Is the presence of abnormal prion protein in the renal glomeruli of feline species presenting with FSE authentic?
Stephane Lezmi , Thierry GM Baron and Anna A Bencsik
BMC Veterinary Research 2010, 6:41doi:10.1186/1746-6148-6-41
Published: 4 August 2010
Abstract (provisional) In a recent paper written by Hilbe et al (BMC vet res, 2009), the nature and specificity of the prion protein deposition in the kidney of feline species affected with feline spongiform encephalopathy (FSE) were clearly considered doubtful. This article was brought to our attention because we published several years ago an immunodetection of abnormal prion protein in the kidney of a cheetah affected with FSE. At this time we were convinced of its specificity but without having all the possibilities to demonstrate it. As previously published by another group, the presence of abnormal prion protein in some renal glomeruli in domestic cats affected with FSE is indeed generally considered as doubtful mainly because of low intensity detected in this organ and because control kidneys from safe animals present also a weak prion immunolabelling. Here we revisit these studies and thought it would be helpful to relay our last data to the readers of BMC Vet res for future reference on this subject. Here we come back on our material as it is possible to study and demonstrate the specificity of prion immunodetection using the PET-Blot method (Paraffin Embedded Tissue - Blot). It is admitted that this method allows detecting the Proteinase K (PK) resistant form of the abnormal prion protein (PrPres) without any confusion with unspecific immunoreaction. We re-analysed the kidney tissue versus adrenal gland and brain samples from the same cheetah affected with TSE using this PET-Blot method. The PET-Blot analysis revealed specific PrPres detection within the brain, adrenal gland and some glomeruli of the kidney, with a complete identicalness compared to our previous detection using immunohistochemistry. In conclusion, these new data enable us to confirm with assurance the presence of specific abnormal prion protein in the adrenal gland and in the kidney of the cheetah affected with FSE. It also emphasizes the usefulness for the re-examination of any available tissue blocks with the PET-Blot method as a sensitive complementary tool in case of doubtful PrP IHC results.
These new results enable us to confirm confidently the presence of specific abnormal prion protein in the adrenal gland and in the kidney of the cheetah affected with FSE. This question is important because it becomes evidenced that urine may sustain transmission of certain forms of the transmissible spongiform encephalopathy (TSE) diseases, such as hamsters carrying infectious particles. More recently the kidney was found to accumulate abnormal PrP in other species too such as sheep [17, 18], and the urinary secretion of pathological form of PrP is seriously considered [19, 20]. Even if the origin of the production of this infectious prion particles are not yet clearly identified, the specific detection of PrPres within the glomeruli of the kidney of cheetah with FSE is in total accordance with this point.
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Subject: CWD/POTENTIAL SOURCE/URINE/HUNTERS ? (Mrs. Doe Pee Doe in Estrus)
Date: Sun, 14 Jul 2002 08:42:51 -0700
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy To: BSE-L@uni-karlsruhe.de
######## Bovine Spongiform Encephalopathy #########
1: Hum Reprod 2002 Jul;17(7):1676-80 Bye-bye urinary gonadotrophins?: Is there a risk of prion diseaseafter the administration of urinary-derived gonadotrophins?
Department of Reproductive Medicine, The General Infirmary, LeedsLS2 9NS, UK. E-mail: firstname.lastname@example.org
Concern has been raised recently about the possibility of prionproteins appearing in the urine of animals and, possibly, humansaffected by prion disease [scrapie, bovine spongiform encephalopathy(BSE) and Creutzfeldt Jakob disease (CJD)]. A debate has started inwhich the suggestion has been made that the purification of human urinefor the provision of gonadotrophins should be discontinued. Thealternative would be to use recombinantly-derived gonadotrophinpreparations. The recombinant products, however, rely upon bovine serumduring the cell culture process and could potentially also be exposed toabnormal prion proteins. It is reassuring that the different types ofgonadotrophin preparations that are currently available are producedwith either urine or bovine serum that is sourced from countries that atthe present time appear to be free of BSE and new variant CJD. We cantherefore be reassured that the gonadotrophins that we usetherapeutically appear to be equally safe.
what about the 100% deer urine they use to atract deer ?
just one example of many below;
CWD/POTENTIAL SOURCE/URINE/HUNTERS ?
