The gastric pathogen Helicobacter pylori is associated with a progression to gastric cancer. The specific targets of H. pylori that might influence this progression are still unclear. Previous studies indicated that the gastric hormone gastrin, which may be increased in H. pylori infection, stimulates gastric expression of plasminogen activator inhibitor (PAI)-2, which is an inhibitor of the urokinase plasminogen activator and has previously been shown to be increased in gastric adenocarcinoma. Here, we report that H. pylori also increases PAI-2 expression. In gastric biopsies of H. pylori-positive subjects there was increased PAI-2, including subjects with plasma gastrin concentrations in the normal range. PAI-2 was expressed mainly in chief and mucous cells. In a gastric cancer cell line (AGS), H. pylori increased PAI-2 expression, which was associated with inhibition of H. pylori-stimulated cell invasion and apoptosis. The induction of PAI-2 by H. pylori was mediated by release of interleukin-8 and activation of cyclooxygenase-2, and interestingly, gastrin stimulated PAI-2 expression by similar paracrine pathways. The activation of NFB was required for interleukin-8 and cyclooxygenase-2 activation but did not occur in cells responding to these paracrine mediators. The data suggest that induction of PAI-2 is a specific target in H. pylori infection, mediated at least partly by paracrine factors; induction of PAI-2 inhibits cell invasion and apoptosis and is a candidate for influencing the progression to gastric cancer.

Canine acute diarrhoea is frequently observed in first opinion practice, though little is known about commonly used diagnostic or therapeutic management plans, including use of antimicrobials. This retrospective observational study utilised electronic health records augmented with practitioner-completed questionnaires from 3,189 cases (3,159 dogs) collected from 179 volunteer veterinary practices between April 2014 and January 2017. We used multivariable analysis to explore factors potentially associated with pharmaceutical agent prescription, and resolution of clinical signs by 10 days post-initial presentation. Use of bacteriological and/or parasitological diagnostic tests were uncommon (3.2% of cases, 95% confidence interval, CI, 2.4–4.0), though systemic antimicrobials were the most commonly prescribed pharmaceutical agents (49.7% of cases, 95% CI 46.1–53.2). Such prescription was associated with haemorrhagic diarrhoea (odds ratio, OR, 4.1; 95% CI 3.4–5.0), body temperature in excess of 39.0°C, or moderate/severe cases (OR 1.3, 95% CI 1.1–1.7). Gastrointestinal agents (e.g., antacids) were prescribed to 37.7% of cases (95% CI 35.4–39.9), and were most frequently prescribed to vomiting dogs regardless of presence (OR 46.4, 95% CI 19.4–110.8) or absence of blood (OR 17.1, 95% CI 13.4–21.9). Endoparasiticides/endectocides were prescribed to 7.8% of cases (95% CI 6.8–9.0), such prescription being less frequent for moderate/severe cases (OR 0.5, 95% CI 0.4–0.7), though more frequent when weight loss was recorded (OR 3.4, 95% CI 1.3–9.0). Gastrointestinal nutraceuticals (e.g., probiotics) were dispensed to 60.8% of cases (95% CI 57.1–64.6), these cases less frequently presenting with moderate/severe clinical signs (OR 0.6, 95% CI 0.5–0.8). Nearly a quarter of cases were judged lost to follow-up ( n =754). Insured (OR 0.7, 95% CI 0.5–0.9); neutered (OR 0.4, 95% CI 0.3–0.5), or vaccinated dogs (OR 0.3, 95% CI 0.3–0.4) were less commonly lost to follow-up. Of remaining dogs, clinical signs were deemed resolved in 95.4% of cases (95% CI 94.6–96.2). Provision of dietary modification advice and gastrointestinal nutraceuticals alone were positively associated with resolution (OR 2.8, 95% CI 1.3–6.1); no such associations were found for pharmaceutical agents, including antimicrobials. Hence, this study supports the view that antimicrobials are largely unnecessary for acute diarrhoea cases; this being of particular importance when considering the global threat posed by antimicrobial resistance.

The lack of population health surveillance for companion animal populations leaves them vulnerable to the effects of novel diseases without means of early detection. We present evidence on the effectiveness of a system that enabled early detection and rapid response a canine gastroenteritis outbreak in the United Kingdom. In January 2020, prolific vomiting among dogs was sporadically reported in the United Kingdom. Electronic health records from a nationwide sentinel network of veterinary practices confirmed a significant increase in dogs with signs of gastroenteric disease. Male dogs and dogs living with other vomiting dogs were more likely to be affected. Diet and vaccination status were not associated with the disease; however, a canine enteric coronavirus was significantly associated with illness. The system we describe potentially fills a gap in surveillance in neglected populations and could provide a blueprint for other countries.

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