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1.
Eur Rev Med Pharmacol Sci ; 28(12): 3836-3840, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38946381

RESUMO

OBJECTIVE: The non-invasive detection of Helicobacter pylori (H. pylori) and its resistance to clarithromycin and levofloxacin significantly improves the management of infected patients by enabling tailored eradication treatments without the need for endoscopic procedures. This study aimed to assess the effectiveness of real-time PCR (RT-PCR) assays in identifying H. pylori infection and antibiotic resistance in stool and gastric biopsy specimens. PATIENTS AND METHODS: Stool and gastric biopsy samples were collected from patients within three days of post-hospitalization. A total of 115 samples were analyzed for H. pylori infection, and an additional 115 samples were evaluated for resistance to clarithromycin and levofloxacin using an RT-PCR-based molecular test. Statistical analyses were performed using (SPSS 26.0 IBM Corp., Armonk, NY, USA). RESULTS: Among 115 patients (53 males, average age 50.8±13.2 years), H. pylori was detected in 93.1% of stool samples and 93.9% of gastric biopsies. The RT-PCR assay demonstrated a sensitivity of 99.1% and a specificity of 100%, with an overall diagnostic accuracy of 99.1%. Clarithromycin resistance was found in 37.3% of stool and 46.9% of gastric biopsy specimens, with the assay showing 79.6% sensitivity and 98.4% specificity. Levofloxacin resistance was identified in 32.1% of stool samples and 31.3% of gastric biopsies, with 86.3% sensitivity and 91.1% specificity of the molecular test. CONCLUSIONS: The RT-PCR-based detection of H. pylori and its resistance to clarithromycin and levofloxacin in stool samples represents a promising approach to enhance eradication therapy outcomes, potentially improving treatment efficacy. Chictr.org.cn: ChiCTR2300070267.


Assuntos
Antibacterianos , Claritromicina , Farmacorresistência Bacteriana , Fezes , Infecções por Helicobacter , Helicobacter pylori , Levofloxacino , Reação em Cadeia da Polimerase em Tempo Real , Humanos , Levofloxacino/farmacologia , Levofloxacino/uso terapêutico , Claritromicina/farmacologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Helicobacter pylori/genética , Fezes/microbiologia , Masculino , Pessoa de Meia-Idade , Feminino , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Adulto , Idoso , Testes de Sensibilidade Microbiana
2.
World J Gastroenterol ; 30(24): 3086-3105, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38983958

RESUMO

BACKGROUND: Helicobacter pylori (HP), the most common pathogenic microorganism in the stomach, can induce inflammatory reactions in the gastric mucosa, causing chronic gastritis and even gastric cancer. HP infection affects over 4.4 billion people globally, with a worldwide infection rate of up to 50%. The multidrug resistance of HP poses a serious challenge to eradication. It has been de-monstrated that compared to bismuth quadruple therapy, Qingre Huashi decoction (QHD) combined with triple therapy exhibits comparable eradication rates but with a lower incidence of adverse reactions; in addition, QHD can directly inhibit and kill HP in vitro. AIM: To explore the effect and mechanism of QHD on clinically multidrug-resistant and strong biofilm-forming HP. METHODS: In this study, 12 HP strains were isolated in vitro after biopsy during gastroscopy of HP-infected patients. In vitro, the minimum inhibitory concentration (MIC) values for clinical HP strains and biofilm quantification were determined through the E-test method and crystal violet staining, respectively. The most robust biofilm-forming strain of HP was selected, and QHD was evaluated for its inhibitory and bactericidal effects on the strain with strong biofilm formation. This assessment was performed using agar dilution, E-test, killing dynamics, and transmission electron microscopy (TEM). The study also explored the impact of QHD on antibiotic resistance in these HP strains with strong biofilm formation. Crystalline violet method, scanning electron microscopy, laser confocal scanning microscopy, and (p)ppGpp chromatographic identification were employed to evaluate the effect of QHD on biofilm in strong biofilm-forming HP strains. The effect of QHD on biofilm and efflux pump-related gene expression was evaluated by quantitative polymerase chain reaction. Non-targeted metabolomics with UHPLC-MS/MS was used to identify potential metabolic pathways and biomarkers which were different between the NC and QHD groups. RESULTS: HP could form biofilms of different degrees in vitro, and the intensity of formation was associated with the drug resistance of the strain. QHD had strong bacteriostatic and bactericidal effects on HP, with MICs of 32-64 mg/mL. QHD could inhibit the biofilm formation of the strong biofilm-forming HP strains, disrupt the biofilm structure, lower the accumulation of (p)ppGpp, decrease the expression of biofilm-related genes including LuxS, Spot, glup (HP1174), NapA, and CagE, and reduce the expression of efflux pump-related genes such as HP0605, HP0971, HP1327, and HP1489. Based on metabolomic analysis, QHD induced oxidative stress in HP, enhanced metabolism, and potentially inhibited relevant signaling pathways by upregulating adenosine monophosphate (AMP), thereby affecting HP growth, metabolism, and protein synthesis. CONCLUSION: QHD exerts bacteriostatic and bactericidal effects on HP, and reduces HP drug resistance by inhibiting HP biofilm formation, destroying its biofilm structure, inhibiting the expression of biofilm-related genes and efflux pump-related genes, enhancing HP metabolism, and activating AMP in HP.


