Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.131
Filtrar
1.
Isr Med Assoc J ; 23(1): 38-42, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33443341

RESUMO

BACKGROUND: The antibiotic resistance profile of Helicobacter pylori (H. pylori) is constantly changing. Up-to-date and reliable data for the effectiveness of first-line H. pylori treatment protocols are necessary to provide evidence-based best-practice guidelines. OBJECTIVES: To determine the effectiveness, compliance and safety of first-line treatment for H. pylori in Israel. METHODS: An observational, prospective, multicenter study was conducted in tertiary referral centers in Israel, as part of the European registry on H. pylori management (Hp-EuReg). H. pylori-infected patients were included from 2013 to March 2020. Data collected included demographics, clinical data, diagnostic tests, previous eradication attempts, current treatment, compliance, adverse events, and treatment outcome result. RESULTS: In total, 242 patients were registered, including 121 (50%) who received first-line therapy, 41% of these individuals received clarithromycin based triple therapy and 58.9% received a four-drug regimen. The overall effectiveness of first-line therapy was 85% and 86% by modified intention-to-treat and per protocol analyses, respectively. The effectiveness of both sequential and concomitant therapies was 100% while clarithromycin-based triple therapy achieved an eradication rate of 79%. Treatment eradication was higher among patients who received high dose proton pump inhibitor (PPI) compared to those treated with low dose PPI (100% vs. 81.5% respectively, P < 0.01). No difference in treatment effectiveness was found between 7-, 10-, and 14-day treatment. CONCLUSIONS: The effectiveness of clarithromycin-based triple therapy is suboptimal. First-line treatment of H. pylori infection should consist of four drugs, including high dose PPI, according to international guidelines.


Assuntos
Antibacterianos , Claritromicina/administração & dosagem , Infecções por Helicobacter , Helicobacter pylori/efeitos dos fármacos , Inibidores da Bomba de Prótons/administração & dosagem , Antibacterianos/administração & dosagem , Antibacterianos/classificação , Relação Dose-Resposta a Droga , Quimioterapia Combinada/métodos , Quimioterapia Combinada/estatística & dados numéricos , Feminino , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Humanos , Israel/epidemiologia , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Sistema de Registros/estatística & dados numéricos , Retratamento/métodos , Retratamento/estatística & dados numéricos , Resultado do Tratamento
2.
Mol Cell ; 80(2): 210-226.e7, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33002424

RESUMO

Many bacterial pathogens regulate their virulence genes via phase variation, whereby length-variable simple sequence repeats control the transcription or coding potential of those genes. Here, we have exploited this relationship between DNA structure and physiological function to discover a globally acting small RNA (sRNA) regulator of virulence in the gastric pathogen Helicobacter pylori. Our study reports the first sRNA whose expression is affected by a variable thymine (T) stretch in its promoter. We show the sRNA post-transcriptionally represses multiple major pathogenicity factors of H. pylori, including CagA and VacA, by base pairing to their mRNAs. We further demonstrate transcription of the sRNA is regulated by the nickel-responsive transcriptional regulator NikR (thus named NikS for nickel-regulated sRNA), thereby linking virulence factor regulation to nickel concentrations. Using in-vitro infection experiments, we demonstrate NikS affects host cell internalization and epithelial barrier disruption. Together, our results show NikS is a phase-variable, post-transcriptional global regulator of virulence properties in H. pylori.


Assuntos
Helicobacter pylori/genética , Helicobacter pylori/patogenicidade , RNA Bacteriano/genética , Sequências Repetitivas de Ácido Nucleico/genética , Fatores de Virulência/metabolismo , Proteínas de Bactérias/metabolismo , Sequência de Bases , Contagem de Colônia Microbiana , Endocitose/efeitos dos fármacos , Deleção de Genes , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Helicobacter pylori/efeitos dos fármacos , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Níquel/farmacologia , Fenótipo , Regiões Promotoras Genéticas , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transcrição Genética/efeitos dos fármacos
3.
Medicine (Baltimore) ; 99(43): e22869, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120827

RESUMO

BACKGROUND: Chronic gastritis is a very common chronic gastric mucosal inflammatory disease in China. Long-term chronic inflammation will aggravate the disease and develop towards gastric cancer. Clinically, infection with Helicobacter pylori (H pylori) is a common cause. The application of antibiotics to eradicate H pylori has been reported to have produced drug resistance. However, the application of Shengyang Yiwei Decoction(SYD) in traditional Chinese medicine has resulted in significant clinical effects and small side effects. It is used for the treatment of chronic gastritis and other diseases, but there is a lack of systematic reviews on the treatment of chronic gastritis by SYD. This article reviews the efficacy and safety of SYD in the treatment of chronic gastritis. METHODS: The registration date for the randomized controlled trials is set by the database to October 15, 2020. Through searching the following 8 Chinese and English electronic databases: Cochrane Library, Embase, PubMed, Science Net, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Science Journal Database and Wanfang Database to analyze. The main results were clinical efficacy, H pylori infection clearance rate, symptom score and quality of life, and 1-year recurrence rate. Finally, Stata 15 was used for meta-analysis. RESULTS: This study will provide the latest evidence for the treatment of chronic gastritis by SYD in the following aspects: clinical efficacy, H pylori infection clearance rate, quality of life, symptom score, and 1-year recurrence rate. CONCLUSION: The results of this study will provide evidence for evaluating the effectiveness of SYD in chronic gastritis treatment. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/AZKUQ.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Gastrite/tratamento farmacológico , Medicina Tradicional Chinesa/métodos , China/epidemiologia , Doença Crônica , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Gastrite/microbiologia , Gastrite/psicologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Segurança , Resultado do Tratamento
4.
Isr Med Assoc J ; 22(10): 628-632, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33070487

