Re: Stan - Valtrex and adenosine?

[Guest guest]

Hi Natasa,

It was actually adeonsine levels. The small study was done by Dr. Baker and

published at a

DAN! conference and netcasted about a year or two ago. It was spoken about

again at the

last Think Tank during my Valtex presenation and Dr. Baker included it in his

presention

on Thiols at this past conference.

I was procrastinating finding the slide and uploading it, so thank you for the

question. It's

now in the FILES section as: " Acyclovir Adenosine Slide - Dr. Baker "

Additionallly, this was an email earlier in the year from Jill PhD:

" Acyclovir is a PNP (purine nucleoside phosphorylase) inhibitor - it inhibits

this early step

in de novo purine synthesis. Adenosine is a purine so its de novo synthesis

would be

inhibited and adenosine levels would drop. Sid and I have documented a decrease

in

adenosine levels with Acyclovir in kids with elevated levels - he presented it

last year at

DAN. I believe it blocks viral replication by the insertion of a pyrimidine

analog that blocks

DNA synthesis. "

And if that isn't enough, I don't think it's the whole story, because in some

cases where

adenosine was low, alcyclovir seemed to raised it, so rather than a lowering

effect it is a

modulation effect.

I would like to duplicate this work in another study. I'm working on that now.

- Stan

>

> Hi Stan, I recall you mentioned there might be a connection between

> Valtrex and adenosine (or adenosine receptors?) - could you please give

> some more details. Was your observation/report based on changed

> adenosine levels pre and post Valtrex or something else? Any idea what

> might be at play there?

>

> TIA

> Natasa

>

[Guest guest]

Hi Natasa,

It was actually adeonsine levels. The small study was done by Dr. Baker and

published at a

DAN! conference and netcasted about a year or two ago. It was spoken about

again at the

last Think Tank during my Valtex presenation and Dr. Baker included it in his

presention

on Thiols at this past conference.

I was procrastinating finding the slide and uploading it, so thank you for the

question. It's

now in the FILES section as: " Acyclovir Adenosine Slide - Dr. Baker "

Additionallly, this was an email earlier in the year from Jill PhD:

" Acyclovir is a PNP (purine nucleoside phosphorylase) inhibitor - it inhibits

this early step

in de novo purine synthesis. Adenosine is a purine so its de novo synthesis

would be

inhibited and adenosine levels would drop. Sid and I have documented a decrease

in

adenosine levels with Acyclovir in kids with elevated levels - he presented it

last year at

DAN. I believe it blocks viral replication by the insertion of a pyrimidine

analog that blocks

DNA synthesis. "

And if that isn't enough, I don't think it's the whole story, because in some

cases where

adenosine was low, alcyclovir seemed to raised it, so rather than a lowering

effect it is a

modulation effect.

I would like to duplicate this work in another study. I'm working on that now.

- Stan

>

> Hi Stan, I recall you mentioned there might be a connection between

> Valtrex and adenosine (or adenosine receptors?) - could you please give

> some more details. Was your observation/report based on changed

> adenosine levels pre and post Valtrex or something else? Any idea what

> might be at play there?

>

> TIA

> Natasa

>

[Guest guest]

That is really interesting and my feeling is it could turn out to be

very important, not just in terms of regulating adenosine levels (which

could be a downstream occurence) but of regulating adenosine RECEPTORS

activities.

have a look at this: http://www.people.memphis.edu/~pbridson/research.htm

I especially liked the bit re acyclovir:

"...These and related compounds selectively affect biological processes by

interacting with enzymes or receptors in place of the natural ligands that

they resemble."

and:

"it is well known that ... adenosine is a component of nucleic acids, and that its

nucleotides ... play important roles in cellular

metabolism. Less well known is the fact that adenosine itself regulates

metabolic activity by acting as a neurotransmitter .... Ligands for adenosine receptors in the central

nervous system may be useful in the treatment of cognitive disorders,

Parkinson's disease, and psychoses.."

Furthermore adenosine receptors are closely linked to many other

channels and receptors on membrane surface, and notably many of those

closely linked channels often pop up in monogenetic autism disorders...

Natasa

p.s. if anyone is remotely interested in a ligand/protein binding here is a great explanation:

http://www.york.ac.uk/depts/chem/staff/elaborate/packages/binding/binding-why.html

> >> > Hi Stan, I recall you mentioned there might be a connection between> > Valtrex and adenosine (or adenosine receptors?) - could you please give> > some more details. Was your observation/report based on changed> > adenosine levels pre and post Valtrex or something else? Any idea what> > might be at play there?> > > > TIA> > Natasa> >>

[Guest guest]

That is really interesting and my feeling is it could turn out to be

very important, not just in terms of regulating adenosine levels (which

could be a downstream occurence) but of regulating adenosine RECEPTORS

activities.

have a look at this: http://www.people.memphis.edu/~pbridson/research.htm

I especially liked the bit re acyclovir:

"...These and related compounds selectively affect biological processes by

interacting with enzymes or receptors in place of the natural ligands that

they resemble."

and:

"it is well known that ... adenosine is a component of nucleic acids, and that its

nucleotides ... play important roles in cellular

metabolism. Less well known is the fact that adenosine itself regulates

metabolic activity by acting as a neurotransmitter .... Ligands for adenosine receptors in the central

nervous system may be useful in the treatment of cognitive disorders,

Parkinson's disease, and psychoses.."

