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From: TSS ()
Subject: FATEPriDE Environmental Factors that Affect the Development of Prion Diseases
Date: February 18, 2006 at 9:24 am PST

FATEPriDE

Environmental Factors that Affect the Development of Prion Diseases.

Project funded by the European Commission under the Quality of Life Programme.

Contract No: QLK4-CT-2002-02723

Project No: QLRT-2001-02723

Start Date

1st January 2003

Duration

36 months plus 6 month extension

Partners

1. The University of Bristol, UK (Co-ordinator)
2. National Environment Research Council-The British Geological Society, UK
3. University of Bath, UK
4. Free University of Berlin, Germany
5. University of Iceland, Iceland
6. Universita degli studi di Perugia, Italy
7. Universite Joseph Fourier Grenoble, France
8. Alpine Institute of Environmental Dynamics, France

Introduction

The work proposed here brings together top EU geo and biochemists focusing on determining the environmental factors that affect the development of prion diseases such as scrapie, bovine spongiform enchpalitis (BSE), chronic wasting disease (CWD) and Creutzfeld-Jacobs disease (CJD). First the geographical distribution of manganese and copper in soils will be investigated as risk factors. This will be undertaken due to the fact that prion diseases often are found in clusters. It now has been established that the normal metal for prion protein is copper but if that metal is replaced with manganese, the structure of the prion protein is altered. The role of organophosphate pesticides will also be investigated because it has been suggested that copper is complexed with organophosphate, preventing copper absorption.

Objectives

There is clear evidence that the occurrence of prion diseases often has a non-random distribution, suggesting a link to some environmental factors. The work proposed here will investigate risk factors, including the role of trace elements and organophosphates. Analysis of regional variation in local manganese/copper levels will be determined and compared to the incidence of the diseases. The ability of manganese and/or organophosphates in influencing conversion of the prion protein to an abnormal and/or infectious protein will be determined. In combination with geographical occurrence and geo-chemical considerations this program will identify whether these environmental considerations should be acted upon to bring about effective prevention or at least risk minimalisation of prion diseases in the EU and further afield.

Description of the Work

Recently it has been suggested that disbalance in dietary trace-elements and/or exposure to organophosphates might either cause or be a risk factor for prion disease development. In particular, high incidence of scrapie (e.g. in Iceland), chronic wasting disease, and in Slovakia and Italy CJD are associated with regions where soil and foliage are reported to be low in copper and high in manganese. This proposal will address whether exposure to a diet that has a high manganese/copper ratio can influence prion disease will also be addressed. In particular, we shall investigate this theory at the level of protein, cells, animals as well as geographical and geo-chemical associations with prion diseases. Animal models of prion disease and sheep from farms in regions of high scrapie will be investigated for a possible influence of level of manganese and copper on incidence or onset of these diseases. Bio-chemical and biophysical techniques will be used to investigate interaction of the prion protein with copper and manganese to determine the mechanism by which Mn substitution for Cu influences conversion to the abnormal isoform of the protein and whether such conversion results in protein that is infectious in mouse bioassay for infectivity. Additionally, a cell culture model will be used to generate abnormal prion protein by exposure to manganese. Cell culture model of infection will be used to assay whether prion disease alters manganese metabolism and transport of manganese into cells. The level of expression of the prion protein is in itself a risk factor for prion disease as it shortens the incubation time for the disease. This research will result in understanding of the role of disbalance in the trace elements Cu and Mn on the onset and mechanisms behind the occurrence of prion diseases and will for the first time define whether there are environmental risk factors for prion diseases.

Milestones and Expected Results

The study proposed here will produce a geo-chemical map of Europe for manganese and copper. These maps will be used to target field areas where prion diseases have occurred as clusters. The bio-chemical studies will establish whether the replacement of manganese for copper in prion protein is a risk factor for the disease _development_. Organophosphate will also be investigated as a risk factor. The study aims at minimising the risk of prion diseases for humans and animals in the EU.

