Topic: TWO not ONE Na-Ca channels...TRPM8 AND TRPC6...PLA2
Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
For SERIOUS researchers only PLEASE.
I realize most of you who are suffering with neuro lyme will not be able to understand the following.
Those who are able to think clearly are
trying desperately
to figure out how to help those who are suffering the mental and physical consequences of this infection because abx. ALONE are not curing this infection.
It appears photon therapy -> the closure of the TRPM8 channel which prevents Na and Ca from going INTO the cells.
The animation of that happening is here:
http://neurobio.drexel.edu/SesslerWeb/sessler.php Bb NEEDS Na and Ca to go into the cells. It needs Na for its Na-ATPase and NaCl for motility. Ca activates an enzyme Bb uses to metabolize alanine and proline.
It has a PKC inhibitor to intentionally trigger Ca to go into the cell...makes sense...Bb "says" it does not want Ca to go into the cell...so we send it in.
Pretty sneaky.
(Na influx is also triggered).
Bb uses those 2 electrolytes (Na and Ca), but has an anti-porter for Na and has a gene to export Ca.
In they go...out they go...in they go...out they go.
That is the TRPM8 "cold activated" channel. We respond by sending in "de-icers"...NaCl and CaCl...when we really need MgCl (another "de-icer" to go in). Bb is triggering the more reactive minerals (Na and Ca) to go into the cells.
It appears (thanks for the Methylene blue link!)that the MAOI inhibitors work by increasing GTP which -> the closure of that channel...and no Na or Ca can go in. That should lead to Bb's destruction.
Guess what is a MAOI inhibitor and INactivates PKC?
It appears NO (nitric oxide) binds to guanylate cyclase (sGC) -> GTP
which ***via magnesium*** -> cGMP +
***PPi*** (pyrophosphate).
Don't "stop" with just increasing GTP to close the Na-Ca channel.
Now that cell needs Mg to make PPi.
That PPi can help us to do this: ADP-> ATP.
So... do we make more NO to speed up the process (binding it to sGC)-> more GTP
OR
Do we inhibit sGC (=soluble guanylate cyclase) which might keep GTP levels higher longer?
It appears we need to get and then keep GTP levels up and THEN we need Mg to increase PPi (pyrophosphate) which is needed to make ATP.
For those of you who have been here a long time may remember my "H16" posts.
It took me a LONG time to figure out that connection.
Apparently "H16" represents vascular damage.
ATP has 16 hydrogens in its molecular FORMULA and so do many other things, INCLUDING Rocephin.
But...the way the elements are assembled, their STRUCTURE is what makes a difference whether they work or not.
C30H16O8 =
Hypericin is a *red-coloured* anthraquinone-derivative, which is together with Hyperforin one of the principal active constituents of Hypericum (Saint John's wort).
Hypericin is believed to act as an antibiotic and non-specific kinase inhibitor.
Hypericin may inhibit the action of the enzyme dopamine β-hydroxylase, leading to increased dopamine levels, although thus possibly
decreasing norepinephrine and epinephrine (= noradrenaline and adrenaline).
The large chromophore system in the molecule means that it can cause photosensitivity when ingested beyond threshold amounts.
Because hypericin accumulates preferentially on cancerous tissues, it is also used as an indicator of cancerous cells.
In addition, hypericin is under research as an agent in *photodynamic therapy*,
whereby a biochemical is absorbed by an organism to be later activated with spectrum-specific light
from specialized lamps or laser sources, for therapeutic purposes."
Notice the SLIGHT spelling difference between hypericin (C30H16O8 in St. John's Wort) and hypercinin (MAOI)!
I have to think this thru:
"Hyperforin is believed to be the primary active constituent responsible for the antidepressant and anxiolytic properties of the extracts of St. John's wort.
It acts as a *reuptake inhibitor of monoamines*, including serotonin, norepinephrine, dopamine, and of GABA and glutamate... It appears to exert these effects by activating the transient receptor potential ion channel TRPC6.
Activation of TRPC6 ***induces the entry of sodium and calcium*** into the cell which causes inhibition of monoamine reuptake.
Hyperforin is also thought to be responsible for the induction of the cytochrome P450 enzymes CYP3A4 and CYP2C9 by binding to and activating the pregnane X receptor."
It appears BOTH TRPM8 AND TRPM6 channels can be/are present in cancer....shoot!!! (Breast cancer for one)
This is what inhibits BOTH of those Na-Ca channels:
N-(p-amylcinnamoyl)anthranilic acid (ACA).
ACA has previously been reported to *inhibit phospholipase A2.*
OHHHHHH...that's where inhibiting PLA2 comes into play!