RESUMO

BACKGROUND: Antimicrobial resistance is the main determinant for Helicobacter pylori treatment failure. Regional antimicrobial susceptibility testing is essential for appropriate antibiotic selection to achieve high eradication rates. OBJECTIVES: To assess primary and secondary H. pylori resistance in isolates recovered from Israeli naïve and treatment failures. To identify predictors of resistance. METHODS: In this retrospective study, in vitro activity of isolated H. pylori in Israel was tested against metronidazole, clarithromycin, tetracycline, amoxicillin, and levofloxacin in 128 isolates: 106 from treatment failures and 22 from naïve untreated patients. The minimal inhibitory concentration values were determined according to the Etest instructions. Treatment failures previously failed at least one treatment regimen. RESULTS: No resistance to amoxicillin and tetracycline was detected. Resistance to metronidazole and clarithromycin was high in H. pylori isolates both from treated and untreated patients: 68.9%, 68.2% for metronidazole (P = 0.95); 53.8%, 59.1% for clarithromycin (P = 0.64), respectively. Dual resistance to clarithromycin and metronidazole was seen in 45.3% and 50%, respectively (P = 0.68). Resistance to levofloxacin was detected in two (1.9%) isolates from treated patients. Simultaneous resistance to clarithromycin, metronidazole, and levofloxacin was seen in an isolate from a treated patient. Age was the only predictor of resistance to metronidazole and clarithromycin. CONCLUSIONS: The resistance rates to both single and dual metronidazole and clarithromycin in isolates recovered from both Israeli naïve and treated patients is high. Low resistance renders levofloxacin an attractive option for second or third line treatment. Therapeutic outcome would benefit from susceptibility testing after treatment failure.


Assuntos
Claritromicina/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Metronidazol/farmacologia , Centros Médicos Acadêmicos , Adulto , Distribuição de Qui-Quadrado , Estudos de Coortes , Estudos Transversais , Feminino , Infecções por Helicobacter/diagnóstico , Humanos , Israel , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Estatísticas não Paramétricas
5.
PLoS One ; 15(9): e0238944, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32966303

RESUMO

BACKGROUND AND AIMS: Patients that have failed therapy for Helicobacter pylori (H. pylori) infection are incompletely characterized. The aim of this study was to characterize a H. pylori treatment resistant cohort compared to the cohorts of newly diagnosed, earlier eradicated and non-infected. MATERIAL AND METHODS: Patients were selected from routine referrals to the Endoscopy units at three different Norwegian hospitals. In all four cohorts, gastric biopsies were scored according to the Sydney classification, and symptoms according to the Gastrointestinal Symptom Rating Scale score, including sub-scores for upper gastrointestinal symptoms and functional bowel symptoms. Patients in the H. pylori resistant group were treated with a triple therapy regimen that consisted of levofloxacin, amoxicillin and a proton pump inhibitor. RESULTS: We included 185 patients, 42 H. pylori treatment resistant, 50 newly diagnosed, 61 previously H. pylori eradicated and 32 never infected. The treatment-resistant cohort had higher scores for upper gastrointestinal symptoms and functional bowel symptoms compared to the other groups except for the group being never H. pylori infected. The H. pylori resistant patients had lower Sydney scores than patients with newly diagnosed H. pylori infection. The triple combination showed a high efficacy of 91% to eradicate H. pylori. CONCLUSIONS: Patients with treatment-resistant H. pylori infection had more gastrointestinal symptoms, but a lower Sydney score than patients with newly diagnosed infection. A treatment regimen including levofloxacin showed a high efficacy in eradicating H. pylori in patients that previously had failed eradication treatment.


Assuntos
Farmacorresistência Bacteriana/efeitos dos fármacos , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Idoso , Amoxicilina/uso terapêutico , Antibacterianos/farmacologia , Quimioterapia Combinada , Feminino , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/fisiopatologia , Helicobacter pylori/metabolismo , Helicobacter pylori/patogenicidade , Humanos , Levofloxacino/uso terapêutico , Masculino , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons/uso terapêutico
6.
Medicine (Baltimore) ; 99(38): e22137, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957336

RESUMO

BACKGROUND: Helicobacter pylori (HP) infection causes many diseases, such as peptic ulcers, gastritis and gastric cancer, and MALToma. It has been gradually accepted that all HP-infected patients should be treated because HP is regarded as an infection. Therefore, the importance of selecting the optimal treatment regimen has increased. Although the 14-day standard triple therapy (STT) is recommended in the current guidelines, prolonging treatment duration is controversial in real practice because of inconsistent results from previous data and the risk of adverse effects. Additionally, the effect of STT using ilaprazole has not been reported until now. We aimed to compare the eradication rate between 7 and 10 days STT using ilaprazole. METHODS: A prospective randomized controlled trial was conducted, which was divided into 2 treatment groups: the control group was 7 days of STT, and the test group was 10 days of STT. The eradication regimen was 10 mg ilaprazole, 500 mg clarithromycin, and 1000 mg amoxicillin twice daily. We included patients who were diagnosed with positive results of H pylori examination. We compared the HP eradication rate according to treatment duration, CYP2C19 subtype and endoscopic diagnosis. RESULTS: We enrolled a total of 254 patients consisting of 127 patients in each treatment arm. The eradication rates of the control and test groups were 65.4% (82/127) and 74.8% (95/127), respectively, in the intention-to-treat analysis (P = .1). In the per-protocol analysis, 70.3% (83/118) and 82.6% (94/115) were eradicated in each group, which was statistically significant (P = .027). The CYP2C19 subtype was examined in 230 patients. The eradication rate was 79.2% (57/72), 75.4% (92/122), and 72.2% (26/36) in each group, which was not significantly different (P = .704). CONCLUSION: Ten-day STT was more effective than 7-day STT for HP eradication. The eradication rate was not affected by the CYP2C19 genotype.


