Multiple Chemical Sensitivity Etiology
Airway Genetics and Ambient Combustion Aerosol
SPC 29 Airway to Systemic: Dysfunction of Detox Enzymes - Terlecky
SPC 29 Airway to Systemic: Dysfunction of Detox Enzymes - Terlecky
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)
SPC 29 Airway to Systemic: Dysfunction of Detox Enzymes - Terlecky
Please choose the Incorrect Statement
Spc 29a)
TERLECKY S. ET AL. PEROXISOMES AND AGING. 1763;12:1749-54 2006:
"...there are circumstances in which the tightly regulated balance of hydrogen peroxide producing and degrading activities in peroxisomes is upset - leading to the net production and accumulation of hydrogen peroxide and downstream reactive oxygen species. The factor most essentially involved is catalase, which is missorted in aging, missing or present at reduced levels in certain disease states, and inactivated in response to exposure to specific antibiotics...
...Many individuals worldwide are hypocatalasemic, not due to aging's effects, but rather to a reduction in cellular catalase expression (Eaton 1995, Wen 1988) or stability (Eaton 1995, Crawford 1988)...
...Cells from a hypocatalasemic patient (expressing approximately 25% of normal catalase levels) were found to have accumulated hydrogen peroxide and harbored age-associated pathologies (Wood 2006)..."DeLuca 2010 found catalase activity in MCS patients 30% of normal.
SPC 29b)
"...Notwithstanding the absence of genetic defects in CYPs, recent studies have increasingly implicated various inflammatory stimuli, first of all, pro-inflammatory cytokines (Chun 2002, Nadin 1995, Tapner 1996, Tinel 1999) to cause changes in the activities and expression levels of CYPs through nitric oxide signalling (Chun 2002, Stadler 1994). For example, drug metabolizing CYPs such as CYP3A4 and CYP2B6, which are constitutively expressed in human mono nuclear cells, have been significantly repressed by IFN Gamma or IL-2 (Liptrott 2009)...
...Our results suggest that serious and multiple dysfunctions of chemical defense systems found in MCS patients may mainly not depend on genetic defects, but instead may rely on non-genetic modifications of metabolizing/antioxidant enzyme expression and/or activity, mediated by redox active agents such as NO and inflammatory cytokines..."Found elevated in MCS patients (Dantoft 2014, Deluca 2010)
...Dysfunction of two major antioxidant enzymes and depletion of glutathione inevitably leads to severe oxidative stress and impaired elimination of phase 1 oxidation metabolites. Excessive amounts of hydrogen peroxide due to catalase deficiency will initiate a non enzymatic free radical driven chain reaction of lipid peroxidation implicated in a number of human pathologies..."
SPC 29c)
"...In all instances, sensory neurons release 10-200 fold higher levels of IL-6 (pro-inflammatory cytokine) relative to epithelial cells... Found elevated in MCS patients (Dantoft 2014)...conditions associated with chemical pollutants are characterized by damage to the epithelial barrier that lines the airways..."
SPC 29d)
"...a persistent ongoing airway inflammatory process the result of exposure to air pollutants in a sequential and chronic manner...the imbalance and dysregulation of cytokines and their ample systemic effects..." Found elevated in MCS patients (Dantoft 2014)
SPC 29e)
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 such as TNF alpha, IL 6 and IL-1beta... Found elevated in MCS patients (Dantoft 2014)...these cytokines can activate endothelial cells in the BBB, disrupt the BBB...and trigger cascades...results in increased expression of nitric oxide synthase...and nitric oxide production that opens the BBB..."
SPC 29f)
Biopsy of MCS subjects
....There are defects in the tight junctions between respiratory epithelial cells, focal desquamation of the epithelial cells in places, hypertrophy of glandular structures, lymphocytic infiltrates, and proliferation of sensory nerve fibers..."
SPC 29g)
"...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 29h)
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..."
"...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 29i)
Exposure to ACA PM activates sensory nerves in damaged airway epithelium releasing inflammatory cytokines that become systemic ( Calderon-Garciduenas 2008, 2000, Veronesi 2001).
SPC 29j)
MCS people have exposed sensory nerve fibers (Meggs 1997) and elevated cytokines (Dantoft 2014) - those recognized by Veronesi 2001 and Calderon-Garciduenas 2008.
SPC 29k)
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 29L)
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 2010, Deluca 2010, Taylor-Clark 2010, Caceres 2009, Anand 2008, Bessac 2008), Nassenstein 2008, Bautista 2006, Inoue 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)
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