Eradication of <Emphasis Type="Italic">Helicobacter pylori</Emphasis> Infection

Helicobacter pylori infects about 50 % of the world’s population, causing at a minimum chronic gastritis. A subset of infected patients will ultimately develop gastric or duodenal ulcer disease, gastric adenocarcinoma, or MALT (mucosa-associated lymphoid tissue) lymphoma. Eradication of H. pylori requires complex regimens that include acid suppression and multiple antibiotics. The efficacy of treatment using what were once considered standard regimens have declined in recent years, mainly due to widespread development of antibiotic resistance. Addition of bismuth to standard triple therapy regimens, use of alternate antibiotics, or development of alternative regimens using known therapies in novel combinations have improved treatment efficacy in specific populations, but overall success of eradication remains less than ideal. Novel regimens under investigation either in vivo or in vitro, involving increased acid suppression ideally with fewer antibiotics or development of non-antibiotic treatment targets, show promise for future therapy.     

Gastric Infection by <Emphasis Type="Italic">Helicobacter pylori</Emphasis>

Helicobacter pylori infects half of the world’s population and plays a causal role in ulcer disease and gastric cancer. This pathogenic neutralophile uniquely colonizes the acidic gastric milieu through the process of acid acclimation. Acid acclimation is the ability of the organism to maintain periplasmic pH near neutrality in an acidic environment to prevent a fall in cytoplasmic pH in order to maintain viability and growth in acid. Recently, due to an increase in antibiotic resistance, the rate of H. pylori eradication has fallen below 80% generating renewed interest in novel eradication regimens and targets. In this article, we review the gastric biology of H. pylori and acid acclimation, various detection procedures, antibiotic resistance and the role that gastric acidity plays in the susceptibility of the organism to antibiotics currently in use and propose several novel drug targets that would promote eradication in the absence of antibiotics.     

Association of <Emphasis Type="Italic">Lewis</Emphasis> and <Emphasis Type="Italic">Secretor</Emphasis> gene polymorphisms and <Emphasis Type="Italic">Helicobacter pylori</Emphasis> seropositivity among Japanese-Brazilians

Background Secretor (Se) and Lewis (Le) genes are involved in the synthesis of Lewis b (Le^b) and type I antigens throughout the body, especially in the epithelial cells of gastric mucosa. Helicobacter pylori can attach to the gastric epithelial cells with the blood group antigen-binding adhesin, which binds to Le^b or H type I carbohydrate structures. In a previous study, a marked association between H. pylori seropositivity and polymorphism of the Se and Le genes was observed among Japanese outpatients of a gastroenterology clinic. The present work aims to investigate the associations between Se and Le gene polymorphisms and H. pylori infection among Japanese-Brazilians.Methods The subjects consisted of 942 healthy volunteer Japanese-Brazilians, who were tested for the presence of anti-H. pylori IgG antibodies and genotyped for Se and Le polymorphisms.Results The sex-age-adjusted odds ratios (aORs) for H. pylori seropositivity were 0.99 for the Sese genotype relative to the SeSe genotype (95% confidence interval [CI], 0.73–1.33), and 1.03 for sese relative to SeSe (95% CI, 0.71–1.48). On the other hand, the aOR for the subjects with the le allele (Lele or lele) relative to the LeLe genotype was 1.48 (95% CI, 1.07–1.79). When the Se and Le genotypes were analyzed in combination according to risk group, no statistically significant association was observed.Conclusions These results are inconsistent with previous work and may have been modulated by an external factor or some other unidentified factor. Japanese-Brazilians are genotypically the same as Japanese, but their lifestyle is adapted to that of Brazil. Further investigations are necessary to clarify this influence on susceptibility to H. pylori infection.     