Assuntos
2-Piridinilmetilsulfinilbenzimidazóis/administração & dosagem , Amoxicilina/administração & dosagem , Antibacterianos/administração & dosagem , Claritromicina/administração & dosagem , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
7.
Ars pharm ; 61(3): 163-168, jul.-sept. 2020. tab, ilus, graf
Artigo em Inglês | IBECS | ID: ibc-195118

RESUMO

INTRODUCTION: The aim of the present study was to develop and to characterize the floating raft system (FRS) of Amoxicillin to enhance gastric residence time and drug release to target Helicobacter pylori effectively. METHOD: In the present study, guar gum, glyceryl monostearate (GMS), calcium carbonate were selected as factors. Gelation duration (h), floating lag time (min), and % Cumulative drug release (CDR) were selected as responses. 23 factorial design with replicates was selected for experimentation. RESULTS: It was observed that guar gum and GMS were the major factors affecting gelation duration, increase in the quantity of both guar gum and GMS increased gelation duration i.e., sustained gelation period (24 h). Floating time increased with an increase in the amount of guar gum and calcium carbonate, whereas an increase in the quantity of GMS decreased floating time. Guar gum, calcium carbonate, and GMS exhibited an antagonistic effect on % CDR. Contour plots were used to identify design space; further numerical analysis yielded 12 best solutions based on desirability. FRS exhibited greater AUCo-t, Cmax, tmax, and t1/2 when compared to marketed formulation approximately 2.30 folds enhancement and prolongation with a sustained release for greater than 24 h that might be due to better gelation CONCLUSIONS: It can be concluded that the floating raft system was successfully developed by the Design of experiment (DoE) application with fewer trails and by utilizing easily available excipients for better floating, gelation, and sustained delivery of the drug


INTRODUCCIÓN: El objetivo del presente estudio fue formular y caracterizar el Sistema Flotante (FRS, siglas en Inglés) de Amoxicilina para prolongar el tiempo de residencia gástrica y liberación del fármaco para el enfoque efectivo del Helicobacter pylori. MÉTODO: Para el presente estudio se seleccionaron como factores goma guar, Monoestearato de glicerilo (GMS), carbonato de calcio. Como reacciones, se seleccionaros el período de congelación (h), el lapso de flotación (min), y el porcentaje acumulado de liberación del fármaco (CDR). Para la experimentación se seleccionaron el diseño factorial 23 con réplicas. RESULTADOS: Se observó que la goma guar y el GMS fueron los factores principales que afectaron el período de congelación y mostraron un efecto sinérgico (positivo). Mientras que la goma guar y el carbonato de calcio mostraron un efecto positivo y el GMS mostró un efecto antagónico (negativo) en el lapso de flotación. El porcentaje CDR mostró un efecto antagónico en todos los factores. Se emplearon curvas de nivel para identificar el diseño del espacio, análisis numéricos posteriores produjeron 12 soluciones óptimas en base a la deseabilidad. El FRS mostró un mayor AUCo-t, Cmax, tmaxy t1/2 cuando se comparó con la formulación comercial, aproximadamente 2.30 cambios múltiplos y prolongación con liberación sostenida por más de 24 h que pudo deberse a una mejor congelación. CONCLUSIONES: Se puede concluir que el sistema flotante se desarrolló satisfactoriamente por la aplicación del Diseño de Experimentos (DoE) con menores ensayos y utilizando fácilmente los excipientes disponibles para una mejor flotación, congelación y suministro constante del fármaco


Assuntos
Composição de Medicamentos/métodos , Amoxicilina/química , Infecções por Helicobacter/tratamento farmacológico , Liberação Controlada de Fármacos , Técnicas In Vitro , Helicobacter pylori/efeitos dos fármacos , Amoxicilina/farmacologia , Congelamento , Cyamopsis/química , Carbonato de Cálcio/química , Análise de Variância , Antibacterianos/farmacocinética , Amoxicilina/farmacocinética
8.
Medicine (Baltimore) ; 99(32): e20761, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769862