Assuntos
Antibacterianos , Biofilmes , Medicamentos de Ervas Chinesas , Infecções por Helicobacter , Helicobacter pylori , Testes de Sensibilidade Microbiana , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Biofilmes/efeitos dos fármacos , Humanos , Medicamentos de Ervas Chinesas/farmacologia , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Gastroscopia
3.
Helicobacter ; 29(4): e13111, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39001621

RESUMO

BACKGROUND: The influence of indications for Helicobacter pylori investigation on prescriptions and effectiveness is unknown. The aim of the study was to assess the impact of indications for H. pylori investigation on prescriptions, effectiveness, compliance, and tolerance. METHODS: International, prospective, non-interventional registry of the management of H. pylori infection by European gastroenterologists (Hp-EuReg). Treatment-näive patients registered from 2013 to 2023 at e-CRF AEG-REDCap were analyzed. The effectiveness was assessed by modified intention-to-treat analysis. RESULTS: Overall, 53,636 treatment-naïve cases from 34 countries were included. Most frequent indications were: dyspepsia with normal endoscopy (49%), non-investigated dyspepsia (20%), duodenal ulcer (11%), gastric ulcer (7.7%), and gastroesophageal reflux disease (GERD) (2.6%). Therapy effectiveness varied by indication: duodenal ulcer (91%), gastric ulcer (90%), preneoplastic lesions (90%), dyspepsia with normal endoscopy (89%), GERD (88%), and non-investigated dyspepsia (87%). Bismuth-metronidazole-tetracycline and clarithromycin-amoxicillin-bismuth quadruple therapies achieved 90% effectiveness in all indications except GERD. Concomitant clarithromycin-amoxicillin-tinidazole/metronidazole reached 90% cure rates except in patients with non-investigated dyspepsia; whereas sequential clarithromycin-amoxicillin-tinidazole/metronidazole proved optimal (≥90%) in patients with gastric ulcer only. Adverse events were higher in patients treated for dyspepsia with normal endoscopy and duodenal ulcer compared with the remaining indications (23% and 28%, p < 0.001). Therapeutic compliance was higher in patients with duodenal ulcer and preneoplastic lesions (98% and 99%, p < 0.001). CONCLUSION: In Europe, patients with gastric or duodenal ulcers and preneoplastic lesions showed higher H. pylori treatment effectiveness. Bismuth and non-bismuth quadruple therapies achieved optimal results in almost all indications. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02328131.


Assuntos
Antibacterianos , Infecções por Helicobacter , Helicobacter pylori , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Antibacterianos/uso terapêutico , Quimioterapia Combinada , Europa (Continente) , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Estudos Prospectivos , Resultado do Tratamento
4.
Nutrients ; 16(13)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38999803

RESUMO

Helicobacter pylori infection affects over 50% of the world's population and leads to chronic inflammation and gastric disorders, being the main pathogen correlated to gastric cancer development. Increasing antibiotic resistance levels are a major global concern and alternative treatments are needed. Soybean peptides and other compounds might be an alternative in the treatment to avoid, eradicate and/or control symptoms of H. pylori infection. This study aimed to characterize a lunasin-enriched soybean extract (LSE) using proteomics tools and to evaluate its antioxidant, anti-inflammatory and antibacterial properties against H. pylori infection. By LC-MS/MS analysis, 124 proteins were identified, with 2S albumin (lunasin and large-chain subunits) being the fourth most abundant protein (8.9%). Lunasin consists of 44 amino acid residues and an intramolecular disulfide bond. LSE at a low dose (0.0625 mg/mL) reduced ROS production in both H. pylori-infected and non-infected AGS gastric cells. This led to a significant reduction of 6.71% in the levels of pro-inflammatory interleukin (IL)-8. LSE also showed antibacterial activity against H. pylori, which can be attributed to other soybean proteins and phenolic compounds. Our findings suggest that LSE might be a promising alternative in the management of H. pylori infection and its associated symptoms.


Assuntos
Antibacterianos , Glycine max , Infecções por Helicobacter , Helicobacter pylori , Extratos Vegetais , Proteômica , Proteínas de Soja , Helicobacter pylori/efeitos dos fármacos , Infecções por Helicobacter/tratamento farmacológico , Glycine max/química , Proteômica/métodos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Proteínas de Soja/farmacologia , Antibacterianos/farmacologia , Humanos , Antioxidantes/farmacologia , Anti-Inflamatórios/farmacologia , Espectrometria de Massas em Tandem , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Proteínas de Armazenamento de Sementes/farmacologia
5.
Nutrients ; 16(13)2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38999888

RESUMO

Gastric cancer is an aggressive and multifactorial disease. Helicobacter pylori (H. pylori) is identified as a significant etiological factor in gastric cancer. Although only a fraction of patients infected with H. pylori progresses to gastric cancer, bacterial infection is critical in the pathology and development of this malignancy. The pathogenic mechanisms of this bacterium involve the disruption of the gastric epithelial barrier and the induction of chronic inflammation, oxidative stress, angiogenesis and metastasis. Adherence molecules, virulence (CagA and VacA) and colonization (urease) factors are important in its pathogenicity. On the other hand, resveratrol is a natural polyphenol with anti-inflammatory and antioxidant properties. Resveratrol also inhibits cancer cell proliferation and angiogenesis, suggesting a role as a potential therapeutic agent against cancer. This review explores resveratrol as an alternative cancer treatment, particularly against H. pylori-induced gastric cancer, due to its ability to mitigate the pathogenic effects induced by bacterial infection. Resveratrol has shown efficacy in reducing the proliferation of gastric cancer cells in vitro and in vivo. Moreover, the synergistic effects of resveratrol with chemotherapy and radiotherapy underline its therapeutic potential. However, further research is needed to fully describe its efficacy and safety in treating gastric cancer.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Resveratrol , Neoplasias Gástricas , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/tratamento farmacológico , Humanos , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/patogenicidade , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Proliferação de Células/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico
6.
Clin Exp Dent Res ; 10(4): e927, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38973212

