Multiple Chemical Sensitivity Etiology

Airway Genetics and Ambient Combustion Aerosol

SPC 30 Airway to Systemic: Dysfunction of Detox Enzymes - Khatsenko

Links: 35 CAR Test SPC Questions
CAR Warm Up
SPC 1 Introduction: South Pole CAR (SPC) - A Character Test
SPC 2 South Pole CAR: ACA PM, Band Cell, and Monocyte Drop
SPC 3 ACA PM and ME/CFS: Do We Hear An Echo?
SPC 4 ACA UFPM: In the RBC - Through the BBB
SPC 5 ACA UFPM: IL-1 beta, RBC, BBB, - MCS and ME/CFS
SPC 6 ACA UFPM: Nerve Penetration
SPC 7 ACA UFPM: Olfactory, BBB, AD, PD, MCS, and ME/CFS
SPC 8 ACA PM: Gastro-Inflammation, Immunity, Vagal Circuitry
SPC 9 Veronesi: Sensory Nerve Insight
SPC 10 Kimata: Histamine Warning - Return to Masking
SPC 11 Central Sensitization: Intense, Repeated, and Sustained Inputs

On CAR
SPC 12 Disease Conditions Begin: Airway Epithelial Injury
SPC 13 Exposed Sensory Nerves - TRPA1
SPC 14 Exposed TRPA1: Central Sensitization
SPC 15 ACA: Loud and Clear
SPC 16 Airway Cytokine Release: Principle Mediator of Systemic Inflammation
SPC 17 Calderon-Garciduenas: Airway to Systemic: Putting It Together
SPC 18 Airway Gaps - Exposed Nerves - UFPM to the CNS
SPC 19 ACA PM: Months and Years Residence Time
SPC 20 Airway Gaps: Reduced Detox Enzyme Intervention
SPC 21 Solvents and Pesticides Primary: Shoe Fits Glove?
SPC 22 Veronesi and Roy: Genetic Difference in Airway Sensitivity

SPC 23 Jung Was Right Sort Of
SPC 24 Veronesi and Jung: A Perfect Match
SPC 25 Tailpipe and Chimney Emissions: Horizontal Coning
SPC 26 How Far Symptoms Travel: 25 Years, 500 Locations, 22 States
SPC 27 Not Into That Kind of Entertaining
SPC 28 Does it Cost More Than Money?
SPC 29 Airway to Systemic: Dysfunction of Detox Enzymes - Terlecky
SPC 30 Airway to systemic: Dysfunction of Detox Enzymes - Khatsenko
SPC 31 Gerde and Stadler: Benzo[a]pyrene Forever?
SPC 32 Phase I and II Detox Enzymes Defined

Lifestyle Change
SPC 33 ACA Catastrophic Consequences
SPC 34 Impossibly Good City Design
SPC 35 South Pole CAR Test: Satisfaction Guarantee

MCS 3 Definition and Concensus Criteria

MCS 3a Criteria Amendment Research Points (CAR)

MCS 3aa Etiology: Concensus Author CAR Test (SPC)

MCS 3b CAR References

SPC 30 Airway to Systemic: Dysfunction of Detox Enzymes - Khatsenko

Please choose the Incorrect Statement

SPC 30a)

KHATSENKO 1993:

"...(i) LPS (bacterial lipopolysaccharides) induces the release of intermediary cytokines, which, in turn, induce NOS activity in Kupffer cells and hepatocytes; (ii) NO binds to heme iron in cytochromes P450 and prevents oxygen binding, thereby blocking enzyme activity; (iii) NO may also enhance degradation of cytochromes P450 by nitrosylation of heme or thiols in P450 apoprotein or impair transcriptional activation of P450...

...In summary, cytokine induced overproduction of NO could explain attenuation of activity, content, and transcription of cytochromes P450 by a diverse array of immunostimulants..."

SPC 30b)

 DEERING-RICE 2011:

"...A number of studies have correlated responses to urban PM, including DEP (diesel exhaust particles) with activation of airway sensory neurons, particularly C and A beta fibers that express Transient  Receptor Potential Ankyrin-1 (TRPA1), TRP Vanilloid-1 (TRPV1), and substance P... Found elevated in MCS patients (Kimata 2004) (Hazari 2011, Teles 2009, Anand 2008, Nassenstein 2008, Kobayashi 2005)...

SPC 30c)

KIMATA 2004:

"...plasma levels of SP (substance P), VIP (vasoactive intestinal peptide), and NGF (nerve growth factor), but not histamine are significantly (p<0.01 by ANOVA) elevated in sMCS patients...

exposure to VOC further increased levels of SP, VIP, and NGF...exposure to VOC also increased plasma histamine levels...

these results indicate that sMCS patients may suffer from ongoing neurogenic inflammation which is aggravated by VOC..."

SPC 30d)

OSLUND 2008:

"...substance P...Found elevated in MCS patients (Kimata 2004)... primes and activates human neutrophils for superoxide, H2O2, and nitric oxide production (Sterner-Kock 1999, Tanabe 1996)..."

SPC 30e)

DANTOFT 2014:

"...plasma levels of IL-1 beta, IL-2, IL-4, and IL-6 were found to be statistically significantly increased in MCS, TNF alpha was borderline enhanced, whereas IL-13 was downregulated..."

SPC 30f)

CALDERON-GARCIDUENAS 2008:

"...sustained exposures to significant levels of air pollutants including UFPM (ultrafine particulate matter) , PM2.5 (less than 2.5 microns), and PM-LPS produce brain neuroinflammation and neurodegeneration through at least four pathways:

1  Induction of upper respiratory, lung epithelial, and endothelial injury leading to persistent chronic inflammation in the respiratory tract and systemic inflammation. The systemic inflammation is accompanied by the production of pro-inflammatory cytokines..."

