Chronic pancreatitis in farmed pigs fed excessive zinc oxide.

Most of the pigs on a farm in Aichi Prefecture, Japan had chronic diarrhea and severe wasting. The pigs had consumed 8,000 ppm zinc oxide (ZnO) as a feed additive. The pancreas of each of 4 autopsied pigs was less than half the normal size. Acinar cells were considerably decreased. Epithelial duct-like cells were increased and tested positive for cytokeratin AE1/AE3, Ki67, PGP9.5, and Sox9. Pancreatic islet cells were decreased and shrunken. The α and δ cells were relatively decreased, and their distribution was abnormal. Islet cells were positive for PGP9.5. The livers and kidneys had high accumulations of zinc (Zn; 788 µg/g and 613 µg/g, respectively). Copper was deficient in the liver, likely as a result of Zn poisoning. Our immunohistologic examination suggested that the high dose of ZnO could influence the function of islet cells in addition to that of acinar cells. Given that colistin sulfate has been banned as a feed additive in order to reduce antimicrobial use in Japan, the use of ZnO in the livestock industry is expected to increase. Zn supplementation of pig feed must be monitored to prevent Zn poisoning and contamination of soil and water.

HPV 16-E6-mediated degradation of intrinsic p53 is compensated by upregulation of p53 gene expression in normal cervical keratinocytes.

In this study we investigated the relationship between the development of either HSILs (high-grade squamous intraepithelial lesions) or invasive cancers of the uterine cervix and the p53 codon 72 polymorphisms consisting of arginine (Arg)- or proline (Pro)-encoded allele in Japanese populations. Furthermore, we determined if intrinsic p53 is affected by the p53-degradation activities of human papillomavirus type 16 (HPV 16)-E6 in normal cervical keratinocytes with each p53 codon 72 genotype. Using PCR with p53 codon 72 polymorphic allele-specific primers, p53 genotypes of 112 normal cervical specimens and 88 cervical lesions including 44 HSILs and 44 invasive cancers were determined. The expression levels of p53 proteins and mRNAs in keratinocytes following the expression of HPV 16-E6 from an HPV 16-E6-expressing recombinant adenovirus were analyzed. The frequencies of p53 genotypes, Pro/Pro, Arg/Pro and Arg/Arg were, respectively, 12, 49 and 39% in controls; and 18, 55 and 27% in HSILs; and 11, 41 and 48% in invasive cancers. The expression levels of the p53 proteins in normal human keratinocytes of each p53 codon 72 genotype were not affected by the introduction of HPV 16-E6, whereas the p53 mRNAs were found to be upregulated regardless of the p53 genotypes when HPV 16-E6 was expressed. In statistical analysis, no relationships between p53 genotypes and the development of cervical neoplasias were found. Furthermore, we demonstrated that p53 protein expression levels in normal cervical keratinocytes is not affected by the p53-degradation activities of HPV E6, probably due to a tight transcriptional regulation of p53.