RESUMO

The regimens containing levofloxacin (LVX) have been recommended as an alternate to standard triple therapy to treat Helicobacter pylori infections and H pylori mixed infection always lead to H pylori chronic infection. Although the molecular mechanism of LVX resistance with gyrA gene mutation has been clearly understood in H pylori, other genes involved in antibiotic resistance remain unclear. Efflux pump plays an important role in clinically relevant multidrug resistance. Furthermore, the relationship between the strains with different LVX level-resistances from individuals is also unknown.Helicobacter pylori monoclonal strains were isolated from patients with eradication failure. E test was used to detect the minimal inhibitory concentration of LVX. One lower-level LVX-resistant clone and 2 higher-level LVX-resistant clones from the same patient were selected to sequence the complete genomes. Single-nucleotide variants (SNVs) and mutations were extracted and analyzed from gryA and resistance-nodulation-division family efflux genes.Two clones with higher-level resistance had the mutation pattern of Asn87Lys and one lower-level LVX-resistant clone had an Asp91Asn mutation. Compared to clones with higher-level resistance, the higher genetic variations were found in genes belonging to the resistance-nodulation-division family in H pylori strains with lower-level resistance to LVX. There were significantly more SNVs of Hp0970 (hefE) and Hp1329 (hefI) in the lower-level LVX-resistant clone than those in the higher-level LVX-resistant clones (P = .044).The mutation pattern of the Asn87Lys of the gyrA gene confers a higher resistance to LVX than that of the Asp91Asn in H pylori. Increase in the number of SNVs of the Hp0970 (hefE) and Hp1329 (hefI) genes change the resistance to LVX. Twelve mutations verified by Sanger sequencing in Hp0970 (hefE) and Hp1329 (hefI) may decrease resistant levels to LVX.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Levofloxacino/farmacologia , Mutação/genética , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Sequenciamento de Nucleotídeos em Larga Escala , Humanos
9.
Gastroenterol. hepatol. (Ed. impr.) ; 43(6): 301-309, jun.-jul. 2020. graf, tab
Artigo em Inglês | IBECS | ID: ibc-193512

RESUMO

BACKGROUND: The Maastricht V Consensus recommends quadruple therapies as first-line Helicobacter pylori treatment in high clarithromycin (CLA) resistance areas. AIMS: To compare efficacy, side effects and compliance between quadruple concomitant non-bismuth vs bismuth quadruple therapy. METHOD: Prospective study enrolling H. pylori-positive patients. Omeprazol and a three-in-one formulation of bismuth-metronidazol-tetracycline (OBMT-3/1) for 10 days, or combination of omeprazol-clarithromycin-amoxicillin-metronidazol (OCAM) for 14 days, were prescribed. Eradication outcome was assessed by urea breath test or histology. Side effects and compliance were recorded during the treatment period with specific questionnaires. RESULTS: 404 patients were recruited (median age 53 years; 62.87% women). In 382 (183 with OCAM, 199 with OBMT-3/1) the post-treatment test result was available. The eradication rates were 85.94% (CI95%: 80.20-90.52) with OCAM and 88.21% (CI95%: 83.09-92.22) with OBMT-3/1 (p = 0.595) in intention-to-treat analysis, whilst in per protocol analysis they were 91.12% (CI95%: 85.78-94.95) and 96.17% (CI95%: 92.28-98.45) respectively (p = 0.083). Compliance over 90% was 91.35% with OCAM and 92.04% with OBMT-3/1 (p = 0.951). Some side effect was present in 94.02% with OCAM and in 88.89% with OBMT-3/1 (p = 0.109), being longer (12 vs 7 days, p < 0.0001) and more severe (p < 0.0001) with OCAM. CONCLUSIONS: In a high CLA-resistance area, there are no differences between OBMT-3/1 and OCAM in H. pylori eradication and compliance rates, but OBMT-3/1 achieves a higher safety profile


ANTECEDENTES: El Consenso de Maastricht V recomienda tetraterapias como tratamiento de primera línea de Helicobacter pylori en áreas con elevada resistencia a claritromicina (CLA). OBJETIVOS: Comparar la eficacia, los efectos secundarios y el cumplimiento terapéutico entre la tetraterapia sin bismuto y la tetraterapia con bismuto. MÉTODO: Estudio prospectivo que incluyó a pacientes con H. pylori. Se prescribió omeprazol y una formulación 3 en uno de bismuto-metronidazol-tetraciclina (OBMT-3/1) durante 10 días, o una combinación de omeprazol-claritromicina-amoxicilina-metronidazol (OCAM) durante 14 días. El resultado de la erradicación se evaluó mediante una prueba de aliento con urea o histología. Los efectos secundarios y el cumplimiento terapéutico se registraron durante el período de tratamiento empleando cuestionarios específicos. RESULTADOS: Se incluyeron 404 pacientes (mediana de edad de 53 años; un 62,87% de mujeres). El resultado de la prueba posterior al tratamiento estuvo disponible en 382 pacientes (183 con OCAM, 199 con OBMT-3/1). Las tasas de erradicación fueron del 85,94% (IC 95%: 80,20-90,52) con OCAM y del 88,21% (IC 95%: 83,09-92,22) con OBMT-3/1 (p = 0,595) en el análisis por intención de tratar, mientras que en el análisis por protocolo fueron del 91,12% (IC 95%: 85,78-94,95) y del 96,17% (IC 95%: 92,28-98,45), respectivamente (p = 0,083). El cumplimiento terapéutico superior al 90% fue del 91,35% con OCAM y del 92,04% con OBMT-3/1 (p = 0,951). Se observaron efectos secundarios en el 94,02% de los pacientes tratados con OCAM y en el 88,89% de los tratados con OBMT-3/1 (p = 0,109), y fueron más prolongados (12 frente a 7 días, p < 0,0001) y más graves (p < 0,0001) con OCAM. CONCLUSIONES: En un área con elevada resistencia a la CLA no se observan diferencias entre OBMT-3/1 y OCAM en la erradicación de H. pylori ni en las tasas de cumplimiento, pero OBMT-3/1 presenta un perfil de seguridad superior


