scholarly journals An Intelligent Wired Capsule for the Treatment of Helicobacter pylori

2021 ◽  
Vol 12 (1) ◽  
pp. 28
Author(s):  
Anna Luzzi ◽  
Giuseppe Tortora

An endoscopic capsule is a miniaturized ingestible video camera used to acquire images of the gastrointestinal tract wirelessly. Being morphologically equivalent to any ingestible pill, they can be simply swallowed. Endoscopic capsules therefore present an inviting alternative to the traditional endoscope for the examination of the gastrointestinal tract as well for therapeutic purposes. Endoscopic capsules are considered a disruptive technology, as they have revolutionized the examination of the gastrointestinal tract in a relatively short time. The implementation of an active locomotion system can improve the performance of a capsule and, in the solution proposed in this paper, allows providing the capsule the needed power for therapeutic purposes. Alternative therapeutic solutions, based on optical solutions and capsule endoscopy can be applied to patients affected by Helicobacter pylori, a bacterium of the stomach that affects about half of the world population, mainly in developing countries. The infection can be asymptomatic or associated with slight symptomatology. In some cases, it can take to major pathologies or death. The literature reports results deriving from recent applications of photodynamic treatments to H. pylori. Specific wavelengths have been found to exhibit photo-killing capabilities toward the bacterium. Some solutions have been proposed based on the use of endoscopic devices and capsules capable of administering photodynamic therapy inside the stomach. The proposed treatments, however, are invasive and insufficient to achieve long-term eradication. In this work, the administration of photodynamic therapy is proposed, aimed at the eradication of H. pylori by means of an active endoscopic capsule with LED emission. The capsule design, in addition to the therapeutic module aimed at administering an appropriate light intensity at specific wavelengths already demonstrated in the literature, integrates an active locomotion system aimed at maximizing the efficiency of the treatment.


2019 ◽  
Vol 19 (5) ◽  
pp. 376-382 ◽  
Author(s):  
Sachin Jangra ◽  
Gayathri Purushothaman ◽  
Kapil Juvale ◽  
Srimadhavi Ravi ◽  
Aishwarya Menon ◽  
...  

Background & Objective:Helicobacter pylori infection is one of the primary causes of peptic ulcer followed by gastric cancer in the world population. Due to increased occurrences of multi-drug resistance to the currently available antibiotics, there is an urgent need for a new class of drugs against H. pylori. Inosine 5′-monophosphate dehydrogenase (IMPDH), a metabolic enzyme plays a significant role in cell proliferation and cell growth. It catalyses guanine nucleotide synthesis. IMPDH enzyme has been exploited as a target for antiviral, anticancer and immunosuppressive drugs. Recently, bacterial IMPDH has been studied as a potential target for treating bacterial infections. Differences in the structural and kinetic parameters of the eukaryotic and prokaryotic IMPDH make it possible to target bacterial enzyme selectively.Methods:In the current work, we have synthesised and studied the effect of substituted 3-aryldiazenyl indoles on Helicobacter pylori IMPDH (HpIMPDH) activity. The synthesised molecules were examined for their inhibitory potential against recombinant HpIMPDH.Results:In this study, compounds 1 and 2 were found to be the most potent inhibitors amongst the database with IC50 of 0.8 ± 0.02µM and 1 ± 0.03 µM, respectively.Conclusion:When compared to the most potent known HpIMPDH inhibitor molecule C91, 1 was only four-fold less potent and can be a good lead for further development of selective and potent inhibitors of HpIMPDH.



1998 ◽  
Vol 42 (10) ◽  
pp. 2492-2494 ◽  
Author(s):  
Naoki Nagahara ◽  
Yohko Akiyama ◽  
Masafumi Nakao ◽  
Mayumi Tada ◽  
Megumi Kitano ◽  
...  

