Elimination of prions by branched polyamines and implications for therapeutics

We report that branched polyamines, including polyamidoamide dendimers, polypropyleneimine, and polyethyleneimine, are able to purge PrPSc, the protease-resistant isoform of the prion protein, from scrapie-infected neuroblastoma (ScN2a) cells in culture. The removal of PrPSc by these compounds depends on both the concentration of branched polymer and the duration of exposure. Chronic exposure of ScN2a cells to low noncytotoxic concentrations of branched polyamines for 1 wk reduced PrPSc to an undetectable level, a condition that persisted at least 3 wk after removal of the compound. Structure–activity analysis revealed that a high surface density of primary amino groups is required for polyamines to eliminate PrPSc effectively from cells. The removal of PrPSc by branched polyamines is attenuated by chloroquine in living cells, and exposure of scrapie-infected brain extracts with branched polyamines at acidic pH rendered the PrPSc susceptible to protease in vitro, suggesting that endosomes or lysozomes may be the site of action. Our studies suggest that branched polyamines might be useful therapeutic agents for treatment of prion diseases and perhaps a variety of other degenerative disorders.

Applications of informatics in veterinary medicine

This study used the peer-reviewed biomedical literature to define the veterinary informatics knowledgebase and associated subspecialties, and assesses the level of activity in the field over the thirty-year period from 1966 through 1995. Grateful Med was used to search the MEDLINE bibliographic database for articles that shared one or more Medical Subject Headings (MeSH) keywords from the veterinary and medical informatics subject headings. Each of ninety-five MeSH medical informatics terms was assigned to one of twelve veterinary informatics subspecialties. The number of articles retrieved by each MeSH keyword and subspecialty was calculated. A total of 611 articles were retrieved, representing the contributions of 1,338 authors published in 153 journals. The field experienced slow growth over the twenty-year period from 1966 through 1985. In the following decade, the cumulative number of veterinary informatics articles almost tripled and the percentage of veterinary-related articles that included an informatics component increased almost two-and-one-half fold. Despite this recent growth, the number of veterinary-related articles with an informatics component has never exceeded 1% of either the veterinary or medical informatics literature over the past thirty years, and representation of veterinary subspecialties in the literature varied widely.