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Helicobacter pylori/efeitos dos fármacos , Infecções por Helicobacter/tratamento farmacológico , Bismuto/uso terapêutico , Infecções por Helicobacter/prevenção & controle , Resultado do Tratamento , Erradicação de Doenças/métodos , Estudos Prospectivos , Omeprazol/uso terapêutico , Claritromicina/uso terapêutico , Amoxicilina/uso terapêutico , Metronidazol/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos
10.
Life Sci ; 256: 117977, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32603822

RESUMO

AIMS: Silibinin is the major component of flavonolignans complex mixture (Silymarin), which is obtained from Silybum marianum (L.) Gaertn. Despite several reports about silibinin, little is known about its effects on gastric diseases. Then, the present study aims to evaluate the silibinin effect against Helicobacter pylori infection, gastric tumor cells and immunomodulation. MAIN METHODS: The anti-H. pylori effect was performed on 43504 and 43629 strains by minimum inhibitory concentration (MIC) determination, observing morphological alterations by scanning electron microscopy and in silico evaluation by molecular docking. Immunomodulatory activity (Interleukins-6 and 10, TNF-α and NO inhibition) was determined in H. pylori-stimulated macrophages and the cytotoxic activity on gastric adenocarcinoma cells prior and after metabolization by S9 fraction. KEY FINDINGS: Silibinin showed anti-H. pylori activity with MIC of 256 µg/mL, promoted important morphological changes in the bacterial cell wall, as blebs and clusters, suggesting interaction with Penicillin Binding Protein (PBP) subunits. Immunomodulatory potential was observed at 50 µg/mL with the inhibition of produced cytokines and NO by H. pylori-stimulated macrophages of 100% for TNF-ɑ, 56.83% for IL-6, and 70.29% for IL-10 and 73.33% for NO. Moreover, silibinin demonstrated significant cytotoxic activity on adenocarcinoma cells (CI50: 60.17 ± 0.95 µg/mL) with a higher selectivity index (SI: 1.52) compared to cisplatin. After metabolization silibinin showed an increase of cytotoxicity with a CI50 six-fold decrease (10.46 ± 0.25). SIGNIFICANCE: The use of silibinin may become an important alternative tool in the prevention and treatment of H. pylori infection and, consequently, in gastric cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Infecções por Helicobacter/prevenção & controle , Helicobacter pylori/efeitos dos fármacos , Simulação de Acoplamento Molecular/métodos , Silibina/farmacologia , Neoplasias Gástricas/prevenção & controle , Animais , Antineoplásicos Fitogênicos/uso terapêutico , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Infecções por Helicobacter/patologia , Helicobacter pylori/fisiologia , Camundongos , Testes de Sensibilidade Microbiana/métodos , Células RAW 264.7 , Silibina/química , Silibina/uso terapêutico , Neoplasias Gástricas/patologia
11.
JAMA Netw Open ; 3(6): e206628, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32589229

RESUMO

Importance: The associations of lifestyle factors with gastric cancer (GC) are still underexplored in populations in China. Long-term nutritional supplementation may prevent GC in high-risk populations, but the possible effect modification by lifestyle factors remains unknown. Objective: To evaluate how lifestyle factors, including smoking, alcohol intake, and diet, may change the risk of GC incidence and mortality and whether the effects of vitamin and garlic supplementation on GC are associated with major lifestyle factors. Design, Setting, and Participants: This is a secondary analysis of the Shandong Intervention Trial, a masked, randomized, placebo-controlled trial that aimed to assess the effect of vitamin and garlic supplementations and Helicobacter pylori treatment on GC in a factorial design with 22.3 years of follow-up. The study took place in Linqu County, Shandong province, China, a high-risk area for GC. Data were collected from Jully 1995 to December 2017. Overall, 3365 participants aged 35 to 64 years identified in 13 randomly selected villages who agreed to undergo gastroscopy were invited to participate in the trial and were included in the analysis. Data analysis was conducted from March to May 2019. Interventions: Participants received vitamin and garlic supplementation for 7.3 years, H pylori treatment for 2 weeks (among participants with H pylori ), or placebo. Main Outcomes and Measures: The primary outcomes were GC incidence and GC mortality (1995-2017). We also examined the progression of gastric lesions (1995-2003) as a secondary outcome. Results: Of the 3365 participants (mean [SD] age, 47.1 [9.2] years; 1639 [48.7%] women), 1677 (49.8%) were randomized to receive active vitamin supplementation, with 1688 (50.2%) receiving placebo, and 1678 (49.9%) receiving active garlic supplementation, with 1687 (50.1%) receiving placebo. Overall, 151 GC cases (4.5%) and 94 GC deaths (2.8%) were identified. Smoking was associated with increased risk of GC incidence (odds ratio, 1.72; 95% CI, 1.003-2.93) and mortality (hazard ratio [HR], 2.01; 95% CI, 1.01-3.98). Smoking was not associated with changes to the effects of vitamin or garlic supplementation. The protective effect on GC mortality associated with garlic supplementation was observed only among those not drinking alcohol (never drank alcohol: HR, 0.33; 95% CI, 0.15-0.75; ever drank alcohol: HR, 0.92; 95% CI, 0.55-1.54; P for interaction = .03), and significant interactions were only seen among participants with H pylori (never drank alcohol: HR, 0.31; 95% CI, 0.12-0.78; ever drank alcohol: HR, 0.91; 95% CI, 0.52-1.60; P for interaction = .04). No significant interactions between vitamin supplementation and lifestyle factors were found. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, smoking was associated with an increased risk of GC incidence and mortality. Not drinking alcohol was associated with a stronger beneficial effect of garlic supplementation on GC prevention. Our findings provide new insights into lifestyle intervention for GC prevention, suggesting that mass GC prevention strategies may need to be tailored to specific population subgroups to maximize the potential beneficial effect. Trial Registration: ClinicalTrials.gov Identifier: NCT00339768.