ABSTRACT In an effort to augment the anti-Helicobacter pylorieffect of amoxicillin, mucoadhesive microspheres, which have the ability to reside in the gastrointestinal tract for an extended period, were prepared. The microspheres contained the antimicrobial agent and an adhesive polymer (carboxyvinyl polymer) powder dispersed in waxy hydrogenated castor oil. The percentage of amoxicillin remaining in the stomach both 2 and 4 h after oral administration of the mucoadhesive microspheres to Mongolian gerbils under fed conditions was about three times higher than that after administration in the form of a 0.5% methylcellulose suspension. The in vivo clearance ofH. pylori following oral administration of the mucoadhesive microspheres and the 0.5% methylcellulose suspension to infected Mongolian gerbils was examined under fed conditions. The mucoadhesive microspheres and the 0.5% methylcellulose suspension both showed anti-H. pylori effects in this experimental model of infection, but the required dose of amoxicillin was effectively reduced by a factor of 10 when the mucoadhesive microspheres were used. In conclusion, the mucoadhesive microspheres more effectively cleared H. pylori from the gastrointestinal tract than the 0.5% methylcellulose suspension due to the prolonged gastrointestinal residence time resulting from mucoadhesion. A dosage form consisting of mucoadhesive microspheres containing an appropriate antimicrobial agent should be useful for the eradication of H. pylori.



2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Zhi-Ning Ye ◽  
Harry Hua-Xiang Xia ◽  
Ran Zhang ◽  
Lan Li ◽  
Li-Hao Wu ◽  
...  

Aim. The fecal microbiota transplantation by washed preparation was recently coined as washed microbiota transplantation (WMT). This pilot study is aimed at exploring the feasibility and efficacy of WMT on Helicobacter pylori eradication. Methods. Consecutive patients who had been treated with WMT for various indications and who were positive for H. pylori infection before WMT treatment but had never received eradication therapy for H. pylori infection were invited to take a follow-up 13C-urea breath test. The associations of demographic, clinical factors, and laboratory indicators for gastric function and intestinal barrier function with the therapeutic effect were determined. Results. A total of 32 eligible patients were included, and the overall H. pylori eradication rate was 40.6% (13/32). Patients with H. pylori eradication had a higher pepsinogen ratio (PGR) than those without ( 13.00 ± 6.97 vs. 8.31 ± 3.733 ; P = 0.02 ). Female patients had a higher, albeit not statistically significant, eradication rate than male patients (53.85% vs. 31.58%; P = 0.208 ). Compared with lower gastrointestinal tract delivery route, middle gastrointestinal tract delivery route seems to be a more suitable way for the treatment of H. pylori infection (58.33% vs 16.67%; P = 0.152 ). There was no significant difference in other demographic and clinical factors between patients with and without H. pylori eradication. Conclusion. H. pylori infection is eradicated in a proportion of patients who have received WMT. An increased pre-WMT PGR appears to be associated with the therapeutic effect. Further studies are required to confirm the efficacy of WMT, especially in combination with currently recommended regimens in randomized controlled trials.



Author(s):  
Sandra FRUGIS ◽  
Nicolau Gregori CZECZKO ◽  
Osvaldo MALAFAIA ◽  
Artur Adolfo PARADA ◽  
Paula Bechara POLETTI ◽  
...  

ABSTRACT Background: Helicobacter pylori has been extensively studied since 1982 it is estimated that 50% of the world population is affected. The literature lacks studies that show the change of its prevalence in the same population over time. Aim: To compare the prevalence of H. pylori in 10 years interval in a population that was submitted to upper endoscopy in the same endoscopy service. Method: Observational, retrospective and cross-sectional study comparing the prevalence of H. pylori in two samples with 10 years apart (2004 and 2014) who underwent endoscopy with biopsy and urease. Patients were studied in three consecutive months of 2004, compared to three consecutive months of 2014. The total number of patients was 2536, and 1406 in 2004 and 1130 in 2014. Results: There were positive for H. pylori in 17 % of the sample as a whole. There was a significant decrease in the prevalence from 19.3% in 2004 to 14.1% in 2014 (p<0.005). Conclusion: There was a 5.2% reduction in the prevalence of H. pylori comparing two periods of three consecutive months with 10 years apart in two equivalent population samples.



2014 ◽  
Vol 56 (3) ◽  
pp. 197-200 ◽  
Author(s):  
Simone Ulrich Picoli ◽  
Luiz Edmundo Mazzoleni ◽  
Heriberto Fernández ◽  
Laura Renata De Bona ◽  
Erli Neuhauss ◽  
...  

