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Ultrafine particles in the air and neurological diseases

Kathy

Well-known member
There is finally acknowledgement that ultrafine particles (particulate matter less than 1.0 micron -PM<1) found in air pollution can translocate from the lungs and nasal passages.

Part Fibre Toxicol. 2006 Sep 8;3:13

Translocation and potential neurological effects of fine and ultrafine particles a critical update.

Peters A, Veronesi B, Calderon-Garciduenas L, Gehr P, Chen LC, Geiser M, Reed W, Rothen-Rutishauser B, Schurch S, Schulz H.
Institute of Epidemiology, GSF-National Research Center for Environment and Health, Neuherberg, Germany. [email protected]

ABSTRACT: Particulate air pollution has been associated with respiratory and cardiovascular disease. Evidence for cardiovascular and neurodegenerative effects of ambient particles was reviewed as part of a workshop. The purpose of this critical update is to summarize the evidence presented for the mechanisms involved in the translocation of particles from the lung to other organs and to highlight the potential of particles to cause neurodegenerative effects.Fine and ultrafine particles, after deposition on the surfactant film at the air-liquid interface, are displaced by surface forces exerted on them by surfactant film and may then interact with primary target cells upon this displacement. Ultrafine and fine particles can then penetrate through the different tissue compartments of the lungs and eventually reach the capillaries and circulating cells or constituents, e.g. erythrocytes. These particles are then translocated by the circulation to other organs including the liver, the spleen, the kidneys, the heart and the brain, where they may be deposited. It remains to be shown by which mechanisms ultrafine particles penetrate through pulmonary tissue and enter capillaries. In addition to translocation of ultrafine particles through the tissue, fine and coarse particles may be phagocytized by macrophages and dendritic cells which may carry the particles to lymph nodes in the lung or to those closely associated with the lungs. There is the potential for neurodegenerative consequence of particle entry to the brain. Histological evidence of neurodegeneration has been reported in both canine and human brains exposed to high ambient PM levels, suggesting the potential for neurotoxic consequences of PM-CNS entry. PM mediated damage may be caused by the oxidative stress pathway. Thus, oxidative stress due to nutrition, age, genetics among others may increase the susceptibility for neurodegenerative diseases. The relationship between PM exposure and CNS degeneration can also be detected under controlled experimental conditions. Transgenic mice (Apo E -/-), known to have high base line levels of oxidative stress, were exposed by inhalation to well characterized, concentrated ambient air pollution. Morphometric analysis of the CNS indicated unequivocally that the brain is a critical target for PM exposure and implicated oxidative stress as a predisposing factor that links PM exposure and susceptibility to neurodegeneration.Together, these data present evidence for potential translocation of ambient particles on organs distant from the lung and the neurodegenerative consequences of exposure to air pollutants.
PMID: 16961926
This paper is free on-line.


Toxicol Sci. 2006 Jul;92(1):201-10. Epub 2006 Apr 19

Tissue manganese concentrations in young male rhesus monkeys following subchronic manganese sulfate inhalation.

Dorman DC, Struve MF, Marshall MW, Parkinson CU, James RA, Wong BA.
CIIT Centers for Health Research, 6 Davis Drive, PO Box 12137, Research Triangle Park, NC 27709-2137, USA. [email protected]

