Inflammatory bowel diseases (IBDs) such as Crohn's disease and ulcerative colitis are chronic inflammatory disorders of the intestinal tract with excessive production of cytokines, adhesion molecules, and reactive oxygen species. Although nitric oxide (NO) is reported to be involved in the onset and progression of IBDs, it remains controversial as to whether NO is toxic or protective in experimental colitis. We investigated the effects of oral nitrite as a NO donor on dextran sulfate sodium (DSS)-induced acute colitis in mice. Mice were fed DSS in their drinking water with or without nitrite for up to 7days. The severity of colitis was assessed by disease activity index (DAI) observed over the experimental period, as well as by the other parameters, including colon lengths, hematocrit levels, and histological scores at day 7. DSS treatment induced severe colitis by day 7 with exacerbation in DAI and histological scores. We first observed a significant decrease in colonic nitrite levels and increase in colonic TNF-alpha expression at day 3 after DSS treatment, followed by increased colonic myeloperoxidase (MPO) activity and increased colonic expressions of both inducible NO synthase (iNOS) and heme oxygenase-1 (HO-1) at day 7. Oral nitrite supplementation to colitis mice reversed colonic nitrite levels and TNF-alpha expression to that of normal control mice at day 3, resulting in the reduction of MPO activity as well as iNOS and HO-1 expressions in colonic tissues with clinical and histological improvements at day 7. These results suggest that oral nitrite inhibits inflammatory process of DSS-induced experimental colitis by supplying nitrite-derived NO instead of impaired colonic NOS activity.

Keywords： adrenal insufficiency, isolated ACTH deficiency, hypercalcemia, vitamin D analogue, hemodialysis 〈Abstract〉 A 62 year old male, who had been undergoing hemodialysis for 19 years and 3 months, experienced a loss of appetite and diarrhea for one month. He developed a fever and low blood pressure during dialysis and was admitted to our hospital, Saitama Sekishinkai Hospital. Hypercalcemia (corrected calcium＝11.8 mg/dL), hypoglycemia, and eosinophilia were observed. He stopped taking precipitated calcium carbonate and maxacalcitol (a vitamin D derivative) and was administered antibiotics due to a suspected infection. The antibiotics did not alleviate his symptoms, and there was no improvement in his laboratory test results. A subsequent examination revealed that his serum basal cortisol (0.4 µg/dL) and adrenocorticotropic hormone ( ＜1.5 pg/mL) levels were low, which resulted in him being diagnosed with secondary adrenal insufficiency. He was treated with hydrocortisone, after which his symptoms, hypercalcemia, hypoglycemia, and eosinophilia were ameliorated. Calcium containing phosphate binders and vitamin D analogues are often used for the management of chronic kidney disease mineral bone disorder in patients undergoing long term hemodialysis. We eventually diagnosed our patient with adrenal insufficiency, after excluding iatrogenic hypercalcemia.

Due to its rarity, adrenal hemorrhage is difficult to diagnose, and its precise etiology has remained unknown. One of the pivotal mechanisms of adrenal hemorrhage is the thrombosis of the adrenal vein, which could be due to thrombophilia. However, detailed pathological evaluation of resected adrenal glands is usually required for definitive diagnosis. Here, we report a case of a cortisol-secreting adenoma with concomitant foci of hemorrhage due to antiphospholipid syndrome diagnosed both clinically and pathologically. In addition, the tumor in this case was pathologically diagnosed as cortisol-secreting adenoma, although the patient did not necessarily fulfill the clinical diagnostic criteria of full-blown Cushing or sub-clinical Cushing syndrome during the clinical course, which also did highlight the importance of detailed histopathological investigations of resected adrenocortical lesions.

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