Pylori-related Disorders Research Articles

In vitro evaluation of novel mefenamic acid derivatives as potential α-glucosidase and urease inhibitors: Design, synthesis, in silico and cytotoxic studies

This study aim to synthesize new 1,3,4-oxadiazole derivatives incorporating mefenamic acid as promising α-glucosidase and urease inhibitors, potentially leading to the treatment of postprandial hyperglycemia as well as H. pylori related disorders. In this regards, we have designed a series of Mefenamic acid derivatives. The synthetic compounds were structurally elucidated through 1H NMR, 13C NMR and HR-EIMS analysis. The biological evaluation of these derivatives against α-glucosidase and urease enzyme depicted some novel derivatives with potent inhibition against the said enzymes. All the derivatives exhibited potent inhibition against α-glucosidase enzymes with IC50 ranging from 25.81 ± 1.63–113.61 ± 1.31 µM against standard drug acarbose (IC50 = 375.82 ± 1.76 µM) while with respect to urease these derivatives possessed inhibitory potential varied between IC50 = 8.04 ± 1.01–58.18 ± 1.03 µM against the standard thiourea (IC50 = 21.0 ± 1.76 µM). The cell viability results revealed that all of the derivatives were found least cytotoxic. Furthermore, molecular docking studies of the most potent derivatives identify number of key features involved in binding interactions between potential inhibitors and the enzyme's active site.

Patients with Whipple's disease have a high prevalence of Helicobacter pylori infection

IntroductionWhipple's disease is a rare systemic infection due to an impaired immunological response against T. whipplei in genetically predisposed individuals. Since we previously noted development of H. pylori related complications in some patients with Whipple's disease, our aim was to study the prevalence of H. pylori infection and H. pylori related disorders in Whipple's disease. MethodsWhipple's disease patients diagnosed from Jan-2002 to Dec-2021 and two controls per patient, matched for age, gender, ethnicity and year of H. pylori testing were enrolled. Results34 patients with Whipple's disease and 68 controls were enrolled. H. pylori infection (13/34 vs 8/68, p<0.01), H. pylori-related gastritis (p<0.01) and gastric atrophy (p = 0.01) were significantly more common in patients with Whipple's disease than controls. H. pylori infection and Whipple's disease were diagnosed synchronously in 6/13 patients, and during follow-up in the remaining 7. Interestingly, these last 7 patients were all on trimethoprim-sulfamethoxazole long-term therapy. Two patients developed H. pylori-related gastric malignancies during follow-up. No patients on doxycycline developed H. pylori infection. ConclusionsH. pylori infection and related disorders are common in patients with Whipple's disease and should always be excluded both at time of diagnosis and during follow-up. These findings should be taken into account when selecting antibiotics for Whipple's disease long-term prophylaxis.

Helicobacter pylori antigenic Lpp20 is a structural homologue of Tipα and promotes epithelial-mesenchymal transition

BackgroundHelicobacter pylori is a bacterium that affects about 50% of the world population and, despite being often asymptomatic, it is responsible of several gastric diseases, from gastritis to gastric cancer. The protein Lpp20 (HP1456) plays an important role in bacterium survival and host colonization, but the possibility that it might be involved in the etiology of H. pylori-related disorders is an unexplored issue. Lpp20 is a lipoprotein bound to the external membrane of the bacterium, but it is also secreted inside vesicles along with other two proteins of the same operon, i.e. HP1454 and HP1457. ResultsIn this study we determined the crystal structure of Lpp20 and we found that it has a fold similar to a carcinogenic factor released by H. pylori, namely Tipα. We demonstrate that Lpp20 promotes cell migration and E-cadherin down-regulation in gastric cancer cells, two events recalling the epithelial–mesenchymal transition (EMT) process. Differently from Tipα, Lpp20 also stimulates cell proliferation. ConclusionsThis identifies Lpp20 as a new pathogenic factor produced by H. pylori that promotes EMT and thereby the progression of cancer to the metastatic state.

Mo1971 The Prevalence of Eosinophilic Esophagitis in Japanese Children and Adolescents

Background and Aims: The epidemiology of gastrointestinal disorder is poorly described among Japanese children. Our aim is to clarify the trend of GI diseases' prevalence at Pediatric GI practice in Japan over the last decade. Methods: Children and adolescents with GI symptoms from 2001 to 2011 were identified by endoscopic databases at Shinshu University Hospital and Showa Inan General Hospital. Procedures were performed by pediatric GIs and routine biopsies were taken from every landmark. The prevalence of newly diagnosed GI disorders, especially Helicobacter pylori related disorders, eosinophilic gastrointestinal diseases (EGIDs) and inflammatory bowel disorder (IBD), are evaluated. Results: In total, 772 procedures (534 esophagogastroduodenoscopy[EGD] and 237 colonoscopy[CS]) were performed for 552 Japanese children and adolescents (54% female, average 11.47±4.57 year). Of 552 patients, 93 (18%) had H. pylori infection, and 27 (29%) of H. pylori positive subjects had peptic ulcer (22 duodenal ulcer and 5 gastric ulcer). Twenty-two patients (4%) were diagnosed as EGIDs (11 eosinophilic gastroenteritis, 11 eosinophilic colitis and no patient of eosinophilic esophagitis despite routine biopsies from esophagus). Twelve patients were diagnosed as IBD (10 Ulcerative colitis and 2 Crohn's disease). The trend of each disorder was shown in Figure 1. Conclusion: EGIDs have increased dramatically in a few years. On the other hand, H. pyori infection decreased almost one-fifth over 10 years in Japanese children.

