Methods:  Animals were given loxoprofen (10–100 mg/kg p.o.) and killed 24 h later. Lafutidine (10 and 30 mg/kg), cimetidine (100 mg/kg) or famotidine (30 mg/kg) was given twice p.o. at 0.5 h before and 6 h after loxoprofen. Omeprazole (100 mg/kg) was given p.o. once 0.5 h before. Ampicillin (800 mg/kg) was given p.o. twice at 24 h and 0.5 h before loxoprofen, while 16,16-dimethyl prostaglandin E2 (dmPGE2; 0.01 mg/kg) was given i.v. twice at 5 min before and 6 h after. Results:  Loxoprofen dose-dependently produced hemorrhagic lesions in the small intestine, accompanied by invasion of enterobacteria and increased inducible nitric oxide

synthase (iNOS) expression as well as myeloperoxidase activity in the mucosa. The ulcerogenic response to loxoprofen (60 mg/kg) was significantly prevented by lafutidine BYL719 (30 mg/kg), similar to dmPGE2 and ampicillin,

and the effect of lafutidine was totally attenuated by ablation of CSN. Neither cimetidine, famotidine nor omeprazole had a significant effect against these lesions. Lafutidine alone increased mucus secretion and reverted the decreased mucus response to loxoprofen, resulting in suppression of bacterial invasion and iNOS expression. In addition, loxoprofen downregulated Muc2 expression, and this response was totally reversed by lafutidine mediated by CSN. Conclusion:  Lafutidine protects the small intestine against loxoprofen-induced lesions, essentially mediated by the CSN, and this effect may be functionally Ku-0059436 research buy associated with increased Muc2 expression/mucus secretion, an important factor in the suppression of bacterial invasion. “
“Minimal hepatic encephalopathy (MHE) in cirrhosis is associated with impaired driving skills and increased risk of motor vehicle accidents (MVAs). Detection and treatment of MHE has the potential to reduce costs and morbidity associated with MVAs. We conducted a cost-effectiveness analysis to assess the benefits

of different strategies of MHE diagnosis MCE and treatment for reducing MVA-related societal costs. The analyses compared five MHE management strategies: (1) presumptive treatment of all cirrhosis patients; (2) diagnosis by neuropsychological exam (NPE) with treatment; (3) diagnosis by standard psychometric tests (SPTs) with treatment; (4) diagnosis by rapid screening using inhibitory control test (ICT) with treatment; and (5) no MHE diagnosis or treatment (status quo). Treatments considered were lactulose or rifaximin, which were assumed to reduce the MVA rate to the level of similarly aged noncirrhosis patients with benefit adjusted for treatment compliance. A Markov model followed a simulated cohort of 1,000 cirrhosis patients without overt hepatic encephalopathy (OHE), from entry into treatment, through MHE development, and later OHE, when they exited the modeled cohort.