Rich Van K: Multiple Chemical Sensitivity

Discussion in 'Fibromyalgia Main Forum' started by Slayadragon, Oct 10, 2009.

  1. Slayadragon

    Slayadragon New Member

    Hi Rich,

    You wrote

    >Just for completeness, let me say that I think that multiple chemical sensitivity can arise when glutathione becomes depleted in the sustentacular (suppporting) cells in the olfactory epithelium in the nose. I think that's the link between CFS and MCS.


    I've been meaning to talk with you about MCS for a while, and so I'm really happy that you brought this up.

    Obviously MCS is a frequent result of Sick Building Syndrome. The question of whether mold or something else is the underlying cause often is discussed.

    MCS often occurs in CFS patients, many of whom are not aware of having experienced heavy mold exposures. The question of whether mold or something else is the underlying cause is discussed here as well.

    Mold seems to have the potential of leading to MCS in at least two ways:

    1. Satratoxins appear to have the ability to "poke holes" in the blood-brain barrier (BBB), thus allowing other toxins to enter. (Below is some more info from that same dissertation I sent you earlier.)

    Some other toxins such as formadehyde do have the ability to penetrate the BBB, but I've yet to find any others that act in such a way as to let other toxins to enter as well. I need to talk to someone like the toxicologist Jack Thrasher about this. (You don't have his e-mail, do you? Or have any other suggestions of people who might know)

    2. Satroxins (per our discussion yesterday) seem to have the potential of depleting reduced glutathione, thus leading to the effect you mention above.

    I would imagine that since mold is something that is breathed in, this would have a particularly strong effect on the cells in the nose. Most other sources of oxidative stress would not seem to have a disproportionately strong effect on this organ.


    *


    Now let me share a little bit of anecdotal experience.

    Several of us have managed to make our MCS disappear as a result of mold avoidance.

    People occasionally have expressed skepticism about this, due to their contention that holes in the BBB cannot be repaired.

    I'm not sure about whether the BBB can be repaired. But based on our experiences, I tend to think that it is true.

    The MCS only stays gone insofar as mold avoidance is rigorously pursued. Stopping it for even a little while makes the MCS come back at full force.

    I had moderate MCS prior to addressing mold. It's gone. However, if I get heavy mold exposures for more than a day or two, it comes back as strong as it ever was.

    For instance, about a year ago I went to Texas (a place that turns out to be the inner ring of the Mold Inferno) to buy a travel trailer. I got hit with a lot of mold over the course of a few days.

    When I went to the trailer factory, I noted some chemicals. The chemicals didn't bother me though.

    I took the trailer and slept in it for the night. At first it was fine. Halfway through the night, I woke up to find that it had become horrendously awful. Stupidly, I spent several more hours in it waiting for morning. After that, I couldn't step into it for more than 30 seconds without feeling far more sick than I usually do even around a good bit of mold.

    I spent the next 24 hours spitting out a total of two cups of saliva that tasted like the chemicals in the trailer. (I wonder why my saliva serves as such a good emergency detox mechanism?)

    I've had this happen at other times too. Even when I know I'm being affected by mold, an environment will feel okay. Then suddenly it will become horrendously bad. Then after the effects of the mold have gone away, the environment will feel okay again.

    Erik seems to have this exact thing happen to an even greater extent.

    Erik's MCS was much worse than mine. He states that it was the MCS (rather than his CFS) that Dan Peterson expressed particular concern when recommending Ampligen to him in 1997. (Erik recalls the statement to be: "You have become a universal reactor and are at the point where most people commit suicide because life becomes basically unbearable.)

    On one day during my visit to Lake Tahoe last year, Erik and I went on a tour of a variety of moldy buildings. We were careful not to get too badly hit by the mold, and it was having only a modest effect on each of us.

    Then we went to a supermarket that Erik says he visits all the time and that's fine with regard to mold.

    We shopped for about 30 minutes without incident. Then in the blink of an eye, he became very confused and seemed on the verge of fainting. He quickly became fine after we left the store. He stated that it was due to the chemicals in the store (which I didn't notice) rather than to any mold.

    What interests me in my experiences and in observing his is the manner in which the MCS comes back. It's almost like there's an on/off switch. The chemicals either aren't bothersome at all or they're horrendously bothersome.

    So it seems to me that Erik and I both indeed must still have BBB's with holes in them (his apparently like swiss cheese). It's just that the mold avoidance is doing something that provides a buffer. Your comment above seems like it's a good explanation.

    Does it surprise you that there would be an on/off effect (with no period of time when the chemicals are just moderately bothersome)?

    Another question is that remark of Dr. Peterson's about Ampligen being the answer to the problem. Apparently he had seen patients like Erik before and had good results on them with the drug. (I'm going to hazard an unsubstantiated guess that the supermold is especially good at punching holes in the BBB and that others of Erik's severity presented in IV by 1997, after an extended period of exposure to that mold.)

    Ampligen improves the immune system so that various pathogens (including HHV6a and, presumably, XMRV) are brought under control. Would that, in your opinion, rectify the situation with glutathione that you posit above?

    Having the potential of falling off the edge on a split second with the MCS feels pretty precarious, by the way. It would be nice to have some warning that the buffer (if that's what it is) is going to run out. I would think that would be especially the case for Erik since his underlying MCS is so much more severe than mine, but for me too.


    Thanks for this and for your other previous comments. You really were on a great roll yesterday!

    Best, Lisa


    *

    http://etd.lib.ttu.edu/theses/available/etd-05252005-163223/unrestricted/Karunasena_Enusha_Diss.pdf

    OR

    http://etd.lib.ttu.edu/theses/available/etd-05252005-163223/


    CHAPTER III
    THE TOXOLOGICAL EFFECTS OF SATRATOXIN H
    ON HUMAN BRAIN CAPILLARY ENDOTHELIAL CELLS (HBCEC)

    Brain capillary endothelial cells are one of the tissues that form the blood
    brain barrier (BBB) [1]. The German microbiologist Ehrlich was the first to identify
    its existence more than 100 years ago [1]. The blood brain barrier consists of
    tissues that prevent microorganisms and toxic chemical compounds from
    entering into the brain tissue.

    The only substances able to readily diffuse across
    the barrier are small and lipophilic compounds [1]. Large compounds, such as
    glucose and hydrophilic elements pass through active transport membrane
    proteins [1].

    The fundamental elements of the BBB are the adherens and tight
    junctions which hold endothelial cells (ECs) together; second, the P-glycoprotein
    receptors that eject materials from the central nervous system (CNS); and third,
    the process of transcytosis which limits the influx of materials into the CNS [1].
    The final component is the astrocyte processes that cover the ECs [1].

    Some of the receptors that bind molecules for transport are transferrin and
    P-glycoprotein [1]. These membrane transport systems are a component of the
    limited transfer of materials across the BBB [1]. Other distinguishing features of
    the BBB are the limited number of endocytic vesicles, which limit transcellular
    34
    flux [1].

