scholarly journals Selective killing of Helicobacter pylori with pH-responsive helix–coil conformation transitionable antimicrobial polypeptides

2017 ◽  
Vol 114 (48) ◽  
pp. 12675-12680 ◽  
Author(s):  
Menghua Xiong ◽  
Yan Bao ◽  
Xin Xu ◽  
Hua Wang ◽  
Zhiyuan Han ◽  
...  

Current clinical treatment of Helicobacter pylori infection, the main etiological factor in the development of gastritis, gastric ulcers, and gastric carcinoma, requires a combination of at least two antibiotics and one proton pump inhibitor. However, such triple therapy suffers from progressively decreased therapeutic efficacy due to the drug resistance and undesired killing of the commensal bacteria due to poor selectivity. Here, we report the development of antimicrobial polypeptide-based monotherapy, which can specifically kill H. pylori under acidic pH in the stomach while inducing minimal toxicity to commensal bacteria under physiological pH. Specifically, we designed a class of pH-sensitive, helix–coil conformation transitionable antimicrobial polypeptides (HCT-AMPs) (PGA)m-r-(PHLG-MHH)n, bearing randomly distributed negatively charged glutamic acid and positively charged poly(γ-6-N-(methyldihexylammonium)hexyl-l-glutamate) (PHLG-MHH) residues. The HCT-AMPs showed unappreciable toxicity at physiological pH when they adopted random coiled conformation. Under acidic condition in the stomach, they transformed to the helical structure and exhibited potent antibacterial activity against H. pylori, including clinically isolated drug-resistant strains. After oral gavage, the HCT-AMPs afforded comparable H. pylori killing efficacy to the triple-therapy approach while inducing minimal toxicity against normal tissues and commensal bacteria, in comparison with the remarkable killing of commensal bacteria by 65% and 86% in the ileal contents and feces, respectively, following triple therapy. This strategy renders an effective approach to specifically target and kill H. pylori in the stomach while not harming the commensal bacteria/normal tissues.

2020 ◽  
Author(s):  
Chia-Jung Kuo ◽  
Cheng-Yu Lin ◽  
Puo-Hsien Le ◽  
Pi-Yueh Chang ◽  
Chih-Ho Lai ◽  
...  

Abstract Background: There is no current standard rescue treatment for dual drug-resistant strains of Helicobacter pylori. This aim of this study was to investigate the efficacy of rifabutin-based triple therapy for patients infected with dual drug-resistant strains to clarithromycin and levofloxacin.Methods: After two or three H. pylori treatment failures, patients underwent upper endoscopy with tissue biopsies. Phenotypic and genotypic resistance was determined using agar dilution test and polymerase chain reaction with direct sequencing, respectively. Patients infected with dual drug-resistant (clarithromycin and levofloxacin) strains and received rifabutin based triple therapy (rifabutin 150 mg bid, amoxicillin 1 g bid and esomeprazole 40 mg bid for 10 days) were enrolled. Eradication status was determined by 13C-urea breath test four weeks after treatment completion. Results: A total of 39 patients infected with dual drug-resistant strains were enrolled in this study, with a mean age of 55.9 years. The eradication rate was 79.5% (31/39). Adverse event was reported in 23.1% (9/39) of patients but mild and tolerable. In univariate analysis, no factor was identified as an independent predictor of eradication failure. Conclusions: Our current study demonstrated that rifabutin-based triple therapy was well tolerated and yielded an acceptable eradication rate for patients infected with dual drug-resistant strains of H. pylori.


2020 ◽  
Vol 18 ◽  
Author(s):  
Mohammed Hussien Ahmed ◽  
Sherief Abd-Elsalam ◽  
Aya Mohammed Mahrous

Introduction: Helicobacter pylori eradication remains a problematic issue. We are in an urgent need for finding a treatment regimen that achieves eradication at a low cost and less side effect. Recent published results showing a high rate of resistance and with clarithromycin-based treatment regimens. The aim of the study was to compare moxifloxacin therapy and classic clarithromycin triple therapy in H. pylori eradication. Methods: This was a pilot study that enrolled 60 patients with helicobacter pylori associated gastritis. Diagnosis was done by assessment of H. pylori Ag in the stool. The patients were randomly assigned to receive either moxifloxacin based therapy (Group A), or clarithromycin based therapy (Group B) for two weeks. We stopped the treatment for another two weeks then reevaluation for cure was done. Results: 90 % of patients had negative H. pylori Ag in the stool after 2 weeks of stoppage of the treatment in group A versus 66.7 % in Group B. None of the patients in both groups had major side effects. Conclusion: Moxifloxacin-based therapy showed higher eradication power and less resistance when compared to clarithromycin triple therapy.