Assuntos
Alho/química , Helicobacter pylori/efeitos dos fármacos , Neoplasias Gástricas/prevenção & controle , Vitaminas/farmacologia , Adulto , Compostos Alílicos/farmacologia , Estudos de Casos e Controles , China/epidemiologia , Suplementos Nutricionais/efeitos adversos , Feminino , Gastroscopia/métodos , Humanos , Incidência , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Sulfetos/farmacologia
12.
Int J Infect Dis ; 97: 102-107, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32474200

RESUMO

OBJECTIVES: Bhutan suffers from a high prevalence of Helicobacter pylori (H. pylori) infection and gastric cancer-related mortality. In preparation for a countrywide H. pylori eradication program, the antibiotic resistance patterns of H. pylori infection were surveyed in different geographical regions. METHODS: Dyspeptic patients in 6 districts including Thimphu, Punakha, Wangdue, Trongsa, Bumthang, and Haa underwent upper gastrointestinal endoscopy during GASTROCAMP and were enrolled between December 2010 and April 2015. Gastric biopsies were obtained for rapid urease test, histopathology, and H. pylori culture. Antimicrobial susceptibility testing was later performed if the culture was positive. RESULTS: A total of 1178 patients were surveyed. The overall H. pylori infection in Bhutan was 66.2%. Punakha had the highest prevalence of H. pylori infection (85.6%). Thimphu and Punakha (city areas) had higher prevalence of H. pylori infection than rural districts (73.5% vs 63.3%, OR=1.61, 95% CI 1.22-2.13, p=0.0008). There were 357 patients (30.3%) with positive H. pylori culture completed antimicrobial susceptibility testing. The mean age was 40.5 years with female predominance (57.1%). No amoxicillin resistant strains were found. Metronidazole resistance was 81% followed by levofloxacin resistance (8.1%). Clarithromycin (2%) and tetracycline (0.6%) resistance was rare except in Thimphu, the capital city (10%) vs 0% in rural areas, p<0.001. The metronidazole resistance rate remained stable at approximately 80% during the past 5 years of study. Levofloxacin-resistant strains gradually rose from 5.3% in 2010 to 9.9% in 2015. CONCLUSIONS: Bhutan had a high prevalence of H. pylori infection. Metronidazole resistance was extremely high, whereas clarithromycin resistance was quite low in this specific area. Antibiotic resistance pattern could be good evidence for guiding a proper treatment regimen for H. pylori infection in Bhutan.


Assuntos
Farmacorresistência Bacteriana , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/efeitos dos fármacos , Adulto , Amoxicilina/farmacologia , Antibacterianos/farmacologia , Butão/epidemiologia , Claritromicina/farmacologia , Feminino , Infecções por Helicobacter/microbiologia , Helicobacter pylori/isolamento & purificação , Humanos , Levofloxacino/farmacologia , Masculino , Metronidazol/farmacologia , Pessoa de Meia-Idade , Prevalência , Tetraciclina/farmacologia
14.
J Vet Sci ; 21(3): e39, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32476313

RESUMO

BACKGROUND: There are various Helicobacter species colonizing the stomachs of animals. Although Helicobacter species usually cause asymptomatic infection in the hosts, clinical signs can occur due to gastritis associated with Helicobacter in animals. Among them, Helicobacter pylori is strongly associated with chronic gastritis, gastric ulcers, and gastric cancers. As the standard therapies used to treat H. pylori have proven insufficient, alternative options are needed to prevent and eradicate the diseases associated with this bacterium. Cheonwangbosim-dan (CBD), a traditional herbal formula that is popular in East Asia, has been commonly used for arterial or auricular flutter, neurosis, insomnia, and cardiac malfunction-induced disease. OBJECTIVES: The present study investigated the antimicrobial effect of CBD on H. pylori-infected human gastric carcinoma AGS cells and model mice. METHODS: AGS cells were infected with H. pylori and treated with a variety of concentrations of CBD or antibiotics. Mice were given 3 oral inoculations with H. pylori and then dosed with CBD (100 or 500 mg/kg) for 4 weeks or with standard antibiotics for 1 week. One week after the last treatment, gastric samples were collected and examined by histopathological analysis, real-time quantitative polymerase chain reaction, and immunoblotting. RESULTS: Our results showed that CBD treatment of AGS cells significantly reduced the H. pylori-induced elevations of interleukin-8, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). In the animal model, CBD treatment inhibited the colonization of H. pylori and the levels of malondialdehyde, inflammation, proinflammatory cytokines, iNOS, and COX-2 in gastric tissues. CBD also decreased the phosphorylation levels of p38 mitogen-activated protein kinase family. CONCLUSIONS: This study suggests that CBD might be a prospective candidate for treating H. pylori-induced gastric injury.