    Tight junctions between the cells maintain a low level of paracellular flux
    [1]. It are these two features that distinguish ECs of the BBB compared to other
    EC of different tissues [1]. The tight junctions between cells are formed by
    specific proteins. One group is termed cadherin, another is occludin [1]. Cadherin
    forms a single-pass transmembrane glycoprotein and is considered a major cell-
    to-cell adhesion molecule [1]. Occludin is a four-pass transmembrane that is
    similar to connexin, a protein commonly found in gap junctions [1].

    In the event of
    EC damage, the junctions are compromised and the tightness of the BBB is lost
    [1]. Thus, the junctions play a critical role in the infrastructure of the BBB [1].

    Studies conducted on gap-junctional intracellular communication in
    Chinese hamster ovary (CHO) V79 cells after exposure to members of the
    trichothecene family, (T-2 toxin and vomitoxin) demonstrated the ability of these
    toxins to decrease metabolic cooperation associated with gap-junctional
    intracellular communication [2]. Gap-junctional communication allows for
    metabolic cooperation between cells which regulate cell proliferation,
    differentiation, and development [2].

    When this form of cellular communication
    decreases, tumors are able to form [2]. These studies suggested that low doses
    of trichothecenes maybe tumorgenic [2]. These studies further demonstrated the
    function of junctions between cells and the potential devastation trichothecene
    toxins may induce in the integrity of cell communication and development [2]. It
    further potentates the devastating effects that may result to junctions associated
    with the integrity of the BBB [2].
    35

    In the event that the BBB is damaged, inflammatory responses can
    contribute to CNS injury. The accumulation of evidence that demonstrates the
    negative effects due to inflammation on the CNS continues to expand.

    Studies
    have demonstrated that regardless of the causative agent or event, such as
    infection, trauma, ischemia, necrosis, or hemorrhage, the inflammatory response
    generates further damage [3].

    There are four major events that are used to
    describe inflammation as stated by Celsus: pain, tumor, rubor, and heat [3].

    The
    events that lead to this pathology are the increase in blood flow to the site of
    injury, followed by increased capillary permeability of ECs to allow the release of
    secretory mediators that recruit immune cells to enter damaged tissues [3].

    Cells
    that arrive at the site include neutrophils, macrophages, mast cells, lymphocytes,
    platelets, dendritic cells, and fibroblasts [3].

    Chemokines released by endothelial
    cells and the expression of adhesion molecule receptors on the surface, allow
    endothelial cells to interact with leukocytes [3].

    Leukocytes are able to pass
    through the endothelial cell layer to the site of inflammation. The process of
    inflammation is intended to repair injured tissues; however this mechanism tends
    to induce greater damage to the CNS upon activation [3].

    Diseases such as
    multiple sclerosis, Alzheimer’s, rheumatoid arthritis, and systemic lupus
    erythematosus (SLE) all demonstrate events of inflammation that lead to damage
    in the CNS [3].

    Cytokines released by immune cells, such as tumor necrosis
    factor- alpha (TNF-?), are suggested to have an effect on the endothelial cells of
    the BBB, leading to the rupture of the BBB in inflammation associated diseases
    36
    [3,4].

    TNF- ? is able to induce the expression of adhesion molecule receptors on
    ECs, which allow the binding and passage of lymphocytes and leukocytes [3,4].


    In addition to the passage of T cells, studies have demonstrated that B cells,
    dendritic cells, natural killer (NK) cells, mast cells, and macrophage or monocytes
    also pass through the BBB [3,4]. TNF- ? is also able to activate the production of
    nitric oxide in macrophage which leads to greater permeability across the BBB [3,
    4].

    In addition to TNF-?, interleukin-6 (IL-6) is also associated with
    proinflammatory events, and is produced in conjunction with TNF-? and IL-1 [3].
    Diseases associated with inflammation and CNS damage have demonstrated the
    expression of IL-6 in the brain [3, 4]. These events led to studies which
    demonstrated that the high expression of IL-6 in the CNS of mice resulted in
    ataxia, tremor, motor impairment and seizures [3, 4].

    Similar events are seen in
    individuals exposed to trichothecene mycotoxins in SBS conditions [5].

    Although
    the function of inflammation is to repair damaged tissues, the effects in the CNS
    tend towards damage versus repair [2, 3, 4]. The events described may be the
    reason why inflammatory events in the CNS lead to toxic effects in the ECs and
    damage to the BBB [2, 3, 4].

    Studies conducted with trichothecenes have demonstrated disruption of
    biochemical pathways in immune cells and other cell types that evidence events
    of inflammation and apoptosis. Studies conducted with T-2 toxin on L-6
    myoblasts demonstrated the ability of T-2 toxin to disrupt glucose transport,
    amino acid uptake, and calcium efflux decreases across the cellular membrane
    37
    [6].

    This study suggested the ability of T-2 toxin to disrupt cell membrane integrity
    and activity [6]. The authors further suggested the ability of T-2 toxin to disable
    the activity of mitochondrial and nuclear membranes in cells, which could lead to
    apoptotic events [6].

    Studies have also demonstrated the ability of cells to induce mitochondrial
    damage and lipid peroxidation, which activates apoptosis pathways [7,8]. Studies
    conducted by Pace et. al., have demonstrated the ability of T-2 toxin to inhibit
    mitochondrial protein synthesis [8].

    Mitochondria, like prokaryotes, contain 70S
    ribosome compared to eukaryotes, which have 80S ribosomes [8].
    Trichothecenes are known to inhibit eukaryotic protein synthesis; however, these
    studies demonstrate the ability of T-2 toxin to inhibit the electron transport chain
    (ETC) in mitochondria and non-specific inhibition of protein synthesis [8]. If
    mitochondrial protein synthesis and ETC activity are inhibited in a dose-
    dependent manner by T-2 toxin, this would suggest that apoptotic events may be
    activated due to mitochondrial damage by trichothecenes [8].

    Further evidence of apoptotic events induced by trichothecene exposure
    has been elucidated. Experiments conducted with different trichothecenes have
    demonstrated variations in apoptotic induction. These results showed that
    structural nuances between trichothecenes can determine the degree of c-Jun N-
    terminal kinase (JNK/p38) activation [9]. JNK-p38 is expressed as a ribotoxic
    stress response that signals apoptotic pathways [9].

    These events imply the
    ability of trichothecenes to activate rapid apoptosis by inhibiting protein
    38
    translation and activating JNK/p38 [9]. Studies conducted by Pestka et. al., have
    demonstrated the ability of trichothecenes and specifically satratoxins to induce
    apoptosis in leukocytes both in vitro and in vivo [9]. Further studies conducted by
    this group have demonstrated the ability of satratoxins to activate JNK/p38 and
    other kinases associated with apoptosis [9]. These kinases include several
    groups of mitogen activated protein kinases (MAPKs), such as extracellular
    signal-regulated protein kinase (ERK), p38, and stress associated protein kinase/
    c-Jun N-terminal kinase (SAPK/JNK) at low doses in murine macrophages [9].