1970 ◽  
Vol 4 (3) ◽  
pp. 48-57
Author(s):  
Isabela Maria A. Ribeiro Simões ◽  
Ana Carolina Mauad Coli ◽  
Roseane de Souza Candido Irulegui

Objetivo: Determinar a prevalência de lesões benignas e neoplasia gástrica através do estudo de biópsias realizadas em um Hospital Escola do Sul de Minas Gerais, no período entre 2007 e 2011. Materiais e Métodos: A pesquisa documental foi quantitativa e retrospectiva, baseada na análise dos registros de biópsias e prontuários. Realizou-se o levantamento de dados referentes à idade, gênero, cor, profissão, diagnóstico histopatológico e presença de Helicobacter pylori nas amostras. Resultados: O número total de biópsias gástricas analisadas foi de 1225, cujo perfil populacional encontrado foi: idade média de 56,75 anos, sexo masculino (52%), cor branca (81,9 %), aposentado (30%). Os diagnósticos mais frequentes foram: gastrites (71,9%), pólipos (14,2%), adenocarcinomas (5,9%), úlceras gástricas (6%), linfomas (0,4%), sem alterações (0,4%) e outros (1,2%). Em outros, encontram-se achados de malignidade, metaplasia e xantelasma gástrico. Em relação à presença de Helicobacter pylori nas amostras, o resultado encontrado foi de24% positivas, 46% negativas e 30% não pesquisadas. Conclusão: Os resultados confirmam a alta frequência das doenças gástricas e sua incidência nas diversas faixas etárias, além do envolvimento do H. pylori em tais afecções. É de grande importância a caracterização dos dados epidemiológicos, o que permite prováveis direcionamentos para programas de prevenção e informação para a população. Palavras-chave: biópsia gástrica, gastropatia, perfil epidemiológico.  ABSTRACTObjective: To determine the prevalence of benign lesions and gastric cancer through study of biopsies performed at a school hospital in southern Minas Gerais, in the period between 2007 and 2011.Materials and Methods: The research was quantitative and retrospective, based on analysis of biopsies records and medical records. We conducted the survey data regarding age, sex, color, profession, histopathological diagnosis and the presence of Helicobacter pylori in the samples. Results: The total number of gastric biopsies analyzed was 1225. Population listing was found: mean age of 56.75 years, male (52%), white (81.9%), retired (30%). The most frequent diagnoses were gastritis (71.9%), polyps (14.2%), adenocarcinomas (5.9%), gastric ulcers (6%), lymphoma (0.4%), unchanged (0, 4%) and others (1.2%). In others, there are: findings of malignancy, metaplasia, gastric xanthelasma. Regarding the presence of Helicobacter pylori in the sample, the result was: 24% positive, 46% negative, 30% non searched. Conclusion: The results confirm the high frequency of gastric diseases and their incidence in the various age groups additionally to the involvement of H. pylori in such conditions. It is of great importance to characterize the epidemiological data, allowing probable directions for prevention and information programs for population. Keywords: gastric biopsy, gastropathy, epidemiological profile


2005 ◽  
Vol 42 (2) ◽  
pp. 111-115 ◽  
Author(s):  
Laura Cidrão Frota ◽  
Maria do Perpétuo Socorro Saldanha da Cunha ◽  
Carlos René Lima Luz ◽  
Antonio Haroldo de Araujo-Filho ◽  
Luciano A. S. Frota ◽  
...  

