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Human and animal data have demonstrated H.pylori induced platelet aggregation in gastric vasculature. Formation of platelet aggregates may contribute to the pathogenesis of H.pylori associated gastric injury and may also [...]

Although COX-1 is often referred to as a constitutively expressed gene, we have previously described induction of COX-1 as well as COX-2 by H. pylori suggesting that COX-1 may contribute [...]

There is growing evidence that H. pylori exerts some of its effects on the stomach by actions on the gastric vasculature. We have shown upregulation of both isoforms of COX [...]

Several studies have demonstrated that H. pylori induces COX-2 in gastric mucosa and suggested that this may explain the increased risk of gastric cancer with H. pylori infection. We have [...]

C. Steele [1] K. Sheehan [2] E. Kay [2] D. Fitzgerald [3] F.E. Murray [1,3] (1.) Gastrointestinal Unit, Beaumont Hospital Dublin; (2.) Dept of Pathology, Beaumont Hospital Dublin; (3.) Dept [...]

Introduction: The role of the eosinophil, which is a common inflammatory cell in inflamed gastrointestinal mucosa in inflammatory bowel disease (IBD) is uncertain. We have previously shown that eosinophils specifically [...]

Aims: COX-2 plays a crucial role in colorectal carcinogenesis and selective COX-2 inhibitors have been shown to have antineoplastic effects in vitro and in vivo. The precise mechanisms underlying these [...]

Introduction: The role of the eosinophil, which is a common inflammatory cell in inflamed gastrointestinal mucosa in inflammatory bowel disease (IBD) is uncertain. Many of the symptoms of IBD are [...]

Introduction: The role of the eosinophil, which is a common inflammatory cell in inflamed gastrointestinal mucosa in inflammatory bowel disease (IBD) is uncertain. Eosinophils may lead to symptoms through the [...]

Aims: γ-Catenin (Plakoglobin) is a member of the catenin family. It functions in cell adhesion and the WNT signalling pathway. Defects in both WNT signalling and COX-2 expression play important [...]

Aims: Folate supplementation appears to reduce colorectal cancer (CRC) risk. CRC risk is also modulated by the C to T polymorphism at position 677 of the methylenetetrahydrofolate reductase (MTHFR) gene, [...]

Background: Helicobacter pylori induces cyclooxygenase activity in the stomach, although the COX isoform and cellular source are unclear. A potential source is the vascular endothelial cell, which plays a role in regulating mucosal blood flow and inflammatory cell infiltration. Methods: We examined the effect of four strains (toxigenic and non-toxigenic) of H. pylori on COX isoform expression in vascular endothelial cells. Prostaglandin synthesis was measured by enzyme immunoassay and COX isozyme expression determined by Western blot and RT-PCR. Gene induction was examined using 5′ deletion constructs of the COX-1 and COX-2 promoters coupled with luciferase. Results: All H. pylori strains induced prostaglandin generation and expression of both COX-1 and COX-2 in HUVEC, although this was most pronounced with the highly toxigenic strain H. pylori 60190. Treatment of the cells with selective COX inhibitors demonstrated that COX-1 was predominantly responsible for the enhanced generation of prostacyclin induced by H. pylori 60190. Similar results were seen with H. pylori broth culture filtrates, suggesting that a secreted product was responsible. Induction of COX-2 reflected both enhanced gene expression and stabilization of the mRNA. Conclusions: H. pylori increased both COX-1 and COX-2 activity in vascular endothelial cells. This increased generation of endothelial cell prostacyclin may play a role in modulating mucosal blood flow, platelet function and inflammatory cell infiltration in response to H. pylori infection. The regulation of COX-1 at the transcriptional level by H. pylori described in this study is a novel finding and calls into question the traditional description of COX-1 as a purely constitutive, housekeeping gene. [ABSTRACT FROM AUTHOR]

The management of dyspepsia has been radically altered by the discovery of the role of Helicobacter pylori and the advent of proton pump inhibitors (PPIs). The use of PPIs alone as antisecretory agents and as part of triple therapy regimens for H. pylori eradication accounts for a significant percentage of any healthcare system’s drug budget. Thus, it is important to take into account a variety of factors when devising a formulary and considering which PPIs to include. Consideration of 3 factors are particularly crucial in this process, namely therapeutic efficacy, tolerability and cost but several other clinical and economic parameters should also be considered. The mechanisms of action of all 4 PPIs currently available (omeprazole, lansoprazole, pantoprazole and rabeprazole) are very similar, with any small differences in pharmacological properties unlikely to be of clinical significance. Therapeutic efficacy in patients with acute reflux oesophagitis is again very similar for all 4 PPIs at their standard dosages; all agents are superior to H-antagonists. Data on maintenance therapy for reflux oesophagitis also suggest similar efficacy for omeprazole and lansoprazole; data on pantoprazole and rabeprazole are awaited. For the treatment of H. pylori-related ulcers, the consensus at present is for PPI-based triple therapy. Again, all PPIs seem equally efficacious for this indication but pantoprazole and rabeprazole have yet to receive licences for H. pylori eradication therapy (HPET) in most countries. Drug tolerability is another critical issue to consider in formulary inclusion decisions. As a class, the PPIs are well tolerated. Minor drug interactions are reported for omeprazole, lansoprazole and rabeprazole but not for pantoprazole. However, whether or not this is significant in clinical practice is open to debate. Most of the pharmacoeconomic data in these indicators, to date, relate to omeprazole and, to a lesser extent, lansoprazole. Certainly, the studies on these 2 drugs confirm the superior cost effectiveness of PPIs over H-antagonists in the treatment of reflux oesophagitis and peptic ulceration in both the short and long terms. Although data are awaited, there is no reason to suggest that this will be any different for pantoprazole and rabeprazole. PPI-based triple therapy for H. pylori eradication appears to be the most cost-effective treatment option for H. pylori-related peptic ulcer disease. It is clear that PPIs are superior in several regards to previously used medications in the treatment of dyspepsia. Which PPI(s) to include in a particular formulary is a more difficult decision. On review of many criteria involved in formulary decisions, differences between the individual PPIs appear minimal. The relative acquisition costs of the PPIs vary nationally and internationally and this may be a critical factor in formulary inclusion decisions. However, one should not ignore non-economic factors, as these should form the basis of any sound drug policies. [ABSTRACT FROM AUTHOR]

