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New Prion Research

Mike

Well-known member
What can we learn from the oral intake of prions by sheep?
N Sales, PhD *
Department of Infectology, The Scripps Research Institute, 5353 Parkside Drive, Jupiter, Florida, USA
email: N Sales ([email protected])

*Correspondence to N Sales, Department of Infectology, The Scripps Research Institute, 5353 Parkside Drive, Jupiter, Florida, USA.

Keywords
prion • scrapie • sheep • ingestion • vCJD • BSE • TSE

Abstract
The central nervous system is the ultimate target of prions, the agents responsible for fatal neurodegenerative diseases known as transmissible spongiform encephalopathies (TSEs). The neuro-invasive phase and its related clinical signs take place after a long incubation period. During this asymptomatic phase, however, active transport and replication of the infectious agent take place in peripheral sites. The oral infection route has been extensively studied because of its implication in the recent epidemic of bovine spongiform encephalopathy (BSE) in cattle and of the resulting human cases of variant Creutzfeldt-Jakob disease (vCJD). Rodent models have been useful in studying some aspects of this pathogenesis. Now, new data on the initial steps of oral infection have been obtained in sheep. This species is naturally infected with scrapie by horizontal transmission and there is strong evidence implicating the oral route. Furthermore, the existence of resistant and susceptible genotypes offers the possibility of comparative studies. The data were obtained using surgical and biochemical procedures to modulate the efficiency of oral infection and show that, in sheep, the abnormal prion protein (PrP) associated with the infectious agent crosses the intact intestinal barrier at the level of the enterocytes and then passes rapidly into lymph. These steps are identical in susceptible and resistant sheep. Thereafter, replication takes place in lymphoid structures. Other results in the same study indicate that alimentary fluids almost completely degrade the PrP of the inoculum. Though not directly transposable to human diseases, in which it is not possible to study these early stages, these data allow the elaboration of a simplified concept for the pathogenesis of TSEs. They also suggest that human contamination at the level of the oral cavity might be more important than previously suspected. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Received: 27 January 2006; Accepted: 27 January 2006[/b]
 

Mike

Well-known member
There may be DORMANT BSE CARRIERS?


Science 3 December 2004:
Vol. 306. no. 5702, pp. 1692 - 1693
DOI: 10.1126/science.1106679

Prev | Table of Contents | Next
Perspectives
BIOMEDICINE:
Prion Dormancy and Disease
Robin W. Carrell

There are reports that the variant Creutzfedlt-Jacob disease (vCJD) epidemic in the United Kingdom is on the wane, having peaked at 150 cases. However, as Carrell points out in a taut Perspective, two surveys in the United Kingdom compounded by a new study of transgenic mice carrying variant forms of the human prion protein (Wadsworth et al.) suggest that there may be many dormant carriers of vCJD, who remain healthy but potentially could be infective to susceptible individuals.
The author is at the Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 2XY, UK. E-mail: [email protected]
 

Kathy

Well-known member
Another study using artificial methods of transmission:

"The data were obtained using surgical and biochemical procedures to modulate the efficiency of oral infection..."

Many things can be done this way, that are not indicative of "natural" occurrences. This makes such findings no different than "iatrogenic" transmission.

Perhaps everyone, should check out this new article which just came out in Nature Magazine.

Death of Alzheimer victim linked to aluminium pollution
Brain autopsy of pollution victim rekindles contaminant fears.

Michael Hopkin

Fears of a link between aluminium and Alzheimer's disease have been reignited by the case of a British woman who died of the illness 16 years after an industrial accident polluted her local drinking water.

An autopsy on Carole Cross's brain showed that she was suffering from a rare form of early-onset Alzheimer's when she died in May 2004, and also revealed the presence of high levels of aluminium in her tissues. The researchers who investigated her brain cannot say whether the aluminium was the cause, but point out that the woman had no family history of dementia.

The polluting incident occurred in 1988 when a truck driver mistakenly emptied some 20 tonnes of aluminium sulphate — used in the early stages of wastewater treatment — into a tank containing drinking water destined for the village of Camelford in Cornwall, UK. An estimated 20,000 people may have been exposed to high levels of the chemical for several weeks.

