Clinical and pathological examination of mycotoxicosis as an associated risk factor for colic in equine.

A retrospective cohort study was conducted on two Egyptian horse farms with most of horses were suffered from abdominal pain to describe the associations between the occurrence of mycotoxicosis and equine colic. The farms owner complain was an unexpected increase in number of colic cases and deaths among horses. The association between colic and risk factors (sex, type of food either dry or mixed with roughages and hematobiochemical parameters) was compared using independent sample T-test. The associations between possible prognostic indicators for colic caused by mycotoxicosis was estimated using logistic regression analysis model. The cumulative incidence, incidence rates for colic attacks, survival rate among diseased horses were additionally estimated. Our results showed that a total of 24 out of the 132 horses suffered from colic due to feeding of ration contaminated with high percent of mycotoxin including Aflatoxins, Ochratoxins and or fusarium mycotoxins. The total cumulative incidence of colic due to mycotoxicosis was 19.7%. The horses fed on dry rations had more chance of developing colic than horses fed on mixed rations (P < 0.05). The overall incidence rate of colic due to mycotoxicosis was estimated at 18 colic attack/1000 horse/month. The mortality rate of horses suffered from colic due to mycotoxicosis was estimated at 5.9% (5/85), while the case fatality rate was estimated at 25% (n = 5/20). Inconclusion, our results showed that mycotoxicosis are considered an important risks factor for colic cases development in equine practice.

A knock-in mouse model reveals roles for nuclear Apc in cell proliferation, Wnt signal inhibition and tumor suppression.

Mutation of the tumor suppressor adenomatous polyposis coli (APC) is considered an initiating step in the genesis of the vast majority of colorectal cancers. APC inhibits the Wnt-signaling pathway by targeting the proto-oncogene ß-catenin for destruction by cytoplasmic proteasomes. In the presence of a Wnt signal, or in the absence of functional APC, ß-catenin can serve as a transcription cofactor for genes required for cell proliferation such as cyclin-D1 and c-Myc. In cultured cells, APC shuttles between the nucleus and the cytoplasm, with nuclear APC implicated in the inhibition of Wnt target gene expression. Adopting a genetic approach to evaluate the functions of nuclear APC in the context of a whole organism, we generated a mouse model with mutations that inactivate the nuclear localization signals (NLSs) of Apc (Apc(mNLS)). Apc(mNLS/mNLS) mice are viable and fractionation of mouse embryonic fibroblasts (MEFs) isolated from these mice revealed a significant reduction in nuclear Apc as compared with Apc(+/+) MEFs. The levels of Apc and ß-catenin protein were not significantly altered in small intestinal epithelia from Apc(mNLS/mNLS) mice. Compared with Apc(+/+) mice, Apc(mNLS/mNLS) mice showed increased proliferation in epithelial cells from the jejunum, ileum and colon. These same tissues from Apc(mNLS/mNLS) mice showed more mRNA from three genes upregulated in response to canonical Wnt signal, c-Myc, axin-2 and cyclin-D1, and less mRNA from Hath-1, which is downregulated in response to Wnt. These observations suggest a role for nuclear Apc in the inhibition of canonical Wnt signaling and the control of epithelial proliferation in intestinal tissue. Furthermore, we found Apc(Min/+) mice, which harbor a mutation that truncates Apc, to have an increased polyp size and multiplicity if they also carry the Apc(mNLS) allele. Taken together, this analysis of the novel Apc(mNLS) mouse model supports a role for nuclear Apc in the control of Wnt target genes, intestinal epithelial cell proliferation and polyp formation.