MCS – Multiple Chemical Sensitivity at “General and Applied Toxicology, 3rd Edit

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MCS – Multiple Chemical Sensitivity at “General and Applied Toxicology,

3rd Editionâ€

_http://www.csn-deutschland.de/blog/en/mcs-%E2%80%93-multiple-chemical-sensi

tivity-at-%E2%80%9Cgeneral-and-applied-toxicology-3rd-edition%E2%80%9D/_

(http://www.csn-deutschland.de/blog/en/mcs-–-multiple-chemical-sensitivity-at-\

“

general-and-applied-toxicology-3rd-editionâ€/)

 

Letter from Martin L. Pall, Saturday 6th June 2009

 

 

I was delighted when I was asked by the three editors of the future

publication, **General and Applied Toxicology, 3rd Edition** (_John Wiley and

Sons_ (http://eu.wiley.com/WileyCDA/) ) to write a review on multiple

chemical sensitivity (MCS) for this prestigious multivolume set. MCS, as I am

sure

you know, has been largely ignored by toxicologists in general and I was

delighted that these three prominent scientists, all of whom had extensive

published research on the actions of chemicals implicated in MCS, asked me

to write such an article. This was important recognition not only for my own

work on MCS but also that MCS is now recognized as a toxicological

phenomenon.

 

 

The paper, entitled Multiple Chemical Sensitivity: Toxicological Questions

and Mechanisms is the most extensively documented publication on MCS, and

will be a 54 page chapter in this multivolume set. While the majority of

this paper comes from my earlier publications on MCS, it also contains

several very important sections that are largely novel.

 

 

1. There are seven classes of chemicals implicated in MCS and all seven of

these can indirectly produce a common response in the body, increased NMDA

activity. Furthermore, animal studies have shown that members of all seven

of these classes of chemicals can have their toxic responses lowered by

using an NMDA antagonist. This clearly demonstrates not only that they

produce such increased NMDA activity but those increases play an important role

in producing the toxic responses to these chemicals. Given that we previously

had six types of evidence implicating excessive NMDA activity in MCS, we

now have compelling evidence that this common response plays a key role in

MCS.

 

 

2. The role of these chemicals acting as toxicants in MCS has been

confirmed by four genetic studies, showing that genes that determine the rate

of

metabolism of these chemicals, influence susceptibility to MCS (only three

were available when the review was written). These studies implicate six

genes as determining such susceptibility, all of which have roles in the

metabolism of chemicals otherwise implicated in initiating cases of MCS. It

follows that the roles of chemicals in initiating cases of MCS is undeniable.

 

 

3. There have been a series of published studies reporting objectively

measurable responses to low level chemical exposure among MCS cases that are

distinct from any responses in normals. At least three of these should be

practical specific biomarker tests that can be applied in clinical settings.

All of these studies are consistent with the NO/ONOO- cycle mechanism as it

is thought to play out in MCS and all provide, therefore, evidence

supporting this mechanism. We have been in great need for such specific

biomarker

tests for MCS and these and other approaches to developing such tests must

be further studied and may provide recognized specific biomarker tests in

the near future, in my judgment.

 

 

4. All except one of the elements of the NO/ONOO- cycle as it is thought

to play out in MCS have been studied in animal models and all elements

studied are implicated in these animal models. It follows that one can make a

strong case for a NO/ONOO- cycle mechanism based on animal model studies

alone.

 

 

5. The paper finishes with a list of five areas of future research which

are in most need of further study, in my judgment.

 

 

We do have observational evidence that a protocol based on down-regulating

the NO/ONOO- cycle mechanism is helpful in the treatment of most cases of

MCS as well as most cases of ME/CFS and most cases of fibromyalgia.

However, at this point this treatment fails to produce any substantial number of

cures and seems to be quite variable in the extent of improvements apparently

produced by it. Nevertheless, this approach does produce substantial

apparent improvements in many people who have been ill for one, two or more

decades. It is my hope that we will be able to add a second phase to such

treatment that may start to produce at least some such cures, but that is a

hope

at this point.

 

 

Autor:

_Martin L. Pall_ (http://www.thetenthparadigm.org/) , Professor Emeritus of

Biochemistry and Basic Medical Sciences, Saturday 6th June 2009

(Letter reprinted by CSN with personal permission)

 

RELATED ARTICLES by Dr Martin Pall

 

Multiple Chemical Sensitivity (MCS)

Neural Sensitization and the NO/ONOO- Cycle. The nitric oxide response

predicts that this mode of action is consistent with a NO/ONOO- cycle

mechanism. Pesticide and Solvent Action in MCS.Certain additional types of

chemicals

may also act via this common mechanism, including certain oxidants such as

chlorine gas and certain mold toxins, both of which may act via vanilloid

receptor stimulation to increase NMDA activity. MCS is the most complex of

these illnesses and has been the most challenging of them to explain. Among

its most puzzling features is the following:

_http://molecular.biosciences.wsu.edu/Faculty/pall/pall_mcs.htm_ (htt

p://molecular.biosciences.wsu.edu/Faculty/pall/pall_mcs.htm)

 

 

Multiple Chemical Sensitivity - The End of Controversy

Elevated Nitric Oxide/Peroxynitrite/NMDA Model of MCS..The combination of

all four of these mechanisms, each acting at a different level and

therefore expected to act synergistically with each other, that produces the

exquisite chemical sensitivity reported in MCS.

