Helicobacter pylori has been cultured from the inflamed gastric mucosae of naturally infected cats; the lesions in H. pylori-infected cat stomachs mimic many of the features seen in H. pylori-infected human stomachs. To determine whether H. pylori-negative specific-pathogen-free cats with normal gastric mucosae were susceptible to colonization by this bacterium and whether gastritis developed after infections, four H. pylori-negative cats treated with cimetidine were orally dosed three times with 3 ml (1.5 ؋ 10 8 CFU/ml) of H. pylori every 4 days. All four cats became persistently colonized as determined by gastric cultures and PCRs from serial gastric biopsy samples and necropsy samples at 7 months postinfection. H. pylori was not isolated from the two control cats, nor were their gastric tissues positive by PCR; one of the two cats had a few focal lymphocytic aggregates in the body submucosa, whereas the second cat had a normal gastric mucosa. All four H. pylori-infected cats had multifocal gastritis consisting of lymphoid aggregates plus multiple large lymphoid nodules, which were most noticeable in the antral mucosa. In addition, one H. pylori-infected cat had a moderate diffuse infiltration of polymorphonuclear leukocytes in the subglandular region of the antrum. H. pylori-like organisms were focally distributed in glandular crypts of the antrum. Two of the H. pylori-infected cats had significant (eightfold) increases over baseline in levels of immunoglobulin G H. pylori serum antibody. The H. pylori isolates from the four experimentally infected cats had restriction fragment length polymorphism patterns specific for the flaA gene that were identical to those of the inoculating strain. H. pylori readily colonizes the cat stomach and produces persistent gastritis.

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The antidepressant activity of the N-methyl-D-aspartate (NMDA) receptor channel blocker, ketamine, has led to the investigation of negative allosteric modulators (NAMs) selective for the NR2B receptor subtype. The clinical development of NR2B NAMs would benefit from a translational pharmacodynamic biomarker that demonstrates brain penetration and functional inhibition of NR2B receptors in preclinical species and humans. Quantitative electroencephalography (qEEG) is a translational measure that can be used to demonstrate pharmacodynamic effects across species. NMDA receptor channel blockers, such as ketamine and phencyclidine, increase the EEG gamma power band, which has been used as a pharmacodynamic biomarker in the development of NMDA receptor antagonists. However, detailed qEEG studies with ketamine or NR2B NAMs are lacking in nonhuman primates. The aim of the present study was to determine the effects on the qEEG power spectra of the NR2B NAMs traxoprodil (CP-101,606) and BMT-108908 in nonhuman primates, and to compare them to the NMDA receptor channel blockers, ketamine and lanicemine. Cynomolgus monkeys were surgically implanted with EEG radio-telemetry transmitters, and qEEG was measured after vehicle or drug administration. The relative power for a number of frequency bands was determined. Ketamine and lanicemine increased relative gamma power, whereas the NR2B NAMs traxoprodil and BMT-108908 had no effect. Robust decreases in beta power were elicited by ketamine, traxoprodil and BMT-108908; and these agents also produced decreases in alpha power and increases in delta power at the doses tested. These results suggest that measurement of power spectra in the beta and delta bands may represent a translational pharmacodynamic biomarker to demonstrate functional effects of NR2B NAMs. The results of these studies may help guide the selection of qEEG measures that can be incorporated into early clinical evaluation of NR2B NAMs in healthy humans.

These results suggest that though prior infection with H. mustelae may confer some protection against reinfection, such protection is not universal in all circumstances; that susceptibility to reinfection by contact with infected animals varies between individuals; and that age may be a factor in this individual variability. These results are applicable to studies of reinfection after eradication of H. pylori in humans.

Oral vaccination of young ferrets with Hml and 50 micrograms MDP increased the risk of Helicobacter-associated mucosal ulceration in the proximal duodenum, which was associated with low humoral (but significant cell-mediated) immune responses to H. mustelae. In retrospect, the frequency of vaccination may have suppressed the systemic humoral immune response, thereby promoting mucosal damage by H. mustelae. The 50-microgram dose of MDP enhanced the cell-mediated immune response, which indirectly contributed to development of severe lesions. The increased frequency of mucosal damage associated with this vaccination regimen enhances the value of the ferret model for studying duodenal ulceration secondary to Helicobacter infection.

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