Dr. David S. Bell:
"Iltmangel i cellerne og
Neuro-immun udmattelse"

Professor Martin Pall:
NO/ONOO sygdomsmodellen
 

Mail vedrørende Pall's nye artikel om MCS i "General and Applied Toxicology"

Af cand. hort. Helle Rasmussen
Jeg har skrevet til biokemikeren, professor emeritus Martin Pall, i forbindelse med hans nye hjemmeside www.thetenthparadigm.org  og vedrørende hans to nye artikler om MCS og ME/CFS, som begge vil blive publiceret i fremstående kompendier/tidsskrifter.

Jeg har modtaget nedenstående svar fra ham den 6. juni 2009, som jeg videresender med tilladelse.

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Dear Helle Rasmussen:
Thank you very much for your message. I am responding by discussing the MCS toxicology review alone, but will perhaps respond regarding the ME/CFS paper later. You are welcome to forward this information, as you wish.

I was delighted when I was asked by the three editors of the future publication, "General and Applied Toxicology, 3rd Edition" 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. Let me add that I am a PhD, not an MD and none of this should be viewed as medical advice.

There has been considerable interest in copying or translating this paper, but I have been unable to obtain any clear guidance from the publisher (John Wiley and Sons) on under what conditions either of these could be done. I am, therefore, working on a shorter version of this paper that I will hold the copyright on which will be the MCS web page of my new web site. I will be able to give permission, therefore, for others to translate this shorter version or copy the English version. I had hoped to have this shorter paper completed before now, but it needs a couple of more weeks of work.

My very best wishes to you,

Martin L. Pall