A possible target of antioxidative therapy for diabetic vascular complications-vascular NAD(P)H oxidase.

A growing body of evidence has shown that oxidative stress may be involved in the development of vascular complications associated with diabetes. However, the molecular mechanism for increased reactive oxygen species (ROS) production in diabetes remains uncertain. Among various possible mechanisms, attention have increasingly been paid to NAD(P)H oxidase as the most important source of ROS production in vascular cells. High glucose level stimulates ROS production through protein kinase C (PKC)-dependent activation of vascular NAD(P)H oxidase. Furthermore, the expression of NAD(P)H oxidase components is increased in micro- and macrovascular tissues of diabetic animals in association with various functional disorders and histochemical abnormalities. These results suggest that vascular NAD(P)H oxidase-driven ROS production may contribute to the onset or development of diabetic micro- or macrovascular complications. In this point of view, the possible new strategy of antioxidative therapy for diabetic vascular complications is discussed in this review.

Oral supplementation of branched-chain amino acid improves nutritional status in elderly patients on chronic haemodialysis.

BACKGROUND: Anorexia may be associated with decreased plasma levels of branched-chain amino acids (BCAA). In malnourished elderly haemodialysis (HD) patients, oral BCAA supplementation may improve anorexia, resulting in improved nutritional status. METHODS: Among 44 elderly (age >70 years) patients on chronic HD, 28 patients with low plasma albumin concentration (<3.5 g/dl) were classified as the malnourished group; they also suffered from anorexia. The other 16 patients did not complain of anorexia and were classified as the well-nourished group. We performed a 12-month, placebo-controlled, double-blind study on the malnourished group. Fourteen patients each received daily oral BCAA supplementation (12 g/day) or a placebo in random order in a crossover trial for 6 months. Body fat percentage, lean body mass, plasma albumin concentration, dietary protein and caloric intakes, and plasma amino acid profiles were monitored. RESULTS: Lower plasma levels of BCAA and lower protein and caloric intakes were found in the malnourished group as compared to the well-nourished group. In BCAA-treated malnourished patients, anorexia and poor oral protein and caloric intakes improved within a month concomitant with the improvement in plasma BCAA levels over the values in well-nourished patients. After 6 months of BCAA supplementation, anthropometric indices showed a statistically significant increase and mean plasma albumin concentration increased from 3.31 g/dl to 3.93 g/dl. After exchanging BCAA for a placebo, spontaneous oral food intake decreased, but the favourable nutritional status persisted for the next 6 months. In 14 patients initially treated with a placebo, no significant changes in nutritional parameters were observed during the first 6 months. However, positive results were obtained by BCAA supplementation during the subsequent 6 months, and mean plasma albumin concentration increased from 3.27 g/dl to 3.81 g/dl. CONCLUSIONS: Normalization of low plasma levels of BCAA by oral supplementation can reduce anorexia and significantly improve overall nutritional status in elderly malnourished HD patients.

The beneficial effect of mesalazine on esophageal ulcers in intestinal Behcet's disease.

Intestinal Behcet's disease in a 19-year-old girl was diagnosed because of the history of recurrent oral aphthous ulcers and typical endoscopic findings of esophageal and ileal ulcers. Her symptoms (e.g., dysphagia and retrosternal pain) were gradually relieved by treatment with prednisolone and total parenteral nutrition. However, about one month later, oral and esophageal ulcers appeared again. Mesalazine was added. Oral and esophageal ulcers healed promptly, and have not relapsed for about one year. Although mesalazine appears to act locally in the small intestine and colon, the therapeutic effect of mesalazine in this case may be explained by the systemic antiinflammatory effect. This case suggests that mesalazine is an effective drug and is a good candidate in the treatment of intestinal Behcet's disease, especially accompanied with esophageal involvement.