RESUMO

OBJECTIVES: Helicobacter pylori gastric infection strongly correlates with gastric diseases such as chronic gastritis, functional dyspepsia, and complications such as peptic ulcers and gastric cancer. In developing countries, systemic therapies are not usually successful due to elevated antibiotic resistance. Additionally, oral H. pylori infection and periodontal disease correlate with gastric treatment failures. This study aimed to explore the effect of an integral therapy, comprising oral hygiene and concomitant systemic treatment, to increase the eradication of gastric infection and recurrences. MATERIALS AND METHODS: A prospective, randomized, four-arm, parallel-group, open-label clinical trial was conducted to investigate the efficacy of integral therapy to eradicate gastric H. pylori infection and avoid recurrences in double-positive (real-time PCR oral and gastric infection) patients. Oral hygiene involved mouthwash with neutral electrolyzed water (NEW), with or without periodontal treatment. One hundred patients were equally distributed into four groups: NS, NS-PT, NEW, and NEW-PT. All patients had concomitant systemic therapy and additionally, the following oral treatments: mouthwash with normal saline (NS), periodontal treatment and mouthwash with normal saline (NS-PT), mouthwash with NEW (NEW), and periodontal treatment and mouthwash with NEW (NEW-PT). Gastric and oral infection and symptoms were evaluated one and four months after treatments. RESULTS: Integral therapy with NEW-PT increased gastric eradication rates compared with NS or NS-PT (84%-96% vs. 20%-56%; p < 0.001). Even more, a protective effect of 81.2% (RR = 0.1877; 95% CI: 0.0658-0.5355; p = 0.0018) against recurrences and 76.6% (RR = 0.2439; 95% CI: 0.1380-0.4310; p < 0.001) against treatment failure (eradication of infection and associated symptoms) was observed in patients from the NEW and NEW-PT groups. CONCLUSIONS: Implementation of oral hygiene and systemic treatment can increase the eradication of gastric infection, associated symptoms, and recurrences. NEW is recommended as an antiseptic mouthwash due to its efficacy and short- and long-term safety.


Assuntos
Antibacterianos , Infecções por Helicobacter , Helicobacter pylori , Antissépticos Bucais , Higiene Bucal , Humanos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Masculino , Feminino , Antissépticos Bucais/uso terapêutico , Antissépticos Bucais/administração & dosagem , Estudos Prospectivos , Adulto , Pessoa de Meia-Idade , Higiene Bucal/métodos , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Resultado do Tratamento , Recidiva , Prevenção Secundária/métodos , Idoso , Terapia Combinada
7.
Helicobacter ; 29(4): e13079, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38984661

RESUMO

BACKGROUND: Eradicating Helicobacter pylori infection by bismuth quadruple therapy (BQT) is effective. However, the effect of BQT and subsequent fecal microbiota transplant (FMT) on the gut microbiota is less known. MATERIALS AND METHODS: This prospective randomized controlled trial was conducted at a tertiary hospital in China from January 2019 to October 2020, with the primary endpoints the effect of BQT on the gut microbiota and the effect of FMT on the gut microbiota after bismuth quadruple therapy eradication therapy. A 14-day BQT with amoxicillin and clarithromycin was administered to H. pylori-positive subjects, and after eradication therapy, patients received a one-time FMT or placebo treatment. We then collected stool samples to assess the effects of 14-day BQT and FMT on the gut microbiota. 16 s rDNA and metagenomic sequencing were used to analyze the structure and function of intestinal flora. We also used Gastrointestinal Symptom Rating Scale (GSRS) to evaluate gastrointestinal symptom during treatment. RESULTS: A total of 30 patients were recruited and 15 were assigned to either FMT or placebo groups. After eradication therapy, alpha-diversity was decreased in both groups. At the phylum level, the abundance of Bacteroidetes and Firmicutes decreased, while Proteobacteria increased. At the genus level, the abundance of beneficial bacteria decreased, while pathogenic bacteria increased. Eradication therapy reduced some resistance genes abundance while increased the resistance genes abundance linked to Escherichia coli. While they all returned to baseline by Week 10. Besides, the difference was observed in Week 10 by the diarrhea score between two groups. Compared to Week 2, the GSRS total score and diarrhea score decreased in Week 3 only in FMT group. CONCLUSIONS: The balance of intestinal flora in patients can be considerably impacted by BQT in the short term, but it has reverted back to baseline by Week 10. FMT can alleviate gastrointestinal symptoms even if there was no evidence it promoted restoration of intestinal flora.