Mrs. Doe Pee Doe in Estrus
Model FDE1 Mrs. Doe Pee's Doe in Estrus is made from Estrus urinecollected at the peak of the rut, blended with Fresh Doe Urine for anextremely effective buck enticer. Use pre-rut before the does come intoheat. Use during full rut when bucks are most active. Use duringpost-rut when bucks are still actively looking for does. 1 oz.
ELK SCENT/SPRAY BOTTLE * Works anytime of the year* 100 % Cow Elk-in-Heat urine (2oz.)* Economical - mix with water in spray mist bottle* Use wind to your advantage Product Code WP-ESB $9.95 http://www.elkinc.com/Scent.asp
prions in urine? [PDF] A URINE TEST FOR THE IN-VIVO DIAGNOSIS OF PRION DISEASES
see full text ;
Wednesday, March 18, 2009
Detection of CWD Prions in Urine and Saliva of Deer by Transgenic Mouse Bioassay
Fecal transmission of AA amyloidosis in the cheetah contributes to high incidence of disease
Beiru Zhang*†, Yumi Une‡, Xiaoying Fu*, Jingmin Yan*, FengXia Ge*, Junjie Yao*§, Jinko Sawashita*, Masayuki Mori*, Hiroshi Tomozawa¶, Fuyuki Kametani , and Keiichi Higuchi*‡** *Department of Aging Biology, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, and ¶Division of Laboratory Animal Research, Research Center for Human and Environmental Science, Shinshu University, 3-1-1, Asahi, Matsumoto 390-8621, Japan; †Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China; ‡Laboratory of Veterinary Pathology, School of Veterinary Medicine, Azabu University, 1-17-71 Fuchinobe, Sagamihara, Kanagawa 229-8501, Japan; §The Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Tokyo 183-8508, Japan; and Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, Tokyo 156-8585, Japan Edited by Reed B. Wickner, National Institutes of Health, Bethesda, MD, and approved April 1, 2008 (received for review January 16, 2008)
AA amyloidosis is one of the principal causes of morbidity and mortality in captive cheetahs (Acinonyx jubatus), which are in danger of extinction, but little is known about the underlying mechanisms. Given the transmissible characteristics of AA amyloidosis, transmission between captive cheetahs may be a possible mechanism involved in the high incidence of AA amyloidosis. In this study of animals with AA amyloidosis, we found that cheetah feces contained AA amyloid fibrils that were different from those of the liver with regard to molecular weight and shape and had greater transmissibility. The infectious activity of fecal AA amyloid fibrils was reduced or abolished by the protein denaturants 6 M guanidine HCl and formic acid or by AA immunodepletion. Thus, we propose that feces are a vehicle of transmission that may accelerate AA amyloidosis in captive cheetah populations. These results provide a pathogenesis for AA amyloidosis and suggest possible measures for rescuing cheetahs from extinction.