Furthermore adenosine receptors are closely linked to many other

channels and receptors on membrane surface, and notably many of those

closely linked channels often pop up in monogenetic autism disorders...

Natasa

p.s. if anyone is remotely interested in a ligand/protein binding here is a great explanation:

http://www.york.ac.uk/depts/chem/staff/elaborate/packages/binding/binding-why.html

> >> > Hi Stan, I recall you mentioned there might be a connection between> > Valtrex and adenosine (or adenosine receptors?) - could you please give> > some more details. Was your observation/report based on changed> > adenosine levels pre and post Valtrex or something else? Any idea what> > might be at play there?> > > > TIA> > Natasa> >>

[Guest guest]

Nice find.

I wonder if that's part of the answer to the question about how Valtrex also

raises low

levels of adenosine. It actually may be replacing some missing element to

adenosine in

these kids to raise low levels but it also can block high levels. Really

interesting.

And it's a neurotransmitter. This is very interesting too.

I took a peek at clinical symptoms of high adenosine and the first thing I found

the article

" Role of Endogenous Adenosine as a Modulator of Syncope Induced During Tilt

Testing "

http://circ.ahajournals.org/cgi/content/full/circulationaha;106/5/569

which led me to, " What you need to know about Vasovagal Syncope "

http://www.londoncardiac.ca/pages/vvs.htm

Both of which are talking about reduced blood flow.

I don't know if it is related but we do know that SPECT scans indicate that our

kids have

reduced blood flow to parts of the brain. Again, it might be a stretch, but I

thought that

was interesting.

[Also I noticed how high adenosine can cause immune supression in this article.]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

cmd=Retrieve & db=pubmed & dopt=Abstract & list_uids=11992407 & query_hl=1 & itool=pub

med_docsum

Adenosine acts through an A3 receptor to prevent the induction of murine

anti-CD3-

activated killer T cells.

[Then found an example of a person with a negative herpes PCR who had herpes on

the

brain and high adeonosine.]

Clin Infect Dis. 2003 Jul 1;37(1):147-8. Related Articles, Links

High levels of adenosine deaminase in a patient with herpetic encephalitis and

initial

negative PCR results.

-Gomez M, -Ruz MA, Jimenez-Alonso J.

Publication Types:

Case Reports

Letter

PMID: 12830421 [PubMed - indexed for MEDLINE]

So understanding more about adenosine and adenosine modulation may seem more and

more important.

I have to run for a bit, but I think this discussion will continue.

- Stan

> > >

> > > Hi Stan, I recall you mentioned there might be a connection between

> > > Valtrex and adenosine (or adenosine receptors?) - could you please

> give

> > > some more details. Was your observation/report based on changed

> > > adenosine levels pre and post Valtrex or something else? Any idea

> what

> > > might be at play there?

> > >

> > > TIA

> > > Natasa

> > >

> >

>

[Guest guest]

Nice find.

I wonder if that's part of the answer to the question about how Valtrex also

raises low

levels of adenosine. It actually may be replacing some missing element to

adenosine in

these kids to raise low levels but it also can block high levels. Really

interesting.

And it's a neurotransmitter. This is very interesting too.

I took a peek at clinical symptoms of high adenosine and the first thing I found

the article

" Role of Endogenous Adenosine as a Modulator of Syncope Induced During Tilt

Testing "

http://circ.ahajournals.org/cgi/content/full/circulationaha;106/5/569

which led me to, " What you need to know about Vasovagal Syncope "

http://www.londoncardiac.ca/pages/vvs.htm

Both of which are talking about reduced blood flow.

I don't know if it is related but we do know that SPECT scans indicate that our

kids have

reduced blood flow to parts of the brain. Again, it might be a stretch, but I

thought that

was interesting.

[Also I noticed how high adenosine can cause immune supression in this article.]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

cmd=Retrieve & db=pubmed & dopt=Abstract & list_uids=11992407 & query_hl=1 & itool=pub

med_docsum

Adenosine acts through an A3 receptor to prevent the induction of murine

anti-CD3-

activated killer T cells.

[Then found an example of a person with a negative herpes PCR who had herpes on

the

brain and high adeonosine.]

Clin Infect Dis. 2003 Jul 1;37(1):147-8. Related Articles, Links

High levels of adenosine deaminase in a patient with herpetic encephalitis and

initial

negative PCR results.

-Gomez M, -Ruz MA, Jimenez-Alonso J.

Publication Types:

Case Reports

Letter

PMID: 12830421 [PubMed - indexed for MEDLINE]

So understanding more about adenosine and adenosine modulation may seem more and

more important.

I have to run for a bit, but I think this discussion will continue.

- Stan

> > >

> > > Hi Stan, I recall you mentioned there might be a connection between

> > > Valtrex and adenosine (or adenosine receptors?) - could you please

> give

> > > some more details. Was your observation/report based on changed

> > > adenosine levels pre and post Valtrex or something else? Any idea

> what

> > > might be at play there?

> > >

> > > TIA

> > > Natasa

> > >

> >

>