Excellent Neurology Study Done In India - A Must Read

Hello All,

I'm back from CA., and have much to share, but am still mulling over all the data from the tests, so give me a few days to group it together. I found this study from India tonight, and thought it was quite profound. Here's part of it, and I think it is quite profound. Everyone should read through it thoroughly, as it could very much pertain to us, even though it's comparing other diseases to control subjects. My question is, does the body make digoxin. Apparently so. Is that a pro-arrhythmic med, and if so, could it be in our own systems, causing arrhythmia?

[www.neurologyindia.com]

Discussion

The increase in the activity of HMG CoA reductase, a
key enzyme in the isoprenoid pathway in all these
disorders, suggests an upregulation of this pathway
which agrees with the increase in the level of digoxin,
a product of this pathway. On the other hand, the level
of ubiquinone, which is also a product of this pathway,
is decreased. This probably may be due to the fact that
less of the concerned precursor (farnesyl
pyrophosphate) is channeled for the synthesis of the
side chain of ubiquinone. It may also be due to
decrease in the synthesis of the aromatic ring portion
of ubiquinone which is derived from the aromatic
amino acid, tyrosine. The decrease in tyrosine
observed in these disorders supports this view.
The important observations made in all the disorders,
in this study are : (a) increase in endogenous digoxin
in these disorders, (b) increase in tryptophan levels
along with all its catabolites (namely serotonin, 5-
hydroxyindoleacetic acid, quinolinic acid, kynurenic
acid, strychnine and nicotine) and (c) decrease in
levels of tyrosine and its catabolites, namely
dopamine, epinephrine and norepinephrine.
Morphine, which is derived from tyrosine, was not
detectable in any of these disorders except in MS.
Free fatty acids compete with tryptophan for albumin
binding, and the increase in the plasma free fatty acid
observed in these disorders may result in less
tryptophan binding with consequent increase in free
tryptophan. Digoxin is reported to increase
catecholaminergic transmission and catecholamines
promote lipolysis with resultant increase in free fatty
acid and consequent increase in free tryptophan and
its transport. Decrease in albumin, consequent to
membrane Na+-K+ ATPase inhibition related
hypomagnesaemia induced blockade of protein
synthesis, may cause decrease in its binding to
tryptophan. The net effect of all these factors is that
more free tryptophan is available to cross the blood
brain barrier. The decrease in the plasma level of
tyrosine in these patients may be the result of
competition between it and tryptophan, for the same
transport system and also probably of the differential
effect of digoxin in promoting tryptophan transport.
Na+-K+ ATPase inhibition can also result from
decreased levels of dopamine, noradrenaline,
morphine and thyroxine and increased levels of
serotonin, nicotine, strychnine and quinolinic acid.19
It is known that inhibition of this enzyme leads to
increase in intracellular calcium due to increase in
Na+-K+ exchange, increased entry of calcium via
voltage gated calcium channel, and increased release
of calcium from intracellular endoplasmic reticulum
calcium stores.20 The increase in intracellular calcium
by displacing magnesium from its binding sites leads
to a decrease in functional availability of magnesium.
Decrease in magnesium inhibits Na+-K+ ATPase
further, as ATP-magnesium complex is the actual
substrate for the reaction. Thus, there is a progressive
inhibition of Na+-K+ ATPase, triggered by an initial
insult.
(FRAN) Increased intracellular calcium in the postsynaptic
neuron can activate calcium dependent NMDA signal
transduction system.21 The plasma membrane
neurotransmitter transporter of glutamate in the glial
cell and presynaptic neuron is coupled to a sodium
gradient,22 which is disrupted by inhibition of Na+-K+
ATPase resulting in decreased clearance of glutamate,
by presynaptic and glial uptake at the end of synaptic
transmission. By this mechanism, membrane Na+-K+
ATPase inhibition can promote glutamatergic
transmission. Strychnine displaces glycine from its
binding site and inhibits glycinergic inhibitory
transmission in the brain.23 The glycine is free to bind
to the strychnine insensitive site of the NMDA
receptor and promote NMDA transmission

Another part:

Intracellular magnesium deficiency can lead to
decreased ATP synthesis and defective formation of
dolichol phosphate required for N-glycosylation and
also decreased formation of nucleoside diphosphate
sugars for O-glycosylation. This leads to defective
glycoconjugate synthesis. Defective glycosylation of
endogenous myelin glycoprotein antigen can lead to
defective formation of MHC-antigen complex.29
Defective presentation of myelin glycoprotein antigen
to the CD8+ cell can explain the immune
dysregulation in MS.30 Defective glycoproteins can
lead to altered contact inhibition and oncogenesis.
Defectively processed glycoproteins accumulate as
they resist lysosomal digestion, leading to neuronal
degeneration, as in the case of amyloid.31 Defective
glycoproteins can also result in disordered synaptic
connectivity and functional disorders like epilepsy
and schizophrenia.