Assuntos
Antibacterianos , Bismuto , Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Infecções por Helicobacter , Helicobacter pylori , Humanos , Infecções por Helicobacter/terapia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Transplante de Microbiota Fecal/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Helicobacter pylori/efeitos dos fármacos , Adulto , Antibacterianos/uso terapêutico , Estudos Prospectivos , Bismuto/uso terapêutico , Quimioterapia Combinada , China , Amoxicilina/uso terapêutico , Claritromicina/uso terapêutico , Resultado do Tratamento , Idoso , Fezes/microbiologia
8.
Helicobacter ; 29(1): e13046, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38984721

RESUMO

BACKGROUND: Map-like redness is a newly identified endoscopic risk factor for gastric cancer in patients who received Helicobacter pylori eradication therapy. However, the incidence rate of map-like redness in patients who received eradication, and the risk factors for the development of map-like redness remain unclear. We hence aimed to investigate the incidence rate of map-like redness at 1-year post H. pylori eradication, and evaluated its associations with map-like redness and gastric cancer in relation with gastric condition. MATERIALS AND METHODS: Endoscopic severity of gastritis and map-like redness were retrospectively evaluated according to the Kyoto Classification of Gastritis in patients who had undergone endoscopy before and after H. pylori eradication therapy. RESULTS: The incidence rate of map-like redness for all 328 patients at a mean of 1.2 ± 0.6 years after eradication was 25.3% (95% confidence interval [CI]: 20.7%-30.4%). Patients who developed map-like redness were older, had more severe atrophy and intestinal metaplasia, a higher total score of the Kyoto Classification of Gastritis both before and after eradication, and a higher rate of gastric cancer history than patients who did not have map-like redness. On multivariate analysis, risk of map-like redness was increased in patients with intestinal metaplasia (odds ratio [OR]: 2.794, 95% CI: 1.155-6.757) and taking acid inhibitors (OR: 1.948, 95% CI: 1.070-3.547). Characteristics of H. pylori-positive patients with gastric cancer history were patients who were older (OR: 1.033, 95% CI: 1.001-1.066), taking acid inhibitors (OR: 4.456, 95% CI: 2.340-8.484), and with occurrence of map-like redness after eradication therapy (OR: 2.432, 95% CI: 1.264-4.679). CONCLUSIONS: Map-like redness is observed in one fourth of patients at 1-year post eradication. Patients who developed map-like redness were found to have severe intestinal metaplasia and taking acid inhibitors, and hence such patients require increased attention at surveillance endoscopy.


Assuntos
Gastrite , Infecções por Helicobacter , Helicobacter pylori , Humanos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/complicações , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Idoso , Gastrite/microbiologia , Gastrite/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Adulto , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/epidemiologia , Incidência , Antibacterianos/uso terapêutico , Antibacterianos/efeitos adversos
9.
Helicobacter ; 29(3): e13106, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38984746

RESUMO

Patients receiving hemodialysis (HD) often develop gastrointestinal diseases. Recently, although in general population, clinical guidelines for Helicobacter pylori have strongly recommended its eradication in patients to prevent gastric cancer, optimal eradication regimen and optimal dosage of drugs for patients receiving HD have not been established, due to possible incidence of adverse events. Some antimicrobial agents used in eradication therapy, particularly amoxicillin, can exacerbate renal dysfunction. Given the delayed pharmacokinetics of drugs in patients receiving HD compared with those in healthy individuals, drug regimen and dosage should be considered to minimize adverse effects. Although previous studies have investigated the benefits of eradication therapy for patients receiving HD, because most studies were small in terms of the number of enrolled patients, it is hard to show evidence. The numbers of eradication in HD patients have recently increased, and it is important to provide an optimal regimen. The consideration of eradication in patients undergoing HD with a reduction in the drug dose by 1/2-1/3 may prevent adverse events. Additionally, another important consideration is whether adverse events can be prevented while maintaining a similar eradication rate with reduced drug dosages. Recent meta-analysis findings indicate comparable eradication rates in patients receiving HD and healthy individuals, both with the same dosage regimen and at a reduced dosage regimen, with no significant differences (relative risk [RR] for successful eradication: 0.85 [95% confidence interval (CI): 0.48-1.50]). Unlike with the same dosage regimen (RR for adverse events: 3.15 [95% CI: 1.93-5.13]), the adverse events in the dosage reduction regimen were similar to those in healthy individuals (RR: 1.26 [95% CI: 0.23-6.99]). From a pharmacological perspective, the eradication regimen in patients receiving HD should consider the dosage (1/2-1/3 dosage), dosing number (bid), dosing timing of drugs (after HD), and susceptibility to antimicrobial agents.


Assuntos
Antibacterianos , Infecções por Helicobacter , Helicobacter pylori , Diálise Renal , Humanos , Infecções por Helicobacter/tratamento farmacológico , Diálise Renal/efeitos adversos , Antibacterianos/efeitos adversos , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Antibacterianos/farmacocinética , Helicobacter pylori/efeitos dos fármacos
10.
Helicobacter ; 29(4): e13110, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39001634

RESUMO

BACKGROUND: Antimicrobial-resistant Helicobacter pylori (H. pylori) poses a significant public health concern, especially given the limited therapeutic options for azithromycin-resistant strains. Hence, there is a necessity for new studies to reconsider the use of azithromycin, which has diminished in effectiveness against numerous strains. Thus, we aimed to augment azithromycin's anti-Helicobacter properties by combining it with curcumin in different formulations, including curcumin in clove oil, curcumin nano-gold emulsion, and curcumin nanoemulsion. METHODS: The antimicrobial activities of the investigated compounds, both individually and in combination with other anti-Helicobacter drugs, were evaluated. Their antibiofilm and anti-virulence properties were assessed using both phenotypic and genotypic methods, alongside molecular docking studies. Our findings were further validated through mouse protection assays and histopathological analysis. RESULTS: We observed high anti-Helicobacter activities of curcumin, especially curcumin nanoemulsion. A synergistic effect was detected between curcumin nanoemulsion and azithromycin with fraction inhibitory concentration index (FICI) values <0.5. The curcumin nanoemulsion was the most active anti-biofilm and anti-virulence compound among the examined substances. The biofilm-correlated virulence genes (babA and hopQ) and ureA genes were downregulated (fold change <1) post-treatment with curcumin nanoemulsion. On the protein level, the anti-virulence activities of curcumin nanoemulsion were documented based on molecular docking studies. These findings aligned with histopathological scoring of challenge mice, affirming the superior efficacy of curcumin nanoemulsion/azithromycin combination. CONCLUSION: The anti-Helicobacter activities of all curcumin physical forms pose significant challenges due to their higher  minimum inhibitory concentration (MIC) values exceeding the maximum permissible level. However, using curcumin nanoemulsion at sub-MIC levels could enhance the anti-Helicobacter activity of azithromycin and exhibit anti-virulence properties, thereby improving patient outcomes and addressing resistant pathogens. Therefore, more extensive studies are necessary to assess the safety of incorporating curcumin nanoemulsion into H. pylori treatment.


