Airway Genetics and Ambient Combustion Aerosol

SPC 5 ACA UFPM: IL-1 beta, RBC, BBB, - MCS and ME/CFS

SPC 5 ACA UFPM: IL-1 beta, RBC, BBB, - MCS and ME/CFS

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 Consensus Criteria

MCS 3a Criteria Amendment Research Points (CAR)

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

MCS 3b CAR References

SPC 5 ACA UFPM: IL-1 beta, RBC, BBB, - MCS and ME/CFS

Please choose the Incorrect Statement
SPC 5a)

CALDERON-GARCIDUENAS 2008:
"...exposure to air pollution and brain damage includes a chronic inflammatory process involving the respiratory tract, which results in a systemic inflammatory response with the production of inflammatory mediators...

SPC 5b)
...ultrafine PM (UFPM), particulate-matter-associated lipopolysaccharides (PM-LPS) and metal uptake..through olfactory neurons, cranial nerves such as the trigeminal and vagus, the systemic circulation and macrophage-like cells loaded with PM from the lungs (Calderon-Garciduenas 2004, 2003a, 2003b, 2002, 2001)...

SPC 5c)
...An intact BBB (blood-brain barrier) is necessary for the proper functioning of the CNS by actively controlling cellular and molecular trafficing between the systemic circulation and the brain parenchyma (Abbott 2005). Brain capillaries represent the largest surface area-CNS interface where tight intercellular junctions constitute the morphological basis of the BBB (Lossinsky 2004)...

SPC 5d)
...LPS and IL-1beta upregulate adhesion molecules, increase leukocyte migration across the CNS endothelial cells, and regulate BBB permeability (Hickey 2001, Rothwell 2000)...whereas TNFalpha and IL-6 disrupt the BBB through the release of endothelial nitric oxide (Farkas 2006)...
...circulating cytokines can gain access to the brain by being transported across the BBB (Nguyen 2002, Rivest 2001, Pan 2001) and are able to evoke additional inflammatory mediator expression by vascular associated microglia (brain macrophages) (Griffin 2002), further increasing the permeability of the BBB (Blamire 2000). IL-1beta is the most important molecule capable of modulating cerebral functions during systemic and localized inflammation (Ferrari 2006, Griffin 2002, Rothwell 2000)...

SPC 5e)
...A critical finding is the endothelial nuclear NFkB activation present in the brain capillaries of young exposed subjects. NFkB activation depends on vivid stimuli such as cytokines, LPS, and DNA damage (Pahl 1999); activation is tightly regulated and quickly shortened through feedback inhibition following the initial activating stimulus (Xiao 2006). However, persistent activation (i.e. continuous exposure to significant levels of cytokines, UFPM, and/or PM-LPS) results in deleterious effects..."

SPC 5f)
IL-1beta and IL-6 are major figures of the respiratory-systemic-CNS inflammatory process (Gabay 2007, Ferrari 2006, Hickey 2001, Rothwell 2000, Le 1987). Those with MCS and ME/CFS have elevation of IL-1beta, IL-6, and other cytokines with increased COX-2 (cyclooxygenase-2), NFkB (nuclear factor kB), and iNOS (inducible nitric oxide synthase) confirmed in ME/CFS (Maes 2007a, 2007b).

SPC 5g)

ORRIOLS 2009:

"... Our finding of brain SPECT hypoactivity in these areas and also in frontal-subcortical circuits (Salmon 2001) could, in part, explain neurocognitive defects in MCS patients. Neurologic dysfunction observed prior to chemical exposure could point to persistent subclinical neurologic changes. In fact, basal SPECT brain cortical hypoactivity was found in our patients. In animal models, inflammation and permanent damage of the olfactory neuronal pathways could result from translocation of inhaled ultrafine particles to the brain (Elder 2006)..."

SPC 5h)

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 5i)
MAES 2012:
"...Inflammatory and oxidative and nitrosative stress (IO & NS) pathways play a key role in the pathophysiology of ME/CFS (Maes 2010). The findings encompass a low grade inflammation, as indicated by an increased production of nuclear factor kB (NKkB), and cyclooxygenase (COX-2), and inducible nitric oxide synthase (iNOS) (Maes 2007a, 2007b); immune activation with increased expression of activation markers, e.g. CD8+ and CD38+ and HLA-DR+ markers (Lorusso 2009); increased levels of cytokines including interleukin(IL)-1 alpha, IL-1beta, IL-4, IL-5, IL-6 and lowered IL-8, IL-13, and IL-15 levels (Fletcher 2009, Lorusso 2009)..."

SPC 5j)

With the persistent 24/7/365 exposure to UFPM and PM LPS, and by PM induced release of proinflammatory cytokines from airway sensory nerves, alveolar macrophages, and epithelial cells (Hiraiwa 2014, 2013, Hogg 2009, Calderon-Garciduenas 2008, 2003, 2001 Goto 2004, Mukae 2001, Veronesi 2001, Meggs 1997) supporting systemic inflammation - including IL-1beta and IL-6 to which brain blood vessels express receptors - increased permeability and penetration of the BBB becomes an issue. A more precise question concerns what proportion of the inflammation and permanent damage of the olfactory neuronal pathways reflected by neurologic dysfunction and SPECT hypoactivity in MCS patients (Orriols 2009) is due to UFPM penetration by way of the BBB compared to directly via the olfactory or trigeminal nerves in the damaged airway epithelium.

SPC 5k)
Its nonsense to consider that once the tennis court-sized airway epithelium develops defects - and the innate inflammatory immune system which it represents becomes proinflammatory - allowing more penetration and releasing excessive mediators into the circulation to influence close and distant events - that the whole organism can go down.
We have better things to do. We love our high speed cars and trucks. When people get sick as they get older - its just old age.

SPC 23 Jung Was Right Sort Of

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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SPC 5 ACA UFPM: IL-1 beta, RBC, BBB, - MCS and ME/CFS

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