What does phospholipase A2 do?
Phospholipase A2 (PLA2) catalyzes the hydrolysis of the sn-2 position of membrane glycerophospholipids to
*liberate arachidonic acid (AA)*,
a precursor of eicosanoids including prostaglandins (PGs) and leukotrienes (LTs).
I've told you...too much AA is being produced! Great need to counter it with a LOT of EPA - an omega 3.
What inhibits PLA2?
Glucocorticoids indirectly inhibit the activity of phospholipase A2.
Glucocorticoids are naturally-produced steroid hormones, or synthetic compounds, that inhibit the process of inflammation.
What is a far better and safer way to inhibit inflammation?
If you didn't say the anti-inflammatory, Mg...shame on you!
Go to the following link to see which mineral inhibits PLA2:
Yes, lithium also impacts PLA2 (drives it down) and lithium can -> hypermagnesemia...helping the brain.
But that mineral (Li) is very very difficult to balance and tolerate because we need so little of that reactive mineral...THE most reactive mineral. LiCl helps, but I don't think it CURES.
IMO...Mg is the best choice...for your brain and the rest of the body.
High levels of PLA2 are related to heart problems (CAD).
"Second, we observed an inverse correlation between sPLA2 levels and HDL cholesterol levels in men and women. In recent years, evidence is accumulating that HDL cholesterol and inflammation are inversely related."
PPi (= pyrophosphate):
"Pyrophosphate Inhibits Mineralization of Osteoblast Cultures by Binding to Mineral, Up-regulating Osteopontin, and
The infected defense cells are making far too little ATP.
Support your immune system.
Reduce inflammation (ideally with MgCl) WHILE hitting/impacting Bb.
I think if you study the links (animation) and pictures I linked, you will begin to catch onto what I am saying.
Bb is INSIDE many of our defensive cells.
Let's knock Bb off (via increasing GTP and closing the Na-Ca channels), but ALSO help out those defensive cells which have been deprived of sufficient Mg-ATP
to transfer energy to help them "finish their job".
In a perfect world, MgCl IVs should be available to you...given on subsequent days along with IV abx.
We can use our skin to absorb MgCl. MgCl can be purchased from many sources...Liquimins is one. 4ml = 400mg of Mg. It also contains chloride and other nutrients in smaller amts. It runs about $6 for a blue glass bottle of it that has an eyedropper to measure the ml. 4ml = "serving" and 15 "servings" per bottle. 400mg is approximately the RDA level for Mg for an adult.
You can dilute it with *distilled* water and simply spray it on your skin.
I would also take sublingual B6 at the same time.
Remember Valletta's patent...."Magnesium for autoimmune"?
"Chilling induces a *decrease in pyrophosphate-dependent* H+-accumulation"
Bb is triggering intracellular acidosis in the cytoplasm of the cell by lowering PPi levels. The cells are too "cold" and we respond by sending in the WRONG "de-icers".
Once Bb is destroyed IN the defense cell, the body will either then destroy the cell (if there is DNA damage) OR will REPAIR the DNA damage...which CAN happen.
Too many inflammatory cytokines damage OUR DNA. The excessive "free radicals" are really really bad.
Kill Bb (by not allowing Na and Ca to go in) AND give our own defense cells a chance to repair themselves.
Chose ONE path (there IS more than one!) Do NOT combine these paths!!!
1.IV abx. AND IV MgCl...over subsequent days.
Or
2.MgCl (IV) and far infrared
Or
3.MgCl and Rife therapy
Or
4.Pycnogenol + HBO
Or
5,vitamin c (timed release is likely the best) + green tea extract
in addition to alanine, proline and lysine.
Follow bottle directions...I have no idea of the timing and doses needed...go slow.
IF you "herx" consider ACZ zeolite to bind NH3 (ammonia).
If you want to feel better pretty fast and are NOT TAKING ANY THING ELSE:
Mg citrate, 100mg - cut 200mg pills in half + (1)B complex + (1)lecithin...every 2 hours for 5 doses per day will help a lot.
You will feel the difference in as little as 3 days. Your mind will clear, you will feel less depressed, etc.
But in a few days, after feeling better, you WILL "herx" and panic. You will think lyme is back, is worse.
You "expect" to herx from abx. as Bb is destroyed, but are surprised when other things...even natural things...do the same.
Keep pumping in probiotics...lots and lots of varieties.
I am so grateful for all of your research.. I wish so much that I could understand it...
Would a LightWorks be enough to use?? And if so is there a certain way to be using it??