Assuntos
Antibacterianos , Azitromicina , Biofilmes , Curcumina , Infecções por Helicobacter , Simulação de Acoplamento Molecular , Azitromicina/farmacologia , Azitromicina/química , Animais , Antibacterianos/farmacologia , Antibacterianos/química , Camundongos , Biofilmes/efeitos dos fármacos , Curcumina/farmacologia , Curcumina/química , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/genética , Testes de Sensibilidade Microbiana , Sinergismo Farmacológico , Produtos Biológicos/farmacologia , Produtos Biológicos/química , Virulência/efeitos dos fármacos , Feminino
11.
Helicobacter ; 29(4): e13101, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38987862

RESUMO

BACKGROUND: Latin America has a high prevalence of Helicobacter pylori in children that may lead to peptic ulcer disease and eventually gastric cancer in adulthood. Successful eradication is hindered by rising antimicrobial resistance. We summarize H. pylori resistance rates in Latin American children from 2008 to 2023. MATERIAL AND METHODS: Systematic review following PRISMA guidelines and National Heart, Lung, and Blood Institute checklist to assess risk of bias (PROSPERO CRD42024517108) that included original cross-sectional observational studies reporting resistance to commonly used antibiotics in Latin American children and adolescents. We searched in PubMed, LILACS, and SciELO databases. RESULTS: Of 51 studies, 45 were excluded. The quality of the six analyzed studies (297 H. pylori-positive samples) was satisfactory. Phenotypic methods (N = 3) reported higher resistance rates than genotypic studies (N = 3). Clarithromycin resistance ranged from 8.0% to 26.7% (6 studies; 297 samples), metronidazole from 1.9% to 40.2% (4 studies; 211 samples), amoxicillin from 0% to 10.4% (3 studies; 158 samples), tetracycline resistance was not detected (3 studies; 158 samples), and levofloxacin resistance was 2.8% (1 study; 36 samples). CONCLUSION: Scarce Latin American studies on H. pylori resistance, along with methodological heterogeneity, hinder conclusive findings. Clarithromycin and metronidazole (first-line drugs) resistance is worrisome, likely impacting lower eradication rates. Urgent systematic surveillance or individual testing before treatment is necessary to enhance eradication.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Infecções por Helicobacter , Helicobacter pylori , Humanos , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/genética , Helicobacter pylori/isolamento & purificação , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , América Latina/epidemiologia , Adolescente , Criança , Antibacterianos/farmacologia , Pré-Escolar , Testes de Sensibilidade Microbiana , Estudos Transversais
12.
Signal Transduct Target Ther ; 9(1): 183, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38972904

RESUMO

Helicobacter pylori (H. pylori) is currently recognized as the primary carcinogenic pathogen associated with gastric tumorigenesis, and its high prevalence and resistance make it difficult to tackle. A graph neural network-based deep learning model, employing different training sets of 13,638 molecules for pre-training and fine-tuning, was aided in predicting and exploring novel molecules against H. pylori. A positively predicted novel berberine derivative 8 with 3,13-disubstituted alkene exhibited a potency against all tested drug-susceptible and resistant H. pylori strains with minimum inhibitory concentrations (MICs) of 0.25-0.5 µg/mL. Pharmacokinetic studies demonstrated an ideal gastric retention of 8, with the stomach concentration significantly higher than its MIC at 24 h post dose. Oral administration of 8 and omeprazole (OPZ) showed a comparable gastric bacterial reduction (2.2-log reduction) to the triple-therapy, namely OPZ + amoxicillin (AMX) + clarithromycin (CLA) without obvious disturbance on the intestinal flora. A combination of OPZ, AMX, CLA, and 8 could further decrease the bacteria load (2.8-log reduction). More importantly, the mono-therapy of 8 exhibited comparable eradication to both triple-therapy (OPZ + AMX + CLA) and quadruple-therapy (OPZ + AMX + CLA + bismuth citrate) groups. SecA and BamD, playing a major role in outer membrane protein (OMP) transport and assembling, were identified and verified as the direct targets of 8 by employing the chemoproteomics technique. In summary, by targeting the relatively conserved OMPs transport and assembling system, 8 has the potential to be developed as a novel anti-H. pylori candidate, especially for the eradication of drug-resistant strains.


