formed, peroxynitrite reacts relatively slowly with biological molecules, making it a selective oxidant. Inside your body, peroxynitrites modify tyrosine molecules in proteins to create a new substance, nitrotyrosine and nitration of a structural protein.7 These changes from nitration are visible in human biopsy of ALS, atherosclerosis, inflammatory bowel disease, myocardial ischemia and septic lung disease.8

Significant oxidative stress from peroxynitrites may also result in single-strand breaks of DNA.9 This pathway of oxidative destruction triggered by low−frequency radiation emitted from mobile devices may partially explain the unprecedented growth rate of chronic disease since 1990.10 This, truly, is a far greater concern than brain tumors, when it comes to the hazards of cellphones.

Once you understand cellphones can contribute to these chronic diseases — not just brain tumors — you may be more motivated to limit your exposure. Although the top health threats continue to be cardiovascular disease, cancer and infections, the rates of increase noted for the following diseases and disorders is astounding. Some of them were not even public knowledge prior to 1980.11 "



Elevated Peroxynitrite as the Cause of Chronic Fatigue Syndrome

https://www.tandfonline.com/doi/abs/10.1300/J092v07n04_05


Elevated, sustained peroxynitrite levels as the cause of chronic fatigue syndrome.

https://www.ncbi.nlm.nih.gov/pubmed/10790736


New Theory on Explanations for Chronic Fatigue Syndrome

https://www.prohealth.com/library/new-theory-on-explanations-for-chronic-fatigue-syndrome-19645


Wi-Fi is an important threat to human health

https://www.sciencedirect.com/science/article/pii/S0013935118300355



It look`s like there is direct effect from EMF radiation to calcium and peroxynitrite levels , and other effects also, which cause issues with mitochondrions , which are power house of the cell`s . CFS have problems with the power in cell mitochondrions ? So trying to limit EMF exposure look to be something that might help with CFS and infact all living as it is not healthy to anyone .

 

[Archie]

Now i start wonder if Carbon-60, also known as C60, buckminsterfullerene could have helpfull effects to the above mentioned chain reactions , reactive oxygen species ( ROS ) and nitric oxide ( NO ) etc ?

https://www.nexusnewsfeed.com/artic...0-reducing-the-oxidative-stress-of-emf-and-5g


There was allready a own topic for C60

https://forums.phoenixrising.me/ind...from-c60-supplement.62658/page-2#post-1022835


"
Concluding remarks
Defense against peroxynitrite occurs at various levels ; de-
fense strategies can vary between tissues and between subcel-
lular compartments. The damaging potential of peroxynitrite
is mediated by reactive oxidizing and nitrating species formed
during the reaction of peroxynitrite with biomolecules. There-
fore, cellular strategies of antioxidant defense not speci¢c to
peroxynitrite may also play a role in defense against damage
due to peroxynitrite."



https://core.ac.uk/download/pdf/81108761.pdf

http://www.drmarcochover.com/ponencia2011/archivos/pall.pdf

How Can We Cure NO/ONOO− Cycle Diseases?

http://www.townsendletter.com/FebMarch2010/cureNO0210.html


C60 might be something that prevent forming peroxynitrite , if i understand right it`s main effect is being very good antioxidant on cell level .

 

[Archie]

Rooibos tea contains Gallic acid , which is a Peroxynitrite scavenger , and Rooibos seems to be good for brain https://ikaasss.wordpress.com/2010/01/23/rooibos-for-brain-body-and-more/

There are also other natural compounds that are Peroxynitrite scavengers.


https://www.tapatalk.com/groups/herbsmxf/gallic-acid-sources-that-are-food-grade-t4271540.html

 

[frozenborderline]

Good point @Murph I've been told we can't taste calcium, its so ubiquitous.

They sure are. I suspect we woukd need to read a few hundred papers to fully understand what's going on. I sure wish out doctors knew more about this...


Low pregnenolone was one of the findings mentioned at the Symposium. My doctor put me on it, but I can only toleratate about 10mg. Any more and my estrogen goes through the roof, which is not good as I had an estrogen-driven cancer. I've heard it can promote testosterone in other patients. It's worth trying but with some care...

This is possibly because most pregnenolone on the market has diosgenin as an impurity, since it’s synthesized from that One would think trace amounts of diosgenin wouldn’t matter but it’s an extremely potent estrogen, active in the mcg range

 

[Learner1]

Diosgenin can convert into any hormone. It is useful to monitor hormones until one understands one's individual tendencies to convert and use hormones.

 

[frozenborderline]

Interesting. In tuning the brain, Goldstein mentions p2x receptors, purinergic signaling, and says agonism may be excitatory ans inflammatory. He says that drugs that influence ca2+ Flux may halal be purinergic receptor antagonists. @Iritu1021 you May have already known this but this seems to be a anticipation of naviauxs theory in Goldstein’s work. I wonder which drugs Goldstein is speaking of. He kinda glosses over this

 

[frozenborderline]

I have to explore Akt issue more in-depth but check out arteseminin/artesunate: https://academic.oup.com/cid/article/47/6/804/325924

I was just looking at Artesunate Bc of looking at hhv-6 in cfs. I wonder if artemisin has similar effect

 

[Iritu1021]

I was just looking at Artesunate Bc of looking at hhv-6 in cfs. I wonder if artemisin has similar effect

I've seen one article that said there are some slight differences. Both seem to work against EBV and other herpes family viruses but artesunate was effective against hepatitis while artesimine wasn't.