<Emphasis Type="Italic">Helicobacter bilis</Emphasis> Colonization Enhances Susceptibility to Typhlocolitis Following an Inflammatory Trigger

Background  

Aberrant mucosal immune responses to antigens of the resident microbiota are a significant cause of inflammatory bowel diseases (IBD), as are genetic and environmental factors. Previous work from our laboratory demonstrated that Helicobacter bilis colonization of immunocompetent, defined microbiota mice induced antigen-specific immune responses to the resident microbiota, yet these mice failed to develop colitis, suggesting that the immunological provocation induced by H. bilis alone was insufficient to induce disease.     

Effect of <Emphasis Type="Italic">Helicobacter pylori</Emphasis> Infection on Symptoms of Gastroenteritis Due to Enteropathogenic <Emphasis Type="Italic">Escherichia coli</Emphasis> in Adults

Background  

Helicobacter pylori can cause hypochlorhydria in some hosts and predispose to diarrheal infections.     

<Emphasis Type="Italic">Helicobacter pylori</Emphasis> Infection and Idiopathic Thrombocytopenic Purpura

A treatment strategy for idiopathic thrombocytopenic purpura (ITP) is considered with the aim of cure or management of the bleeding tendency. In 1998, Gasbarrini et al reported a high prevalence of Helicobacter pylori infection in patients with ITP and showed that platelet recovery occurred after eradication therapy in most cases. Since then, many studies were performed to evaluate eradication therapy. This article discusses the incidence of H pylori infection in ITP, characteristic clinical features in H pylori-positive ITP, the effectiveness of eradication on platelet count increase, and the mechanisms of development of ITP by H pylori infection. Overall, there was a positive association between H pylori infection and ITP, and eradication of bacterium was accompanied by a significant increase in platelet counts in more than 50% of H pylori-positive ITP cases. These findings suggest that H pylori infection is involved in the mechanisms of thrombocytopenia in most cases of ITP in middle-aged and older patients. This approach could be beneficial to some ITP patients, but there were some uncertainties raised. To confirm the effectiveness of eradication therapy in H pylori-positive ITP, prospective studies conducted in several countries with a new treatment protocol are required, with a large number of ITP cases and longer follow-up.     

<Emphasis Type="Italic">Helicobacter pylori</Emphasis> Infection in Anterior Uveitis*

Abstract Background: Despite intensive research, the etiology of acute anterior uveitis (AAU) remains poorly defined. Infection with gram-negative bacteria such as Yersinia, Salmonella, Shigella, and Chlamydia have already been suggested as a possible trigger event for AAU. Helicobacter pylori is also a gram-negative bacterium, shares the lipopolysaccharides, but did not attract the attention of many ophthalmologists until recently. Having in mind the relatively high incidence of H. pylori infection in the population, we propose that H. pylori may also be a trigger factor for AAU. Patients and Methods: The presence of anti-H. pylori antibodies in matching serum and aqueous humor samples of 15 idiopathic AAU patients was determined using a commercial Western blot assay. Control serum and aqueous humor were obtained from five patients undergoing cataract surgery. Results: Six out of 15 AAU patients (40%) were serum-positive for H. pylori, and half of these (n = 3) also had anti-H. pylori antibodies in the aqueous humor. All five aqueous humor and sera controls tested negative for H. pylori infection. Conclusion: These are the first results demonstrating anti-H. pylori antibodies in the aqueous humor of AAU patients. Further studies are needed to demonstrate whether this antibody is indeed locally produced. Our data may provide first evidence for a causative link between H. pylori infection and AAU.*Presented at the 7th Congress of the International Ocular Inflammation Society, Padova, Italy, 2003.     

<Emphasis Type="Italic">cagA</Emphasis> Gene and Protein Status Among Iranian <Emphasis Type="Italic">Helicobacter pylori</Emphasis> Strains

The wide geographic genetic diversity of Helicobacter pylori (Hp) and, in particular, the varying prevalence of cagA in different countries has been documented repeatedly. This study was designed to determine the frequency of cagA in Iranian Hp strains by means of genotyping and assessment of host antibodies. Helicobacter pylori strains from 235 patients, including 174 non-ulcer dyspepsia, 25 peptic ulcer and 36 gastric cancer patients, were studied. The frequencies of the 5′, middle and 3′ terminal regions of the cagA gene were 90.6, 57.6, 89%, respectively, with no correlation to the clinical outcomes. Antibodies against the CagA protein were present in 90.7% of patients. Multiple biopsy sampling in 97 cases revealed multiple infection in 16.5% of the patients. Sequencing of the seven variants of the 3′ end of the cagA gene revealed no clustering and the distribution of the Iranian strains among those of other countries. Our results from the genotyping and serology analyses confirm that the majority of Iranian Hp strains are cagA-positive.     