BACKGROUND: Optimal anti-Helicobacter pylori treatment has not yet been established. AIM: To evaluate H. pylori eradication using tetracycline and furazolidone versus amoxicillin and azithromycin in lansoprazole based triple therapy in northeastern of Brazil. PATIENTS AND METHODS: One hundred and four patients with H. pylori infection, as determined by rapid urease testing and histology, were randomly assigned to receive either: lansoprazole (30 mg q.d.), tetracycline (500 mg q.i.d.), and furazolidone (200 mg t.i.d.) for 7 days (LTF; n = 52); or lansoprazole (30 mg b.i.d.) and amoxicillin (1 g b.i.d.) for 1 week, plus azithromycin (500 mg q.d.) for the first 3 days (LAAz; n = 52). H. pylori eradication was assessed 3 months following completion of therapy by means of rapid urease testing, histology and a 14C-urea breath test. RESULTS: H. pylori eradication was achieved in 46 of 52 (88.4%, 95% CI: 77.5%-95.1%) patients in LTF group and in 14 of 52 (26.9%, 95% CI: 16.2%-40,1%) patients in LAAz group. On a per-protocol analysis, eradication rates were 91.8% (95% CI: 81.4%-97.3%) and 28.5% (95% CI: 17.2%-42.3%), respectively in LTF and LAAz groups. CONCLUSION: The LAAz regimen yielded unacceptably low eradication rates. On the other hand, the LTF scheme represents a suitable alternative for H. pylori eradication.


mBio ◽  
2017 ◽  
Vol 8 (4) ◽  
Author(s):  
Alevtina Gall ◽  
Ryan G. Gaudet ◽  
Scott D. Gray-Owen ◽  
Nina R. Salama

ABSTRACT Helicobacter pylori is a bacterial pathogen that colonizes the human stomach, causing inflammation which, in some cases, leads to gastric ulcers and cancer. The clinical outcome of infection depends on a complex interplay of bacterial, host genetic, and environmental factors. Although H. pylori is recognized by both the innate and adaptive immune systems, this rarely results in bacterial clearance. Gastric epithelial cells are the first line of defense against H. pylori and alert the immune system to bacterial presence. Cytosolic delivery of proinflammatory bacterial factors through the cag type 4 secretion system ( cag -T4SS) has long been appreciated as the major mechanism by which gastric epithelial cells detect H. pylori . Classically attributed to the peptidoglycan sensor NOD1, recent work has highlighted the role of NOD1-independent pathways in detecting H. pylori ; however, the bacterial and host factors involved have remained unknown. Here, we show that bacterially derived heptose-1,7-bisphosphate (HBP), a metabolic precursor in lipopolysaccharide (LPS) biosynthesis, is delivered to the host cytosol through the cag -T4SS, where it activates the host tumor necrosis factor receptor-associated factor (TRAF)-interacting protein with forkhead-associated domain (TIFA)-dependent cytosolic surveillance pathway. This response, which is independent of NOD1, drives robust NF-κB-dependent inflammation within hours of infection and precedes NOD1 activation. We also found that the CagA toxin contributes to the NF-κB-driven response subsequent to TIFA and NOD1 activation. Taken together, our results indicate that the sequential activation of TIFA, NOD1, and CagA delivery drives the initial inflammatory response in gastric epithelial cells, orchestrating the subsequent recruitment of immune cells and leading to chronic gastritis. IMPORTANCE H. pylori is a globally prevalent cause of gastric and duodenal ulcers and cancer. H. pylori antibiotic resistance is rapidly increasing, and a vaccine remains elusive. The earliest immune response to H. pylori is initiated by gastric epithelial cells and sets the stage for the subsequent immunopathogenesis. This study revealed that host TIFA and H. pylori -derived HBP are critical effectors of innate immune signaling that account for much of the inflammatory response to H. pylori in gastric epithelial cells. HBP is delivered to the host cell via the cag -T4SS at a time point that precedes activation of the previously described NOD1 and CagA inflammatory pathways. Manipulation of the TIFA-driven immune response in the host and/or targeting of ADP-heptose biosynthesis enzymes in H. pylori may therefore provide novel strategies that may be therapeutically harnessed to achieve bacterial clearance.


2015 ◽  
Vol 3 (1) ◽  
Author(s):  
Vudumula Vijaya Lakshmi

Helicobacter pylori (H. pylori) has a role in the multifactorial etiology of peptic ulcer disease. A link between H. pylori infection and duodenal ulcer disease is now established. Other contributing factors and their interaction with the organism may initiate the ulcerative process. The fact that eradication of H. pylori infection leads to a long-term cure in the majority of duodenal ulcer patients and the fact that the prevalence of infection is higher in ulcer patients than in the normal population are cogent arguments in favor of it being the primary cause of the ulceration. This study was under taken at the Department of surgery, Narayana medical college, Nellore from January 2007 to July 2008. A total of 150 patients with duodenal ulcers, gastric ulcers, antral gastritis, gastric carcinoma and dyspepsia of any kind were studied. Maximum number of cases were in the age group of 31 years to 50 years among both sexes and number of cases gradually decreased after 50 years of age in males and females. Males were more in number and male to female ratio is (2.75:1) approximately 3:1.