Introduction: Helicobacter pylori is a bacteria which infects half the world population and is an important cause of gastric cancer. The eradication therapy is not always effective because resistance to antimicrobials may occur. The aim of this study was to determine the susceptibility profile of H. pylori to amoxicillin, clarithromycin and ciprofloxacin in the population of Southern Brazil. Material and methods: Fifty four samples of H. pylori were evaluated. The antibiotics susceptibility was determined according to the guidelines of the British Society for Antimicrobial Chemotherapy and the Comité de l'Antibiogramme de la Société Française de Microbiologie. Results: Six (11.1%) H. pylori isolates were resistant to clarithromycin, one (1.9%) to amoxicillin and three (5.5%) to ciprofloxacin. These indices of resistance are considered satisfactory and show that all of these antibiotics can be used in the empirical therapy. Conclusion: The antibiotics amoxicillin and clarithromycin are still a good option for first line anti-H. pylori treatment in the population of Southern Brazil.



Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6658
Author(s):  
Ishani P. Kalatuwawege ◽  
Medha J. Gunaratna ◽  
Dinusha N. Udukala

Gastrointestinal tract infection caused by Helicobacter pylori is a common virulent disease found worldwide, and the infection rate is much higher in developing countries than in developed ones. In the pathogenesis of H. pylori in the gastrointestinal tract, the secretion of the urease enzyme plays a major role. Therefore, inhibition of urease is a better approach against H. pylori infection. In the present study, a series of syn and anti isomers of N-substituted indole-3-carbaldehyde oxime derivatives was synthesized via Schiff base reaction of appropriate carbaldehyde derivatives with hydroxylamine hydrochloride. The in vitro urease inhibitory activities of those derivatives were evaluated against that of Macrotyloma uniflorum urease using the modified Berthelot reaction. Out of the tested compounds, compound 8 (IC50 = 0.0516 ± 0.0035 mM) and compound 9 (IC50 = 0.0345 ± 0.0008 mM) were identified as the derivatives with potent urease inhibitory activity with compared to thiourea (IC50 = 0.2387 ± 0.0048 mM). Additionally, in silico studies for all oxime compounds were performed to investigate the binding interactions with the active site of the urease enzyme compared to thiourea. Furthermore, the drug-likeness of the synthesized oxime compounds was also predicted.



2020 ◽  
Vol 10 (1) ◽  
pp. 20-27
Author(s):  
Jakob Knorr ◽  
Steffen Backert ◽  
Nicole Tegtmeyer

The gastric pathogen Helicobacter pylori colonizes approximately half of the human world population. The bacterium injects the effector protein cytotoxin associated gene A (CagA) via a type-IV secretion system into host epithelial cells, where the protein becomes phosphorylated at specific EPIYA-motifs by cellular kinases. Inside the host cell, CagA can interact with over 25 different proteins in both phosphorylation-dependent and phosphorylation-independent manners, resulting in manipulation of host-cell signaling pathways. During the course of an H. pylori infection, certain host-cell proteins undergo tyrosine dephosphorylation in a CagA-dependent manner, including the actin-binding proteins cortactin and vinculin. A predominant response of intracellular CagA is the binding and activation of tyrosine phosphatase, the human Src-homology-region-2-domain-containing-phosphatase-2 (SHP2). Here, we considered the possibility that activated SHP2 might be responsible for the dephosphorylation of cortactin and vinculin. To investigate this, phosphatase inhibitor studies were performed. Additionally, a complete knockout mutant of SHP2 in AGS cells was created by CRISPR/Cas9 technology, and these cells were infected with H. pylori. However, neither the presence of an inhibitor nor the inactivation of SHP2 prevented the dephosphorylation of cortactin and vinculin upon CagA delivery. Tyrosine dephosphorylation of these proteins is therefore independent of SHP2 and instead must be caused by another, as yet unidentified, protein tyrosine phosphatase.



