Airway Genetics and Ambient Combustion Aerosol

SPC 7 ACA UFPM: Olfactory, BBB, AD, PD, MCS, and ME/CFS

SPC 7 ACA UFPM: Olfactory, BBB, AD, PD, 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 Concensus Criteria

MCS 3a Criteria Amendment Research Points (CAR)

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

MCS 3b CAR References

SPC 7 ACA UFPM: Olfactory, BBB, AD, PD, MCS, and ME/CFS

Please choose the Incorrect Statement

SPC 7a)

BLOCK 2009:
"...Major sources of PM2.5 include oil refineries, metal processing facilities, tailpipe and brake emissions from mobile sources, residential fuel combustion, power plants and wildfires (Muhlfeld 2008, Rothen-Rutishauser 2008, Valavanidis 2008).

However, UFPM is widely implicated in PM-associated pathology, as their nanometer size makes these particles the most effective size for lung deposition, penetration, and effects extending beyond the respiratory tract (Craig 2008). The primary contributors to UFPM are tailpipe emissions from mobile sources (motor vehicles, aircraft, and marine vessels) (Muhlfeld 2008)...
...Alarmingly, UFPM levels are unmonitored and unregulated in the USA, but exposure is estimated to be high..."

SPC 7b)

GILLESPIE 2013:
"...Numerous clinical and experimental studies have...identified the brain to be neurochemically and neuropathologically affected by various types and sizes of PM air pollution (Gerlofs-Nijland 2010, Campbell 2009, 2005, Calderon-Garciduenas 2008, 2007, Sunyer 2008, Zanchi 2008, Sirivelu 2006, Block 2004)...
...In the central nervous system (CNS), oxidative stress is largely mediated by microglia, which are macrophage-like, phagocytic cells that are activated by a broad range of stimuli, including PM (Sama 2007, Block 2004) and nanoparticles (Long 2006). Once activated, the microglia produce multiple reactive oxygen species (ROS) such as hydrogen peroxide, hydroxyl radicals and peroxynitrites (Block 2007, Fariss 2005) that can diffuse from their plasma membrane and damage nearby neurons..."

SPC 7c)

BLOCK 2009:

"...Ultrafine (nano-size particles) and fine particles are the most notorious of air pollution components, penetrating lung tissue compartments to reach the capillaries and circulating cells, or constituents (e.g. erythrocytes) (Valavanidis 2008)...
...ultrafine particles have a large surface to volume ratio (Rothen-Rutishauser 2008) and easily penetrate cellular membranes (Geiser 2005). This provides insight into why UFPM is able to traverse traditional barriers in the lung and the BBB, including why PM is found in neurons and carried in erythrocytes...

SPC 7d)
...The nasal olfactory pathway is believed to be a key portal of entry, where inhaled nanoparticles have been shown to reach trigeminal nerves, brainstem, and hippocampus (Wang 2008, 2007)...particulate matter has been observed in human olfactory bulb periglomerular neurons and particles smaller than 100nm were observed in intraluminal erythrocytes from frontal lobe and trigeminal ganglia capillaries (Calderon-Garciduenas 2008)...air pollution components reach the brain (Peters 2006), even penetrating deep into the parenchyma...
...Alzheimer's (AD) and Parkinsons Disease Disease (PD) share early pathology in the olfactory bulb, nuclei, and pathways, with olfactory deficits being one of the earliest findings in both diseases (Doty 2008)...

SPC 7e)
...As the most prevalent neurodegenerative disease (Hirtz 2007), Alzheimer's Disease (AD) affects more than 4 million people in the United States and an estimated 27 million are affected worldwide (Wimo 2006). Parkinsons Disease (PD) is a devastating movement disorder and is the second most prevalent neurodegenerative disease (Hirtz 2007), affecting 1-2% of the population over the age of 50 (Thomas 2007)..."

DATLA 2007 :

"...Parkinson's disease (PD) is a progressive neurodegenerative disease affecting about 1.6% of the general population aged over 65 (deRijk 1997)...

...The clinical symptoms of PD, manifest as the loss of initiation and control of movement and appear only after a substantial loss of dopaminergic neurons (50-60%) in the substantia nigra pars compacta (SNpc) in the midbrain (Pakkenberg 1991)..."

SPC 7f)

BLOCK 2004:
"...DEP (diesel exhaust particles) are selectively toxic to DA (dopaminergic) neurons through microglia-mediated ROS production...

...A predominant pathology of PD is the specific degeneration of DA neurons, while other neuronal subtypes remain generally unaffected. The neuron-glia culture model used in this study demonstrates that DEP neurotoxicity is selective to DA neurons...

...DA neurons possess reduced antioxidant capacity, as evidenced by low intracellular glutathione that render DA neurons more vulnerable to oxidative stress and microglial activation, relative to other cell types (Loeffler 1994). Additionally, the mesencephalon houses the SN and contains 4.5 times as many microglia when compared with the cortex (Kim 2000)...