    Additional work conducted by other researchers has shown apoptotic events in
    lymphoid organs of mice exposed to trichothecenes [10]. These studies
    demonstrated in vivo activity that correlates to events observed in in vitro
    analysis.

    In addition, this research demonstrates the ability of trichothecenes to
    induce pathological events that may contribute to leukopenia and other
    immunosuppressive events in individuals exposed to SBS conditions [10].
    Recent reports have demonstrated that S. chartarum spores in the presence of
    Streptomyces californicus are able to induce S. californicus to produce biological
    compounds that arrest cell cycle activity [11, 12].

    S. chartarum alone was found
    to induce apoptosis in macrophages, but unable to induce cell cycle arrest. S.
    californicus was unable to inhibit cell cycle activity without the presence of S.
    chartarum spores [11, 12]. These events demonstrate additive and synergistic
    toxicity induced by S.chartarum [11, 12].
    39

    Previous in vivo studies conducted with T-2 toxin have demonstrated the
    ability of trichothecenes to induce neurotoxic events when toxin was injected into
    brain tissue directly [13, 14]. These studies suggested the ability of
    trichothecenes to produce cytotoxic events, inflammation, and apoptosis, which
    illustrate the potential immunopathological events that have been witnessed in
    neurophysiological studies conducted with trichothecenes in murine and rat
    models.

    T-2 toxin has been closely evaluated for its effects in livestock and
    poultry [15, 16, 17, 18]. T-2 toxin is a common contaminant of feed for animals,
    and is associated with lethargy, ataxia, emesis, and feed refusal in animals and
    humans [15, 16, 17, 18].

    There is evidence of T-2 toxin transforming
    neurotransmitter balance [17]. Increases in neurotransmitter concentrations, such
    as catecholamines and serotonin are associated with loss of appetite [17].

    These neurotransmitters are synthesized from specific amino acids, and the
    transfer of these amino acids across the blood-brain barrier is highly regulated by
    transport proteins [17].

    When the BBB is compromised, studies have
    demonstrated changes in the passage of these amino acids into the CNS,
    leading to changes in neurotransmitter concentrations [17].

    These studies have
    demonstrated that the ingestion of T-2 toxin leads to changes in amino acid
    permeability across the BBB, which could lead to the neurological effects
    observed in animals exposed to trichothecene mycotoxins [17].

    Other animal
    studies conducted with trichothecenes have demonstrated the ability of these
    agents to cause neurological events regardless of the administration route [13].
    40

    Experimental evidence indicated that T-2 toxin administered intracerebrally (i.c.)
    or subcutaneously (s.c.) resulted in similar events [13]. Rats exposed via either
    route demonstrated depression of respiration and muscle paralysis, followed by
    convulsions which led to death [13]. These results demonstrated that regardless
    of the route of exposure, systemic distribution of trichothecenes can reach the
    brain, resulting in neurological events [13].

    Further evidence showed that low
    levels of T-2 toxin were responsible for the changes in the metabolism of brain
    biogenic monoamines, compared to lethal doses [13]. Previous analyses have
    demonstrated that the disruption of monoamine metabolism could alter food
    intake by altering hormone secretion, peristaltic contractions, or thermal
    regulation.

    The above studies provided evidence which suggested low levels of
    trichothecenes were able to injure CNS activity and disrupt the integrity of the
    BBB. There is also evidence that suggested the stimulation of endothelial cells by
    trichothecenes led to pro-inflammatory activity. This continuous stimulation of
    pro-inflammatory events appeared to further aggravate the CNS in addition to the
    BBB.

    In the present experiments, human vascular endothelial cells were
    exposed to satratoxin H, LPS, and oxidative stress conditions to evaluate the
    cellular pathways that were activated. Cells were also evaluated for additive
    effects, due to exposure from satratoxin H and LPS, satratoxin H and H202. The
    purpose of these experiments was to determine what effects low doses of a
    41
    trichothecene mycotoxin from S.chartarum would induce in cells that compose
    the BBB. The objective was to utilize HBCEC as an in vitro model to determine
    the mechanism of toxicity produced by exposure to satratoxin H.


    Compared to the negative control cells that received water, cells exposed to
    100ng/ml SH, and 1000ng/ml SH, and LPS demonstrated early and late stages
    of apoptosis, whereas the control cells did not have a red stain in the nucleus of
    the cell. To further evaluate apoptosis, cytochrome C levels from cell extracts
    were evaluated using an ELISA method. These results demonstrated that a
    significantly increased amount (P< 0.05) of cytochrome C was released from
    cells exposed to 10ng/ml, 100ng/ml, LPS, 10ng/ml + LPS, and 10ng/ml + H202.
    These results can be seen in figure 11.

    An additional indicator of apoptosis is oxidative stress. In the event of
    oxidative stress, glutathione (GSH) acts as a reducing agent against reactive
    oxygen species (ROS) such as lipid radicals and peroxides.

    However, if GSH
    levels in a cell are insufficient to compensate for the degree of oxidative stress,
    both apoptotic and inflammatory pathways are further activated.

    To determine
    whether mycotoxins increased oxidative stress levels in HBCEC, a quantitative
    method was used to determine the levels of GSH present in cell extracts
    exposed to various experimental conditions.

    The results demonstrated a
    significant decrease (P> 0.05) in the concentration of GSH (µg/ml) in cells
    exposed to 100ng/ml SH, 1000ng/ml SH, LPS, H202, 10ng/ml + LPS, 10ng/ml +
    H202. These results are seen in Figure 12. The production of lipid peroxidation,
    51
    further demonstrates the degree of oxidative stress induced on HBCECs.


    64
    CONCLUSIONS
    Results from the adhesion mo le receptor expression on HBCEC
    demonstrate that satratoxin H levels of 100ng/ml and 1000ng/ml are able to
    induce inflammatory pathway activation alone.

    Additive effects are demonstrated
    with very low concentrations of SH, such as 10ng/ml in the presence of
    inflammatory agents such as LPS and H202.

    Similar concentrations of the
    mycotoxin are able to induce apoptotic pathways leading to the activation of early
    stages of apoptosis in the presence of 100ng/ml SH, however evidence of late
    stages of apoptosis are observed with 1000ng/ml and 10ng/ml + LPS or 10ng/ml
    H202.

    These results demonstrate the ability of satratoxins to induce apoptotic
    pathways at the same concentrations that inflammatory pathways are being
    activated.

    This suggests that low levels of inflammation and apoptotic events can
    be induced in the presence of moderate levels of SH, and low levels of SH are
    able to induce similar events in the presence of other inflammatory agents and
    oxidative stress conditions, as demonstrated by the levels of GSH and
    cytochrome C in cell extracts.