2020 ◽  
Author(s):  
Mohammad Chehelgerdi ◽  
Abbas Doosti

Abstract Background Helicobacter pylori (H. pylori) infect more than half of the world population, and they cause different serious diseases such as gastric carcinomas. This study aims to design a vaccine on the basis of cagW against H. pylori infection. After pcDNA3.1 (+)-cagW-CS-NPs complex is produced, it will be administered into the muscles of healthy BALB/c mice in order to study the effect of this DNA vaccine on the interleukin status of mice, representing its effect on the immune system. After that, the results will be compared with the control groups comprising the administration of cagW-pCDNA3.1 (+) vaccine, the administration of chitosan and the administration of PBS in the muscles of mice.Methods The cagW gene of H. pylori was amplified by employing PCR, whose product was then cloned into the pcDNA3.1 (+) vector, and this cloning was confirmed by PCR and BamHI/EcoRV restriction enzyme digestion. CagW gene DNA vaccine was encapsulated in chitosan nanoparticles (pcDNA3.1 (+)-cagW-CS-NPs) using a complex co-acervation method. The stability and in vitro expression of chitosan nanoparticles were studied by DNase I digestion and transfection, and the immune responses elicited in specific pathogen-free (SPF) mice by the pcDNA3.1 (+)-cagW-CS-NPs were evaluated. Apart from that, the protective potential pcDNA3.1 (+)-cagW-CS-NPs was evaluated by challenging with H.pylori.Results The pcDNA3.1 (+)-cagW-CS-NPs comprises cagW gene of H. pylori that is encapsulated in chitosan nanoparticles, produced with good morphology, high stability, a mean diameter of 117.7 nm, and a zeta potential of + 5.64 mV. Moreover, it was confirmed that chitosan encapsulation protects the DNA plasmid from DNase I digestion, and the immunofluorescence assay showed that the cagW gene could express in HDF cells and maintain good bioactivity at the same time. In comparison to the mice immunized with the control plasmid, in vivo immunization revealed that mice immunized with pcDNA3.1 (+)-cagW-NPs showed better immune responses and prolonged release of the plasmid DNA.Conclusions This research proves chitosan-DNA nanoparticles as potent immunization candidates against H. pylori infection and paves the way for further developments in novel vaccines encapsulated in chitosan nanoparticles.



2019 ◽  
Vol 14 (14) ◽  
pp. 1199-1205
Author(s):  
Ilaria Baccani ◽  
Paola Faraoni ◽  
Matilde Marini ◽  
Alessio Gnerucci ◽  
Barbara Orsini ◽  
...  

Aim: The objective of this study was to investigate the possible synergy between doxycycline and photodynamic therapy against Helicobacter pylori and to evaluate the possible side effects on adenocarcinoma gastric cells with and without protoporphyrin IX. Materials & methods: Three H. pylori strains (ATCC 700392, 43504 and 49503) were grown on solid medium either with, or without, doxycycline at subinhibitory concentrations, and irradiated for 10, 20 and 30 minutes with a 400 nm-peaked light source. The phototoxicity tests on AGS cells were evaluated by MTT assay. Results: The photodynamic therapy and doxycycline combination showed an antibacterial synergistic effect with no significant toxicities. Conclusion: The synergistic treatment could be considered as an interesting therapeutic option.



Author(s):  
Augusto F. Uberti ◽  
Natália Callai-Silva ◽  
Matheus V. C. Grahl ◽  
Angela R. Piovesan ◽  
Eduarda G. Nachtigall ◽  
...  

Alzheimer&rsquo;s disease (AD) causes dementia and memory loss in the elderly. Deposits of beta-amyloid peptide and hyperphosphorylated tau protein are present in AD&rsquo;s brain. A filtrate of Helicobacter pylori&rsquo;s culture was previously found to induce hyperphosphorylation of tau in vivo, suggesting that bacterial exotoxins could permeate the blood brain barrier and directly induce tau&rsquo;s phosphorylation. H. pylori, which infects ~60% of the world population and causes gastritis and gastric cancer, produces a pro-inflammatory urease (HPU). Here the neurotoxic potential of HPU was investigated in cultured cells and in rats. SH-SY5Y neuroblastoma cells exposed HPU (50-300 nM) produced reactive oxygen species (ROS) and had an increased [Ca2+]i. HPU-treated BV-2 microglial cells produced ROS, cytokines IL-1&beta; and TNF-&alpha;, expressed Iba1 and showed reduced viability, consistent with a neurotoxic effect of HPU. Rats received daily i.p. HPU (5 &micro;g) for 7 days. Hyperphosphorylation of tau at Thr205, Ser199 and Ser396 sites was seen in hippocampal homogenates of treated rats, with no alterations in total tau or GSK-3b levels. HPU was not detected in the brain homogenates. Behavioral tests were performed to assess cognitive impairments. Our findings support previous data suggesting an association between infection by H. pylori and tauopathies such as AD, possibly mediated by its urease.



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