Re: Re: and Chelation-some abstracts

[Guest guest]

I just wanted to be more specific - he did say that he

feared that the immune system may have been damaged.

I wanted to repost an old post from Raptor regarding

some immune effects that chelation has. It is very

possible that the immunomodulating effects of

chelation could be part of the reason some children

respond, as there are multiple subclasses of immune

dysfunction present. It wouldn't be the first time

that a therapy that helped someone was thought to be

for one reason when something else entirely was going

on.

BTW - there has been very little discussion over the

last year regarding the actual primary findings behind

the hypothesis - Cytokines. By limiting our

discussions to the therapy (antivirals, antifungals,

SSRIs, sometimes IMGG and antibiotics when needed, we

are leaving out a great deal of information about the

much bigger picture of . (We also used to have

Kutapressin which was the big guns and not available

anymore and the 'replacement' is not trusted by Dr G

at this time.) I'll try to repost some good info

regarding this, and maybe if we discuss some of it, we

could give further explanations about where Dr G is

coming from when he rejects some therapies out there.

Here's the repost re chelation w/some notes from

Raptor. As you read it, it brings up the cytokine

issues and was also referencing to some other

therapies being mentioned at the time. It hits on the

key problem - over-riding the body's protective

mechanisms....

" Is it possible that metals are not the problem and

those who see benefits are seeing them for a

completely different reason. Chelation pulls other

ions like calcium which would have effects on

cytokines. If I'm remembering correctly, some

research on ALA and glutathione seemed to indicate

they could actually make a non-toxic level of

mercury.....toxic.

The abstract below on TTFD says it can act as a

potassium channel blocker. Evidently that might lead

to immune suppression. According to another abstract

below, (and info on OMIM) MT's are induced by the

cytokine IL-6, which may not be such a great thing

since the upregulation is in response to oxidative

stress.

More than normal doses of supplements can offset some

of the metabolic problems. The question is what are

the long term effects from over-riding the body's

protective measures. "

Neuropharmacology 1998;37(3):313-22 Related Articles,

Links

Thiamine and its derivatives inhibit delayed rectifier

potassium channels of

rat cultured cortical neurons.

Houzen H, Kanno M.

Department of Pharmacology, Hokkaido University School

of Medicine, Sapporo,

Japan. hohzen@...

We examined the effects of thiamine and its

derivatives on voltage-gated ion

channels of neuronal cells isolated from fetal

forebrain cortex and cultured

for 6-14 days. Under the whole-cell voltage clamp,

thiamine

tetrahydrofurfuryl disulfide (TTFD), a

membrane-permeable derivative of

thiamine, inhibited the delayed rectifier K+ current

(IK) in a

concentration-dependent manner (10(-4)-10(-3) M).

The IK-suppressing effect was also observed by

internal perfusion with 1 mM

thiamine, but not by the external application of

thiamine, indicating the

poor permeability of thiamine through the cell

membrane. However, thiamine

which was applied directly to the intracellular side

of patch membranes in

the inside-out configuration failed to decrease the

open probability of the

single IK channel. In contrast, thiamine diphosphate

decreased both the open

probability and the open-time of the channel without

changing the single

channel conductance.

These results suggest that phosphorylated thiamine can

function as an

endogenous K+ channel blocker in neuronal cells. TTFD,

when applied

extracellularly at a concentration of 1 mM, prolonged

the action potential

(AP) duration of neurons (172.8 +/- 6.6%) without

changing the resting

membrane potential or AP amplitude, while the same

concentration of thiamine

did not influence any parameters of the AP, implying

that TTFD may cause the

potentiation of neuronal AP through the inhibition of

IK.

PMID: 9681929 [PubMed - indexed for MEDLINE]

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Proc Natl Acad Sci U S A 1999 Sep 14;96(19):10917-21

Related Articles, Links

Inhibition of T cell proliferation by selective block

of Ca(2+)-activated

K(+) channels.

Jensen BS, Odum N, nsen NK, sen P,

Olesen SP.

NeuroSearch A/S, 93 Pederstrupvej DK-2750 Ballerup,

Denmark.

bsj@...

T lymphocytes express a plethora of distinct ion

channels that participate

in the control of calcium homeostasis and signal

transduction. Potassium

channels play a critical role in the modulation of T

cell calcium signaling,

and the significance of the voltage-dependent K

channel, Kv1.3, is well

established. The recent cloning of the

Ca(2+)-activated,

intermediate-conductance K(+) channel (IK channel) has

enabled a detailed

investigation of the role of this highly

Ca(2+)-sensitive K(+) channel in

the calcium signaling and subsequent regulation of T

cell proliferation.