    In addition, the ability of the mycotoxins to induce
    cell shrinkage at moderate to low levels of SH demonstrate the potential ability of
    these agents to compromise the integrity of the BBB which could lead to further
    neurological damage from mycotoxins or other harmful agents.

    The presence of
    lipid peroxidation in cells exposed to moderate concentrations of SH and additive
    conditions, further demonstrates the ability of the mycotoxins to amplify cellular
    65
    damage through the indirect production of lipid radicals and other ROS.

    The
    results further suggest that low to moderate levels of SH are able to induce
    inflammatory and apoptotic pathways that amplify the cellular damage by the
    continuous activation of these biological pathways.

    [This Message was Edited on 10/11/2009]
    [This Message was Edited on 10/11/2009]
  2. Slayadragon

    Slayadragon New Member

  3. richvank

    richvank New Member

    Hi, Slaya.

    Sorry I didn't get back to you sooner. It's been quite a week, with all the interactions over the newly discovered XMRV, and I was pretty caught up in that. I'll insert some comments at asterisks in your post, quoted below:


    You wrote

    >Just for completeness, let me say that I think that multiple chemical sensitivity can arise when glutathione becomes depleted in the sustentacular (suppporting) cells in the olfactory epithelium in the nose. I think that's the link between CFS and MCS.

    ***I should add that some of the other cell types in the olfactory epithelium probably undergo glutathione depletion, also.

    ***Just to give some basis for this hypothesis: During the Vietnam war, I was in the Army and did research on explosives detection, which continues to be a largely unsolved problem for the military, as evidenced by the continuing casualties from roadside bombs and suicide bombers. One of the ways we tried to detect explosives was by the use of "sniffers." This was the colloquial name for devices that sensed vapor coming from explosives, sort of "electronic noses."

    ***One of the major challenges for this type of detector is that the military explosives, such as TNT, don't have a very high vapor pressure at ambient temperatures, so there isn't much vapor from the explosive in the surrounding air, to be detected. So one has to use a very sensitive type of detecting device. This leads to another problem. If this device happens to get a very big "whiff" of the vapor, such as because there is a lot of explosive present close by, and it is kind of warm, the detector becomes "swamped." Then it's useless until the vapor is cleared out of it, and it tends to adhere to surfaces.

    ***So we learned that it was necessary to provide for a way to clear the detector rapidly, such as by a "bake-out" of the front-end sample acquisition section.

    ***O.K., so much for the "war stories." My point is that we were just learning something that the nose in animals and people had been doing for a very long time! That is, it has provision to clear out an acquired vapor sample so that it can be sensitive soon thereafter to new samples coming in with the inhaled air. How does it do that? It does it with cytochrome P450 enzymes, just as are used in Phase I detox in the liver. The concentrations of CYP450 enzymes are actually higher in the sustentacular (supporting) cells of the olfactory epithelium (a patch of surface in the upper part of the nasal cavity on each side) than they are in liver cells. So these enzymes "deactivate" the vapor molecules, and then they are carried away by the blood, to be disposed of in the urine or the bile.

    ***It's important to note that the CYP450 enzymes produce superoxide ions in these reactions, and they in turn must be dealt with by superoxide dismutase (forming hydrogen peroxide) and then either by glutathione, together with glutathione peroxidase, or by catalase. If they are not taken care of, they will damage the cells of the olfactory epithelium.

    ***What I suspect is that when glutathione becomes depleted in these cells, as part of the systemic glutathione depletion that occurs in CFS, the resulting oxidizing species (superoxide ions, hydrogen peroxide, and possibly peroxynitrite, formed by reactions of superoxide with nitric oxide) damage the cell membranes on the sustentacular cells, and also on the adjoining olfactory neurons. These neurons are connected directly to the olfactory bulbs of the brain, and they constitute the shortest paths from the outside to the brain.

    ***I suggest that the inhaled volatile chemicals are able to enter the olfactory neurons, and from there are able to pass rapidly into the brain, bypassing the blood-brain barrier. Once in the brain, they interact with the neurons and produce MCS symptoms.

    ***One piece of supporting evidence for this pathway is the rapid response that people with MCS have to chemical vapors in the air. I think it is too fast to involve entry into the lungs, diffusion into the blood from the lungs, and transport of blood to the cells of the brain.

    ***A person with MCS responds to a whole range of volatile chemicals. I think this can be explained by the above mechanism.

    ***Another feature of MCS is that in some cases it is reversible, and in others, it doesn't seem to be reversible. I think that the difference depends on whether permanent damage has been done to the barrier function of the olfactory epithelium or not. In cases in which a person's MCS dates back to an acute high exposure event involving a particular chemical, I think it is more likely that permanent damage was done. Perhaps stem cell therapy will help in these cases.

    ***In cases in which MCS is reversible, I suspect that permanent damage was not done. As soon as glutathione levels are restored, the barrier function begins to operate normally again.

    ***Another support for this hypothesis is that Dr. Grace Ziem (together with pharmacist Jim Seymour at Key Pharmacy in Kent, Washington) has found that a simple glutathione nasal spray (it doesn't have to be a nebulizer) can give fast relief from MCS in many cases.


    I've been meaning to talk with you about MCS for a while, and so I'm really happy that you brought this up.

    Obviously MCS is a frequent result of Sick Building Syndrome. The question of whether mold or something else is the underlying cause often is discussed.

    MCS often occurs in CFS patients, many of whom are not aware of having experienced heavy mold exposures. The question of whether mold or something else is the underlying cause is discussed here as well.

    Mold seems to have the potential of leading to MCS in at least two ways:

    1. Satratoxins appear to have the ability to "poke holes" in the blood-brain barrier (BBB), thus allowing other toxins to enter. (Below is some more info from that same dissertation I sent you earlier.)

    ***I'd just like to note that they may not be acting on the blood-brain barrier, but on the barrier function of the olfactory epithelium, though the blood-brain barrier could well be "leaky" also. I remember a hypothesis paper by Logan et al. a few years ago about that.

    Some other toxins such as formadehyde do have the ability to penetrate the BBB, but I've yet to find any others that act in such a way as to let other toxins to enter as well. I need to talk to someone like the toxicologist Jack Thrasher about this. (You don't have his e-mail, do you? Or have any other suggestions of people who might know)

    ***No, I don't have his email address.

    2. Satroxins (per our discussion yesterday) seem to have the potential of depleting reduced glutathione, thus leading to the effect you mention above.

    ***Right. That's the basis for the hypothesis I've suggested to connect mold to both CFS and MCS.

    I would imagine that since mold is something that is breathed in, this would have a particularly strong effect on the cells in the nose. Most other sources of oxidative stress would not seem to have a disproportionately strong effect on this organ.

    ***See the argument above. I suggest that anything that lowers glutathione could give rise to the oxidative stress that damages the barrier function. Or, if glutathione is already depleted, I suggest that a wide range of volatile species could enter the brain via the damaged olfactory epithelium.


