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Background and Purpose:Mesalamine is the first-line therapy for colitis, but it lacks potency and is only effective for mild-to-moderate forms of this disease. Hydrogen sulphide has been shown to be a potent, endogenous anti-inflammatory substance, modulating leukocyte-endothelial adhesion and leukocyte migration. The purpose of this study was to determine if an H2S-releasing derivative of mesalamine (ATB-429) would exhibit increased potency and effectiveness in a mouse model of colitis.Experimental Approach:Colitis was induced in mice with trinitrobenzene sulphonic acid and the effects of ATB-429 and mesalamine were compared in several treatment regimens. The severity of colitis was determined using several indices, including a disease activity score (comprised of scores for diarrhea, weight loss and fecal blood), colonic myeloperoxidase activity and macroscopic/microscopic scoring of tissue injury.Key Results:Irrespective of the treatment regiment, ATB-429 was more effective than mesalamine in reducing the severity of colitis. ATB-429 was particularly effective in reducing granulocyte infiltration into the colonic tissue (by ∼70%), as well as reducing the expression of mRNA for several key proinflammatory cytokines/chemokines (e.g., TNFα, IFNγ). Treatment with ADT-OH, the H2S-releasing moiety of ATB-429, did not affect severity of colitis.Conclusions and Implications:ATB-429 exhibits a marked increase in anti-inflammatory activity and potency in a murine model of colitis, as compared to mesalamine. These results are consistent with recently described anti-inflammatory effects of H2S. ATB-429 may represent an attractive alternative to mesalamine for the treatment of inflammatory bowel disease.British Journal of Pharmacology (2007) 150, 996–1002. doi:10.1038/sj.bjp.0707193; published online 5 March 2007 [ABSTRACT FROM AUTHOR]

Background: Altered visceral perception is common in functional dyspepsia (FD). Dopaminergic pathways control gastrointestinal motility, but whether they modulate visceral sensitivity is unknown. Aim: To investigate whether levosulpiride, a D2 antagonist, modulates gastric sensitivity and compliance in dyspeptic patients. Methods: Eight healthy subjects and 16 dyspeptic patients underwent graded gastric distensions using a tensostat. In dyspeptic patients the same isotonic distensions were repeated during either levosulpiride or saline administration. Eight FD patients were evaluated after 4-week treatment with oral levosulpiride. Gastrointestinal symptoms were evaluated using a 100 mm visual analogue score. Perception was scored on a scale of 0 to 6. Results: Although healthy subjects and FD patients had similar gastric compliance, FD patients tolerated lower tension levels. At the same distending tension levels, levosulpiride decreased gastric compliance and perception score (14 ± 6% and 38 ± 10% change, respectively; P < 0.05 vs. saline) only in FD patients. Isotonic distensions exhibited very reproducible perception. Chronic levosulpiride administration significantly reduced dyspeptic symptoms and increased discomfort threshold. Conclusions: Compared with healthy subjects, FD patients show marked gastric hypersensitivity. In FD patients levosulpiride decreased the perception of gastric distension with an action unrelated to change of gastric tone. Chronic levosulpiride administration significantly ameliorates gastrointestinal symptoms and increases the discomfort threshold. [ABSTRACT FROM AUTHOR]

7-11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK [ABSTRACT FROM AUTHOR]

An abstract of the article "Nitric oxide protects against HIV gp120 endothelial injury," by S. Fiorucci and colleagues is presented.

Examines the stimulation of bombesin in the pancreatic growth of large mammals. Effect of bombesin in body weight; Role of bombesin in the increase rate of pancreatic acinar cell proliferation; Mechanism of mitogen-activated protein kinase phosphorylation.