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A 71-year-old male presented with gastrointestinal bleeding. Double-balloon endoscopy revealed diffuse thickening of the wall and a shallow ulcer measuring approximately 10cm in the mid jejunum. Biopsy revealed diffuse proliferation of large lymphoid cells that were immunohistochemically positive for CD3, CD5, and bcl-2 but negative for CK, CD10, CD20, and bcl-6. The cyclin D1 labeling index was 3% and the MIB-1 labeling index was 61%. On the basis of these findings, he was diagnosed with peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) of the small intestine. Following four courses of THP-COP chemotherapy, he developed intestinal perforation and underwent partial resection of the small intestine. He is currently undergoing further chemotherapy.

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INTRODUCTION: We investigated the effect of Ricetrienol, which is an anti-oxidant extracted from rice bran, and α-tocopherol on the adipocytokine abnormalities and fatty liver in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. MATERIALS AND METHODS: A total of 18 OLETF rats were bred using a 30% sucrose solution (the diabetic group; DM), whereas another 18 OLETF rats were bred using ordinary water (the non-diabetic obese group; OB) as drinking water, respectively. After the sucrose-fed rats developed diabetes, all of the rats from the diabetic and obese groups were randomly divided into three groups. Then each group was fed either standard chow (DM-S, OB-S group), 0.05% Ricetrienol-containing chow (DM-R, OB-R group) or 0.05%α-tocopherol-containing chow (DM-A, OB-A group), respectively. After 12 weeks of feeding, all the rats were killed. Plasma insulin, adiponectin, resistin and leptin were assayed by enzyme immunoassay. Histopathological findings of liver tissue were scored according to Brunt and Kleiner's method, and triglyceride contents of the liver tissue were investigated. RESULTS: Plasma adiponectin was significantly reduced in DM-S compared with OB-S, but it had significantly increased in DM-R and DM-A as opposed to DM-S. Plasma resistin showed a significant increase in DM-S compared with OB-S, but it was significantly reduced in DM-A than in DM-S. Though the triglyceride contents of liver tissue significantly increased in DM-S as opposed to OB-S, they were significantly reduced in DM-R compared with DM-S. Histopathological scores were significantly higher in DM-S than OB-S. CONCLUSIONS: The present study shows that Ricetrienol might prevent adipocytokine abnormalities and fatty liver in OLETF diabetic rats. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00090.x, 2011).

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We investigated the preventive effects of ferulic acid (FA) and alpha-tocopherol (AT) on the progression of diabetic nephropathy. Otsuka Long-Evans Tokushima Fatty (OLETF) and Long-Evans Tokushima Otsuka (LETO) rats were used as type 2 diabetes and non-diabetes models, respectively. Two-thirds of the OLETF rats were fed 0.2% FA-containing or 0.5% AT-containing chow. Diabetic nephropathy was assessed based on urinary protein excretion and pathological changes which were scored based on the percentages of extracellular matrix area in the glomerular area. Furthermore, renal messenger RNA (mRNA) expression of intercellular adhesion molecule-1 (ICAM-1), cyclooxygenase-2 (COX-2) and transforming growth factor-beta1 (TGF-beta1) was quantified by real-time polymerase chain reaction. After 12 weeks of FA- or AT-supplementation, urinary protein in untreated-OLETF group was significantly higher than that in LETO group, thus FA-supplementation significantly decreased urinary protein excretion. Pathological scores in FA-supplemented group were significantly lower than those in untreated OLETF group. Supplementation with either FA or AT significantly prevented the elevation of TGF-beta1 mRNA expression caused by diabetes. Treatment with neither FA nor AT had a significant effect on COX-2 or ICAM-1 mRNA expressions. We have demonstrated the preventative effects of FA on diabetic nephropathy via suppression of TGF-beta1 upregulation, furthermore FA may be more potent than AT.

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Oxidative stress and the gene expression at the transcriptional level of antioxidant enzymes were investigated in two models of diabetes in mice. We used KKAy mice as a model of obese insulin-resistant diabetes, and streptozotocin-induced diabetic mice (STZ mice) as a model of insulin-deficient diabetes. C57BL mice and saline-injected ICR mice were used as the respective non-diabetic controls. To assess oxidative damage, plasma malonedialdehyde (MDA), urine 8-isoprostane and 8-hydroxy deoxyguanosine (8-OHdG) were measured. The mRNA expression of antioxidant enzymes, superoxide dismutase 1 (SOD-1) and glutathione peroxidase 1 (GPx-1) in the kidney and heart were quantified using a real-time polymerase chain reaction. The KKAy mice demonstrated moderate hyperglycemia and hyperlipidemia, and the STZ mice showed severe hyperglycemia and hypolipidemia. The KKAy mice, but not the STZ mice, showed elevated plasma MDA relative to the non-diabetic controls. Urine 8-isoprostane and 8-OHdG in both diabetic mouse groups increased significantly. The urine oxidative stress markers in the severely hyperglycemic STZ mice were higher than those in the moderately hyperglycemic KKAy mice. Although GPx-1 and SOD-1 showed elevated mRNA expression in the KKAy mice in the kidney and heart, in the STZ mice they did not increase compared to the controls. The compensatory up-regulation of the mRNA expression of antioxidant enzymes may be impaired in the insulin-deficient severely hyperglycemic state.

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Oxidative stress is now considered to be a key factor in the development of diabetes and its complications. In this study, we examined the anti-oxidative effects of a crude lipophilic rice bran extract, Ricetrienol, which contains alpha-tocopherol, tocotrienol and phytosterol, in obese diabetic KKAy mice. We used KKAy mice fed a normal diet (DM group) or a diet including 0.1% Ricetrienol (RT group), and non-diabetic C57BL mice (C group). After 6 weeks, body weight, HbA1c, plasma glucose, lipids, peroxylipid (malonedialdehyde, MDA), alpha-tocopherol and glutathione peroxidase 1 (GPx) mRNA expression in the kidney were measured. At 1 week and at the end of the experimental period, urine 8-isoprostane and 8-hydroxy deoxyguanosine (8-OHdG) were also measured. Ricetrienol administration did not affect hyperglycemia, body weight or hyperlipidemia. Plasma MDA, urine 8-isoprostane and 8-OHdG in the DM group were significantly increased compared with the C group and the elevation of plasma MDA was significantly suppressed by 0.1% Ricetrienol. GPx mRNA expression was significantly increased in the RT group when compared with the C group. Plasma alpha-tocopherol in the RT group was significantly higher than that in the DM group. These findings suggest that Ricetrienol exerts a protective effect against oxidative damage in diabetes mellitus.

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