And more:

: (1) Intracellular magnesium
deficiency can lead to protein tyrosine kinase
dysfunction, an insulin receptor defect.34 (2)
Increased intracellular calcium can lead to increased
G-protein coupled signal transduction of the contra
insulin hormones - glucagon, growth hormone and
adrenaline. (3) Increased intracellular calcium can
open up the mitochondrial PT pore producing
mitochondrial dysfunction; and reduction in
intracellular magnesium can inhibit ATP synthase.
Decreased intra cellular magnesium can also lead to
inhibition of glycolysis and citric acid cycle. Thus
glucose utilization as a whole is decreased. (4)
Increased intracellular calcium can increase the signal
transduction of the G protein coupled platelet
activating factor receptor and thrombin receptor,
producing thrombosis. Intracellular magnesium
deficiency can also produce vasospasm described in
syndrome-X. (5) Nicotine is known to produce
vasospasm. It can also produce autonomic ganglionic
stimulation, adrenal medullary stimulation and carotid
and aortic body stimulation leading to hypertension.23
(6) Nicotine administration has also been reported to
produce significant changes in lipid metabolism

A sentence for PC:

This also leads to volume dysregulation of
mitochondria, causing hyperosmolality of matrix and
expansion of matrix space.

As for myself, I can tell you that I was lowest in tryptophan, but was also low in phenylalanine and tyrosine, with a disruption in my pathway to noradrenalin. Dr. Gersten is prescribing tryptophan and wants me to take tyrosine with N-acetyl tyrosine, as well. I also will be taking reg. B and coenzymated B vitamins, as well a Mg. glycinate, among other supps, that I will let you know in my followup. As you may have noticed in the CR, I was extremely low in molybdenum, which he said was the most important finding.

Jerry,

If you're out there in virtual world, I'd like to do a thread and compare our results, if you have yours, or we can wait for an opportunity to do a discussion and post in the CR if that's alright with Hans. It doesn't matter to me.

Richard,

Good to have you back my friend. I've only had a cursory glance at your posting, but it triggered memories of former discussions on this forum regarding 'natural' digoxin levels. I can't remember the specifics, but the gist was that high digoxin readings have been obtained from individuals NOT on the drug itself.............. Hopefully, someone here will remember more about this, the discussions pertaining to which may have taken place before you joined this forum.

Later,

MIke F.

Thank you, Mike, for welcoming me back. I see where my wife continued on in my absence. We have both been studying every free moment we get, as we're determined to get to the bottom of this. In all our reading, we have never come across the body having natural levels of digoxin. That very much intrigued me, so I'll have to see what I can find, and hopefully if someone out there has something to share, they'll pipe in. I hope you read this study, in its entirety, by going to the link, Mike. It tells the story of the various diseases, their commonalities, and causes. Unfortunately it doesn't say what to do. I have always thought that I could find answers, by studying other diseases, and this study proved that.

I have much to do, in getting ready for my big post on my test results. By the way, my wife met, yet another TWO people with arrhythmias last night at an open house. Something is not right in our world. Erling, it's nice to see you posting here again. I believe you bring a spiritual intelligence and helpfulness to us.

Richard

Richard,

Welcome back.

Mike is correct. You may want to visit

The Isoprenoid Pathway in Lone Atrial Fibrillation with Embolic Stroke by several of the same Indian investigators at
[www.indianheartjournal.org].

I read this and posted about it sometime ago. Because I am left handed
I checked my endogenous digoxin levels. Fortunately they were not elevated.

PC v54

PC,
I am amazed at your detail and thought process. What is your background?

Joe

J.

FYI some people think my thought processes are somewhat demented.

I'm just your basic pathologist (guy that cuts up dead people).

PC v54

PC
I could not resist, my daughters job is to bring you the dead people that you cut up. she transports them but mostly to funeral homes.

Come to think of it maybe she picks them up after you have done your job. (grin)

Ella