Background: Much has been published on the efficacy and cost effectiveness of Helicobacter pylori eradication treatment as an alternative to histamine H2-receptor antagonist maintenance treatment in peptic ulcer disease. However, most studies have analysed and emphasised H. pylori eradication rates rather than management/control of symptoms and the associated cost savings. Although H. pylori eradication therapy is very successful in clearing the infection, dyspeptic symptoms may persist and management of these can be expensive.Objective: The aim of this study was to assess the cost implications in controlling symptoms using either H2-receptor antagonist maintenance therapy or H. pylori eradication therapy in patients with duodenal ulcer disease.Design: This was a non-blind, prospective, randomised, parallel-group study comparing maintenance H2-receptor antagonist treatment using ranitidine with H. pylori eradication therapy, with a 1-year follow-up.Setting: This was a study of outpatients from general practices in Dundee, Scotland, or the Ninewells Hospital, Dundee, gastroenterology clinic.Patients and Participants: 119 patients with confirmed duodenal ulcer, free from active ulceration at study entry but positive for H. pylori infection, who were receiving maintenance H2-receptor antagonist therapy.Interventions: Patients were randomised to receive either continuing maintenance therapy with ranitidine (initially 150 mg daily; 58 patients) or H. pylori eradication therapy using an omeprazole/amoxicillin/metronidazole regimen (or omeprazole/clarithromycin if allergic to penicillin).Main Outcome Measures and Results: Overall, H. pylori eradication rates were 100% per protocol and 95.1% intention-to-treat. At completion of 1 year of follow-up, 12 of the 61 (19.7%) patients successfully eradicated of H. pylori were still dependent on acid suppression for symptom relief. H. pylori eradication treatment was the least-cost strategy in managing/controlling symptoms at 1 year (168 Pounds vs 210 Pounds per patient; 1996 values). However, over time, post-eradication treatment costs were greater than H2-receptor antagonist therapy costs. Any potential savings were directly related to the proportion of patients needing further treatment post-eradication, the cost of endoscopy and the urea breath test.Conclusions: If dyspepsia persists long term, H. pylori eradication treatment may not be the least-cost option for patients with duodenal ulcer. [ABSTRACT FROM AUTHOR]

Background: Clinical studies have suggested an association between cardiovascular disease and infection with H pylori. We have described strain specific H pylori-induced platelet aggregation that involves platelet glycoprotein lb and van Willebrand factor (vWf). We exam ned the role of H pylori antibodies in this aggregation. Methods and Results: Addition of pooled immunoglobin (Ig) and fibrinogen along with H pylori strain 60190 (coated in vWf) to washed platelets led to platelet aggregation (60±4% n=3). Antibodes involved were specific to H pylori as bacteria incubated in pooled g and subsequently washed could support platelet aggregation (49±7%, n=3). To confirm this, pooled Ig was incubated with H pylori or Streptococcus sanguis. Bacteria were removed by centrifugation and the depleted g used in aggregation assays. H pylori-depleted Ig showed greatly reduced platelet aggregation to H pylori (13±9%, n=3, p<0.01) while the S sanguis-depleted Ig was not affected (54±3%, n=3, p=NS). All 20 plasma donors were tested for H pylori seropositivity using a H pylori ELISA. All 4/4 of the positive volunteers consistent y aggregated in response to H pylori while only 2/15 of the H pylori negative donors aggregated consistently (p=0.039, Fisher's Exact Test). The relative risk of H pylori positivity for aggregation was 7.5 (CI 2.0-27.3). Conclusions: H pylori-induced platelet aggregation requires binding of H pylori-specific IgG. This pro-aggregatory phenotype is not unique to H pylori and has been described with S sanguis and P gingivalis. Exposure to oral bacteria such as S sanguis can lead to infective endocarditis and in the case of P gingivalis, to enhancement of atherosclerosis in animal models. Repeated exposure to proaggregatory bacteria such as certain strains of H pylori may not cause coronary artery disease but could accelerate the progression of the disease. Local platelet effects may also contribute to the pathogenesis of H... [ABSTRACT FROM AUTHOR]