Concerned residents are waiting to see whether more people will be similarly affected. Anecdotal reports state that several other villagers are suffering from dementia.

Something in the water

Although only a single case, the discovery has reopened the possibility that aluminium could be linked to Alzheimer's disease, say Christopher Exley, a chemist at Keele University, UK and Margaret Esiri, a University of Oxford neurologist, who publish details of their investigation on Cross in the Journal of Neurology, Neurosurgery and Psychiatry1.

Aluminium is firmly linked to some temporary forms of dementia, Esiri says. Kidney dialysis patients living in areas where water is high in aluminium, for example, sometimes experience 'dialysis dementia', as a result of the large quantities of contaminated water passing through their bodies.

But the link between aluminium and Alzheimer's has been more controversial, says Daniel Perl, a neuropathologist at Mount Sinai School of Medicine in New York, who has written a commentary on the Camelford case2.

Aluminium is often found in the twists of deformed protein, called 'neurofibrillary tangles', that characterize the disease. But there is no strong evidence that it is involved in the disease's onset, Perl cautions. "I realize that's quite a conservative answer," he says. "But show me a couple more cases like this and I might have to change it."

Perl points out that, of the 20 most common elements on Earth, aluminium is the only one not involved in any essential biological process. That's because of its feisty chemistry, he explains. When in solution, aluminium ions are small and highly charged, making them very reactive. "Once aluminium binds to proteins, it sticks for good," he says. "It's like trying to use superglue to mend a Swiss watch."

Accelerated illness

What makes Cross's case interesting is that she had succumbed to a very rare form of Alzheimer's, but had a genetic predisposition, through a gene called APOE, to developing a more common form of the disease later in life, says Esiri. This raises the possibility that her aluminium exposure may have accelerated the onset of disease. Previous studies of transgenic mice expressing a similar gene have shown that feeding them aluminium in drinking water can cause similar symptoms at a young age.

Cross's protein tangles were found in the blood vessels rather than in the brain tissue itself. This is consistent with the idea that the cause of the disease could have originated in the gut, reaching the brain through the bloodstream, Esiri explains.

Combined with the unusually young age at which she died (aged 58), this puts her in a category shared by only a handful of known cases worldwide, Esiri says.

The discovery may also rekindle fears over drinking and cooking using aluminium pots and pans, although Perl says that most aluminium is found in an insoluble form and therefore not dangerous. The only way to ingest aluminium would be by cooking acidic foods such as rhubarb or tomato, which would react with the metal.

The news is worrying for Camelford's residents, says Exley, who carried out the chemical analysis to spot the aluminium in the autopsy samples. "There are still 20,000 people thinking about whether they're susceptible to this chronic disease," he says. "We can't do anything to help them."

Note:
"Aluminium is often found in the twists of deformed protein, called 'neurofibrillary tangles'

Note: Even Stanley Prusiner (American father of the term PRION) is presently stating that the malformation of the prion protein is likely caused by a "multivalent electrostatic" reaction.

Note:
"When in solution, aluminium ions are small and highly charged, making them very reactive. "Once aluminium binds to proteins, it sticks for good,"
 

Econ101

Well-known member
Kathy said:
Another study using artificial methods of transmission:

"The data were obtained using surgical and biochemical procedures to modulate the efficiency of oral infection..."

Many things can be done this way, that are not indicative of "natural" occurrences. This makes such findings no different than "iatrogenic" transmission.

Perhaps everyone, should check out this new article which just came out in Nature Magazine.

Death of Alzheimer victim linked to aluminium pollution
Brain autopsy of pollution victim rekindles contaminant fears.

Michael Hopkin

Fears of a link between aluminium and Alzheimer's disease have been reignited by the case of a British woman who died of the illness 16 years after an industrial accident polluted her local drinking water.

An autopsy on Carole Cross's brain showed that she was suffering from a rare form of early-onset Alzheimer's when she died in May 2004, and also revealed the presence of high levels of aluminium in her tissues. The researchers who investigated her brain cannot say whether the aluminium was the cause, but point out that the woman had no family history of dementia.

