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Inflammatory bowel diseases are associated with increased risk of developing colitis-associated colorectal cancer (CAC). Epidemiological data show that the consumption of ω-3 polyunsaturated fatty acids (ω-3 PUFAs) decreases the risk of sporadic colorectal cancer (CRC). Importantly, recent data have shown that eicosapentaenoic acid-free fatty acid (EPA-FFA) reduces polyp formation and growth in models of familial adenomatous polyposis. However, the effects of dietary EPA-FFA are unknown in CAC. We tested the effectiveness of substituting EPA-FFA, for other dietary fats, in preventing inflammation and cancer in the AOM-DSS model of CAC. The AOM-DSS protocols were designed to evaluate the effect of EPA-FFA on both initiation and promotion of carcinogenesis. We found that EPA-FFA diet strongly decreased tumor multiplicity, incidence and maximum tumor size in the promotion and initiation arms. Moreover EPA-FFA, in particular in the initiation arm, led to reduced cell proliferation and nuclear β-catenin expression, whilst it increased apoptosis. In both arms, EPA-FFA treatment led to increased membrane switch from ω-6 to ω-3 PUFAs and a concomitant reduction in PGE2 production. We observed no significant changes in intestinal inflammation between EPA-FFA treated arms and AOM-DSS controls. Importantly, we found that EPA-FFA treatment restored the loss of Notch signaling found in the AOM-DSS control and resulted in the enrichment of Lactobacillus species in the gut microbiota. Taken together, our data suggest that EPA-FFA is an excellent candidate for CRC chemoprevention in CAC.

La suocera, la nonna, la madre, la terapeuta. L'autrice esamina quattro funzioni materne attraverso le caratteristiche specifiche del loro manifestarsi nel caso di Aurora. Nessuna di queste madri sembra capace di parlare profondamente di emozioni. La madre della paziente vive i propri problemi di depressione e la suocera gioca un ruolo piů maschile che tenero e femminile. Sicché Aurora lamenta il proprio sentirsi una madre difettosa, ma non puň piangere veramente per il problema della figlia. La terapeuta, infine, affida alla razionalitŕ la guarigione di Aurora.

Background and aim: Searching for alternative therapies that are effective, safe and less expensive of those currently used for ulcerative colitis, we investigated the efficacy of a polyphenol extract from apple in rat colitis. Methods: Rats with trinitrobenzensulphonic acid-induced colitis were treated daily with rectal administration of apple polyphenols 10(-4) M for 14 days. COX-2, TNF-alpha, tissue transglutaminase and calpain in colon mucosa samples were assessed by reverse transcription-polymerase chain reaction and western blot analyses. To ascertain the role of tissue transglutaminase in mucosal healing, wounded rat fibroblasts were incubated with cystamine (a tissue transglutaminase activity inhibitor). Results: Colitis was associated with increased COX-2, TNF-alpha, calpain, and tissue transglutaminase mRNA. The protein expression of COX-2, TNF-alpha and calpain was increased whilst tissue transglutaminase was decreased. Apple extract treatment reduced the severity of colitis (p < 0.05) and restored all the considered biomarkers at the baseline level. Apple polyphenols reduced the degradation of tissue transglutaminase protein occurring through calpain action. Apple polyphenols-treated wounded fibroblast recovered within 24 h showing intense immunoreactivity for tissue transglutaminase. Conclusion: The efficacy of apple extract is mediated by its effects on COX-2 and TNF-alpha. The unbalance between calpain and tissue transglutaminase may play a role in colonic damage and future therapeutic interventions in ulcerative colitis can target this mechanisms. (C) 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

summary Background and purpose: Vitamin D (VitD) is involved in homeostasis of calcium and interacts with parathyroid hormone (PTH). Low levels of VitD in chronic liver diseases, in particular in chronic hepatitis C (CHC) was reported. We aimed to determine the levels of VitD and PTH in patients with CHC without cirrhosis to evaluate the disturbance of VitD-PTH axis. Methods: We conduced a caseecontrol studyenrolling59patients with CHCand 59 controls. We determined serum concentration of VitD, PTH, calcium and phosphate. VitD was quantified by chemiluminescence immunoassay. PTH was measured by 2-site chemiluminescent enzyme-labeled immunoassay. Results: The mean value of VitD was 26.28 and 28.43 ng/ml in HCV patients and controls respectively (p < 0.31). The distribution of the severity of VitD deficit in HCV population was the following: 5% had a deficiency, 64% had an insufficiency and 31% had normal levels. No difference was observed in the control group (p < 0.9). The mean value of PTH was 17.04 and 26.7 pg/ml in HCV patients and controls respectively (p < 0.0004). Calcium and phosphate were in the range of normality in both. Conclusions: The VitD deficit is similar in HCV-patients and general population of the same geographic area. Therefore we can state that this is a public health problem.