The correlation in dyspeptic patients of Helicobacter pylori infection with changes in interdigestive gastroduodenal motility patterns but not in gastric emptying.

BACKGROUND: Available data conflict regarding the possible relation between chronic gastritis, Helicobacter pylori (Hp), and gastric motor disorders in nonulcer dyspepsia. The aim of this study, therefore, was (1) to evaluate both gastroduodenal fasting motility and gastric emptying in subjects with functional dyspepsia, with and without gastritis, and (2) to correlate the motility pattern to Hp infection. MATERIALS AND METHODS: Thirty-eight patients were studied, 20 positive for Hp infection (15 with gastritis) and 18 Hp-negative (8 with gastritis). All the subjects underwent 240-minute manometric recording of the interdigestive migrating motor complex, with evaluation of gastric and duodenal motility pattern and scintigraphic study of gastric emptying. RESULTS: Whereas gastric emptying half-time did not differ in the subgroups of dyspeptic patients, a significant reduction of gastric phase IIIs of the migrating motor complex was detected between Hp-positive and Hp-negative subjects, both in overall patients (p < .01) and in patients with gastritis (p < .05). CONCLUSION: Hp infection seems to be related to a reduction of interdigestive gastric activity fronts, though it does not affect gastric emptying. The conflicting data regarding gastric emptying and interdigestive motility in Hp infection could be explained as probably investigating two different functional aspects.

New potent antihyperglycemic agents in db/db mice: synthesis and structure-activity relationship studies of (4-substituted benzyl) (trifluoromethyl)pyrazoles and -pyrazolones.

The synthesis, structure-activity relationship (SAR) studies, and antidiabetic characterization of 1,2-dihydro-4-[[4-(methylthio)phenyl]methyl]-5-(trifluoromethyl)-3H- pyrazol-3-one (as the hydroxy tautomer; WAY-123783, 4) are described. Substitution of 4-methylthio, methylsulfinyl, or ethyl to a benzyl group at C4, in combination with trifluoromethyl at C5 of pyrazol-3-one, generated potent antihyperglycemic agents in obese, diabetic db/db mice (16-30% reduction in plasma glucose at 2 mg/kg). The antihyperglycemic effect was associated with a robust glucosuria (> 8 g/dL) observed in nondiabetic mice. Chemical trapping of four of the seven possible tautomeric forms of the heterocycle by mono- and dialkylation at the acidic hydrogens provided several additional potent analogs (39-43% reduction at 5 mg/kg) of the lead 4 as well as a dialkylated pair of regioisomers that showed separation of the associated glucosuric effect produced by all of the active analogs in normal mice. Further pharmacological characterization of the lead WAY-123783 (ED50 = 9.85 mg/kg, po in db/db mice), in oral and subcutaneous glucose tolerance tests, indicated that unlike the renal and intestinal glucose absorption inhibitor phlorizin, pyrazolone 4 does not effectively block intestinal glucose absorption. SAR and additional pharmacological data reported herein suggest that WAY-123783 represents a new class of potent antihyperglycemic agents which correct hyperglycemia by selective inhibition of renal tubular glucose reabsorption.