High-dose human exposure to manganese results in manganese accumulation in the basal ganglia and dopaminergic neuropathology. Occupational manganese neurotoxicity is most frequently linked with manganese oxide inhalation; however, exposure to other forms of manganese may lead to higher body burdens. The objective of this study was to determine tissue manganese concentrations in rhesus monkeys following subchronic (6 h/day, 5 days/week) manganese sulfate (MnSO(4)) inhalation. A group of monkeys were exposed to either air or MnSO(4) (0.06, 0.3, or 1.5 mg Mn/m(3)) for 65 exposure days before tissue analysis. Additional monkeys were exposed to MnSO(4) at 1.5 mg Mn/m(3) for 15 or 33 exposure days and evaluated immediately thereafter or for 65 exposure days followed by a 45- or 90-day delay before evaluation. Tissue manganese concentrations depended upon the aerosol concentration, exposure duration, and tissue. Monkeys exposed to MnSO(4) at > or = 0.06 mg Mn/m(3) for 65 exposure days or to MnSO(4) at 1.5 mg Mn/m(3) for > or = 15 exposure days developed increased manganese concentrations in the olfactory epithelium, olfactory bulb, olfactory cortex, globus pallidus, putamen, and cerebellum. The olfactory epithelium, olfactory bulb, globus pallidus, caudate, putamen, pituitary gland, and bile developed the greatest relative increase in manganese concentration following MnSO(4) exposure. Tissue manganese concentrations returned to levels observed in the air-exposed animals by 90 days after the end of the subchronic MnSO(4) exposure. These results provide an improved understanding of MnSO(4) exposure conditions that lead to increased concentrations of manganese within the nonhuman primate brain and other tissues.

PMID: 16624849
This study found the translocatin of inhaled manganese, with increased concentrations in areas including the cerebellum and pituitary gland. The pituatary gland is the gland natural hormones are removed from (cadeavors). Human growth hormone injections are admitted to have transmitted CJD - so it is logical to look at the growth hormones derived from cattle. But instead of dealing with this situation in the UK, they just banned naturally derived cattle growth hormones. UK implemented their ban earlier than required by law. This makes me ask, "what metals had accumulated in the pituitary glands of the UK livestock?"


Toxicol Sci. 2006 Jul;92(1):219-27. Epub 2006 Apr 25

Correlation of brain magnetic resonance imaging changes with pallidal manganese concentrations in rhesus monkeys following subchronic manganese inhalation.

Dorman DC, Struve MF, Wong BA, Dye JA, Robertson ID.
CIIT Centers for Health Research, 6 Davis Drive, Research Triangle Park, NC 27709-2137, USA. [email protected]

High-dose manganese exposure is associated with parkinsonism. Because manganese is paramagnetic, its relative distribution within the brain can be examined using magnetic resonance imaging (MRI). Herein, we present the first comprehensive study to use MRI, pallidal index (PI), and T(1) relaxation rate (R1) in concert with chemical analysis to establish a direct association between MRI changes and pallidal manganese concentration in rhesus monkeys following subchronic inhalation of manganese sulfate (MnSO(4)). Monkeys exposed to MnSO(4) at > or = 0.06 mg Mn/m(3) developed increased manganese concentrations in the globus pallidus, putamen, olfactory epithelium, olfactory bulb, and cerebellum. Manganese concentrations within the olfactory system of the MnSO(4)-exposed monkeys demonstrated a decreasing rostral-caudal concentration gradient, a finding consistent with olfactory transport of inhaled manganese. Marked MRI signal hyperintensities were seen within the olfactory bulb and the globus pallidus; however, comparable changes could not be discerned in the intervening tissue. The R1 and PI were correlated with the pallidal manganese concentration. However, increases in white matter manganese concentrations in MnSO(4)-exposed monkeys confounded the PI measurement and may lead to underestimation of pallidal manganese accumulation. Our results indicate that the R1 can be used to estimate regional brain manganese concentrations and may be a reliable biomarker of occupational manganese exposure. To our knowledge, this study is the first to provide evidence of direct olfactory transport of an inhaled metal in a nonhuman primate. Pallidal delivery of manganese, however, likely arises primarily from systemic delivery and not directly from olfactory transport.
PMID: 16638924
MMT is added to almost all the gas in Canada, as a replacement for lead. MMT is a manganese-based product. Aerosalization of the manganese during combustion, would put alot of ultrafine particulate (UFP) into the air. If you've ever driven into a big Canadian city, like Calgary, when there is a weather inversion, you have seen the thick brown crap lying over the cities lower locations. This is related to an old addage, that the rich live high up on the hills and the poor live down in the valleys. This was/is because the air quality is worse in the low lying areas. Time to get the lead out, and the manganese out, and clean up the ultrafine particles that are accummulating in our organs, like our brains.

