Role of vacuolating cytotoxin A in Helicobacter pylori infection and its impact on gastric pathogenesis

causes, via the influence of several virulence factors, persistent infection of the stomach, which leads to severe complications. Vacuolating cytotoxin A (VacA) is observed in almost all clinical strains of H. pylori; however, only some strains produce the toxigenic and pathogenic VacA, which is influenced by the gene sequence variations. VacA exerts its action by causing cell vacuolation and apoptosis. We performed a PubMed search to review the latest literatures published in English language. Areas covered Articles regarding H. pylori VacA and its genotypes, architecture, internalization, and role in gastric infection and pathogenicity are reviewed. We included the search for recently published literature until January 2020. Expert opinion H. pylori VacA plays a crucial role in severe gastric pathogenicity. In addition, VacA mediated in vivo bacterial survival leads to persistent infection and an enhanced bacterial evasion from the action of antibiotics and the innate host defense system, which leads to drug evasion. VacA as a co-stimulator for the CagA phosphorylation may exert a synergistic effect playing an important role in the CagA-mediated pathogenicity

Management of Helicobacter pylori

Meta-analysis has shown that successful Helicobacter pylori eradication therapy improved atrophic gastritis and intestinal metaplasia. Moreover, successful eradication therapy against atrophic gastritis has led to the suppression of the incidence of metachronous gastric cancer. Thus, the Japanese Society for Helicobacter Research concluded that all ‘H. pylori-infected persons’ should be considered for eradication therapy, irrespective of any background diseases. Successful eradication can prevent transmission of this bacterium, and recent publications show that curing H. pylori infection seems to reduce the risk of gastric cancer

Studies on the Mechanism of Bile Pigment Formation in Vivo. III. On the Transition of Biliverdin, and Bilirubin in the Bile of Rabbits.

1. In the bile of rabbits, the metabolisms of biliverdin and bilirubin are in a solucible state, and which have a ratio of 2: 1 in normal animals. 2. In the production of biliverdin, the liver, especially the parenchyma of the liver has a very important role, while that of the reticulo-endothelial system is rather minor. However, in the case of glucose administration, the reduction of bilirubin from biliverdin is performed in the reticulo-endothelial system, thus conferring an important part of this system. 3. The production of bilirubin is performed primarily extrahepatically, and the participation of the extrahepatical reticuloendothelial system is of a conservative nature, thus denying us any willingness to agree to the theory of bilirubin production in the reticulo-endothelial system. 4. On administration of hemolysed blood, bile pigments in bile demonstrate a remarkable increase, while as compared when injected into the auricle veins in cases of administration through the portal vein a decline in the functions of the liver reticulo-endothelial system is seen, causing a decrease in biliverdin amount. In the former modus of administration, an occasional stimulation of the liver reticulo- endothelial system is seen, causing reduction of biliverdin to bilirubin. 5. Concluding from these facts, biliverdin in rabbit bile occupies the role of an intermediate product in the production and metabolism of bilirubin.</p

Editorial: The Role of Mobile Genetic Elements in Bacterial Evolution and Their Adaptability