The Magic 5.... Do they still apply???
What about chlorella?? I use this everyday...
I also use Krill oil daily and still have had no help iwth the inflammation in my brain which keeps me bedridden and debilitaed.
I use Vitamin C, Drink 2 green smoothies daily with raw organic Greens and superfoods, Magnesium malate, Chlorella, B-complex, Matcha Green tea and extract, Juice veggies daily, eat all organic and mostly raw, Hawthorne berry for my heart, daily shots of wheatgrass juice, resevratrol, allicin, .....
All of that for A LONG time and still no improvements....
Is there soemthing I am missing???? I am to start Low Dose Naltrexone... do you have any thoughts on LDN???
Thank you!!!
-------------------- "You'll be surprised to know how far you can go from the point you thought it was the end" Posts: 946 | From Massachusetts | Registered: Apr 2008
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Pinelady
Frequent Contributor (5K+ posts)
Member # 18524
posted
Thanks Marnie for your efforts. Is this safe if you have high blood chloride levels like I do? Have had for over 2 years but doc unconcerned. I am willing to try anything. Already doing the C and green T.
-------------------- Suspected Lyme 07 Test neg One band migrating in IgG region unable to identify.Igenex Jan.09IFA titer 1:40 IND IgM neg pos 31 +++ 34 IND 39 IND 41 IND 83-93 + DX:Neuroborreliosis Posts: 5850 | From Kentucky | Registered: Dec 2008
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seekhelp
Frequent Contributor (5K+ posts)
Member # 15067
posted
Wow!
Posts: 7545 | From The 5th Dimension - The Twilight Zone | Registered: Mar 2008
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Pinelady
Frequent Contributor (5K+ posts)
Member # 18524
posted
Oh I forgot I am also throwing in 800 Vitamin E.
I know only what is needed will be absorbed, but
I think I am trying this on the fact it can
reduce cholesterol significantly maybe it will
pick up some of the bad stuff as well and help
remove. Now I want to add riboflavin. But I don't know the dosage.
-------------------- Suspected Lyme 07 Test neg One band migrating in IgG region unable to identify.Igenex Jan.09IFA titer 1:40 IND IgM neg pos 31 +++ 34 IND 39 IND 41 IND 83-93 + DX:Neuroborreliosis Posts: 5850 | From Kentucky | Registered: Dec 2008
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posted
Marnie - what are your feelings about the theory that Mg contributes to the formation biofilms.
Posts: 137 | From wethersfield ct | Registered: Mar 2006
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Dawn in VA
Frequent Contributor (1K+ posts)
Member # 9693
posted
Marnie, thank you in particular for providing the info ~ where to get the topical MgCl.
The timing of this is tricky for me to get a handle on. I've been using Lightworks infrared for a year or so now and have been taking Mg at various times before applying it. Any idea as to how long to wait b/t ingesting (not topical) Mg (+B6) and infrared?
-------------------- (The ole disclaimer: I'm not a doctor.) Posts: 1349 | From VA | Registered: Jul 2006
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Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
We KNOW Bb locks onto our plasminogen in basement membranes. Plasminogen sorta looks like a "cross". Bb looks to bind in the middle of that cross.
Where are the basement membranes? Picture of the location is here (really close to the blood vessels):
Now...plasminogen converts to plasmin by a VERY abundant enzyme (tPA = tissue plasminogen activator) we have in our blood.
I think plasmin is the "biofilm" which allows Bb a second "cloak" (the first is the SALP 15 protein which it gets from the tick's saliva).
This protein coat may allow for "quorum sensing" which is simply the chemical way the bacteria communicate to each other.
Picture it as the really thick mucous we can "hack" up.
Mg is needed to MAKE all of our enzymes...including one inhibits HMG CoA reductase which stops the cholesterol pathway.
Plasminogen activator (tPA) looks to bind to plasmin and this *inhibits plasmin from degrading fibrin*.
So normally plasmin would degrade fibrin.
Yes inhibiting tPA would be good...but getting tPA down too far = blood too thin which isn't good either. Remember the aspirin warnings? It is good and effective, but too much isn't good.
Heparin used to help for SOME strains of Bb, but not all.
Very little (too little) Mg is absorbed when we take it orally. We can use our largest organ...our skin...to absorb that which we need and to a certain extent avoid the digestive system.
B6 must be sublingual. Our very very strong stomach acids destroy most of it. Source Naturals makes it.
The timing. Good question!!! Apply MgCl (diluted in distilled water) before or right after EM therapies (along with taking a sub B6) OR just AFTER the EM therapies?
My GUESS...BEFORE.