Assuntos
Antibacterianos , Berberina , Aprendizado Profundo , Helicobacter pylori , Helicobacter pylori/efeitos dos fármacos , Berberina/farmacologia , Berberina/química , Berberina/farmacocinética , Antibacterianos/farmacologia , Antibacterianos/química , Humanos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/genética , Animais , Omeprazol/farmacologia , Claritromicina/farmacologia , Amoxicilina/farmacologia
13.
Front Cell Infect Microbiol ; 14: 1419568, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38983115

RESUMO

Background: Helicobacter pylori infection poses a significant health burden worldwide, and its virulence factor CagA plays a pivotal role in its pathogenesis. Methods: In this study, the interaction between H. pylori-infected AGS cells and silver nanoparticles (AgNPs) was investigated, with a focus on the modulation of CagA-mediated responses, investigated by western blotting. Both, the dose-dependent efficacy against H. pylori (growth curves, CFU assay) and the impact of the nanoparticles on AGS cells (MTT assay) were elucidated. Results: AGS cells infected with H. pylori displayed dramatic morphological changes, characterized by elongation and a migratory phenotype, attributed to CagA activity. Preincubation of H. pylori with AgNPs affected these morphological changes in a concentration-dependent manner, suggesting a correlation between AgNPs concentration and CagA function. Conclusion: Our study highlights the nuanced interplay between host-pathogen interactions and the therapeutic potential of AgNPs in combating H. pylori infection and offers valuable insights into the multifaceted dynamics of CagA mediated responses.


Assuntos
Antígenos de Bactérias , Proteínas de Bactérias , Infecções por Helicobacter , Helicobacter pylori , Nanopartículas Metálicas , Transdução de Sinais , Prata , Helicobacter pylori/efeitos dos fármacos , Proteínas de Bactérias/metabolismo , Antígenos de Bactérias/metabolismo , Prata/farmacologia , Prata/metabolismo , Humanos , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Interações Hospedeiro-Patógeno , Células Epiteliais/microbiologia , Fatores de Virulência/metabolismo , Linhagem Celular , Antibacterianos/farmacologia , Linhagem Celular Tumoral
14.
J Agric Food Chem ; 72(28): 15725-15739, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38973111

RESUMO

Indole-3-lactic acid (ILA) has exhibited antimicrobial properties. However, its role in inhibiting Helicobacter pylori infection remains elusive. This study investigated the inhibitory effect of ILA produced by Lacticaseibacillus paracasei on H. pylori, which was further confirmed by cell and animal experiments. 5 mg/mL ILA was sufficient to directly inhibit the growth of H. pylori in vitro, with a urease inhibitory activity reaching 60.94 ± 1.03%, and the cell morphology and structure were destroyed. ILA inhibited 56.5% adhesion of H. pylori to GES-1 and significantly reduced the number of apoptotic cells. Furthermore, ILA suppresses H. pylori colonization by approximately 38% to 63%, reduced inflammation and oxidative stress in H. pylori-infected mice, and enhanced the enrichment and variety of gut microbiota, notably fostering the growth of beneficial bacteria such as Lactobacillus and Bifidobacterium strains. The results support that ILA derived from Lactobacillus can be applicated as a novel prebiotic in anti-H. pylori functional foods.


Assuntos
Células Epiteliais , Mucosa Gástrica , Infecções por Helicobacter , Helicobacter pylori , Indóis , Lacticaseibacillus paracasei , Helicobacter pylori/efeitos dos fármacos , Animais , Camundongos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Humanos , Mucosa Gástrica/microbiologia , Mucosa Gástrica/efeitos dos fármacos , Indóis/farmacologia , Indóis/química , Lacticaseibacillus paracasei/química , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/microbiologia , Antibacterianos/farmacologia , Antibacterianos/química , Inflamação/prevenção & controle , Microbioma Gastrointestinal/efeitos dos fármacos , Masculino , Aderência Bacteriana/efeitos dos fármacos
15.
J Gastrointestin Liver Dis ; 33(2): 164-169, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38944858

RESUMO

BACKGROUND AND AIMS: Early gastric cancers (EGCs) after Helicobacter pylori (H. pylori) eradication often appear as reddish depressed lesions (RDLs); the same features are also appeared in benign stomachs after eradication. We compared clinic-pathological and endoscopic features of benign and neoplastic RDLs after H. pylori eradication. METHODS: 228 neoplastic RDLs after H. pylori eradication were studied. All lesions were divided into neoplastic RDLs (differentiated carcinoma or adenoma, n=114) and benign RDLs (n=114) according to the histology. Clinical and pathological characteristics were compared in neoplastic and benign groups. Endoscopic diagnostic yields using the white light (WL) endoscopy, chromoendoscopy (CE) using indigo carmine dye and the magnifying endoscopy with narrow-band imaging (ME-NBI) were also evaluated in relation to the pathological diagnosis. RESULTS: Size of neoplastic RDLs was larger than that of benign RDLs (p<0.01). Sensitivity, specificity and accuracy for predicting pathological types of RDLs was 70.1%, 52.6% and 61.4% for the WL, 65.8%, 63.1% and 65.4% for the CE, while the ME-NBI scored better with the 88.6%, 88.6%, 99.1% and 93.9% of sensitivity, specificity and accuracy. The accuracy of the ME-NBI was 99.9% (113/114) in the benign RDLs and 89.4% (101/114) for the neoplastic RDLs. Undiagnosed neoplastic RDLs using the ME-NBI were associated with more differentiated tumors such as adenoma and well-differentiated adenocarcinoma (tub1) and the presence of an unclear demarcation line. CONCLUSIONS: ME-NBI is useful to diagnose RDLs after H. pylori eradiation, while some of neoplastic lesions are difficult to diagnose using the ME-NBI.