Discussion It is currently accepted that systemic AA amyloidosis is an increasingly important cause of morbidity and mortality in captive cheetah populations (14). For conservation of this species, therefore, it is critical to elucidate the etiology of AA amyloidosis. As with sheep scrapie and cervid CWD, the routes of transmission are among the most debated and intriguing issues. InfectiousCWDprions in saliva have been identified to be involved in transmission in high-density captive situations (19, 20). Recently, available evidence indicates that an environmental reservoir of infectivity contributes to the continuation of these diseases in affected populations. These infectious agents can be transmitted by flesh flies (21) or hay mites (22) and can directly enter the environment from decomposing carcasses of infected animals (23). Environmental contamination by excreta from infected cervids has also seemed the most plausible explanation for the dissemination of CWD (24). Scrapie-infected hamsters and Creutzfeldt–Jakob disease (CJD) patients were reported to excrete urinary protease-resistant PrP isoform (25), indicating that urinary excretion from infected animals may provide a vector for horizontal transmission. However, there are studies that are not consistent with these findings (26, 27). Perhaps unrecognized nephritic conditions may underlie these discrepant observations, because it has been reported that urinary prion excretion is found only in scrapie-infected mice with lymphocytic nephritis (28). In this study, we observed several bands with high molecular weights that reacted with anti-cheetah AA antiserum in the whole urine sample, but not in the urine pellet in whichAAamyloid fibrils should be recovered. We thought that the possibility for a transmission pathway through urine might be low, but it could not be ruled out. In addition to urine, the alimentary shedding route has been considered as a possible transmission pathway (29). Abnormal prion protein is present in gut-associated lymphoid tissues of mule deer infected with CWD, consistent with an alimentary shedding route (30). In this study, we showed that the fecal fraction from a cheetah with amyloidosis had AA amyloid fibrils and possessed high transmissibility. In mouse AApoAII amyloidosis, regarded recently as another transmissible amyloidosis (5–7), we also demonstrated that the feces could serve as an agent to induce amyloidosis in recipient mice (31). These results shed new light on the etiology involved in the high incidence of AA amyloidosis in cheetahs. In this study, we unexpectedly found that the amyloid fibril fraction from feces had smaller amyloid fibrils and higher sensitivity to denaturation treatment than the liver amyloid fibril fraction. In mammalian prion, it has been demonstrated that there is a very strong correlation between seeding capability and amyloid fibril conformation (32, 33). Similarly, in yeast prion, it also has been indicated that [PSI ] with stronger infectivity typically have less stable fibrils in vivo than strains with weaker infectivity (34), and the prion strain with relatively smaller prion particles is always associated with greater frangibility and increased sensitivity to denaturants (35). The enhanced frangibility is presumably involved in the increase in seeding efficiency and prion infectivity, while the high sensitivity probably results from structural differences in inter-molecular contacts and a shorter, less stable amyloid core. The divergent ultrastructure between the fecal and the liver fibrils identified by transmission electron microscopy may be responsible for the different characteristics of transmissibility and sensitivity to denaturation treatment, analogous to prion protein. It has been reported that AA amyloidosis can be experimentally induced by i.v. or i.p. administration of AA amyloid fibrillar extracts in recipient mice (10). A few recent studies have shown that AA-containing extracts also had amyloid-inducing activity when administered orally to mice (36, 37). In AApoAII amyloidosis, we orted that an oral administration of AApoAII amyloid fibrils induced amyloidosis in recipient mice (38). Thus, it is plausible that oral ingestion of AA-containing fecal matter caused amyloid deposition in the cheetah population. At this juncture, the manner in which fecal matter is initially absorbed by the cheetahs is not clear. This may occur during mutual grooming (licking of the fur contaminated by fecal matter). Recently it was shown that a prion agent could bind to whole soil and common soil minerals and retain infectivity for a prolonged period (23, 39). Thus, soil may act as a reservoir capable of contaminating both food and fur. It is also unknown how AA fibril proteins enter the feces. Because AA amyloidosis was also in the small intestines of AA amyloidosis cheetahs, it is possible that AA proteins enter the feces through exfoliated mucosa. In conclusion, we found that cheetahs with amyloidosis pass fecal matter that had strong seeding efficiency and should be regarded as a transmission medium. To control the incidence of AA amyloidosis and reduce the likelihood of the animal’s extinction, prevention of the transmission with excretion from cheetahs with amyloidosis should be considered along with reduction of precursor SAA levels.
Materials and Methods
Tuesday, September 02, 2008
Fecal transmission of AA amyloidosis in the cheetah contributes to high incidence of disease
Saturday, September 5, 2009
Possible Case of Maternal Transmission of Feline Spongiform Encephalopathy in a Captive Cheetah