title: Development of a 14C-urea breath test in ferrets colonised with Helicobacter mustelae: effects of treatment with bismuth, antibiotics, and urease inhibitors.
abstract: A 14C-urea breath test analogous to its clinical counterpart is described for use in ferrets naturally or experimentally infected with Helicobacter mustelae. The test is performed within a sealed glass metabolism chamber through which air is drawn at a constant rate and expired breath collected into sodium hydroxide. Peak 14CO2 production occurred approximately 1 hour after substrate administration. Both inter- and intra-animal responses were highly reproducible, with mean coefficients of variation less than 10%. Other than enhancing peak 14CO2 levels very slightly, fasting had little influence on the response. In infant animals challenged with H mustelae, breath test activity increased linearly with the total count of culturable bacteria isolated from the antrum. Treatment of established infections with colloidal bismuth subcitrate (DeNol) for 4 weeks resulted in clearance of all detectable bacteria but retention of some breath test activity. Subsequent regrowth of bacteria was parallelled by an increase in the breath test response. Inclusion of amoxycillin and metronidazole in the treatment regimen, however, eradicated all the bacteria and almost totally eliminated 14CO2 production. This response parallels the clinically observed suppressive effect on H pylori achieved with bismuth alone relative to the total eradication seen with triple therapy. A single oral dose of the urease inhibitor, flurofamide, inhibited over 90% of the response for at least 24 hours. Acetohydroxamic acid was less effective. These findings suggest that in the ferret H mustelae model, breath test analysis can be a useful, non-invasive alternative to endoscopy for evaluation of agents affecting either growth of the organism or urease activity.
authors.affiliation: Department of Chemotherapy, Glaxo Group Research Limited, Greenford, Middlesex.
authors.forename: A A
authors.initials: AA
authors.lastname: McColm
authors.forename: J A
authors.initials: JA
authors.lastname: Bagshaw
authors.forename: C F
authors.initials: CF
authors.lastname: O'Malley
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001729:Bismuth / Q000627:therapeutic use; D001944:Breath Tests / Q000379:methods*; D002245:Carbon Dioxide / Q000502:physiology; D002250:Carbon Radioisotopes; D004195:Disease Models, Animal; D005289:Ferrets; D016481:Helicobacter Infections / Q000175:diagnosis* / Q000188:drug therapy*; D014510:Urease / Q000037:antagonists & inhibitors
chemical_list: D000900:Anti-Bacterial Agents; D002250:Carbon Radioisotopes; D002245:Carbon Dioxide; D014510:Urease; D001729:Bismuth