<Emphasis Type="Italic">T-</Emphasis>Scores and <Emphasis Type="Italic">Z</Emphasis>-Scores

Bone mineral density (BMD) can be measured by a variety of techniques at several skeletal sites. Once measured, the manufacturers’ software uses the BMD to calculate a T-score and/or Z-score. Both T-scores and Z-scores are derived by comparison to a reference population on a standard deviation scale. The recommended reference group for the T-score is a young gender-matched population at peak bone mass, while the Z-score should be derived from an age-matched reference population. T-scores and Z-scores are widely quoted in scientific publications on osteoporosis and BMD studies, and are the values used for DXA diagnostic criteria and current clinical guidelines for the management of osteoporosis. Errors in BMD measurement, differences in reference populations, and variations in calculation methods used, can all affect the actual T-score and Z-score value. Attempts to standardize these values have made considerable progress, but inconsistencies remain within and across BMD technologies. This can be a source of confusion for clinicians interpreting BMD results. A clear understanding of T-scores and Z-scores is essential for correct interpretation of BMD studies in clinical practice.     

<Emphasis Type="Italic">Helicobacter pylori</Emphasis> Infection: New Facts in Clinical Management

Purpose

The global prevalence of Helicobacter pylori remains high in spite of its significant downwards trajectory in many regions. The clinical management of H. pylori infection merits guidance to meet ongoing challenges on whom and how to test, prevent, and cure related diseases.

Recent findings

Several international guidelines and consensus reports have updated the management strategies for cure of the H. pylori infection. The definition of H. pylori gastritis as an infectious disease independent of whether or not presenting with clinical manifestations and symptoms has broadened the use of the test and treat strategy. Patients on selected long-term medications, such as aspirin, other anti-platelet agents, NSAIDs, and PPIs should be considered for H. pylori test and treat. Important progress is made with initiatives in primary and secondary gastric cancer prevention. Uncertainties persist in the interpretation of the role of H. pylori in association with extragastric diseases. Selection of therapies needs to address individual antibiotic resistance and regional surveillance of resistance for the adoption of an effective treatment algorithm.

Conclusion

Clinical aspects of H. pylori infection have evolved over time and the therapeutic management requires continuous adaptation. A vaccine is still a non-fulfilled promise. The future will tell us more about the role of H. pylori in interactions with the gut microbiome.

     

Human genetics of <Emphasis Type="Italic">GPR54</Emphasis>

Idiopathic hypogonadotropic hypogonadism (IHH) is a condition characterized by absence of sexual maturation in the setting of low sex steroids and low/normal gonadotropins. Despite its rarity, considerable genetic heterogeneity and phenotypic variability exists in this disorder. Loss of function mutations in a G protein coupled receptor, GPR54, have been shown to cause IHH. Although mutations in GPR54 are not a common cause of this condition, patients bearing mutations are critical to explore genotype-phenotype correlations and gene function. In this review, we will examine the human genetics studies of GPR54, the phenotypic implications of mutations in this gene, and the emerging roles of the kisspeptin/GPR54 pathway.     