The role IK channels play in T cell activation and

proliferation has been

investigated by using various blockers of IK channels.

The Ca(2+)-activated

K(+) current in human T cells is shown by the

whole-cell voltage-clamp

technique to be highly sensitive to clotrimazole,

charybdotoxin, and

nitrendipine, but not to ketoconazole. Clotrimazole,

nitrendipine, and

charybdotoxin block T cell activation induced by

signals that elicit a rise

in intracellular Ca(2+)-e.g., phytohemagglutinin, Con

A, and antigens such

as Candida albicans and tetanus toxin in a

dose-dependent manner. The

release of IFN-gamma from activated T cells is also

inhibited after block of

IK channels by clotrimazole.

Clotrimazole and cyclosporin A act synergistically to

inhibit T cell

proliferation, which confirms that block of IK

channels affects the process

downstream from T cell receptor activation. We suggest

that IK channels

constitute another target for immune suppression.

PMID: 10485926 [PubMed - indexed for MEDLINE]

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Mech Ageing Dev 2003 Apr;124(4):371-8 Related

Articles, Links

Interrelationships among brain, endocrine and immune

response in ageing and

successful ageing: role of metallothionein III

isoform.

Giacconi R, Cipriano C, Muzzioli M, Gasparini N,

Orlando F, Mocchegiani E.

Immunology Center, (Section Nutrition, Immunity and

Ageing), Research

Department Italian National Research Centres on Ageing

(INRCA), Via

Birarelli 8, 60121, Ancona, Italy

Metallothionein-III (MT-III) a brain-specific member

of metallothionein

family contributes to zinc neuronal homeostasis, and

zinc is an important

regulator of many brain functions, including the

activity of hormone

realising factors by hippocampus. Among them,

somatostatin is pivotal

because affecting thyroid hormones turnover and

consequently thymic and

peripheral immune efficiency (Natural Killer, NK) cell

activity.

Somatostatin is in turn affected by somatomedin-C,

which is also

zinc-dependent. Therefore, somatomedin-C may be a

marker of somatostatin

status in the hippocampus. MTs sequester and release

zinc in transient

stress, as it may occur in young age, to protect cells

by reactive oxygen

species.

In order to accomplish this task, MTs are induced by

IL-6 for a prompt

immune and anti-inflammatory response. During ageing,

MTs are high with a

role of sequester of zinc, but with very limited role

in zinc release

because stress-like condition and inflammation is

persistent.

Therefore, high MTs may become to protective in young

age to harmful during

ageing leading to low zinc ion bioavailability for

many body homeostatic

mechanisms, including brain function. As a

consequence, an altered

physiological cascade from the brain (upstream) to

endocrine and immune

system (downstream) may occur.

The aim of this work is to study the role of MT-III in

the

interrelationships among brain-endocrine-immune

response in ageing and

successful ageing. The main results are: (1) MT-III

and IL-6 gene

expressions increase in the hippocampus from old mice,

in comparison with

young and very old mice. (2) Somatomedin-C plasma

levels decrease in old

mice in comparison with young and very old mice. (3)

Low zinc ion

bioavailability (tested by the ratio total

thymulin/active thymulin) is

coupled with altered thyroid hormone turnover and

depressed IL-2 in old mice

in comparison with young and very old mice. (4) 'In

vitro' experiments

display more increments on NK cells activity by adding

zinc-bound active

thymulin than T3 alone.

In conclusion, low MT-III in the hippocampus from

young and very old mice

leads to good zinc ion bioavailability that it is

upstream coupled with

normal hippocampal function affecting downstream

normal thyroid hormones

turnover and satisfactory NK cell activity, via

complete saturation of

zinc-bound active thymulin molecules. Therefore, a

correct MTs homeostasis

is pivotal for brain-endocrine-immune response in

order to reach successful

ageing.

PMID: 12714242 [PubMed - in process]

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Exp Neurol 2002 Sep;177(1):21-31 Related Articles,

Links

Interferon-gamma regulates oxidative stress during

experimental autoimmune

encephalomyelitis.

Espejo C, Penkowa M, Saez- I, Hidalgo J,

A, Montalban X,

ez-Caceres EM.

Unitat de Neuroimmunologia Cli;nica, Hospital Vall

d'Hebron, 08035,

Barcelona, Spain.

Experimental autoimmune encephalomyelitis (EAE) is an

induced inflammatory

and demyelinating disease of the central nervous

system which shares many

clinical and pathological features with and is

considered the animal model

of multiple sclerosis.