SPC 30g)

MUKAE 2001:
"...We conclude that repeated exposure to PM-10 (particulate matter less than 10 microns in diameter) stimulates the bone marrow to increase the production of polymorphonuclear leukocytes (PMN) in the marrow and accelerate the release of more immature PMN into the circulation. The magnitude of these changes was related to the amount of particles phagocytosed by alveolar macrophages..."

HOGG 2009:

"...alveolar macrophages, epithelial and other cells interact with the particles to produce a wide variety of cytokines and chemokines that generate a local inflammatory immune response. These mediators spill over into the blood to stimulate the bone marrow to increase the release of leukocytes from the marrow, and the liver to increase the production of a variety of acute phase proteins. This systemic response is associated with vascular activation and the progression of the atherosclerotic process..."

SPC 30h)

Exposure to ACA PM activates sensory nerves in damaged airway epithelium releasing inflammatory cytokines that become systemic ( Calderon-Garciduenas 2008, 2000, Veronesi 2001).

SPC 30i)
MCS people have exposed sensory nerve fibers (Meggs 1997) and elevated cytokines (Dantoft 2014) - those recognized by Veronesi 2001 and Calderon-Garciduenas 2008.

SPC 30j)
Proatherogenic conditions of severe oxidative stress were found in MCS patients due to inflammatory stimulation of blood cell populations with cytokines - elevated NO, glutathione depletion, catalase deficiency, and a fatty acid profile indicating lipid peroxidation - increased SFA with losses in PUFA, N-6, N-3, arachidonic acid and omega 3 (Deluca 2010).

SPC 30k)
Sensory receptor activation and alveolar macrophage involvement  in damaged airway epithelium due to ACA PM - changes in the innate inflammatory immune system (Hogg 2009, Abbas 2007) - can't result in release of  mediators - neuropeptides, cytokines, chemokines, and growth factors (Dantoft 2014, Maes 2012, Deering-Rice 2011, Hazari 2011, Costa 2010Deluca 2010, Taylor-Clark 2010, Caceres 2009, Anand 2008Bessac 2008), Nassenstein 2008Bautista 2006Inoue 2005, Kobayashi 2005, Veronesi 2001), increase in circulating leukocytes, production of acute phase proteins Hiraiwa 2014, 2013, Hogg 2009, Goto 2004, Mukae 2001), nitric oxide overproduction (Maes 2012, Deluca 2010, Calderon-Garciduenas 2008), and dysfunction of Phase I and II xenobiotic and antioxidant enzymes in a systemic condition of severe oxidative stress (Deluca 2010, Liptrott 2009, Oslund 2008, Chun 2002, Sterner-Kock 1999, Tinel 1999, Tanabe 1996, Tapner 1996, Nadin 1995, Stadler 1994, Khatsenko 1993).

Links: 35 CAR Test SPC Questions
CAR Warm Up
SPC 1 Introduction: South Pole CAR (SPC) - A Character Test
SPC 2 South Pole CAR: ACA PM, Band Cell, and Monocyte Drop
SPC 3 ACA PM and ME/CFS: Do We Hear An Echo?
SPC 4 ACA UFPM: In the RBC - Through the BBB
SPC 5 ACA UFPM: IL-1 beta, RBC, BBB, - MCS and ME/CFS
SPC 6 ACA UFPM: Nerve Penetration
SPC 7 ACA UFPM: Olfactory, BBB, AD, PD, MCS, and ME/CFS
SPC 8 ACA PM: Gastro-Inflammation, Immunity, Vagal Circuitry
SPC 9 Veronesi: Sensory Nerve Insight
SPC 10 Kimata: Histamine Warning - Return to Masking
SPC 11 Central Sensitization: Intense, Repeated, and Sustained Inputs

On CAR
SPC 12 Disease Conditions Begin: Airway Epithelial Injury
SPC 13 Exposed Sensory Nerves - TRPA1
SPC 14 Exposed TRPA1: Central Sensitization
SPC 15 ACA: Loud and Clear
SPC 16 Airway Cytokine Release: Principle Mediator of Systemic Inflammation
SPC 17 Calderon-Garciduenas: Airway to Systemic: Putting It Together
SPC 18 Airway Gaps - Exposed Nerves - UFPM to the CNS
SPC 19 ACA PM: Months and Years Residence Time
SPC 20 Airway Gaps: Reduced Detox Enzyme Intervention
SPC 21 Solvents and Pesticides Primary: Shoe Fits Glove?
SPC 22 Veronesi and Roy: Genetic Difference in Airway Sensitivity

SPC 23 Jung Was Right Sort Of
SPC 24 Veronesi and Jung: A Perfect Match
SPC 25 Tailpipe and Chimney Emissions: Horizontal Coning
SPC 26 How Far Symptoms Travel: 25 Years, 500 Locations, 22 States
SPC 27 Not Into That Kind of Entertaining
SPC 28 Does it Cost More Than Money?
SPC 29 Airway to Systemic: Dysfunction of Detox Enzymes - Terlecky
SPC 30 Airway to systemic: Dysfunction of Detox Enzymes - Khatsenko
SPC 31 Gerde and Stadler: Benzo[a]pyrene Forever?
SPC 32 Phase I and II Detox Enzymes Defined

Lifestyle Change
SPC 33 ACA Catastrophic Consequences
SPC 34 Impossibly Good City Design
SPC 35 South Pole CAR Test: Satisfaction Guarantee

MCS 3 Definition and Concensus Criteria

MCS 3a Criteria Amendment Research Points (CAR)

MCS 3aa Etiology: Concensus Author CAR Test (SPC)

MCS 3b CAR References

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