_http://mcs-america.org/pall.pdf_ (http://mcs-america.org/pall.pdf)

_http://www.ei-resource.org/articles/multiple-chemical-sensitivity-articles/

multiple-chemical-sensitivity-%11-the-end-of-controversy/_

(http://www.ei-resource.org/articles/multiple-chemical-sensitivity-articles/mult\

iple-chemical

-sensitivity--the-end-of-controversy/)

martin_pall phone: 509-335-1246

 

 

Elevated nitric oxide/peroxynitrite theory of multiple chemical

sensitivity: central role of N-methyl-D-aspartate receptors in the sensitivity

mechanism.

_http://www.ei-resource.org/research/multiple-chemical-sensitivity-research/

elevated-nitric-oxide-and-peroxynitrite-theory-of-multiple-chemical-sensitiv

ity/_

(http://www.ei-resource.org/research/multiple-chemical-sensitivity-research/elev\

ated-nitric-oxide-and-peroxynitrite-theory-of-multiple-chemical-se

nsitivity/)

 

 

NOS Partial Uncoupling as a Key Switching Mechanism for the NO/ONOO- Cycle

Short-term stressors, capable of increasing nitric oxide levels, act to

initiate cases of illnesses including chronic fatigue syndrome, multiple

chemical sensitivity, fibromyalgia and posttraumatic stress disorder. These

stressors, acting primarily through the nitric oxide product, peroxynitrite,

are thought to initiate a complex vicious cycle mechanism, known as the

NO/ONOO- cycle that is responsible for chronic illness. The complexity of the

NO/ONOO- cycle raises the question as to whether the mechanism that switches

on this cycle is this complex cycle itself or whether a simpler mechanism

is the primary switch.

_http://dfwcfids.net/index.php?option=com_content & task=view & id=501 & Itemid=13

79_

(http://dfwcfids.net/index.php?option=com_content & task=view & id=501 & Itemid=1379)

 

 

The NO/ONOO- cycle as the etiological mechanism of tinnitus.

Other inner-ear-related defects, such as acute or progressive hearing

loss, vertigo, and dizziness, may also be NO/ONOO cycle diseases. Multiple

agents that down-regulate NO/ONOO- cycle biochemistry are reported to be

helpful in the treatment of tinnitus and related diseases.

_http://www.ncbi_

(http://www.ncbi.nlm.nih.gov/pubmed/18229788?dopt=AbstractPlus)

..nlm.nih.gov/pubmed/18229788?dopt=AbstractPlus

 

_http://dfwcfids.net/index.php?option=com_content & task=view & id=1938 & Itemid=1

379_

(http://dfwcfids.net/index.php?option=com_content & task=view & id=1938 & Itemid=1379)

 

 

Multiple Chemical Sensitivity - The End of Controversy?

The symptoms of MCS sufferers report having on such solvent exposure

include multiorgan pain typically including headache, muscle pain and joint

pain, dizziness, cognitive dysfunction including confusion, lack of memory, and

lack of concentration. These symptoms are often accompanied by some of a

wide range of more variable symptoms.

_http://www.immunesupport.com/library/showarticle.cfm/ID/4371/e/1/T/CFIDS_FM

/_

(http://www.immunesupport.com/library/showarticle.cfm/ID/4371/e/1/T/CFIDS_FM/)

 

 

Antioxidant Suggestions For Down-regulation of the NO/ONOO- Cycle

from Dr. Martin Pall, PhD

_http://www.immunesupport.com/library/showarticle.cfm?id=8075 & T=CFIDS_FM_

(http://www.immunesupport.com/library/showarticle.cfm?id=8075 & T=CFIDS_FM)

 

 

The NO! OH NOO! Theory and Suggestions For Treatment by Martin Pall Ph.D

" contains the most important information on the cause of CFS, FM, MCS &

related illnesses & how to effectively treat them. " " Cases of each of these

illnesses are initiated by short-term stressors, but instead of recovering

after exposure, people become ill with one or more these chronic illnesses.