There is extensive evidence that EAE is a Th1 disease

eliciting secretion of

proinflammatory cytokines like IFN-gamma or TNF-alpha,

and it has been

suggested that cytokine-induced oxidative stress could

have a role in EAE

neuropathology. However, the individual roles of these

and other cytokines

in the pathogenesis of the disease are still

uncertain.

Here we analyze the role of IFN-gamma during EAE by

using both IFN-gamma

receptor-knockout (IFN-gamma R(-/-)) and wild-type

mice, both strains

immunized with peptide 40-55 from rat myelin

oligodendrocyte glycoprotein.

The levels of oxidative stress were determined through

the analysis of

immunoreactivity for inducible NO synthase,

nitrotyrosine, and

malondialdehyde, as well as through the _expression of

the tissue-protective

antioxidant factors metallothionein I+II (MT-I+II).

We also examined the number of cells undergoing

apoptosis as judged by using

the TUNEL technique. The levels of oxidative stress,

MT-I+II, and apoptotic

cell death by EAE were significantly increased in all

mice, though more so

in IFN-gamma R(-/-) mice compared with wild-type mice.

These data support the notion that IFN-gamma has a

protective role against

EAE.

PMID: 12429207 [PubMed - indexed for MEDLINE]

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Exp Gerontol 2002 Jan-Mar;37(2-3):349-57 Related

Articles, Links

MtmRNA gene _expression, via IL-6 and glucocorticoids,

as potential genetic

marker of immunosenescence: lessons from very old mice

and humans.

Mocchegiani E, Giacconi R, Cipriano C, Muzzioli M,

Gasparini N, Moresi R,

Stecconi R, Suzuki H, Cavalieri E, ni E.

Research Department, Section of Nutrition, Immunity

and Ageing, Immunology

Center, INRCA, Via Birarelli 8, 60121 Ancona, Italy.

e.mocchegiani@...

Metallothioneins (MTs) are involved in metal-related

cell homeostasis

because of their high affinity for metals forming

clusters. The main

functional role of MTs is to sequester and/or dispense

zinc participating in

zinc homeostasis, which is relevant in normal immune

response.

Consistent with this role, MTs gene _expression

(MTmRNA) is transcriptionally

induced by a variety of stressing agents to protect

cells from reactive

oxygen species. In order to accomplish this task, MTs

gene _expression is

affected by glucocorticoids and IL-6 for a prompt

immune response.

This protection is peculiar in young-adult age during

transient stress and

inflammatory condition, but not in ageing because

stress-like condition and

inflammation are constant for the whole circadian

cycle. This may lead MTs

to turn-off from role of protection in young age to

deleterious one in

ageing.

The aim is to suggest MTmRNA as potential genetic

marker of

immunosenescence. Liver MTmRNA, IL-6 and

glucocorticoids levels are high,

whereas the bioavailability of zinc ions is low and

natural killer cells

activity is depressed in old and very old mice during

the light period as

compared to young in the same period. An inversion of

nutritional-endocrine-immune profile exclusively

occurs in young mice during

the night showing the existence of immune plasticity.

No inversion occurs in

old mice during the night. As a consequence, no immune

plasticity in old

mice ensues.

By contrast, very old mice remodel the altered MTmRNA

and immune-endocrine

profile during the night up to values of young ones

observed during the

light period. Therefore, the remodelling of MTmRNA may

be involved in the

maintenance of immune plasticity with subsequent

successful ageing.

Thus, MTmRNA, via IL-6 and glucocorticoids, may be

potential genetic marker

of immunosenescence. This assumption is reinforced by

low MTmRNA in

lymphocytes of nonagenarians and young-adult people in

comparison with

elderly and Down's syndrome subjects.

--- Caroline Glover <sfglover@...> wrote:

> I just wanted to throw in here, in response to the

> general conversation,

> that I believe I remember Dr. Goldberg saying that

> he will not treat kids

> who are being chelated and that in the past he has

> found that children who

> have been chelated prior to seeing him do not seem

> to respond as well to the

> treatments. If I remember correctly, he said

> that he feared that might

> indicate that these children had been damaged by the

> chelation.

>

> If anyone remembers the source of these comments

> please feel free to add to

> my comments... maybe it was the old video. I can't

> seem to find it in any

> of the articles on his website.

>

> I'm not trying to start an argument here but merely

> throwing in what I

> remember Dr. G's comments to be on this subject.

>

> Caroline

>

>

>

>

>

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