Biol Trace Elem Res. 2006 Summer;111(1-3):185-97

Brain accumulation of depleted uranium in rats following 3- or 6-month treatment with implanted depleted uranium pellets.

Fitsanakis VA, Erikson KM, Garcia SJ, Evje L, Syversen T, Aschner M.
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA.

Depleted uranium (DU) is used to reinforce armor shielding and increase penetrability of military munitions. Although the data are conflicting, DU has been invoked as a potential etiological factor in Gulf War syndrome. We examined regional brain DU accumulation following surgical implantation of metal pellets in male Sprague-Dawley rats for 3 or 6 mo. Prior to surgery, rats were randomly divided into five groups: Nonsurgical control (NS Control); 0 DU pellets/20 tantalum (Ta) pellets (Sham); 4 DU pellets/16 Ta pellets (Low); 10 DU pellets/10 Ta pellets (Medium); 20 DU pellets/0 Ta pellets (High). Rats were weighed weekly as a measure of general health, with no statistically significant differences observed among groups in either cohort. At the conclusion of the respective studies, animals were perfused with phosphate-buffered saline, pH 7.4, to prevent contamination of brain tissue with DU from blood. Brains were removed and dissected into six regions: cerebellum, brainstem (pons and medulla), midbrain, hippocampus, striatum, and cortex. The uranium content was measured in digested samples as its 238U isotope by high-resolution inductively coupled plasma-mass spectrometry. After 3 mo postimplantation, DU significantly accumulated in all brain regions except the hippocampus in animals receiving the highest dose of DU (p < 0.05). By 6 mo, however, significant accumulation was measured only in the cortex, midbrain, and cerebellum (p < 0.01). Our data suggest that DU implanted in peripheral tissues can preferentially accumulate in specific brain regions.
PMID: 16943605

This study implanted pellets into the rats bodies. The DU still "translocated" to the brain. If it can do this with larger pellets of DU, then the translocation of DU nanoparticles (or other radiological particles like Strontium, etc) evidently can also be readily transferred from the lungs and nasal passages to the brain. And, just like in the first abstract here, they have discovered that this Ultrafine Particulate translocation is responsible for neurological disorders.

The Western Interprovincial Scientific Studies examination of oil and gas emissions in Western Canada has identified a huge deficiency in copper and zinc (lesser in selenium and phosphorous) in thecattle forages.

The WISSA study also identifed strontium, titanium, aluminum, arsenic, calcium, cadmium, copper, lithium, nickel and zinc in the few poorly located particulate monitors (PM<1.0) over the study period Jan. 2002 - Jan 2003. The "strontium and titanium levels are the highest in central Saskatchewan region. Strontium has been associated with natural sodium sulphate deposits that occur in the SS and SC regions." This is also an area experiencing Chronic Wasting Disease in wild deer/elk.

If an animal dies from lead poisoning, and you took the proteins that bound with this lead, concentrated them and injected them into the "special mice", what do you suppose would happen to the mice?
 

Kathy

Well-known member
At this point, I'd like to also point out a study on copper transport proteins:

J Nutr. 2006 Jan;136(1):21-6

Copper transport protein (Ctr1) levels in mice are tissue specific and dependent on copper status.

Kuo YM, Gybina AA, Pyatskowit JW, Gitschier J, Prohaska JR.
Department of Medicine, University of California, San Francisco, CA, USA.