2019 ◽  
Vol 91 (8) ◽  
pp. 28-33 ◽  
Author(s):  
A M Veliev ◽  
I V Maev ◽  
D N Andreev ◽  
D T Dicheva ◽  
A V Zaborovskii ◽  
...  

Aim. Evaluation of the efficacy and safety of quadrupletherapy without bismuth (concomitant therapy) in patients with Helicobacter pylori - associated gastric ulcer and duodenal ulcer in the framework of a comparative research in the population of patients in Russia. Materials and methods. A prospective randomized trial was conducted, which included 210 patients with H. pylori - associated gastric/duodenal ulcer without complications. During the process of randomization, the patients were divided into three equal groups (n=70) depending on the prescribed 10-day scheme of eradication therapy (ET): the first group received the classic triple scheme (Omeprazole 20 mg 2 times a day, Amoxicillin 1000 mg 2 times a day and Clarithromycin 500 mg 2 times a day); the second group received quadruple therapy with bismuth drugs (Omeprazole 20 mg 2 times a day, Tetracycline 500 mg 4 times a day, Metronidazole 500 mg 3 times a day, Bismuth subcitrate potassium 120 mg 4 times a day); the third group received quadruple therapy without bismuth - concomitant therapy (Omeprazole 20 mg 2 times a day, Amoxicillin 1000 mg 2 times a day, Clarithromycin 500 mg 2 times a day and Metronidazole 500 mg 2 times a day). Diagnostics of H. pylori infection during screening and control of eradication was carried out via the fast urease biopsy sample test and urea breath test system. Control of the effectiveness of ET of the microorganism was carried out not earlier than 4 weeks after the end of the treatment. During the course of therapy, the frequency of development of side effects was assessed using a special questionnaire. Results and discussion. The effectiveness of triple therapy was 72.8% (ITT; 95% CI of 62.17-83.54) and 78,4% (PP; 95% CI 68.19-88.72); quadruple therapy with the preparation of bismuth - 80.0% (ITT; 95% CI 70.39-89.6) and 84,8% (PP; 95% CI, 75.96-93.73); quadruple therapy without bismuth - concomitant therapy - 84.2% (ITT; 95% CI 75.54-93.02) and 92.1% (PP; 95% CI 85.43-98.94). Quadruple therapy without bismuth was reliably more effective than the classical triple therapy in the PP selection (p=0.044883). Statistical analysis showed a tendency to poorer effectiveness of ET in patients who had previously used antibiotic therapy (OR 0.4317; 95% CI 0.1776-1.049), and in individuals with a rapid metabolism genotype - CYP2C19*1/*1 (OR 0.12; 95% CI 0.005848-2.4624). The frequency of development of side effects during the use of triple therapy was 18.5% (95% CI of 9.23-27.91), when using quadruple therapy with bismuth - 20.0% (95% CI 10.39-29.6), and with the use of quadruple therapy without bismuth - concomitant therapy - 24.2% (95% CI 13.98-34.58). Conclusion. This prospective randomized study demonstrated the high efficiency of quadruple therapy without bismuth (concomitant therapy) in the framework of eradication of H. pylori infection in Russia.


2017 ◽  
Vol 7 (1) ◽  
pp. 17-22 ◽  
Author(s):  
Banu N Şirvan ◽  
Merve K Usta ◽  
Nuray U Kızılkan ◽  
Nafiye Urgancı