...our data show that DEP activate microglia, that microglia are crucial to DEP-induced DA neurotoxity, that DEP stimulated microglia to produce free radicals (superoxide), and that NADPH oxidase is the source of DEP-induced microglial ROS responsible for DA neurotoxicity..."

SPC 7g)

...The toxicity and immune-stimulating characteristics of DEP in the lung have been linked to both the adsorbed chemicals on the outside of the carbon particle and the physical characteristics of the particle itself (Ma 2002)...
...several compounds known to be toxic to DA neurons (polyaromatic hydrocarbons, quinones, and transition metals) are also found on DEP (Ma 2002). However, most of the potentially neurotoxic compounds adsorbed to DEP induce oxidative stress through redox-cycling with cytochrome P450 activity (Ma 2002, Kumagai 1995) and not through NADPH oxidase activation...
...carbon black particles, which lack all chemical and biological adsorbed compounds, have been shown to produce oxidative stress in cells through the NADPH oxidase pathway (Ma 2002). Together this supports that physiochemical factors of DEP are culpable in microglia activation..."

BAULIG 2003a:

"...In airway epithelial cells, DEP (diesel exhaust particles) via their organic components (polycyclic aromatic hydrocarbons PAHs including benzo[a]pyrene desorbed from the carbonaceous core), modify the cellular redox state...induce phase I (CYP1A1) and phase II (NQO-1) gene expression and can be metabolized,,,numerous genes implicated in detoxification...activated via xenobiotic responsive element and ARE (antioxidant responsive element) as well as in the secretion of proinflammatory cytokines via NFkB responsive element (Bonvallot 2001)..."

BONVALLOT 2001:

"...catalytic activities of cytochrome P450 are known to produce ROS directly and also generate biologic reactive intermediates, including quinones, which produce ROS by redox cycling (Bolton 2000)...

...CB (carbonaceous core) exhibit oxidative properties as they deplete the antioxidant defenses in the epithelial lining fluid (Ziedinski 1999) and induce DNA strand scission in plasmidic DNA (Stone 1998)...

...the carbonaceous core could be considered mostly as a vector allowing the entry of organic compounds into the cells and their slow diffusion leading to sustained stimulation of the cells as native diesel exhaust particles-induced NFkB DNA binding started later but was more persistent than that induced by organic extracts of diesel exhaust particles...(Boland 2000, 1999, Bonvallot 2000, Baeza-Squiban 1999, Bayram 1998, Kumagai 1997, Thomas 1997)..."

SPC 7h)

CALDERON-GARCIDUENAS 2008:

"...Breakdown of the nasal respiratory and olfactory epithelium and the BBB (Blood Brain Barrier) facilitates the access of systemic inflammatory mediators and components of air pollution to the central nervous system (CNS) (Calderon-Garciduenas 2004)...

...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...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...

...2 We strongly support the importance of the olfactory pathway...since olfactory neurons are loaded with PM...will potentially translate into an abnormality in the limbic system...(Bedard 2004)...

..3 The vagus/trigeminal (Lewis 2005) pathways are also crucial, given that PM enters the respiratory and digestive systems...

...4 Direct access of UFPM to the brain, further accentuating an inflammatory response in the brain parenchyma...

...Long term exposure to air pollution should be considered a risk factor for both Alzheimer's and Parkinsons diseases and APOE 4 allele carriers could have a higher risk of developing AD..."

SPC 7i)

ORRIOLS 2009:

"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 [MCS] 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 7j)

Revisiting remarks from SPC 5: 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) - and Orriols 2009 found MCS people have olfactory dysfunction - in that regard members of the AD, PD, MCS family - one might suspect ME/CFS may also join.

There may not be any data on whether AD and PD occur more frequently as a comorbidity with MCS or ME/CFS.

On a personal anecdotal note: some 24 years ago - for 7 months this CAR test author and MCS sufferer took care of a retired music professor with PD named Al Suvak - he preferred his window open while sleeping and when a smoker visited - not smoking in the house but bringing in residue - I was bothered by it and Al's nose would run.

SPC 7k)
We love our cars and trucks - Block 2004 findings that DEP (diesel exhaust particles) are formidable adversaries of the critical Parkinson's Disease (PD) dopaminergic neurons via microglial activation and subsequent oxidative burst - collateral damage of microglia DEP phagocytosis - is just an in vitro study - not to worry.

And just because AD and PD are accompanied with or preceded by olfactory dysfunction indicating airway defects and increased penetration of UFPM including DEP - with PM confirmed in the OB (olfactory bulb) of human subjects (Calderon-Garciduenas 2010, 2008) doesn't matter either.

PD symptoms are not apparent until nearly half the dopaminergic neurons are destroyed (Datla 2007, Merck 1999, Pakkenberg 1991) - do we have termites or what?

We will not admit the thief in the bank vault might have something to do with the robbery. Thousands of studies - we don't like science. Until DEP tells us in their own language they are bad - there is not enough proof - we cannot and will not be convinced - and besides we are proud of Rudolph Diesel's achievement - more miles per gallon of fuel makes a great battlefield advantage and sales incentive. And just to make sure you know where we are coming from: global air and water temperatures are up - therefore it is a mini ice age.