    *


    Now let me share a little bit of anecdotal experience.

    Several of us have managed to make our MCS disappear as a result of mold avoidance.

    ***That's really wonderful! I think it means that the damage to your olfactory epithelium was not permanent.

    People occasionally have expressed skepticism about this, due to their contention that holes in the BBB cannot be repaired.

    ***My wife has MCS (but not CFS or mold illness). Hers began when she was working in a hospital years ago, and was accidentally exposed to a high concentration of ammonia vapor in the air in a room that was being cleaned. So far, it appears that her MCS is permanent, and I suspect that the ammonia did permanent damage to her nasal epithelial barrier function. I don't think that the glutathione depletion mechanism was involved in her case. I think that the ammonia concentration was just so high that it basically "fried" her barrier, and it didn't recover. She continues to have a very rapid sensitivity to a wide range of volatile species.

    I'm not sure about whether the BBB can be repaired. But based on our experiences, I tend to think that it is true.

    ***I think that the BBB can be repaired. I'm not sure that the olfactory epithelial barrier always can. As you may know, the BBB consists of high density epithelial cells with tight junctions between them, lining the capillaries in the brain. These cells can be replaced.

    The MCS only stays gone insofar as mold avoidance is rigorously pursued. Stopping it for even a little while makes the MCS come back at full force.

    ***I think that's very interesting!

    I had moderate MCS prior to addressing mold. It's gone. However, if I get heavy mold exposures for more than a day or two, it comes back as strong as it ever was.

    For instance, about a year ago I went to Texas (a place that turns out to be the inner ring of the Mold Inferno) to buy a travel trailer. I got hit with a lot of mold over the course of a few days.

    When I went to the trailer factory, I noted some chemicals. The chemicals didn't bother me though.

    I took the trailer and slept in it for the night. At first it was fine. Halfway through the night, I woke up to find that it had become horrendously awful. Stupidly, I spent several more hours in it waiting for morning. After that, I couldn't step into it for more than 30 seconds without feeling far more sick than I usually do even around a good bit of mold.

    ***I'm sorry this happened to you. It sounds as though you are not "wasting" this experience, though, and are treating it as an "experiment" from which to learn the mechanism. That's great!

    I spent the next 24 hours spitting out a total of two cups of saliva that tasted like the chemicals in the trailer. (I wonder why my saliva serves as such a good emergency detox mechanism?)

    ***I don't know. Saliva is made by glands that are served by the blood, so I think this means that the expectoration was helping to remove toxins from the blood. Here's another "war story": In Army training, everyone had to go through an experience of being exposed to CS gas, and I think that's still part of basic training. When one is exposed to this gas, it seems as though every orifice in one's head starts dumping fluid--the mouth, the nose, the eyes, and the sweat glands. I guess the body is set up to use its resources to get rid of toxins however it can.

    I've had this happen at other times too. Even when I know I'm being affected by mold, an environment will feel okay. Then suddenly it will become horrendously bad. Then after the effects of the mold have gone away, the environment will feel okay again.

    Erik seems to have this exact thing happen to an even greater extent.

    Erik's MCS was much worse than mine. He states that it was the MCS (rather than his CFS) that Dan Peterson expressed particular concern when recommending Ampligen to him in 1997. (Erik recalls the statement to be: "You have become a universal reactor and are at the point where most people commit suicide because life becomes basically unbearable.)

    On one day during my visit to Lake Tahoe last year, Erik and I went on a tour of a variety of moldy buildings. We were careful not to get too badly hit by the mold, and it was having only a modest effect on each of us.

    Then we went to a supermarket that Erik says he visits all the time and that's fine with regard to mold.

    We shopped for about 30 minutes without incident. Then in the blink of an eye, he became very confused and seemed on the verge of fainting. He quickly became fine after we left the store. He stated that it was due to the chemicals in the store (which I didn't notice) rather than to any mold.

    What interests me in my experiences and in observing his is the manner in which the MCS comes back. It's almost like there's an on/off switch. The chemicals either aren't bothersome at all or they're horrendously bothersome.

    So it seems to me that Erik and I both indeed must still have BBB's with holes in them (his apparently like swiss cheese). It's just that the mold avoidance is doing something that provides a buffer. Your comment above seems like it's a good explanation.

    Does it surprise you that there would be an on/off effect (with no period of time when the chemicals are just moderately bothersome)?

    ***It does seem like a very fast change. I can only suggest that perhaps the glutathione level was already a little low in the olfactory epithelium, and the presence of the mold toxin is just the straw that breaks the camel's back.

    Another question is that remark of Dr. Peterson's about Ampligen being the answer to the problem. Apparently he had seen patients like Erik before and had good results on them with the drug. (I'm going to hazard an unsubstantiated guess that the supermold is especially good at punching holes in the BBB and that others of Erik's severity presented in IV by 1997, after an extended period of exposure to that mold.)

    Ampligen improves the immune system so that various pathogens (including HHV6a and, presumably, XMRV) are brought under control. Would that, in your opinion, rectify the situation with glutathione that you posit above?

    ***Sorry, I don't know how Ampligen works, so I can't say what the connection might be. I should study it.

    Having the potential of falling off the edge on a split second with the MCS feels pretty precarious, by the way. It would be nice to have some warning that the buffer (if that's what it is) is going to run out. I would think that would be especially the case for Erik since his underlying MCS is so much more severe than mine, but for me too.

    ***Yes, I can see the problem.

    Thanks for this and for your other previous comments. You really were on a great roll
    yesterday!

    ***Thank YOU, Lisa. You know how to ask the right questions.

    Best, Lisa

    ***Best to you, too!

    ***Rich


    *

    http://etd.lib.ttu.edu/theses/available/etd-05252005-163223/unrestricted/Karunasena_Enusha_Diss.pdf

    OR

    http://etd.lib.ttu.edu/theses/available/etd-05252005-163223/


    CHAPTER III
    THE TOXOLOGICAL EFFECTS OF SATRATOXIN H
    ON HUMAN BRAIN CAPILLARY ENDOTHELIAL CELLS (HBCEC)

    Brain capillary endothelial cells are one of the tissues that form the blood
    brain barrier (BBB) [1]. The German microbiologist Ehrlich was the first to identify
    its existence more than 100 years ago [1]. The blood brain barrier consists of
    tissues that prevent microorganisms and toxic chemical compounds from
    entering into the brain tissue.

    The only substances able to readily diffuse across
    the barrier are small and lipophilic compounds [1]. Large compounds, such as
    glucose and hydrophilic elements pass through active transport membrane
    proteins [1].

    The fundamental elements of the BBB are the adherens and tight
    junctions which hold endothelial cells (ECs) together; second, the P-glycoprotein
    receptors that eject materials from the central nervous system (CNS); and third,
    the process of transcytosis which limits the influx of materials into the CNS [1].
    The final component is the astrocyte processes that cover the ECs [1].