Effects of <Emphasis Type="Italic">Helicobacter pylori</Emphasis> Infection on the Expressions of Bax and Bcl<Emphasis Type="Italic">-2</Emphasis> in Patients with Chronic Gastritis and Gastric Cancer

The aim of the present study is to evaluate the influence of Helicobacter pylori on Bax and Bcl-2 mRNA and protein levels in patients with chronic gastritis and gastric cancer. The study included 217 patients, of which 26 were uninfected; 127 had chronic gastritis and were H. pylori-positive, and 64 had gastric cancer. Bacterial genotypes were evaluated by PCR, and the expression values were determined by quantitative real-time PCR and immunohistochemistry. Our data showed that the up-regulationary effects of H. pylori infection on the pro-apoptotic gene, Bax, were stronger than its induction of Bcl-2; this effect may increase apoptosis in patients with chronic gastritis. In patients with gastric cancer, the up-regulation of the anti-apoptotic gene, Bcl-2, counteracted the pro-apoptotic effects of Bax, leading to a deregulation of apoptosis-associated gene expression, favoring cell proliferation. Thus, the disturbance in Bax and Bcl-2 balance, induced by H. pylori, might be important in gastric cancer development.     

Infection with Specific <Emphasis Type="Italic">Helicobacter pylori</Emphasis>-<Emphasis Type="Italic">cag</Emphasis> Pathogenicity Island Strains Is Associated with <Emphasis Type="Italic">Interleukin-1B</Emphasis> Gene Polymorphisms in Venezuelan Chronic Gastritis Patients

Background  

The cag pathogenicity island (cag-PAI) is one of the major virulence factors of Helicobacter pylori, showing considerable geographic variation.     

<Emphasis Type="Italic">Aspergillus</Emphasis> and <Emphasis Type="Italic">Penicillium</Emphasis> allergens: Focus on proteases

Penicillium and Aspergillus species are prevalent airborne fungi. It is imperative to identify and characterize their major allergens. Alkaline and/or vacuolar serine proteases are major allergens of several prevalent Penicillium and Aspergillus species. They are also major immunoglobulin (Ig) E-reacting components of the most prevalent airborne yeast, Rhodotorula mucilaginosa, and the most prevalent Cladosporium species, C. cladosporioides. IgE cross-reactivity has been detected among these major pan-fungal serine protease allergens. In addition, the alkaline serine protease of P. chrysogenum (Pen ch 13) induces histamine release from basophils of asthmatic patients, degrades the tight junction protein occludin, and stimulates release of proinflammatory mediators from human bronchial epithelial cells. In addition to induction of IgE and inflammatory airway responses, the alkaline serine protease allergen of A. fumigatus (Asp f 13) has synergistic effects on Asp f 2-induced immune response in mice. Studies of these serine protease major allergens elucidate the diverse allergic disease mechanisms and facilitate the development of better therapeutic strategies.     

Diagnosis and treatment of <Emphasis Type="Italic">Helicobacter pylori</Emphasis>

Opinion statement Helicobacter pylori infection remains a ubiquitous infection, especially in populations with poor socioeconomic conditions. Severe clinical outcomes of chronic infection include peptic ulcer disease and gastric cancer. Consensus meetings have developed guidelines for diagnosis, treatment, and management of H. pylori infection and related disorders in various populations. Clear benefits are obtained for H. pylori eradication in peptic ulcer disease and gastric mucosa-associated lymphoid tissue lymphoma. Most authorities agree that first-degree relatives of gastric cancer patients should undergo testing for H. pylori infection. H. pylori eradication in dyspepsia remains controversial. Global investigations continue to identify specific host and bacterial factors that are responsible for H. pylori-related inflammatory processes and development of clinical disease. Effective eradication regimens have been identified. The proton pump inhibitor (PPI)-based triple therapies are considered first-line therapy because of high patient compliance and good eradication rates. “Quadruple therapy” with bismuth-metronidazoletetracycline plus a PPI is another first-line therapy with a similar eradication rate. This therapy is preferred in patients with penicillin allergy or prior exposure to clarithromycin. Rescue regimens are being developed because of rising antimicrobial resistance to metronidazole and clarithromycin in H. pylori strains. Emerging rescue combination therapies include furazolidone, rifabutin, and quinolones. These combination regimens are still preliminary and should be reserved for patients who have failed first-line therapies. Vaccine development remains elusive.