The polluting incident occurred in 1988 when a truck driver mistakenly emptied some 20 tonnes of aluminium sulphate — used in the early stages of wastewater treatment — into a tank containing drinking water destined for the village of Camelford in Cornwall, UK. An estimated 20,000 people may have been exposed to high levels of the chemical for several weeks.

Concerned residents are waiting to see whether more people will be similarly affected. Anecdotal reports state that several other villagers are suffering from dementia.

Something in the water

Although only a single case, the discovery has reopened the possibility that aluminium could be linked to Alzheimer's disease, say Christopher Exley, a chemist at Keele University, UK and Margaret Esiri, a University of Oxford neurologist, who publish details of their investigation on Cross in the Journal of Neurology, Neurosurgery and Psychiatry1.

Aluminium is firmly linked to some temporary forms of dementia, Esiri says. Kidney dialysis patients living in areas where water is high in aluminium, for example, sometimes experience 'dialysis dementia', as a result of the large quantities of contaminated water passing through their bodies.

But the link between aluminium and Alzheimer's has been more controversial, says Daniel Perl, a neuropathologist at Mount Sinai School of Medicine in New York, who has written a commentary on the Camelford case2.

Aluminium is often found in the twists of deformed protein, called 'neurofibrillary tangles', that characterize the disease. But there is no strong evidence that it is involved in the disease's onset, Perl cautions. "I realize that's quite a conservative answer," he says. "But show me a couple more cases like this and I might have to change it."

Perl points out that, of the 20 most common elements on Earth, aluminium is the only one not involved in any essential biological process. That's because of its feisty chemistry, he explains. When in solution, aluminium ions are small and highly charged, making them very reactive. "Once aluminium binds to proteins, it sticks for good," he says. "It's like trying to use superglue to mend a Swiss watch."

Accelerated illness

What makes Cross's case interesting is that she had succumbed to a very rare form of Alzheimer's, but had a genetic predisposition, through a gene called APOE, to developing a more common form of the disease later in life, says Esiri. This raises the possibility that her aluminium exposure may have accelerated the onset of disease. Previous studies of transgenic mice expressing a similar gene have shown that feeding them aluminium in drinking water can cause similar symptoms at a young age.

Cross's protein tangles were found in the blood vessels rather than in the brain tissue itself. This is consistent with the idea that the cause of the disease could have originated in the gut, reaching the brain through the bloodstream, Esiri explains.

Combined with the unusually young age at which she died (aged 58), this puts her in a category shared by only a handful of known cases worldwide, Esiri says.

The discovery may also rekindle fears over drinking and cooking using aluminium pots and pans, although Perl says that most aluminium is found in an insoluble form and therefore not dangerous. The only way to ingest aluminium would be by cooking acidic foods such as rhubarb or tomato, which would react with the metal.

The news is worrying for Camelford's residents, says Exley, who carried out the chemical analysis to spot the aluminium in the autopsy samples. "There are still 20,000 people thinking about whether they're susceptible to this chronic disease," he says. "We can't do anything to help them."

Note:
"Aluminium is often found in the twists of deformed protein, called 'neurofibrillary tangles'

Note: Even Stanley Prusiner (American father of the term PRION) is presently stating that the malformation of the prion protein is likely caused by a "multivalent electrostatic" reaction.

Note:
"When in solution, aluminium ions are small and highly charged, making them very reactive. "Once aluminium binds to proteins, it sticks for good,"


Aluminum sulfate is used as a coagulant in drinking water. It helps settle the dirt and stuff out of drinking water. If this were the cause, wouldn't we be seeing more problems from this? Just asking.

It creates a strong acid and is also used chemically to tie up amonia, which is a strong base. I think it is used in the poultry business as I had a soil scientist who worked on a study of using aluminum sulfate to tie up phosphorus.