ABSTRACT Aim We aimed to evaluate the role of the addition of Bifidobacterium lactis-containing synbiotic to the triple therapy in the case of Helicobacter pylori eradication, the dyspeptic symptoms, and reducing the side effects of antibiotics. Materials and methods A total of 104 children aged between 5 and 17 years, who were histopathologically diagnosed with H. pylori were enrolled in this study, of whom 100 were included in the analysis. Patients were randomly classified into two groups. In the first group, 50 patients were administered amoxicillin + clarithromycin + lansoprazole for 14 days and B. lactis-containing synbiotic. In the second group, 50 patients were treated with the standard triple therapy. All patients were given information after completion of therapy. Results H. pylori eradication was achieved in 88% in group I who received standard therapy with additional synbiotic and 72% in group II (p = 0.046). The number of patients in the second group who suffered from abdominal pain between the 3rd and 14th day of the treatment was higher (p < 0.05). The addition of probiotics to the triple therapy significantly reduced the frequency of diarrhea, but no significant difference was detected in the frequency of metallic taste (p = 0.04, p = 0.418 respectively). Conclusion The addition of synbiotic to the triple therapy is effective for eradicating H. pylori infection in children and is usually helpful to reduce or eliminate dyspeptic symptoms like abdominal pain, diarrhea, and vomiting. This study suggest that improved tolerance to the eradication treatment also reduces the treatment failure by adding probiotics and encourages the future study using probiotic supplementation in H. pylori treatment. How to cite this article Şirvan BN, Usta MK, Kızılkan NU, Urgancı N. Are Synbiotics added to the Standard Therapy to eradicate Helicobacter Pylori in Children Beneficial? A Randomized Controlled Study. Euroasian J Hepato-Gastroenterol 2017;7(1):17-22.


2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Hsiu-Chi Cheng ◽  
Hsiao-Bai Yang ◽  
Wei-Lun Chang ◽  
Wei-Ying Chen ◽  
Yi-Chun Yeh ◽  
...  

Background. Two major causes of gastric ulcers areHelicobacter pylori(H. pylori) infection and nonsteroidal anti-inflammatory drug (NSAID) use.Aims. This study aimed to determine if there were different expressions of matrix metalloproteinases (MMPs) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) betweenH. pylori-infected and NSAID-related ulcers.Methods. The 126 gastric ulcer patients (H. pyloriinfectedn=46; NSAID relatedn=30; combined with two factorsn=50) provided ulcer and nonulcer tissues for assessment of MMP-3, -7, and -9 and TIMP-1 expression by immunohistochemical staining.Results. Gastric ulcer tissues had significantly higher MMP-3, -7, and -9 and TIMP-1 expressions than nonulcer tissues (P<0.05).H. pylori-infected gastric ulcers had even higher MMP-7, MMP-9, and TIMP-1 expressions in epithelial cells than NSAID-related gastric ulcers (P<0.05). In patients with the two combined factors, gastric ulcers expressed similar proportions of antral ulcers and MMP-7 and MMP-9 intensities to NSAID-related gastric ulcers, but lower MMP-9 and TIMP-1 thanH. pylori-infected gastric ulcers (P<0.05).Conclusions. H. pylori-infected gastric ulcers express higher MMP-7, MMP-9, and TIMP-1 than NSAID-related ulcers. In patients with the two combined factors, ulcer location and MMP-7 and MMP-9 intensities are similar to NSAID use.


2020 ◽  
Vol 13 (11) ◽  
pp. 384
Author(s):  
Hang Yeon Jeong ◽  
Tae Ho Lee ◽  
Ju Gyeong Kim ◽  
Sueun Lee ◽  
Changjong Moon ◽  
...  

We previously reported that 3-pentylcatechol (PC), a synthetic non-allergenic urushiol derivative, inhibited the growth of Helicobacter pylori in an in vitro assay using nutrient agar and broth. In this study, we aimed to investigate the in vivo antimicrobial activity of PC against H. pylori growing in the stomach mucous membrane. Four-week-old male C57BL/6 mice (n = 4) were orally inoculated with H. pylori Sydney Strain-1 (SS-1) for 8 weeks. Thereafter, the mice received PC (1, 5, and 15 mg/kg) and triple therapy (omeprazole, 0.7 mg/kg; metronidazole, 16.7 mg/kg; clarithromycin, 16.7 mg/kg, reference groups) once daily for 10 days. Infiltration of inflammatory cells in gastric tissue was greater in the H. pylori-infected group compared with the control group and lower in both the triple therapy- and PC-treated groups. In addition, upregulation of cytokine mRNA was reversed after infection, upon administration of triple therapy and PC. Interestingly, PC was more effective than triple therapy at all doses, even at 1/15th the dose of triple therapy. In addition, PC demonstrated synergism with triple therapy, even at low concentrations. The results suggest that PC may be more effective against H. pylori than established antibiotics.


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