 

[Learner1]

My doctor gave me both IV artesunate and artemisinin for several months in suppository form.

Even though they both should be effective against EBV and HHV6, I still had both and didn't start improving until I was on Valcyte and IVIG.

Artesunate is a useful drug, but I suspect not having a fucruonal.immunse system didn't allow it to do its j7ob.

 

[xrayspex]

I am using Nimodipine at a very low dose (7.5mg, i.e. 1/4th 30mg tablet). I also tried verapamil and nifedipine, none of which worked better, so I stick with Nimo, because it is very safe with very few adverse effects.

My hypothesis is the problem in my case is "too much", because I consistently get worse whenever I go up with my calcium intake (food, supplements or Vitamin D, all "works" that way).

The problem is you can't do it by eliminating calcium from your diet entirely or going very low on Vitamin D because once you do, parathyroid hormone goes up and the body maintains a certain level of calcium in the blood by taking it from the bones.

I am looking for other ways to reduce intracellular calcium, if anyone has suggestions, I'd appreciate it.

why is going low on vitamin d a way to reduce calcium? I can't tolerate vitamin d or the sun but i have really low vitamin d on blood tests (like a 7)....maybe there is a benefit....except I do have ostepenia but i imagaine I also am at risk for calcium influx

 

[Wonkmonk]

Vitamin D increases calcium absorption from the intestine, so if you have higher Vitamin D you take up more calcium from foods and supplements. So all else equal, with higher Vitamin D you also have more calcium in the body.

But it doesn't make sense to go very low with vitamin D because if it is very low and don't get a certain amoung of calcium from food and supplements, parathyroid hormone gets upregulated, which takes calcium from the bones and uses it to get to a certain level of calcium in the blood.

That's why I avoid having too low calcium. It seems having about 20 ng/ml seems to be OK. If I went lower, parathyroid hormone would be upregulated and I would have the same amount of calcium but wouldn't have the other beneficial effects Vitamin D has (on immune system function for instance).

Did you try Vitamin D2 as a supplement? Perhaps you can tolerate that form. From the sun, we produce Vitamin D3 and most supplements are also D3. D2 is a different, a bit less potent form. Maybe it can be tolerated better. You can also expose white mushrooms to sunlight (in summer and spring, doesn't work in winter), and they produce some Vitamin D2. Perhaps that could be something you can try, too.

 

[Iritu1021]

Sigma 1 agonist may be a possible solution to CNS calcium dysregulation.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4906365/figure/F0009/?report=objectonly

 

[tiredowl]

I see some people mentioning artesunate, does it have a negative effect on mitochondria? I remember reading somewheree that Artemisia derivatives does have an effect on mitochondria, not sure if it was good though.

 

[Learner1]

Yes, it affects mitochondria, which is how some of the benefits occur:

http://www.atmph.org/article.asp?is...me=2;issue=2;spage=37;epage=41;aulast=Anyasor

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128040/

This article discusses some of the benefits, beyond its effectiveness in malaria and cancer treatment:

https://www.hindawi.com/journals/bmri/2016/1489050/

 

[tiredowl]

Learner1, Do you think it will be bad for ME patients to take it? Since we already have issues with our mitochondria working properly... maybe it could make some worse?

 

[Learner1]

I think its a matter of weighing risks and rewards.

The current literature says its extremely effective for cancer. I was given it for stage 3 endometrial and ovarian cancer, and much to my conventional oncologist's surprise, I have not experienced a recurrence in 5 years where his other patients who presented like me and went through the same surgery and chemotherapy unfortunately have.

It is also the first choice for malaria. And it has been shown to be effective for EBV and other viruses.

I was given it for chronic EBV, along with high dose vitamin C, but it didn't faze it. It wasn't until I went on valganciclovir that my EBV became PCR negative and symptoms went away. My immune system wasnt functioning well when I tried the artesunate, and I qualified for IV Immunoglobulins for immunodeficiency, so perhaps if my immune system had been stronger, artesunate might have been more effective as it was in the studies.

And, I ended up with significant mitochondrial damage, which has responded to phospholipid treatment. I have some genetics, like heriditary hemachromatosis and SOD2 SNPs, which I believe made the situation worse, and I had been on carboplatin and paclitaxel, which work by damaging the mitochondria of cancer, and I have some other interesting SNPs, so perhaps it was the additive effect of all of these factors that led to the mitochondrial damage. I have a question in to one of the researchers to try to learn more.

But there are reports of people being on artesunate for prolonged periods experiencing mitochondrial-driven neuropathy, so risks are beginning to be known.

Thank you for asking the questions - it's given me another clue. For you, I think it would depend on what problems you're trying to solve, how serious they are, and the priorities.

And, as I've found, there are ways of mitigating the risks with phospholipids.