    Some of the receptors that bind molecules for transport are transferrin and
    P-glycoprotein [1]. These membrane transport systems are a component of the
    limited transfer of materials across the BBB [1]. Other distinguishing features of
    the BBB are the limited number of endocytic vesicles, which limit transcellular
    34
    flux [1].

    Tight junctions between the cells maintain a low level of paracellular flux
    [1]. It are these two features that distinguish ECs of the BBB compared to other
    EC of different tissues [1]. The tight junctions between cells are formed by
    specific proteins. One group is termed cadherin, another is occludin [1]. Cadherin
    forms a single-pass transmembrane glycoprotein and is considered a major cell-
    to-cell adhesion molecule [1]. Occludin is a four-pass transmembrane that is
    similar to connexin, a protein commonly found in gap junctions [1].

    In the event of
    EC damage, the junctions are compromised and the tightness of the BBB is lost
    [1]. Thus, the junctions play a critical role in the infrastructure of the BBB [1].

    Studies conducted on gap-junctional intracellular communication in
    Chinese hamster ovary (CHO) V79 cells after exposure to members of the
    trichothecene family, (T-2 toxin and vomitoxin) demonstrated the ability of these
    toxins to decrease metabolic cooperation associated with gap-junctional
    intracellular communication [2]. Gap-junctional communication allows for
    metabolic cooperation between cells which regulate cell proliferation,
    differentiation, and development [2].

    When this form of cellular communication
    decreases, tumors are able to form [2]. These studies suggested that low doses
    of trichothecenes maybe tumorgenic [2]. These studies further demonstrated the
    function of junctions between cells and the potential devastation trichothecene
    toxins may induce in the integrity of cell communication and development [2]. It
    further potentates the devastating effects that may result to junctions associated
    with the integrity of the BBB [2].
    35

    In the event that the BBB is damaged, inflammatory responses can
    contribute to CNS injury. The accumulation of evidence that demonstrates the
    negative effects due to inflammation on the CNS continues to expand.

    Studies
    have demonstrated that regardless of the causative agent or event, such as
    infection, trauma, ischemia, necrosis, or hemorrhage, the inflammatory response
    generates further damage [3].

    There are four major events that are used to
    describe inflammation as stated by Celsus: pain, tumor, rubor, and heat [3].

    The
    events that lead to this pathology are the increase in blood flow to the site of
    injury, followed by increased capillary permeability of ECs to allow the release of
    secretory mediators that recruit immune cells to enter damaged tissues [3].

    Cells
    that arrive at the site include neutrophils, macrophages, mast cells, lymphocytes,
    platelets, dendritic cells, and fibroblasts [3].

    Chemokines released by endothelial
    cells and the expression of adhesion molecule receptors on the surface, allow
    endothelial cells to interact with leukocytes [3].

    Leukocytes are able to pass
    through the endothelial cell layer to the site of inflammation. The process of
    inflammation is intended to repair injured tissues; however this mechanism tends
    to induce greater damage to the CNS upon activation [3].

    Diseases such as
    multiple sclerosis, Alzheimer’s, rheumatoid arthritis, and systemic lupus
    erythematosus (SLE) all demonstrate events of inflammation that lead to damage
    in the CNS [3].

    Cytokines released by immune cells, such as tumor necrosis
    factor- alpha (TNF-?), are suggested to have an effect on the endothelial cells of
    the BBB, leading to the rupture of the BBB in inflammation associated diseases
    36
    [3,4].

    TNF- ? is able to induce the expression of adhesion molecule receptors on
    ECs, which allow the binding and passage of lymphocytes and leukocytes [3,4].


    In addition to the passage of T cells, studies have demonstrated that B cells,
    dendritic cells, natural killer (NK) cells, mast cells, and macrophage or monocytes
    also pass through the BBB [3,4]. TNF- ? is also able to activate the production of
    nitric oxide in macrophage which leads to greater permeability across the BBB [3,
    4].

    In addition to TNF-?, interleukin-6 (IL-6) is also associated with
    proinflammatory events, and is produced in conjunction with TNF-? and IL-1 [3].
    Diseases associated with inflammation and CNS damage have demonstrated the
    expression of IL-6 in the brain [3, 4]. These events led to studies which
    demonstrated that the high expression of IL-6 in the CNS of mice resulted in
    ataxia, tremor, motor impairment and seizures [3, 4].

    Similar events are seen in
    individuals exposed to trichothecene mycotoxins in SBS conditions [5].

    Although
    the function of inflammation is to repair damaged tissues, the effects in the CNS
    tend towards damage versus repair [2, 3, 4]. The events described may be the
    reason why inflammatory events in the CNS lead to toxic effects in the ECs and
    damage to the BBB [2, 3, 4].

    Studies conducted with trichothecenes have demonstrated disruption of
    biochemical pathways in immune cells and other cell types that evidence events
    of inflammation and apoptosis. Studies conducted with T-2 toxin on L-6
    myoblasts demonstrated the ability of T-2 toxin to disrupt glucose transport,
    amino acid uptake, and calcium efflux decreases across the cellular membrane
    37
    [6].

    This study suggested the ability of T-2 toxin to disrupt cell membrane integrity
    and activity [6]. The authors further suggested the ability of T-2 toxin to disable
    the activity of mitochondrial and nuclear membranes in cells, which could lead to
    apoptotic events [6].

    Studies have also demonstrated the ability of cells to induce mitochondrial
    damage and lipid peroxidation, which activates apoptosis pathways [7,8]. Studies
    conducted by Pace et. al., have demonstrated the ability of T-2 toxin to inhibit
    mitochondrial protein synthesis [8].

    Mitochondria, like prokaryotes, contain 70S
    ribosome compared to eukaryotes, which have 80S ribosomes [8].
    Trichothecenes are known to inhibit eukaryotic protein synthesis; however, these
    studies demonstrate the ability of T-2 toxin to inhibit the electron transport chain
    (ETC) in mitochondria and non-specific inhibition of protein synthesis [8]. If
    mitochondrial protein synthesis and ETC activity are inhibited in a dose-
    dependent manner by T-2 toxin, this would suggest that apoptotic events may be
    activated due to mitochondrial damage by trichothecenes [8].

    Further evidence of apoptotic events induced by trichothecene exposure
    has been elucidated. Experiments conducted with different trichothecenes have
    demonstrated variations in apoptotic induction. These results showed that
    structural nuances between trichothecenes can determine the degree of c-Jun N-
    terminal kinase (JNK/p38) activation [9]. JNK-p38 is expressed as a ribotoxic
    stress response that signals apoptotic pathways [9].

