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From: TSS ()
Subject: Re: TSE Conference Agenda Agenda for 26 - 29 June 2006, Renaissance Penta Vienna, Austria
Date: May 7, 2006 at 8:24 am PST

In Reply to: TSE Conference Agenda Agenda for 26 - 29 June 2006, Renaissance Penta Vienna, Austria posted by TSS on May 7, 2006 at 8:19 am:

Transmissible Spongiform Encephalopathies Conference Agenda

Day One - 27 June 2006 | Day Two - 28 June 2006

15.00 TSE-safety of human urine-derived pharmaceuticals
Human-derived pharmaceuticals originating from urine are now receiving a similar amount of regulatory attention as blood products. The need and the measures taken by Ferring Pharmaceuticals and other companies to ensure the safety of products such as urinary-derived gonadotrophins and urokinase will be described.
Dr Peter A McAnulty, Senior Director, Non-Clinical Development, Ferring Pharmaceuticals A/S, Denmark

Main Index

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Coincident Scrapie Infection and

Nephritis Lead to Urinary

Prion Excretion

Harald Seeger,1* Mathias Heikenwalder,1* Nicolas Zeller,1

Jan Kranich,1 Petra Schwarz,1 Ariana Gaspert,2 Burkhardt Seifert,3

Gino Miele,1 Adriano Aguzzi1.

Prion infectivity is typically restricted to the central nervous and lymphatic

systems of infected hosts, but chronic inflammation can expand the distribution of

prions. We tested whether chronic inflammatory kidney disorders would trigger

excretion of prion infectivity into urine. Urinary proteins from scrapie-infected

mice with lymphocytic nephritis induced scrapie upon inoculation into noninfected

indicatormice. Prionuria was found in presymptomatic scrapie-infected and in sick

mice, whereas neither prionuria nor urinary PrPSc was detectable in prion-infected

wild-type or PrPC-overexpressing mice, or in nephritic mice inoculated with

noninfectious brain. Thus, urine may provide a vector for horizontal prion transmission,

and inflammation of excretory organs may influence prion spread.


How do prions enter the urine? Upon extrarenal

replication, blood-borne prions may be

excreted by a defective filtration apparatus.

Alternatively, prions may be produced locally

and excreted during leukocyturia. Although

prionemia occurs in many paradigms of

peripheral prion pathogenesis (15, 16), the

latter hypothesis appears more likely, because

prionuria was invariably associated with local

prion replication within kidneys.

Urine from one CJD patient was reported to

elicit prion disease in mice (17, 18), but not in

primates (19). Perhaps unrecognized nephritic

conditions may underlie these discrepant

observations. Inflammation-associated prionuria

may also contribute to horizontal transmission

among sheep, deer, and elk, whose high efficiency

of lateral transmission is not understood.

References and Notes


14 OCTOBER 2005 VOL 310 SCIENCE www.sciencemag.orgtss


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