The stressors implicated include viral, bacterial & in a few cases,

protozoan infections, physical trauma (most commonly to the head & neck but

also

including physical trauma to other regions of the body), chemical exposure

to such chemicals a volatile organic solvents or such pesticides as

organophosphorus/carbamates, organochlorine pesticides or pyrethroid

pesticides,

carbon monoxide exposure, severe psychological stress, certain mold toxins

or ciguatoxin exposure. Each of these diverse stressors can initiate a

process leading to increased nitric oxide levels. In some cases (infection) the

iNOS form of nitric oxide synthase is involved but in most others,

excessive NMDA activity is involved leading to increased nNOS activity. "

_http://phoenix-cfs.org/NO%20ONOO%20Theory%20Treatment%20Pall%2006.htm_

(http://phoenix-cfs.org/NO%20ONOO%20Theory%20Treatment%20Pall%2006.htm)

_http://www.ei-resource.org/articles/chronic-fatigue-syndrome-articles/the-n

o!-oh-noo!-theory-and-suggestions-for-treatment/_

(http://www.ei-resource.org/articles/chronic-fatigue-syndrome-articles/the-no!-o\

h-noo!-theory-and-sugg

estions-for-treatment/)

 

 

The NO! OH NOO!

Theory and Suggestions For Treatment by Martin Pall Ph.D

_http://phoenix-cfs.org/NO%20ONOO%20Theory%20Treatment%20Pall%2006.htm_

(http://phoenix-cfs.org/NO%20ONOO%20Theory%20Treatment%20Pall%2006.htm)

 

 

Neural Sensitization by Dr M Pall

Neural sensitization occurs by activation of brain and nerve cell

N-methyl-D-aspartate(NMDA), which then increases brain nitric oxide (NO).1,2,3

Several vicious biochemical cycles are then set in motion. Nitric oxide forms

a tissue damaging free radical known as peroxynitrite.2,4,5,6

Peroxynitrite depletes energy TP,7,8 which then further increases the

sensitization of

NMDA. 9,10

_http://www.mcsbeaconofhope.com/neural_sensitization_by_dr_marti.htm_

(http://www.mcsbeaconofhope.com/neural_sensitization_by_dr_marti.htm)

 

 

REACTION FACT SHEET / Dr. Pall

Recent research indicates that biochemical changes in the brain (neural

sensitization) perpetuate/increase symptoms with chemical exposure, often

called “reactionsâ€. Nitric oxide is increased, which converts to

peroxynitrite, a tissue damaging free radical. By several pathways,

peroxynitrite is

again converted to more nitric oxide, creating a vicious cycle.

_http://www.mcsbeaconofhope.com/reaction_fact_sheet.htm_

(http://www.mcsbeaconofhope.com/reaction_fact_sheet.htm)

 

 

 

Uncovering the Trigger of Chronic Illness

The NO/ONOO cycle is touted in a press release about Pall’s book as the

first theory to explain how the illnesses mentioned in its title are

initiated, why they are chronic, and how their symptoms are generated. “It

also

provides explanations for the perplexing phenomena they share, including why

these diseases often overlap, why they are often accompanied by other

illnesses (asthma, migraine, tinnitus, lupus, and rheumatoid arthritis), and

why

symptoms and signs are so varied in individuals with the same disease,†the

press release says.

_http://dfwcfids.net/index.php?option=com_content & task=view & id=1143 & Itemid=1

379_

(http://dfwcfids.net/index.php?option=com_content & task=view & id=1143 & Itemid=1379)

 

 

Presentation Martin L. Pall PhD - May 7th review on his latest book

" Explaining Unexplained Illnesses " where he links 14 different disorders, from

asthma and cancer to CFS and FM. plus The Future of Psychogenesis for

Multisystem Illnesses and Professor Pall's Model as described in his latest

book:

" Comparison of " psychogenic theory " , malingering and the NO/ONOO-cycle " .

_http://diagnosesupport.com/main/index2.php?option=com_content & task=view_

(http://diagnosesupport.com/main/index2.php?option=com_content & task=view) &

id=102 & pop=1 & page=0 & Itemid=47

 

 

Nitric Oxide Cycle Theory:

Will It Explain CFS, FM, and Other 'Unexplained' Illnesses? - Q & A with

Martin L. Pall, PhD

_http://www.immunesupport.com/library/showarticle.cfm?id=8071 & T=CFIDS_FM_

(http://www.immunesupport.com/library/showarticle.cfm?id=8071 & T=CFIDS_FM)

_http://www.immunesupport.com/library/showarticle.cfm?id=8071_

(http://www.immunesupport.com/library/showarticle.cfm?id=8071)

 

 

Live Chat with Martin L. Pall, PhD – July 6, 2007: Professor of

Biochemistry Explains Mechanisms of Chronic Fatigue Syndrome and Fibromyalgia &

Suggested Protocol

_http://www.prohealth.com//library/showArticle.cfm?libid=12966_

(http://www.prohealth.com//library/showArticle.cfm?libid=12966)