    These events imply the
    ability of trichothecenes to activate rapid apoptosis by inhibiting protein
    38
    translation and activating JNK/p38 [9]. Studies conducted by Pestka et. al., have
    demonstrated the ability of trichothecenes and specifically satratoxins to induce
    apoptosis in leukocytes both in vitro and in vivo [9]. Further studies conducted by
    this group have demonstrated the ability of satratoxins to activate JNK/p38 and
    other kinases associated with apoptosis [9]. These kinases include several
    groups of mitogen activated protein kinases (MAPKs), such as extracellular
    signal-regulated protein kinase (ERK), p38, and stress associated protein kinase/
    c-Jun N-terminal kinase (SAPK/JNK) at low doses in murine macrophages [9].

    Additional work conducted by other researchers has shown apoptotic events in
    lymphoid organs of mice exposed to trichothecenes [10]. These studies
    demonstrated in vivo activity that correlates to events observed in in vitro
    analysis.

    In addition, this research demonstrates the ability of trichothecenes to
    induce pathological events that may contribute to leukopenia and other
    immunosuppressive events in individuals exposed to SBS conditions [10].
    Recent reports have demonstrated that S. chartarum spores in the presence of
    Streptomyces californicus are able to induce S. californicus to produce biological
    compounds that arrest cell cycle activity [11, 12].

    S. chartarum alone was found
    to induce apoptosis in macrophages, but unable to induce cell cycle arrest. S.
    californicus was unable to inhibit cell cycle activity without the presence of S.
    chartarum spores [11, 12]. These events demonstrate additive and synergistic
    toxicity induced by S.chartarum [11, 12].
    39

    Previous in vivo studies conducted with T-2 toxin have demonstrated the
    ability of trichothecenes to induce neurotoxic events when toxin was injected into
    brain tissue directly [13, 14]. These studies suggested the ability of
    trichothecenes to produce cytotoxic events, inflammation, and apoptosis, which
    illustrate the potential immunopathological events that have been witnessed in
    neurophysiological studies conducted with trichothecenes in murine and rat
    models.

    T-2 toxin has been closely evaluated for its effects in livestock and
    poultry [15, 16, 17, 18]. T-2 toxin is a common contaminant of feed for animals,
    and is associated with lethargy, ataxia, emesis, and feed refusal in animals and
    humans [15, 16, 17, 18].

    There is evidence of T-2 toxin transforming
    neurotransmitter balance [17]. Increases in neurotransmitter concentrations, such
    as catecholamines and serotonin are associated with loss of appetite [17].

    These neurotransmitters are synthesized from specific amino acids, and the
    transfer of these amino acids across the blood-brain barrier is highly regulated by
    transport proteins [17].

    When the BBB is compromised, studies have
    demonstrated changes in the passage of these amino acids into the CNS,
    leading to changes in neurotransmitter concentrations [17].

    These studies have
    demonstrated that the ingestion of T-2 toxin leads to changes in amino acid
    permeability across the BBB, which could lead to the neurological effects
    observed in animals exposed to trichothecene mycotoxins [17].

    Other animal
    studies conducted with trichothecenes have demonstrated the ability of these
    agents to cause neurological events regardless of the administration route [13].
    40

    Experimental evidence indicated that T-2 toxin administered intracerebrally (i.c.)
    or subcutaneously (s.c.) resulted in similar events [13]. Rats exposed via either
    route demonstrated depression of respiration and muscle paralysis, followed by
    convulsions which led to death [13]. These results demonstrated that regardless
    of the route of exposure, systemic distribution of trichothecenes can reach the
    brain, resulting in neurological events [13].

    Further evidence showed that low
    levels of T-2 toxin were responsible for the changes in the metabolism of brain
    biogenic monoamines, compared to lethal doses [13]. Previous analyses have
    demonstrated that the disruption of monoamine metabolism could alter food
    intake by altering hormone secretion, peristaltic contractions, or thermal
    regulation.

    The above studies provided evidence which suggested low levels of
    trichothecenes were able to injure CNS activity and disrupt the integrity of the
    BBB. There is also evidence that suggested the stimulation of endothelial cells by
    trichothecenes led to pro-inflammatory activity. This continuous stimulation of
    pro-inflammatory events appeared to further aggravate the CNS in addition to the
    BBB.

    In the present experiments, human vascular endothelial cells were
    exposed to satratoxin H, LPS, and oxidative stress conditions to evaluate the
    cellular pathways that were activated. Cells were also evaluated for additive
    effects, due to exposure from satratoxin H and LPS, satratoxin H and H202. The
    purpose of these experiments was to determine what effects low doses of a
    41
    trichothecene mycotoxin from S.chartarum would induce in cells that compose
    the BBB. The objective was to utilize HBCEC as an in vitro model to determine
    the mechanism of toxicity produced by exposure to satratoxin H.


    Compared to the negative control cells that received water, cells exposed to
    100ng/ml SH, and 1000ng/ml SH, and LPS demonstrated early and late stages
    of apoptosis, whereas the control cells did not have a red stain in the nucleus of
    the cell. To further evaluate apoptosis, cytochrome C levels from cell extracts
    were evaluated using an ELISA method. These results demonstrated that a
    significantly increased amount (P< 0.05) of cytochrome C was released from
    cells exposed to 10ng/ml, 100ng/ml, LPS, 10ng/ml + LPS, and 10ng/ml + H202.
    These results can be seen in figure 11.

    An additional indicator of apoptosis is oxidative stress. In the event of
    oxidative stress, glutathione (GSH) acts as a reducing agent against reactive
    oxygen species (ROS) such as lipid radicals and peroxides.

    However, if GSH
    levels in a cell are insufficient to compensate for the degree of oxidative stress,
    both apoptotic and inflammatory pathways are further activated.

    To determine
    whether mycotoxins increased oxidative stress levels in HBCEC, a quantitative
    method was used to determine the levels of GSH present in cell extracts
    exposed to various experimental conditions.

    The results demonstrated a
    significant decrease (P> 0.05) in the concentration of GSH (µg/ml) in cells
    exposed to 100ng/ml SH, 1000ng/ml SH, LPS, H202, 10ng/ml + LPS, 10ng/ml +
    H202. These results are seen in Figure 12. The production of lipid peroxidation,
    51
    further demonstrates the degree of oxidative stress induced on HBCECs.


    64
    CONCLUSIONS
    Results from the adhesion mo le receptor expression on HBCEC
    demonstrate that satratoxin H levels of 100ng/ml and 1000ng/ml are able to
    induce inflammatory pathway activation alone.

    Additive effects are demonstrated
    with very low concentrations of SH, such as 10ng/ml in the presence of
    inflammatory agents such as LPS and H202.

    Similar concentrations of the
    mycotoxin are able to induce apoptotic pathways leading to the activation of early
    stages of apoptosis in the presence of 100ng/ml SH, however evidence of late
    stages of apoptosis are observed with 1000ng/ml and 10ng/ml + LPS or 10ng/ml
    H202.

    These results demonstrate the ability of satratoxins to induce apoptotic
    pathways at the same concentrations that inflammatory pathways are being
    activated.