Assuntos
Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Gastrite/tratamento farmacológico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Animais , Carcinoma , Linhagem Celular Tumoral , Masculino , Medicina Tradicional Coreana , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Gástricas
15.
Medicine (Baltimore) ; 99(21): e20361, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481329

RESUMO

INTRODUCTION: Gastric adenocarcinoma of the fundic gland type (GA-FG) is a newly described entity that is characterized by well-differentiated neoplasm with unclear etiopathogenesis. PATIENT CONCERNS: A 60-year-old Chinese man was referred to our hospital for abdominal distension. DIAGNOSIS: Esophagogastroduodenoscopy (EGD) showed a depressed lesion found using in the greater curvature of the stomach. The pathological diagnosis of the biopsy specimens indicated that the tumor was GA-FG (chief cell predominant type, GA-FG-CCP). INTERVENTIONS: Endoscopic submucosal dissection (ESD) was performed. The histopathological examination of the ESD specimen revealed gastric hyperplasia of the fundic gland type around the adenocarcinoma cells. OUTCOMES: The surgical outcomes were good. The EGD showed a scar with no recurrence, and no symptoms were observed 1 year postoperatively during the follow-up. CONCLUSION: We present a rare case of a depressed lesion with a pathogenic expression suggesting gastric hyperplasia of the fundic gland type around the adenocarcinoma cells. Considering the origin of oxyntic mucosa, we consider that it may develop into GA-FG. To understand this issue better, similar cases should be monitored in the future.


Assuntos
Adenocarcinoma/diagnóstico , Mucosa Gástrica/anormalidades , Adenocarcinoma/diagnóstico por imagem , China , Ressecção Endoscópica de Mucosa/métodos , Endoscopia do Sistema Digestório/métodos , Feminino , Mucosa Gástrica/diagnóstico por imagem , Mucosa Gástrica/fisiopatologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/patogenicidade , Humanos , Pessoa de Meia-Idade , Mucina-6/análise , Pepsinogênio A/análise
16.
Virchows Arch ; 477(4): 489-496, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32356024

RESUMO

Pyloric metaplasia (PM) and pseudopyloric metaplasia (PPM) are metaplastic changes resulting in pyloric-type glands in the gastric oxyntic mucosa that mainly occur in chronic gastritis caused by Helicobacter pylori (H. pylori) infection. Focusing on PM and PPM, we classified the histological changes in gastric mucosa according to the Updated Sydney System, using 314 biopsy specimens of gastric greater curvature of the middle body before H. pylori eradication (HPE). Next, the numbers of PM and PPM glands were counted in 47 specimens, and subjects were followed up over 10 years after HPE. PPM was recognized jointly with inflammation, activity, atrophy, and intestinal metaplasia, but PM was recognized more frequently than PPM as atrophy and intestinal metaplasia progressed. Both PM and PPM regressed significantly within 6 years after HPE. Additionally, we demonstrated that PM and PPM are not always coincident with spasmolytic polypeptide-expressing metaplasia (SPEM). In conclusion, PM and PPM are considered different modulations of the same line of differentiation, which are both reversible, with PM potentially emerging from PPM upon progression.


Assuntos
Mucosa Gástrica/patologia , Gastrite/patologia , Infecções por Helicobacter/patologia , Helicobacter pylori/patogenicidade , Biópsia , Diferenciação Celular , Doença Crônica , Mucosa Gástrica/química , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/microbiologia , Gastrite/tratamento farmacológico , Gastrite/metabolismo , Gastrite/microbiologia , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/administração & dosagem , Metaplasia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
17.
Dig Dis ; 38(4): 261-268, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32396919

RESUMO

AIM: Helicobacter pylori infection has been established as a definite risk factor for gastric cancer. However, the consequence of H. pylori eradication on the progression of gastroesophageal reflux disease (GERD) remains controversial. The purpose of our study was to investigate the relationship between H. pylori eradication and the development of GERD. METHODS: A comprehensive, English literature search was performed from January 1990 to April 2019. Only randomized controlled trials (RCT) that evaluated the effect of H. pylori eradication on GERD were included. Meta-analysis of pooled OR was performed using Review Manger 5.1.7. RESULTS: Seventeen articles with 6,889 subjects (intention-to-treat) that fulfilled the inclusion criteria were finally included in the analysis. Of them, 8 RCTs have the similar study design and inclusion criterion, which included patients with H. pylori infection but without GERD at baseline. The OR for the development of erosive GERD after H. pylori eradication was 1.67 (95% CI 1.12-2.48, p = 0.01). The OR for the development of GERD-related symptoms after H. pylori eradication in eradication group compared with control group was 1.04 (95% CI 0.84-1.29, p = 0.71). In addition, 9 RCTs included patients with both baseline H. pylori infection and GERD. The OR for the healing rates and relapse rates after H. pylori eradication in the H. pylori eradication group vs. control group was 0.92 (95% CI 0.47-1.82, p = 0.82) and 1.12 (95% CI 0.60-2.09, p = 0.71), respectively. CONCLUSIONS: Our meta-analyses showed H. pylori eradication may lead to the development of new erosive GERD. However, eradication of H. pylori may affect neither the healing rates nor relapse rates of preexisting GERD.