info:eu-repo/semantics/publishedVersio

<原著>肝右葉切除における短肝静脈, 右肝静脈処理のための前方アプローチ

A simple procedure of right hepatic lobectomy for bulky liver tumors is proposed. The procedure is named "Anterior approach", which is characterized by transection of hepatic parenchyma without mobilization and rotation of the right hepatic lobe. The transection directly reaches the ventral surface of the retrohepatic inferior vena cava first at the portion of caudate process. The hepatic parenchymal transection proceeds from ventral to dorsal and from caudal to cranial. Several dorsal short hepatic veins are severed on the ventral surface of the IVC and the right hepatic vein is finally severed from inside. This method enables the minimization of operative stress and is especially useful for cases with a huge tumor in the right hepatic lobe which invades the diaphragm or thoraco-abdominal wall.巨大肝腫瘍に対する合理的な肝右葉切除法としての前方アプローチを紹介する. 肝右葉切除の標準手技として, 右葉の授動と脱転がある. これは肝の右側から, 肝部下大静脈に注ぐ短肝静脈や右肝静脈の剥離と切離を行う方法であるが, 後区域や右葉全体を占める巨大肝腫瘍の場合には, それらの手技は困難なことが多く, また腫瘍の破裂をきたす恐れもあり危険を伴う. 前方アプローチは, 右葉の脱転を行わずに直接肝実質を切離して, 肝部下大静脈腹側面に到達し, 尾状葉突起から頭側に向かつて肝実質の離断を進める方法である. 肝部下大静脈腹側面に注ぐ短肝静脈を, 順次肝離断面側から剥離処理し, 最後に右肝静脈の離断も同様に行う. 横隔膜浸潤, 胸壁, 腹壁浸潤がある場合には, 肝切離が終了してから合併切除として最後に行う. また本法は, 脱転による残存肝の阻血, 門脈血液鬱滞を回避出来る利点があり, 肝ミトコンドリアの酸化還元状態を反映する動脈血中ケトン体比(AKBR)の術中低下も軽微であることが判明しており, 手術侵襲の点からみても有用である前方アプローチの良い適応は, 1)後区域, 又は右葉全体を占拠するような巨大肝腫瘍の場合, 2)腫蕩が右横隔膜, 胸壁, 腹壁に浸潤している場合, 3)右葉の腫瘍の下大静脈への浸潤が疑われ, 下大静脈合併切除の要否を判定する場合, 4)肝障害のために右葉切除を行うには機能的予備力の点で不安がある場合, などである

Role of Vonoprazan in Helicobacter pylori Eradication Therapy in Japan

Complete eradication of Helicobacter pylori is important for preventing the development of gastric cancer. The outcome of H. pylori eradication therapy is mainly dependent on bacterial susceptibility to antimicrobial agents and potent neutralization of intragastric pH across 24 h, especially when using acid-sensitive antimicrobial agents such as clarithromycin (CLR), amoxicillin and sitafloxacin. However, conventional regimens comprising twice-daily doses (bid) of proton pump inhibitors (PPIs) are generally insufficient for maintaining the required gastric acid secretion for 24 h for successful eradication in all H. pylori-positive patients. Further, the increasing prevalence of CLR-resistant strains with each year has led to a decrease in eradication rates of first-line PPI- and CLR-containing therapies in developed countries, including Japan. In 2015, the potassium-competitive acid blocker vonoprazan (VPZ) became clinically available in Japan. VPZ competitively inhibits H+/K+-ATPase activity more potently than PPIs (e.g., omeprazole, lansoprazole, rabeprazole, pantoprazole, and esomeprazole). Therefore, a VPZ-containing H. pylori eradication regimen is expected to increase the eradication rate compared with conventional regimens containing a standard dose of PPI. In fact, a recent meta-analysis that investigated the efficacy of first-line eradication therapy showed that a VPZ-containing regimen achieved a higher eradication rate than a PPI-containing regimen. While the Maastricht V/Florence Consensus Report recommends selecting a bismuth or non-bismuth quadruple therapy and concomitant therapy for patients living in areas with high prevalence of CLR resistance, a VPZ-containing regimen demonstrates effectiveness for patients infected with CLR-resistant strains and patients living in areas where the prevalence of CLR-resistant strains is &gt;15%. As a next step, studies are needed to determine the factors affecting the clinical outcome of VPZ-containing therapy and optimal VPZ-containing alternative regimens for tailored treatments. In this review, we summarize the advantages and disadvantages of VPZ in H. pylori eradication therapy

Current understanding and management of Helicobacter pylori infection: an updated appraisal [version 1; referees: 3 approved]

In addition to its role in gastric conditions, Helicobacter pylori has been found to contribute to the development of several non-gastric issues in recent years. Eradication therapy is the only effective management strategy to minimize the H. pylori-related gastric cancer and extra-gastric complications. For an effective “test and treat” strategy, diagnosis and therapy are both important. Because the infection is usually asymptomatic, patient selection is a critical issue for timely diagnosis and many clinical and demographic factors should be considered. Clarithromycin and metronidazole resistance rates also need to be considered while eradication therapy is offered. In this report, we discuss the issues which must be taken into account for the correct and timely diagnosis and for the antibiotic therapy-based management of H. pylori infection