Management of Helicobacter pylori-related disorders

The discovery of Helicobacter pylori has opened new opportunities in the management of gastrointestinal disorders, with the cure of chronic ulcer disease now being possible for the first time. The 1994 United States National Institutes of Health Consensus Conference recommended that patients with duodenal or gastric ulcers unrelated to the use of non-steroidal anti-inflammatory drugs (NSAID) should be given eradication therapy. These guidelines were refined at a conference held recently in Maastricht. The updated guidelines strongly recommend treatment in patients with duodenal or gastric ulcer disease, low-grade mucosa-associated lymphoid tissue (MALT) gastric lymphoma, gastritis with severe macro-or microscopic changes and after resection of early gastric cancer. Despite a lack of hard scientific evidence, the guidelines also suggest that eradication treatment is advisable in patients with unequivocally diagnosed functional dyspepsia, a family history of gastric cancer, long-term treatment with proton-pump inhibitors for gastro-oesophageal reflux disease (GORD), planned or existing NSAID treatment, after gastric surgery for ulcer or cancer, or if the patient wants to be treated. Many different therapeutic regimens have been used previously, but at present the best treatment is proton-pump inhibitor-based triple therapy, comprising a proton-pump inhibitor plus two drugs out of clarithromycin, a nitroimidazole and amoxycillin. One-week low-dose triple therapy cures 85-95% of infected patients.

Potent Bactericidal Constituents from Mallotus philippinensis against Clarithromycin and Metronidazole Resistant Strains of Japanese and Pakistani Helicobacter pylori

In the quest for potent anti-Helicobacter pylori agents, we found 70% EtOH extract of Mallotus philippinensis (LAM.) MUELL. (MPM) with strong bactericidal activity at the concentration of 15.6-31.2 mg/l against eight H. pylori strains. Further fractionation and purification of 70% EtOH extract of MPM led to the isolation of 5 compounds, namely 5,7-dihydroxy-8-methyl-6-prenylflavanone (1), 3'-prenylrubranine (2), red compound (3), isorottlerin (4), and rottlerin (5) which were elucidated on the basis of nuclear magnetic resonance and mass spectroscopy. Among the isolated compounds, rottlerin exhibited most potent bactericidal activity with minimum bactericidal concentration (MBC) value of 3.12-6.25 mg/l against several clinical H. pylori isolates including Japanese and Pakistani strains, nine clarithromycin resistant (CR), and seven metronidazole resistant (MR) strains. Minimum inhibitory concentration (MIC) values of CR (8->256 mg/l) and MR (>256 mg/l) strains were analyzed by E test. Moreover, the clarithromycin resistant strains were evaluated for A2143G and A2144G point mutations of 23s rRNA gene to correlate the MBC values with mutation type. Our results revealed the potent in vitro anti-H. pylori activity of MPM and rottlerin, specially against CR and MR strains, which could be gainfully utilized for the development of novel antimicrobials to prevent H. pylori related disorders.

Trends in prescribing proton pump inhibitors in Taiwan: 1997 - 2000.

The prescribing of proton pump inhibitors (PPIs) had increased greatly in recent years worldwide. Aim of our study was to analyze the utilization patterns of PPIs within the National Health Insurance program in Taiwan from 1997 - 2000. The systemic sampling data-sets from the National Health Insurance Research Database served as data sources. Units of measurement for PPIs were numbers of prescription items and defined daily doses (DDDs). To estimate the proportion of the population treated daily with PPIs, numbers of DDDs per 1,000 inhabitants per day were calculated. In order to realize the role of PPIs in treating Helicobacter pylori-related disorders, we also analyzed various combined prescriptions of PPIs with amoxicillin, clarithromycin, metronidazole, tetracycline and bismuth. In the study period, PPI prescriptions increased nearly 2-fold at the outpatient sector and more than 3-fold at the inpatient sector. Men received more PPI prescriptions, as a whole, than women. Most PPIs were prescribed at the outpatient sector: 93.9% in 1997, 92.3% in 1998, 90.4% in 1999 and 87.3% in 2000. The numbers of DDDs per 1,000 inhabitants per day for all kinds of PPIs were 0.59, 0.78, 1.07, and 1.13 from 1997 - 2000, respectively. While the percentage of monotherapy increased from 63.6% in 1997 to 75.5% in 2000, the combination therapies did not experience a rapid and sustained growth. Among the combination therapies, PPI + amoxicillin + metronidazole and PPI + amoxicillin were popular in 1997 and 1998, but triple therapy with PPI + amoxicillin + clarithromycin predominated in 1999 and 2000. Despite increasing use, prescribing volumes of PPIs in Taiwan were far fewer than those in other developed countries. Treatment of Helicobacter pylori-related disorders in Taiwan followed universal standard.

Effect of bismuth and nitecapone on acetaldehyde production by Helicobacter pylori.

We have recently shown that colloidal bismuth subcitrate inhibits cytosolic alcohol dehydrogenase of Helicobacter pylori as well as acetaldehyde production from excess ethanol. We now extend our studies to bismuth subsalicylate and nitecapone, a novel antiulcer agent. Cytosol of H. pylori was incubated with 0.1% or 1% ethanol in the presence of different drug concentrations for 2 h, whereafter acetaldehyde formed was analyzed by head space gas chromatography. In addition, we incubated a culture solution containing intact bacteria with the drugs at 1% ethanol. Bismuth subsalicylate and nitecapone inhibit acetaldehyde formation from 0.1% ethanol by H. pylori cytosol at drug concentrations theoretically achievable in the stomach after intake of therapeutic doses of these drugs. Furthermore, colloidal bismuth subcitrate, bismuth subsalicylate, and nitecapone also inhibit acetaldehyde production by intact H. pylori, although rather high drug concentrations are required for this to occur. Inhibition of H. pylori acetaldehyde formation may be one of the mechanisms by which bismuth and nitecapone exert their effect in the treatment of H. pylori-related disorders.