Studies were conducted to determine distribution of the copper transporter, Ctr1, a transmembrane protein responsible for cellular copper uptake, in adult mice and in suckling mice nursed by either copper-adequate (Cu+) or copper-deficient (Cu-) dams. Western immunoblot analyses, using immunopurified antibody, detected monomeric (23 kDa) and oligomeric forms of Ctr1 in the membrane fraction of several mouse organs. Immunohistochemical analyses detected abundant Ctr1 protein in liver canaliculi; kidney cortex tubules; small intestinal enterocytes; the choroid plexus and capillaries of brain; intercalated disks of heart; mature spermatozoa; epithelium of mammary ducts; and the pigment epithelium, outer limiting membrane, and outer plexiform layer of the retina. Duodenal Ctr1 distribution was different in the adult compared with suckling mice; adult mice demonstrated strong intracellular staining of the enterocyte, whereas apical staining predominated in suckling mice. In Cu- mice at postnatal d 16 (P16), Ctr1 staining was augmented in kidney, duodenum, and choroid plexus, compared with Cu+ mice. Brain immunoblot data indicated that Ctr1 protein in membrane fractions of Cu- mice was 56% higher than Cu+ mice. Cu- mice had lower hemoglobin (56% of Cu+), and lower copper concentration (% of Cu+) in liver (15%), brain (26%), and kidney (65%). These results suggest that Ctr1 protein is expressed in multiple tissues and found in higher levels in selected organs after perinatal copper deficiency. Enhanced Ctr1 levels and redistribution might compensate in part for the decrease in copper supply. Mechanisms for the enhancement in Ctr1 staining remain to be established.
PMID: 16365053

So lets look at how an animals copper levels are determined, alive and dead.

When alive the blood is sampled. Lower hemoglobin should show up with copper deficiency.

When dead, most vets/labs test the liver. However, this study shows that the liver only showed a 15% drop in copper concentration with deficient dietary copper. The brain had a 26% drop in copper, while the kidneys showed a 65% reduction in copper levels.

So, wouldn't it make more sense to test the kidney for copper deficiency. Then, the labs should determine, what metals took the place of copper in the kidneys. Perhaps this would be helpful.

The copper transport protein (Ctr1) is just one of many proteins battling it out for the copper (trying to bind it before the next protein).

Like this one:

Arch Biochem Biophys. 2003 Sep 15;417(2):227-34

Metallochaperone for Cu,Zn-superoxide dismutase (CCS) protein but not mRNA is higher in organs from copper-deficient mice and rats.

Prohaska JR, Broderius M, Brokate B.
Department of Biochemistry and Molecular Biology, University of Minnesota Duluth School of Medicine, 1035 University Drive, Duluth, MN 55812, USA. [email protected]

Cu,Zn-superoxide dismutase (SOD1) is an abundant metalloenzyme important in scavenging superoxide ions. Cu-deficient rats and mice have lower SOD1 activity and protein, possibly because apo-SOD1 is degraded faster than holo-SOD1. SOD1 interacts with and requires its metallochaperone CCS for donating copper. We produced dietary Cu deficiency in rodents to determine if the reduction in SOD1 was related to the level of its specific metallochaperone CCS. CCS levels determined by immunoblot were 2- to 3-fold higher in liver, heart, kidney, and brain from male Cu-deficient rats and mice under a variety of conditions. CCS was also higher in livers of Cu-deficient dams. Interestingly, CCS levels in brain of Cu-deficient mice were also higher even though SOD1 activity and protein were not altered, suggesting that the rise in CCS is correlated with altered Cu status rather than a direct result of lower SOD1. A DNA probe specific for rat CCS detected a single transcript by Northern blot hybridization with liver RNA. CCS mRNA levels in mouse and rat liver were not altered by dietary treatment. These results suggest a posttranscriptional mechanism for higher CCS protein when Cu is limiting in the cell, perhaps due to slower protein turnover. Elevation in CCS level is one of the most dramatic alterations in Cu binding proteins accompanying Cu deficiency and may be useful to assess Cu status.

PMID: 12941305

So many proteins competing for copper!
 

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