Systematic review and meta-analysis: the relationship between the Helicobacter pylori dupA gene and clinical outcomes

<p>Abstract</p> <p>Background</p> <p>In 2005, the first disease-specific <it>Helicobacter pylori </it>virulence factor that induced duodenal ulcer and had a suppressive action on gastric cancer has been identified, and was named duodenal ulcer promoting gene (<it>dupA</it>). However, the importance of the <it>dupA </it>gene on clinical outcomes is conflicting in subsequent studies. The aim of this study was to estimate the magnitude of the risk for clinical outcomes associated with <it>dupA </it>gene.</p> <p>Methods</p> <p>A meta-analysis of case-control studies which provided raw data on the infection rates with the <it>dupA</it>-positive <it>H. pylori </it>detected by polymerase chain reaction was performed.</p> <p>Results</p> <p>Seventeen studies with a total of 2,466 patients were identified in the search. Infection with the <it>dupA</it>-positive <it>H. pylori </it>increased the risk for duodenal ulcer by 1.41-fold (95% confidence interval [CI], 1.12-1.76) overall. Subgroup analysis showed that the summary odds ratio (OR) was 1.57 (95% CI, 1.19-2.06) in Asian countries and 1.09 (95% CI, 0.73-1.62) in Western countries. There was no association between the presence of the <it>dupA </it>gene and gastric cancer and gastric ulcer. Publication bias did not exist.</p> <p>Conclusion</p> <p>Our meta-analysis confirmed the importance of the presence of the <it>dupA </it>gene for duodenal ulcer, especially in Asian countries.</p

Corrigendum: Food Allergy and Helicobacter pylori Infection: A Systematic Review

Introduction: Based on the hygiene hypothesis, a low prevalence of Helicobacter pylori (H. pylori) infection may explain the recent high prevalence of allergic diseases including food allergy. However, there are very few studies that investigate the relationship between H. pylori and food allergy. Summary: We searched for PubMed, Ovid Medline and the Cochrane library for relevant articles published in English from inception to November 2015. The inverse relationship between H. pylori and food allergy remains unproven because of contradictory and limited evidence at the moment. Likewise, only limited studies have examined the relationship between CagA; one of H. pylori virulence factor and food allergy. On the other hand, in vitro evidence seems to point out a role of H. pylori in the causation of food allergy. The inconsistent results from epidemiological data may be due to small sample size, heterogeneous populations and unstandardised methods or food allergens

Pattern and trends of Helicobacter pylori genotypes in gastric cancer: A Kenyan 8-year study

Background: Notable geographic and temporal variations in the prevalence and genotypes of Helicobacter pylori, in relation to gastric pathologies, have been observed; however, their significance and trends in African populations is scarcely described. The aim of this study, was to investigate the association of H. pylori and its respective CagA and vacuolating cytotoxin A (VacA) genotypes with gastric adenocarcinoma, and to describe the trends of H. pylori genotypes over an 8-year period (2012–2019). Materials and methods: A total of 286 samples of gastric cancer cases and benign controls (one-to-one matching), from three main cities in Kenya, between 2012 and 2019 were included. Histologic evaluation, and CagA and VacA genotyping using PCR, was performed. Distribution of H. pylori genotypes was presented in proportions. To determine association, a univariate analysis was conducted using a Wilcoxon rank sum test for continuous variables, and a Chi-squared test or Fisher’s exact test for categorical data. Results: The VacA s1m1 genotype was associated with gastric adenocarcinoma, {odds ratio (OR) = 2.68 [confidence interval (CI) of 95%: 0.83–8.65]; p = 0.108}, whilst VacA s2m2 was associated with a reduced probability of gastric adenocarcinoma [OR = 0.23 (CI 95%: 0.07–0.78); p = 0.031]. No association between cytotoxin associated gene A (CagA) and gastric adenocarcinoma was observed. Conclusion: Over the study period, an increase in all genotypes of H. pylori was seen, and although no predominant genotype was noted, there was significant year-to-year variation, with VacA s1 and VacA s2 showing the greatest variation. VacA s1m1 and VacA s2m2 were associated with increased, and reduced risk of gastric cancer, respectively. Intestinal metaplasia and atrophic gastritis did not appear to be significant in this population