Assuntos
Adenoma , Gastroscopia , Infecções por Helicobacter , Helicobacter pylori , Imagem de Banda Estreita , Valor Preditivo dos Testes , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/microbiologia , Infecções por Helicobacter/patologia , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Pessoa de Meia-Idade , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Masculino , Feminino , Idoso , Imagem de Banda Estreita/métodos , Adenoma/patologia , Adenoma/diagnóstico por imagem , Mucosa Gástrica/patologia , Mucosa Gástrica/diagnóstico por imagem , Mucosa Gástrica/microbiologia , Antibacterianos/uso terapêutico , Adulto , Resultado do Tratamento , Biópsia , Detecção Precoce de Câncer/métodos , Estudos Retrospectivos , Índigo Carmim
16.
BMC Infect Dis ; 24(1): 647, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937679

RESUMO

BACKGROUND: Refractory Helicobacter pylori (H. pylori) infection inevitably increase the difficulty of drug selection. Here, we described our experience with the use of a novel tetravalent IgY against H. pylori for the treatment of patients with refractory H. pylori infection. METHODS: Patients were randomly assigned to receive the standard quadruple therapy (amoxicillin, clarithromycin, omeprazole and bismuth potassium citrate ) for 2 weeks or 250 mg of avian polyclonal IgY orally twice a day for 4 weeks. The binding efficacy of IgY to H. pylori antigens was detected by western blotting13. C-urea breath test was performed to evaluate the eradication therap's efficacy. The side effects of IgY were evaluated via various routine tests. The questionnaire was used to gather clinical symptoms and adverse reactions. RESULTS: Western blot analysis showed that tetravalent IgY simultaneously bind to VacA, HpaA, CagA and UreB of H. pylori. Tetravalent IgY had an eradication rate of 50.74% in patients with refractory H. pylori and an inhibition rate of 50.04% against DOB (delta over baseline) of 13C-urea. The symptom relief rate was 61.76% in thirty-four patients with clinical symptoms, and no adverse reactions were observed during tetravalent IgY treatment period. CONCLUSIONS: Polyclonal avian tetravalent IgY reduced H. pylori infection, and showed good efficacy and safety in the treatment of refractory H. pylori infection patients, which represented an effective therapeutic option of choice for patients with refractory H. pylori infection.


Assuntos
Antibacterianos , Infecções por Helicobacter , Helicobacter pylori , Imunoglobulinas , Humanos , Infecções por Helicobacter/tratamento farmacológico , Masculino , Feminino , Helicobacter pylori/efeitos dos fármacos , Pessoa de Meia-Idade , Imunoglobulinas/uso terapêutico , Imunoglobulinas/administração & dosagem , Adulto , Antibacterianos/uso terapêutico , Antibacterianos/efeitos adversos , Resultado do Tratamento , Idoso , Quimioterapia Combinada , Claritromicina/uso terapêutico , Amoxicilina/uso terapêutico , Amoxicilina/administração & dosagem , Adulto Jovem , Anticorpos Antibacterianos/uso terapêutico
17.
Gut Microbes ; 16(1): 2369336, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38944840

RESUMO

The role of the intratumoral microbiome in gastric cancer (GC) has not been comprehensively assessed. Here, we explored the relationship between the microbial community and GC prognosis and therapy efficacy. Several cancer-associated microbial characteristics were identified, including increased α-diversity, differential ß-diversity, and decreased Helicobacter pylori abundance. After adjusting for clinical features, prognostic analysis revealed 2 phyla, 14 genera, and 5 species associated with the overall survival of patients with GC. Additionally, 2 phyla, 14 genera, and 6 species were associated with adjuvant chemotherapy (ACT) efficacy in patients with stage II - III GC. Furthermore, we classified GC microbiome structures into three microbial subtypes (MS1, MS2 and MS3) with distinguishing features. The MS1 subtype exhibited high immune activity and enrichment of microbiota related to immunotherapy and butyric acid-producing, as well as potential benefits in immunotherapy. MS2 featured the highest α-diversity and activation of the TFF pathway, MS3 was characterized by epithelial-mesenchymal transition and was associated with poor prognosis and reduced ACT efficacy. Collectively, the results of this study provide valuable insights into the microbial characteristics associated with GC prognosis and therapy efficacy.


Assuntos
Neoplasias Gástricas , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/terapia , Humanos , Prognóstico , Masculino , Feminino , Pessoa de Meia-Idade , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética , Microbioma Gastrointestinal , Idoso , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/genética , Helicobacter pylori/fisiologia , Quimioterapia Adjuvante , Resultado do Tratamento
18.
Sci Rep ; 14(1): 14542, 2024 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914675

RESUMO

Antibiotic resistance among bacteria is recognized as the primary factor contributing to the failure of treatment. In this research, our objective was to examine the prevalence of antibiotic resistance in H. pylori bacteria in Palestine. We enlisted 91 individuals suffering from dyspepsia, comprising 49 females and 42 males. These participants underwent esophagogastroduodenoscopy procedures with gastric biopsies. These biopsies were subsequently subjected to microbiological assessments and tested for their susceptibility to various antimicrobial drugs. Among the 91 patients, 38 (41.7%) exhibited the presence of H. pylori. Notably, Ciprofloxacin displayed the highest efficacy against H. pylori, followed by Levofloxacin, Moxifloxacin, and Amoxicillin, with resistance rates of 0%, 0%, 2.6%, and 18.4%, respectively. On the contrary, Metronidazole and Clarithromycin demonstrated the lowest effectiveness, with resistance percentages of 100% and 47.4%, respectively. The outcomes of this investigation emphasize that H. pylori strains within the Palestinian patient group exhibit substantial resistance to conventional first-line antibiotics like clarithromycin and metronidazole. However, alternative agents such as fluoroquinolones and amoxicillin remain efficacious choices. Consequently, we recommend favoring quinolone-based treatment regimens for H. pylori infections and adopting a more judicious approach to antibiotic usage among the Palestinian population.


