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Summary This study aimed to estimate the prevalence and type of chronic gastritis is an asymptomatic working population and to determine whether a combination of serum pepsinogen levels and Helicobacter pylori serology could be used to identify a subgroup with atrophic gastritis at elevated risk of gastric carcinoma. A 10% subsample of 544 male volunteer factory workers aged 18-63 years and participating in a larger study underwent endoscopy and biopsy. Of these men, 29 were seropositive for Helicobacter pylori; all but three (89.7%) had chronic gastritis. Serum pepsinogen A levels increased with progression from a corpus predominant pattern of gastritis through pangastritis to an antral predominant pattern. Nine subjects had corpus atrophy, which was in most cases accompanied by fasting hypochlorhydria and hypergastrinaemia. A combination of pepsinogen A below 80 ng ml-' and Helicobacter pylori seropositivity detected corpus atrophy with sensitivity 88.9% and specificity 92.3%. A second screening stage, using a pepsinogen A/C ratio of below 2.5 as a cut-off, resulted in a reduction in numbers requiring further investigation but with some loss of sensitivity (77.8%). Application of this two-stage screening programme to the original sample of 544 workers would have resulted in 11 (2.2%) men being selected for follow-up, excluding 25 (5.1%) false negatives. Our results suggest that a combination of serum pepsinogen levels and Helicobacter pylori serology could be useful as a biomarker strategy for detection of individuals at increased risk of gastric carcinoma and for non-invasive investigation of the natural history of Helicobacter pylori gastritis.

Aims: Carbon monoxide-releasing molecules (CORMs) are being developed with the ultimate goal of safely utilizing the therapeutic potential of CO clinically, including applications in antimicrobial therapy. Hemes are generally considered the prime targets of CO and CORMs, so we tested this hypothesis using heme-deficient bacteria, applying cellular, transcriptomic, and biochemical tools. Results: CORM-3 [Ru(CO)3Cl(glycinate)] readily penetrated Escherichia coli hemA bacteria and was inhibitory to these and Lactococcus lactis, even though they lack all detectable hemes. Transcriptomic analyses, coupled with mathematical modeling of transcription factor activities, revealed that the response to CORM-3 in hemA bacteria is multifaceted but characterized by markedly elevated expression of iron acquisition and utilization mechanisms, global stress responses, and zinc management processes. Cell membranes are disturbed by CORM-3. Innovation: This work has demonstrated for the first time that CORM-3 (and to a lesser extent its inactivated counterpart) has multiple cellular targets other than hemes. A full understanding of the actions of CORMs is vital to understand their toxic effects. Conclusion: This work has furthered our understanding of the key targets of CORM-3 in bacteria and raises the possibility that the widely reported antimicrobial effects cannot be attributed to classical biochemical targets of CO. This is a vital step in exploiting the potential, already demonstrated, for using optimized CORMs in antimicrobial therapy. Antioxid. Redox Signal. 23, 148–162.

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