http://www.arp-manchester.org.uk/FatePride.htm

a) As regards the involvement of organophosphates in the origin of BSE, no new scientific
information providing evidence or supporting the hypothesis by valid data became
available after the adoption of the last opinion of the SSC on this issue. Consequently
there is no reason for modifying the existing opinions.
b) Regarding the possibility of OP poisoning, the European legislation for registration of
plant protection products and veterinary medicines – addressed in the enquiries – provide
the basis for safe use of registered compounds and their formulations. Regarding the
alleged intoxication cases reported and OP exposure it must be concluded that safety
measures may not have been strictly followed.
References
Brown, D.R., Qin, K., Herms, J.W., Madlung, A., Manson, J., Strome, R., Fraser, P.E., Kruck, T., von
Bohlen, A., Schulz- Schaeffer, W., Giese, A., Westaway, D. and Kretzschmar, H. (1997) The Cellular
Prion Protein Binds Copper In Vivo, Nature, 390, 684-7.
Purdey, M. (2000) Ecosystems Supporting Clusters of Sporadic TSEs Demonstrate Excesses of the Radical-
Generating Divalent Cation Manganese and Deficiencies of Antioxidant Co-Factors Cu, Se, Fe, Zn Medical
Hypotheses, 54, 278-306.
Scientific Steering Committee, 1998. Opinion on possible links between BSE and Organophosphates. Adopted
on 25-26 June 1998
Scientific Steering Committee, 2001. Opinion on Hypotheses on the origin and transmission of BSE. Adopted
on 29-30 November 2001.

http://europa.eu.int/comm/food/fs/sc/ssc/out356_en.pdf

transmission studies do not lie, amplification and transmission!

1: J Infect Dis 1980 Aug;142(2):205-8

Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to
nonhuman primates.

Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.

Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of
sheep and goats were transmitted to squirrel monkeys (Saimiri
sciureus) that were exposed to the infectious agents only by their
nonforced consumption of known infectious tissues. The asymptomatic
incubation period in the one monkey exposed to the virus of kuru was
36 months; that in the two monkeys exposed to the virus of
Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and
that in the two monkeys exposed to the virus of scrapie was 25 and
32 months, respectively. Careful physical examination of the buccal
cavities of all of the monkeys failed to reveal signs or oral
lesions. One additional monkey similarly exposed to kuru has
remained asymptomatic during the 39 months that it has been under
observation.

PMID: 6997404

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract

and for Gods sake, if someone is smearing this cr@p all over there kids
heads for lice and did not come up with a TSE, i would say this is good case study;

UK FARMER WITH BSE

1) None of our animals that contracted BSE were treated with OP's, even
in utero.
2) My kids were treated with OP's as infants to control head lice. This
seems to be endemic as infection waves in UK primary schools (and
possibly elsewhere).
3) One might argue if the continued use of british beef in the UK was
ethical, none the less it happened. We have a duty to learn from it, not
least a duty to learn on behalf of those people who died so horribly....

However, i have never dusputed the remote possibility that ;

Phosmet induces up-regulation of surface levels of the cellular prion protein.
Neuroreport. 9(7):1391-1395, May 11, 1998.
Gordon, Irit 1; Abdulla, Elizabeth M. 1; Campbell, Iain C. 1; Whatley, Stephen A. 1,2
Abstract:
CHRONIC (2 day) exposure of human neuroblastoma cells to the organophosphate pesticide phosmet induced a marked concentration-dependent increase in the levels of PrP present on the cell surface as assessed by biotin labelling and immunoprecipitation. Levels of both phospholipase C (PIPLC)-releasable and non-releasable forms of PrP were increased on the plasma membrane. These increases appear to be due to post-transcriptional mechanisms, since PrP mRNA levels as assessed by Northern blotting were unaffected by phosmet treatment. These data raise the possibility that phosmet exposure could increase the _susceptibility to the prion agent by altering the levels of accessible PrP_.

(C) Lippincott-Raven Publishers.

http://www.neuroreport.com/pt/re/neuroreport/abstract.00001756-199805110-00026.htm;jsessionid=D3XI1RSXL8uyd5FtR23dvWP1753t5Cv0lY8VXIid8eyvzvuM7qJ5!-477899252!-949856144!9001!-1index=1&database=ppvovft&results=1&count=10&searchid=1&nav=search

WHAT some of the OPiest/Metalist dont understand (refuse to understand to further there plight to squash the truth of the ruminant feeding spreads and amplifies the TSE agent) is that no where in science literature does it show that Phosmet or metals _CAUSE_ TSE, there is a big difference. TO distort, confuse, lie about the true aspect of this theory into trying to make people believe that Phosmet and or Metals _CAUSE_ TSE, only weakens the whole aspect of the study. but there will always be those that cannot admit the truth about the amplification and transmission of TSE, want to blame others, and will continue this deceit. ...TSS

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