This looks to be a 2 step process...reduce our inflammatory cytokines AND hit Bb simultaneously.
There are lots of ways to reduce inflammation.
MgCl is the ideal...and IV MgCl is the ideal.
But there is OmegaBrite (which DOES reduce TNF alpha and IL 1 B and it inhibits PLA2 !).
Likely very high doses are needed...spaced out.
Or ...there is Vitamin C and green tea extract...once again, likely high doses spaced out are needed.
I am "doing" the "magic five" as a test. I do NOT have lyme.
I follow the bottle directions, but use the timed release vitamin C that is in a gelatin capsule 'cause "regular" vitamin C does a "number on" my stomach. The gelatin capsules help prevent this.
When I am on the computer too long (often - LOL), my eyes get very red and I pop 2 OmegaBrite capsules which within a short period of time clears my eyes.
Honest.
Ongoing inflammation anywhere in the body is really really bad.
Gotta get TNF alpha and IL 1 B down!
Once the inflammatory cytokines ARE down, it may take LESS of an abx. to do the job. We don't want abx or the EM therapies to work TOO well TOO fast.
Keep pumping in probiotics...with a full glass of water one hour before a meal. The water dilutes the stomach acids and the timing allows them the time to reach the intestine where they can set up "housekeeping" and multiply.
When we die...and our proteins break down, NH3 = ammonia "happens".
I think when Bb dies (lipoprotein cell walls) and the once infected cells die (also made of proteins) this -> excessive and toxic NH3.
A "herx" may simply be excessive TOXIC NH3.
Bind it.
Consider ACZ Zeolite which is FDA approved to be safe. It binds NH3 and is eliminated via the kidneys.
Bb IS triggering the chloride channels.
Frontline, to PREVENT lyme for our DOGS, blocks chloride channels.
Once the chloride channels are activated, we need to take advantage of that fact.
Send in MgCl...LOTS because it is going to take a LOT of this to displace NaCl and CaCl. Na and Ca are more "reactive" minerals and will be used ahead of the needed Mg to make hydrogen.
The inside of the infected cells look to be very very acidic...and cold.
So we send in powerful "de-icers"...NaCl and CaCl.
MgCl is a "de-icer" too.
Chose ONE of the listed ways to rid Bb. Do NOT combine them.
I would ONLY do the "magic five" if I was NOT doing ANY other treatment.
Too much die-off too fast = sepsis = death.
LDN = bandaid. Treats some symptoms, not a cure.
A CURE is what I've been searching for...a safe, cheap (as cheap as possible), and effective cure. Amazingly...there IS more than one way to rid Bb, but they all take TIME.
This infection takes a LONG TIME to be eliminated. Know that upfront. The turtle wins the race. Go slow...the body can NOT handle massive die-off too fast.
Posts: 9481 | From Sunshine State | Registered: Mar 2001
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Dawn in VA
Frequent Contributor (1K+ posts)
Member # 9693
posted
"Consider ACZ Zeolite which is FDA approved to be safe. It binds NH3 and is eliminated via the kidneys."
Thank you for pointing that out- very good to know. I (we) don't always trust the FDA, but am concerned about taking more "drastic" binders like cholesteralamine (sp?) and the like b/c of stomach issues and binding with EVERYTHING.
Kidneys have enough to deal with from other treatments; they would be happy to avoid processing ALL that NH3 to ammonium. Help is good.
Edited to add: Some are concerned about zeolite moving heavy metals around. I will look this up later, but does it specifically bind to NH3 only? I guess other free radicals and maybe some metals too. But maybe molecular size gets too large to go across BBB at that point, so perhaps not too harmful to the noggin'.
I'll place a bet on those lizards and polypeptides in the long run. Just a "gut" feeling. (hey... we need to get Candace Pert involved in Bb research!!)
[ 07-06-2009, 07:10 PM: Message edited by: Dawn in VA ]
-------------------- (The ole disclaimer: I'm not a doctor.) Posts: 1349 | From VA | Registered: Jul 2006
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Pinelady
Frequent Contributor (5K+ posts)
Member # 18524
posted
Marnie I think you are right about the go slow thing. It makes sense if it took a long time to get
to diagnosis to treatment. If you put the brakes on too fast you can still get whiplash even if you
don't hit anything.
-------------------- Suspected Lyme 07 Test neg One band migrating in IgG region unable to identify.Igenex Jan.09IFA titer 1:40 IND IgM neg pos 31 +++ 34 IND 39 IND 41 IND 83-93 + DX:Neuroborreliosis Posts: 5850 | From Kentucky | Registered: Dec 2008
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