Assuntos
Antibacterianos , Infecções por Helicobacter , Helicobacter pylori , Humanos , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Feminino , Masculino , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/epidemiologia , Estudos Transversais , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Adulto , Prevalência , Pessoa de Meia-Idade , Farmacorresistência Bacteriana , Hospitais Universitários , Testes de Sensibilidade Microbiana , Amoxicilina/uso terapêutico , Amoxicilina/farmacologia , Claritromicina/uso terapêutico , Claritromicina/farmacologia , Metronidazol/uso terapêutico , Metronidazol/farmacologia , Levofloxacino/uso terapêutico , Levofloxacino/farmacologia
19.
Eur J Gastroenterol Hepatol ; 36(8): 1000-1009, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38829956

RESUMO

BACKGROUND: There has been an increase in resistance to many of the antimicrobials used to treat Helicobacter pylori ( H. pylori ) nationally and internationally. Primary clarithromycin resistance and dual clarithromycin and metronidazole resistance are high in Ireland. These trends call for an evaluation of best-practice management strategies. OBJECTIVE: The objective of this study was to revise the recommendations for the management of H. pylori infection in adult patients in the Irish healthcare setting. METHODS: The Irish H. pylori working group (IHPWG) was established in 2016 and reconvened in 2023 to evaluate the most up-to-date literature on H. pylori diagnosis, eradication rates and antimicrobial resistance. The 'GRADE' approach was then used to rate the quality of available evidence and grade the resulting recommendations. RESULTS: The Irish H. pylori working group agreed on 14 consensus statements. Key recommendations include (1) routine antimicrobial susceptibility testing to guide therapy is no longer recommended other than for clarithromycin susceptibility testing for first-line treatment (statements 6 and 9), (2) clarithromycin triple therapy should only be prescribed as first-line therapy in cases where clarithromycin susceptibility has been confirmed (statement 9), (3) bismuth quadruple therapy (proton pump inhibitor, bismuth, metronidazole, tetracycline) is the recommended first-line therapy if clarithromycin resistance is unknown or confirmed (statement 10), (4) bismuth quadruple therapy with a proton pump inhibitor, levofloxacin and amoxicillin is the recommended second-line treatment (statement 11) and (5) rifabutin amoxicillin triple therapy is the recommend rescue therapy (statement 12). CONCLUSION: These recommendations are intended to provide the most relevant current best-practice guidelines for the management of H. pylori infection in adults in Ireland.


Assuntos
Antibacterianos , Claritromicina , Quimioterapia Combinada , Infecções por Helicobacter , Helicobacter pylori , Inibidores da Bomba de Prótons , Humanos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/efeitos dos fármacos , Irlanda , Antibacterianos/uso terapêutico , Adulto , Inibidores da Bomba de Prótons/uso terapêutico , Claritromicina/uso terapêutico , Metronidazol/uso terapêutico , Consenso , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana , Resultado do Tratamento , Bismuto/uso terapêutico
20.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(5): 867-875, 2024 May 20.
Artigo em Chinês | MEDLINE | ID: mdl-38862444

RESUMO

OBJECTIVE: To prepare a postbiotic using soybean fermentation product of Lactobacillus paracasei TK1501 and evaluate its inhibitory effect against Helicobacter pylori (Hp) infection in mice. METHODS: L. paracasei TK1501 was cultured for 32 h at 37 ℃ in an anaerobic condition for solid substrate fermentation with a solid to water ratio of 1:1.5 in the substrate and an inoculation density of 5×107 CFU/mL. The postbiotic was isolated and purified using macroporous resin XAD-16N adsorption, cation exchange chromatography and HPLC, and its stability and antibacterial activity were assessed. The inhibitory effect of this postbiotic against Hp infection was evaluated in a mouse model with gastric mucosal Hp infection, which were treated with the postbiotic via gavage for 4 weeks at the dose of 0.02 or 0.1 mL. Serum levels of TNF-α and IL-1ß of the mice were analyzed after the treatments, and gastric tissues of the mice were collected for HE staining. RESULTS: L. paracasei TK1501 postbiotic could be easily degraded by protease and had good thermal stability and tolerance to exposures to acid, base, and organic solvents. In the in vitro experiment, the postbiotic showed strong inhibitory effects in bacterial cultures of Staphylococcus aureus, Hp and other common pathogenic bacteria without obviously affecting the resident bacteria in the digestive tract. In the mouse models, treatment with the postbiotic at the dose of 0.1 mL significantly alleviated Hp infection and lowered the serum levels of TNF-α and IL-1ß of the mice. CONCLUSION: L. paracasei TK1501 postbiotic has strong inhibitory effects on Hp and Staphylococcus aureus but not on normal intestinal flora in mice.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Lacticaseibacillus paracasei , Animais , Camundongos , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Probióticos , Fermentação , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-1beta/metabolismo , Mucosa Gástrica/microbiologia , Glycine max/química , Glycine max/microbiologia , Antibacterianos/farmacologia , Modelos Animais de Doenças
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