ANR-1202, New April 2001. John P. Blake, Extension Poultry Scientist, Professor, and Joseph B. Hess, Extension Poultry Scientist, Associate Professor, both in Poultry Science at Auburn University
Aluminum Sulfate
as a Litter Treatment

Poultry producers have been using aluminum sulfate, commonly referred to as alum, to improve poultry production and reduce negative effects of litter on the environment. Research has shown that alum applications to poultry litter control ammonia volatilization and reduce phosphorus runoff from land fertilized with litter.

The breakdown of uric acid in poultry manure produces the gas ammonia (NH(3)). The gaseous emission of NH(3) can be inhibited if converted to NH(4)(+) (ammonium). This can be accomplished by lowering litter pH. Alum is an acid that produces hydrogen ions (H(+)) when it dissolves. The hydrogen ions produced by this reaction will attach to ammonia to form ammonium, which further reacts with sulfate ions to form ammonium sulfate--(NH(4))(2) SO(4). Ammonium sulfate is a water-soluble fertilizer. As a result of these reactions, the amount of ammonia emitted from the litter will be reduced, which will increase the nitrogen (N) content of the litter. Alum addition to the litter will also result in the precipitation of soluble phosphorus and thus reduce phosphorus runoff. The use of alum in broiler litter management can potentially impact performance and environmental concerns.

Benefits of using alum as a litter treatment include the following:

* Decreases house ammonia levels
* Reduces energy usage
* Improves bird performance
* Precipitates soluble phosphorus
* Reduces phosphorus and heavy metal runoff
* Imposes a drying effect that reduces litter moistur

Seems to me we would see more problems from it if it is the cause, but this isn't my field.
 

flounder

Well-known member
econ,

i don't think kathy herself believes the BSe she is posting.
i use to think she did, but i am not so sure now.
just look at her last posting here in this thread, totally off the charts.
the garbage she posted had nothing to do with the thread topic;


THREAD TOPIC

Posted: Mon Apr 24, 2006 10:08 am Post subject: New Prion Research


KATHY CHANGES TOPIC

Posted: Mon Apr 24, 2006 11:03 am Post subject: Alzheimers case linked to aluminum sulphate spill UK


i have found sometimes, on other list, boards, etc. that discuss this issue i.e. TSE, you always find a few that are willing to do anything to distort, confuse, twist, misconstru, manipulate, etc., just to confuse people, that are already confused enough. there goal, do anything but find the truth.
i think this might be the case here, after reading her last post and the thread it was posted in. just my opinion. ...
 

Kathy

Well-known member
Flounder wrote:

i have found sometimes, on other list, boards, etc. that discuss this issue i.e. TSE, you always find a few that are willing to do anything to distort, confuse, twist, misconstru, manipulate, etc., just to confuse people, that are already confused enough. there goal, do anything but find the truth.

Flounder, TSS, - what an accurrate "Self-portrait"!


You're hallarious flounder!

Any research to do with metal ions binding to proteins is related to prion science, but you wouldn't know that, because you don't look at the science that identifies this connection. Your only concerned with transmission not cause! Experiments like the ones in the abstract posted here, identify how "iatrogenic" transmission can work. The process is far from 'naturally occurring'.

As for the aluminum sulfate article, Econo, the article states that aluminum sulfate was added directly to water which went out to the people of Camelford, UK. During normal operations, the aluminum sulfate would be used in settling tanks/lagoons. The aluminum and the debris it helps to remove from the water, would all "settle" to the bottom of these tanks/lagoons where occasionally it is scraped out.

I know that CFIA and other regulatory agencies are concerned about the buildup of certain materials on farm land after it is spread from sewage lagoons and from these water treatment facilities. I haven't heard of its use with the poultry litter; but, have seen the articles posted about arsenic added to chicken feed and showing up in the litter (accummulating on fields where litter is spread).
 

flounder

Well-known member
kathy also wrote;

Any research to do with metal ions binding to proteins is related to prion science, but you wouldn't know that, because you don't look at the science that identifies this connection. ...

wrong again kathy, you should pay attention, i am very much aware of metal ions binding to proteins and the role they play, but that is not what the thread was about. you just got your NATURE alert for the latest edition, and you were just itching to post it to anything. should have started your own thread, then the ones that wanted to ignore your BSe could have :lol: :lol: :lol:


http://www.google.com/search?svnum=30&as_scoring=d&hl=en&ie=UTF-8&edition=us&q=metal+ions+binding+to+proteins+tss+singeltary&as_drrb=q&as_qdr=d&btnmeta%3Dsearch%3Dsearch=Search+the+Web



TSS
 

Kathy

Well-known member
Ann N Y Acad Sci. 2006 Mar;1066:181-221.