    This suggests that low levels of inflammation and apoptotic events can
    be induced in the presence of moderate levels of SH, and low levels of SH are
    able to induce similar events in the presence of other inflammatory agents and
    oxidative stress conditions, as demonstrated by the levels of GSH and
    cytochrome C in cell extracts.

    In addition, the ability of the mycotoxins to induce
    cell shrinkage at moderate to low levels of SH demonstrate the potential ability of
    these agents to compromise the integrity of the BBB which could lead to further
    neurological damage from mycotoxins or other harmful agents.

    The presence of
    lipid peroxidation in cells exposed to moderate concentrations of SH and additive
    conditions, further demonstrates the ability of the mycotoxins to amplify cellular
    65
    damage through the indirect production of lipid radicals and other ROS.

    The
    results further suggest that low to moderate levels of SH are able to induce
    inflammatory and apoptotic pathways that amplify the cellular damage by the
    continuous activation of these biological pathways.
  4. jenbooks13

    jenbooks13 New Member

    Hi there Rich. Your theory is interesting but I don't think accounts for MCS overall. That's just by my own experience. I do believe it's due to chronic biotoxin, mold toxin, chemical toxin etc overloading the detox system. I have had MCS reactions to stuff I can't really smell (like when I got a new spin dryer, since I have a mini washer up here and air dry my clothes as I react to scented detergent and fabric softener residues in our laundry room). I couldn't smell anything but for the first few weeks when I turned it on and sat beside it waiting for the spin dryer to spin all the moisture out of the clothes, I felt brain foggy and weird. As soon as I turned it off I felt better. I notice now I don't feel that anymore. Something was offgassing from the new motor and once used for a while is less.

    Secondly, I don't react to fresh flowers, or essential oils. I have oil diffusers in my closet. I use orange and tangerine. I have nice aromatic fresh flowers here. I have a night blooming cereus that gave off three sets of huge blooms this year--it's an enormous flower that blossoms only at night and gives off an intense fragrance that fills the whole apartment. I used to put my nose right in it and joyfully inhale the scent. I'm fine in the park or the woods with all the aromas that nature creates from trees, leaves, flowers, grasses, you name it.

    Yet I get sick from new clothes (formaldehyde?), new paint, scented detergents, sometimes very new books just printed, and all kinds of stuff. I just got my boyfriend a hotplate as he had had a small stove leak and I didn't want to risk it, and we turned it on. I couldn't smell anything but felt foggy so asked him to take it home and use it there for a while.

    So olfactory neurons wouldn't explain this while toxicity of chemicals would.
  5. Lono83

    Lono83 New Member

    In Dr. Martin Pall's latest summary of his MCS theory -- http://thetenthparadigm.org/mcs09.htm -- he states:



    MCS Is a Reaction to Chemicals, Not Odors


    It should be clear from the above, that chemicals acting in MCS are not acting on the classic olfactory receptors (15,16), but rather are acting as toxicants. This is opposite many published but undocumented claims that MCS is a response to odors. There is additional evidence arguing against the view that MCS is a reaction to odors. MCS sufferers who are acosmic, having no sense of smell, people who have intense nasal congestion and people whose nasal epithelia have been blocked off with nose clips can all be highly chemically sensitive (1,4). This does not necessarily mean that MCS never impacts the olfactory system. It simply means that MCS is not primarily an olfactory response. A recent study, confirmed this view, showing that the olfactory center in the brain in people with MCS was less sensitive to activation by chemical exposure than in normal controls, rather than being more sensitive (17).

    The references are:

    1. Pall ML (2009) Multiple Chemical Sensitivity: Toxicological Questions and Mechanisms. Chapter XX in General and Applied Toxicology, Bryan Ballantyne, Timothy C. Marrs, Tore Syversen, Eds., John Wiley & Sons, London.

    4. Ashford N, Miller C (1998) Chemical Exposures: Low Levels and High Stakes, 2nd edition. John Wiley & Sons, New York.

    15. Axel R 2005 Scents and sensibility: a molecular logic of olfactory perception (Nobel lecture). Angew Chem Int Ed Engl 44,6110-6127.

    16. Buck L.B. (2005) Unraveling the sense of smell (Nobel lecture). Angew Chem Int Ed Engl 44,6128-6140.

    17. Hillert L, Musabasic V, Berglund H, Ciumas C, Savic I. 2007 Odor processing in multiple chemical sensitivity. Hum Brain Mapp 28,172-182.
  6. richvank

    richvank New Member

    Hi, Jenbooks.

    Thanks for the comments and for sharing your experience with chemical vapors.

    I think it's likely that there is more than one mechanism involved in MCS, and that there are subsets within it, just as there are in CFS. I think it's another heterogeneous population. For example, there are people whose MCS started from a single large acute exposure to a chemical, and then they have been sensitive to a range of chemicals after that. There are others whose MCS came on gradually, and it isn't known whether it will be reversible. Slaya has noted that her MCS is reversible, and depends on mold exposure status.

    I suggest that the mechanism I described may apply to a subset of the MCS population, and not to the entire population.

    You suggested overloading of the detox system as the mechanism in your case. Indeed, there is evidence of a higher frequency of some polymorphisms in enzymes of the detox system in MCS, and I think that would support your suggestion, at least in a subset of MCS. Again, when I use the word subset, I am not using it to describe the size of the affected group.

    With regard to determining the mechanism in a given case, I'm not sure that whether or not an odor is detected is an accurate criterion for whether the substance is entering the brain via the olfactory epithelium. The olfactory epithelium is exposed to all vapors that are inhaled, whether they produce a sensation of odor or not. If the barrier function of the olfactory epithelium is damaged, I think that a variety of substances could enter the brain via that route, whether they are substances that produce a sensation of odor or not.

    Best regards,

    Rich
  7. richvank

    richvank New Member

    Hi, Lono83.

    Thank you for posting the extract from Dr. Pall's MCS summary.

    I think he makes a good point, and I agree with it. As I noted in my post to jenbooks, whether or not a substance provokes a sensation of odor, it could still enter the brain and cause MCS symptoms. I note that Dr. Pall does not rule out entry via the olfactory epithelium
    as a possible route.

    Perhaps a way to determine in a given case whether the offending chemical is coming in via the olfactory epithelium or via inhalation and passage into the blood to be carried to the brain would be to measure the response time. If it is very rapid, as in some cases with which I'm familiar, perhaps that indicates that it's coming in through the olfactory epithelium. If it takes somewhat longer, perhaps its coming in via the blood. I think that both of these times would be measured in seconds, but that the second one would be measurably longer.

    Best regards,

    Rich
  8. jenbooks13

    jenbooks13 New Member

    It certainly seems the olfactory epithelium plays a role--but generally I think MCS is due to toxicants affecting the neurological/immune system. You're right too, a substance can be below obviously detectable threshold and still be detected by the brain.

    Those of with MCS seem to have multiple sensitivities. I have food and drug sensitivities too.