The aim of the present studies was to examine mechanisms by which the rectally administered combination of N-acetylcysteine (NAC) plus mesalamine (5-ASA) affects inducers of inflammation to promote mucosal healing and reduce tissue inflammation in chemically (trinitrobenzene sulfonic acid, TNBS) induced colitis in rats. Experimental findings demonstrate that dual therapy with NAC plus 5-ASA was superior to individual agents in reducing histological measures of colitis. NAC alone and in combination with 5-ASA suppressed COX2 gene expression and prostaglandin E(2) (PGE(2)) levels to control values. Furthermore, NAC plus 5-ASA reduced nitrate generation, an expression of inducible nitric oxide synthase (iNOS) activity, to basal levels and these results were significantly lower than those observed with either NAC or 5-ASA alone. In conclusion, these results indicate that NAC plus 5-ASA exerts therapeutic benefit, in part by countering the actions of PGE(2) and the deleterious effects of oxidative and nitrosative stress induced by TNBS colitis.
The pathogenesis of Brunner gland hamartoma of the duodenum is unknown. This case report describes the chronology of the development of Brunner gland hamartoma from Brunner gland hyperplasia over a 12-year interval. The study subject, a 64-year-old man with chronic iron deficiency anemia, underwent serial upper endoscopies during this period. Repeated endoscopies demonstrated the evolution of Brunner gland hyperplasia, as manifest endoscopically by a submucosal mass, to a pedunculated polyp with histologic features of Brunner gland hamartoma. The duodenal polypoid mass was removed by snare polypectomy. The patient also had a chronic Helicobacter pylori infection of the stomach. This report details the time-dependent evolution of Brunner gland hyperplasia to hamartoma in association with chronic gastric H. pylori infection.
Global assessments of microscopic colitis induced by TNBS indicated that 5-ASA alone significantly changed colonic injury by -31%. Combination therapy with ascorbic acid plus 5-ASA or alpha-tocopherol plus 5-ASA caused further significant change in TNBS colitis by -65 and -82%, respectively. Each of these values was significantly below scores observed with 5-ASA as monotherapy. Reduction in colitis with PBN plus 5-ASA was not different from 5-ASA alone. MPO activity was decreased significantly in response to monotherapy with 5-ASA and each of the antioxidants plus 5-ASA when compared to TNBS. alpha-Tocopherol plus 5-ASA, however, was the only treatment strategy that reduced significantly MPO activity below that recorded for 5-ASA alone. In conclusion, our results indicate that antioxidants other than N-acetylcysteine significantly enhance the therapeutic effectiveness of 5-ASA in the treatment of TNBS colitis. alpha-Tocopherol plus 5-ASA exerted profound anti-inflammatory and reparative effects upon colitis induced by TNBS.
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