Nitric oxide has been shown to be an important factor in the regulation of apoptosis in mesangial cells. The following studies were conducted to determine whether L-arginine, the metabolic precursor of nitric oxide synthesis, directly modulates programmed cell death in response to a variety of stimuli. Cultured rat mesangial cells were exposed for 24-48 h to one of the following four experimental conditions known to induce apoptosis: i) a cytokine combination consisting of interferon-gamma (50 U/ml), interleukin-1 (5 ng/ml), and LPS (10 microg/ml); ii) 0.75 mM hydrogen peroxide; iii) etoposide, 150 microg/ml; and iv) cis-platinum, 100 microg/ml. Addition of L-arginine resulted in a dose-dependent decrease in apoptosis in cytokine-treated RMC. This effect was demonstrable by gel electrophoresis, diphenylamine assay of DNA fragmentation, and an ELISA to detect DNA oligonucleosomes. The effect was not related to increased osmolality of the test media and was not reproduced by the addition of equimolar D-arginine. L-Arginine also reduced apoptosis and necrosis in RMC that were incubated with etoposide and cis-platinum. In contrast, the amino acid had no beneficial effect on RMC survival following exposure to hydrogen peroxide. These findings indicate that several components of the nitric oxide biosynthetic pathway including the precursor and the enzymatic product independently exert direct effects on apoptosis in cultured rat mesangial cells.

28 Allergic (eosinophilic) colitis is a common cause of bloody stools in infants. 30-50% of infants with cow's milk protein sensitivity exhibit sensitivity to soy milk protein. These infants are routinely thought to be effectively treated by the use of a PHF. However, in our clinical experience many of our patients appear to have persistent rectal bleeding on a PHF. A retrospective study was performed on all infants who presented to our Division from 1/97-4/99 with persistent rectal bleeding on a PHF who underwent flexible sigmoidoscopy. There were a total of 42 infants (17 F, 25 M). Mean age of onset of rectal bleeding was 4.5 weeks (range 3 days-20 weeks) with 33.3% <2 weeks, 69.0% <4 weeks and 92.9% <8 weeks. At the onset of symptoms 28.7% were already receiving PHF, 33.3% were fed cow's milk formula, 35.7% soy formula and 2.3% breastmilk. At the time of the procedure all patients had been on a PHF for a minimum of 2 weeks. Pathology revealed the presence of increased numbers of eosinophils in 100% with eosinophilic cryptitis in 66.7% of infants. In conclusion, many infants with allergic (eosinophilic) colitis have persistent rectal bleeding despite prolonged use of a PHF.

Esophageal involvement in patients with Crohn's disease, initially thought to be rare, has been documented with increasing frequency in both retrospective and prospective studies. However, there is no documented standardized medical regimen for treatment of these patients. We report five cases of esophageal Crohn's disease as well as a review of the literature emphasizing therapeutic approach and increased incidence of corticosteroid dependence in these patients. In the past, patients with significant esophageal disease and symptoms have been surgical candidates. We recommend that all patients with symptoms of dysphagia, odynophagia, chest pain, or dyspepsia with documented esophageal Crohn's disease should receive H-2 receptor antagonists as part of their medical regimen. In addition, immunosuppressant agents should be considered as adjuvant therapy in steroid-dependent patients with esophageal disease involvement.

Weinstein, Toba; Valderrama, Elsa*; Pettei, Michael; Levine, Jeremiah Author Information