Protein denaturation and aggregation: cellular responses to denatured and aggregated proteins.

Meredith SC.

Department of Pathology, University of Chicago, 5841 S. Maryland Avenue, MC 6079, Chicago IL 60637. [email protected]

Protein aggregation is a prominent feature of many neurodegenerative diseases, such as Alzheimer's, Huntington's, and Parkinson's diseases, as well as spongiform encephalopathies and systemic amyloidoses. These diseases are sometimes called protein misfolding diseases, but the latter term begs the question of what is the "folded" state of proteins for which normal structure and function are unknown. Amyloid consists of linear, unbranched protein or peptide fibrils of approximately 100 A diameter. These fibrils are composed of a wide variety of proteins that have no sequence homology, and no similarity in three-dimensional structures-and yet, as fibrils, they share a common secondary structure, the beta-sheet. Because of the prominence of amyloid deposits in many of these diseases, much effort has gone into elucidation of fibril structure. Recent advances in solid-state NMR spectroscopy and other biophysical techniques have led to the partial elucidation of fibril structure. Surprisingly at the time, for beta-amyloid, a set of 39-43-amino-acid peptides believed to play a pathogenic role in Alzheimer's disease, the beta-sheets are parallel with all amino acids of the sheets in-register. Since the time of those observations, however, it has become clear that there is no universal structure for amyloid fibrils. While many of the amyloid fibrils described thus far have a parallel beta-sheet structure, some have antiparallel beta-sheets, and other, more subtle structural differences among amyloids exist as well. Amyloids demonstrate conformational plasticity, the ability to adopt more than one stable tertiary fold. Conformational plasticity could account for "strain" differences in prions, and for the fact that a single polypeptide can form different fibril types with conformational differences at the atomic level. More recent data now indicate that the fibrils may not be the most potent or proximate mediators of cyto- and neurotoxicity. This damage is not confined to cell death, but also includes more subtle forms of damage, such as disruption of synaptic plasticity in the central nervous system. Rather than fibrils, prefibrillar aggregates, variously called "micelles," "protofibrils," or ADDLs (beta-amyloid-derived diffusible ligands in the case of beta-amyloid) may be the more proximate mediators of cell damage. These are soluble oligomers of aggregating peptides or proteins, but their structure is very challenging to study, because they are generally difficult to obtain in large enough quantities for high-resolution structural techniques, and they are temporally unstable, rapidly changing into more mature, and eventually fibrillar forms. Consequently, the mechanisms by which they disrupt cellular function are also not well understood. Nevertheless, three broad, overlapping, nonexclusive sets of mechanisms have been proposed as responsible for the cellular damage caused by soluble, oligomeric protein aggregates. These are: (1) disruption of cell membranes and their functions [e.g., by inserting into membranes and disrupting normal ion gradients]; (2) inactivation of normally folded, functional proteins [e.g., by sequestering or localizing transcription factors to the wrong cellular compartment]; and (3) "gumming up the works," by binding to and inactivating components of the quality-control system of cells, such as the proteasome or chaperone proteins.

PMID: 16533927

This too, is new prion research. Researchers, like this one, lump these neurological disorders together (Alzheimer's, Huntington's, and Parkinson's diseases, as well as spongiform encephalopathies and systemic amyloidoses) . They do not ignore science from one field because it is studying something they specifically are not. Good thing some researchers are able to co-operate within various fields of study.

If you wish to be the webmaster, flounder, you should start your own webpage. Then we will be able to ignore you, if we so choose, I know I would.

The board members are perfectly capable of selecting what they want to read or not, they don't need you to 'monitor' things for them.
 

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