Assuntos
Refluxo Gastroesofágico/complicações , Infecções por Helicobacter/complicações , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos de Casos e Controles , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Humanos , Fatores de Risco
18.
Artigo em Inglês | MEDLINE | ID: mdl-32340212

RESUMO

Helicobacter pylori (H. pylori) is a primary etiologic factor in gastric diseases. Sulglycotide is a glycopeptide derived from pig duodenal mucin. Esterification of its carbohydrate chains with sulfate groups creates a potent gastroprotective agent used to treat various gastric diseases. We investigated the inhibitory effects of sulglycotide on adhesion and inflammation after H. pylori infection in human gastric adenocarcinoma cells (AGS cells). H. pylori reference strain 60190 (ATCC 49503) was cultured on Brucella agar supplemented with 10% bovine serum. Sulgylcotide-mediated growth inhibition of H. pylori was evaluated using the broth dilution method. Inhibition of H. pylori adhesion to AGS cells by sulglycotide was assessed using a urease assay. Effects of sulglycotide on the translocation of virulence factors was measured using western blot to detect cytotoxin-associated protein A (CagA) and vacuolating cytotoxin A (VacA) proteins. Inhibition of IL-8 secretion was measured using enzyme-linked immunosorbent assay (ELISA) to determine the effects of sulglycotide on inflammation. Sulglycotide did not inhibit the growth of H. pylori, however, after six and 12 hours of infection on AGS cells, H. pylori adhesion was significantly inhibited by approximately 60% by various concentrations of sulglycotide. Sulglycotide decreased H. pylori virulence factor (CagA and VacA) translocation to AGS cells and inhibited IL-8 secretion. Sulglycotide inhibited H. pylori adhesion and inflammation after infection of AGS cells in vitro. These results support the use of sulglycotide to treat H. pylori infections.


Assuntos
Aderência Bacteriana , Infecções por Helicobacter , Helicobacter pylori , Sialoglicoproteínas , Animais , Aderência Bacteriana/efeitos dos fármacos , Proteínas de Bactérias , Bovinos , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Humanos , Inflamação/tratamento farmacológico , Sialoglicoproteínas/farmacologia , Suínos
19.
Postgrad Med ; 132(6): 512-520, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32281451

RESUMO

Objectives: Helicobacter pylori (H. pylori) infection caused by antibiotic-resistant strains represents a major public health threat that aggressively promotes gastric cancer progression. Antibiotic resistance evaluation is immensely important to counteract its emergence. Here we merely determine the prevalence of antibiotic resistance in H. pylori isolates and its correlation with cagA motifs and the homB gene. Methods: The antibiotic resistance pattern was investigated on 128 H. pylori isolated strains utilizing the disk diffusion method and study the correlation between it and the presence of pathogenic genes, cagA EPIYA motifs and homB gene, were accurately detected using the PCR. Results: The resistance rates to four antibiotics were 70.1% for metronidazole, 35.5% for amoxicillin, 7.2% for clarithromycin and 8.2% for tetracycline. Resistance phenotypes were separated into two groups, single resistance (63.2%) and multi-resistance (12.5%). The prevalence of cagA-ABCC resistant strains and homB+ resistant strains was significantly higher in cancer (p = 0.04 and p = 0.01, respectively) than those of other diseases. The prevalence of cagA-homB + resistance strains was 21.8% and had a significant correlation with PUD. A significant relationship was observed between amoxicillin resistant rate with ABC-homB (p = 0.0006). Conclusion: The Resistance rate to selected antibiotics in Shiraz is higher than years ago. The presence of cagA-homB + is associated with antibiotic resistance and also homB can be used as a marker to antibiotic resistance status prediction in H. pylori isolated in this area.


Assuntos
Antibacterianos , Antígenos de Bactérias/genética , Proteínas da Membrana Bacteriana Externa/genética , Proteínas de Bactérias/genética , Resistência Microbiana a Medicamentos/genética , Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Adulto , Antibacterianos/classificação , Antibacterianos/farmacologia , Feminino , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/genética , Helicobacter pylori/isolamento & purificação , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia
20.
BMC Complement Med Ther ; 20(1): 124, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32321502

RESUMO

BACKGROUND: Kaempferia parviflora (KP) has been used in traditional Thai medicine to cure gastrointestinal disorders since ancient times. Helicobacter pylori is an initiating factor in gastric pathogenesis via activation of massive inflammation, the cumulative effect of which leads to gastric disease progression, including gastric carcinogenesis. Accordingly, the effect of a crude ethyl acetate extract of KP (CEAE-KP) on proinflammatory cytokine production and cell chemotaxis was the focus of this study. METHODS: The cytotoxicity of CEAE-KP (8-128 µg/ml) on AGS (gastric adenocarcinoma) cells was determined at 6, 12 and 24 h using an MTT assay. The effect of CEAE-KP on H. pylori-induced interleukin (IL)-8 production by AGS cells was evaluated by ELISA and RT-PCR. The effect of CEAE-KP on monocyte and neutrophil chemotaxis to H. pylori soluble protein (sHP) and IL-8, respectively, was determined using a Boyden chamber assay with THP-1 or HL-60 cells. RESULTS: CEAE-KP reduced AGS cell viability in a concentration- and time-dependent manner, but at 8-16 µg/ml, it was not cytotoxic after 6-24 h of exposure. Coculture of AGS cells with CEAE-KP at a noncytotoxic concentration of 16 µg/ml and H. pylori reduced IL-8 secretion by ~ 60% at 12 h, which was consistent with the decreased level of mRNA expression, and inhibited neutrophil chemotaxis to IL-8. sHP (100 ng/ml) induced marked monocyte chemoattraction, and this was decreased by ~ 60% by CEAE-KP. CONCLUSION: CEAE-KP might serve as a potent alternative medicine to ameliorate the inflammation mediated by H. pylori infection.


Assuntos
Quimiotaxia de Leucócito/efeitos dos fármacos , Citocinas/metabolismo , Helicobacter pylori/efeitos dos fármacos , Inflamação/tratamento farmacológico , Interleucina-8/metabolismo , Extratos Vegetais/farmacologia , Acetatos , Células HL-60 , Humanos , Células THP-1 , Tailândia , Zingiberaceae/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA