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1.
Rev Med Suisse ; 16(680): 268-271, 2020 Feb 05.
Artigo em Francês | MEDLINE | ID: mdl-32022492

RESUMO

Peptic ulcer induced upper gastrointestinal hemorrhage is a frequent digestive emergency and is one of the most common cause of hospitalization. There are several intrinsic risk factors for peptic ulcer bleed such as advanced age, previous gastro-intestinal hemorrhage, male sex and the presence of Helicobacter pylori. In high risk patients for peptic ulcer disease, gastric protection measures should be considered, most often by treatment with proton pump inhibitors. The eradication of Helicobacter pylori should also be discussed for long-term treatments.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/prevenção & controle , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Helicobacter pylori/patogenicidade , Humanos , Úlcera Péptica/complicações , Inibidores da Bomba de Prótons/uso terapêutico
2.
Zhonghua Er Ke Za Zhi ; 58(1): 41-45, 2020 Jan 02.
Artigo em Chinês | MEDLINE | ID: mdl-31905475

RESUMO

Objective: To evaluate the effectiveness of eradication therapy based on Helicobacter pylori (Hp) susceptibility and CYP2C19 genotype in children with refractory Hp infection. Methods: In this prospective observational cohort study, 156 children with Hp refractory to amoxicillin+clarithromycin+omeprazole triple regimen in Baoding Children's Hospital from December 2017 to May 2018 were enrolled. Ninety-two of them underwent Hp culture and CYP2C19 detection. Seventy-five cases with positive Hp culture were defined as culture successful group and were treated according to Hp susceptibility and CYP2C19 genotype. Seventeen cases with negative Hp culture were defined as culture failed group and were treated only based on the results of CYP2C19 genotype. Sixty-four children who did not have Hp culture and CYP2C19 gene testing were defined as the empirical eradication therapy group and were treated with quadruple regimen (amoxicillin+metronidazole+omeprazole+bismuth). Bacterial resistance, CYP2C19 polymorphism and therapeutic effectiveness between the three groups were compared using chi-square test. Results: Among the 75 positive Hp culture results, 72 (96%) were resistant to clarithromycin, 3 (4%) were resistant to metronidazole, 5 (7%) were resistant to levofloxacin, 5 (7%) were resistant to rifampicin, 1 (1%) was resistant to tetracycline, and none was resistant to amoxicillin and furazolidone. The CYP2C19 polymorphism in 92 patients showed that 43 (47%) were extensive metabolizer (EM), 9 (10%) were poor metabolizer (PM), and 40 (43%) were intermediate metabolizer (IM). In terms of the effectiveness, eradication rate in the culture successful group,culture failed group and empirical eradication therapy group were 99% (74/75), 88% (15/17) and 72% (46/64), respectively (χ(2)=21.325, P<0.05). The eradication rate in the culture successful group was significantly higher than that in empirical eradication therapy group (χ(2)=21.005, P<0.05), while there was no difference between empirical eradication therapy group and culture failed group (χ(2)=1.154, P=0.283). Conclusion: Eradication regimen based on bacterial susceptibility and CYP2C19 genotype should be considered in children with refractory Hp infection.


Assuntos
Citocromo P-450 CYP2C19/genética , Quimioterapia Combinada , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/genética , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/genética , Omeprazol/uso terapêutico , Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Bismuto/uso terapêutico , Criança , Claritromicina/administração & dosagem , Claritromicina/uso terapêutico , Estudos de Coortes , Resistência a Medicamentos/genética , Feminino , Genótipo , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Metronidazol/uso terapêutico , Omeprazol/administração & dosagem , Polimorfismo Genético , Estudos Prospectivos , Resultado do Tratamento
3.
J Enzyme Inhib Med Chem ; 35(1): 404-413, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31880473

RESUMO

A urease inhibitor with good in vivo profile is considered as an alternative agent for treating infections caused by urease-producing bacteria such as Helicobacter pylori. Here, we report a series of N-monosubstituted thioureas, which act as effective urease inhibitors with very low cytotoxicity. One compound (b19) was evaluated in detail and shows promising features for further development as an agent to treat H. pylori caused diseases. Excellent values for the inhibition of b19 against both extracted urease and urease in intact cell were observed, which shows IC50 values of 0.16 ± 0.05 and 3.86 ± 0.10 µM, being 170- and 44-fold more potent than the clinically used drug AHA, respectively. Docking simulations suggested that the monosubstituted thiourea moiety penetrates urea binding site. In addition, b19 is a rapid and reversible urease inhibitor, and displays nM affinity to urease with very slow dissociation (koff=1.60 × 10-3 s-1) from the catalytic domain.


Assuntos
Helicobacter pylori/efeitos dos fármacos , Ureia/farmacologia , Urease/antagonistas & inibidores , Antibacterianos , Relação Dose-Resposta a Droga , Inibidores Enzimáticos , Helicobacter pylori/citologia , Helicobacter pylori/enzimologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade , Ureia/análogos & derivados , Ureia/química , Urease/metabolismo
4.
APMIS ; 128(1): 25-34, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31628820

RESUMO

Eradication failure of Helicobacter pylori infection could play a causal role in progression of gastric disorders. In this study, infection with H. pylori was followed in gastric biopsies of symptomatic adult patients at two phases during 1-year period. Analyses were done to show association of therapeutic regimens with the refractory infection, changes in sequence types (STs) and minimum inhibitory concentration (MIC) values, and progression of histopathological changes. Infection with H. pylori was confirmed in 32.3% (57/170) of the patients. Persistent infection with H. pylori was confirmed in 14 out of the 25 patients (56%) who participated at the second phase of the study. A difference between primary and secondary resistance rates to clarithromycin (49% vs 64.3%), metronidazole (76.36% vs 100%), and ciprofloxacin (45% vs 57.1%) was detected. Although the re-emerged strains in patients with refractory infection did not show alteration in STs, their MIC50 values showed twofold increases for clarithromycin and ciprofloxacin. While ciprofloxacin containing regimens were more successful, failure of metronidazole containing regimens was detected in 77% of the patients. Consequently, inappropriate medication has an impact on refractory H. pylori infection, which could cause to a rise in resistance levels to antibiotics and progression of pathological disorders.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/patologia , Helicobacter pylori/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Técnicas de Tipagem Bacteriana , Biópsia , Ciprofloxacino/farmacologia , Claritromicina/farmacologia , Feminino , Seguimentos , Técnicas Histológicas , Humanos , Concentração Inibidora 50 , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Estômago/microbiologia , Estômago/patologia
5.
World J Microbiol Biotechnol ; 36(1): 3, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31832784

RESUMO

Available disinfection methods and therapies against Helicobacter pylori have multiple disadvantages, such as increased prevalence of antibiotic-resistant strains, which requires the search for novel effective antimicrobial agents against H. pylori. Among them, naturally-occurring antimicrobial compounds, like essential oil components (EOCs), have been reported as substances with anti-H. pylori potential. To avoid the disadvantages associated with using EOCs in their free form, including volatility, low water solubility and intense sensory properties, their immobilisation in inert supports has recently been developed. This study sought to evaluate the inhibitory properties of EOCs immobilised on silica microparticles against H. pylori and to elucidate the mechanism of action of the immobilised antimicrobials. After the preparation and characterisation of the antimicrobial supports, the susceptibility of H. pylori in the presence of the immobilised compounds was assessed by plate count, fluorescent viability staining and direct viable count-fluorescent in situ hybridisation analyses. The antimicrobial supports were found to inhibit H. pylori growth, and to induce morphological and metabolic alterations to the H. pylori membrane, with a minimum bactericidal concentration value between 25 and 50 µg/ml according to the tested EOC. These findings indicate that immobilised EOCs can be used as potential antimicrobial agents for H. pylori clearance and treatment.


Assuntos
Anti-Infecciosos/farmacologia , Helicobacter pylori/efeitos dos fármacos , Óleos Voláteis/farmacologia , Contagem de Colônia Microbiana , Farmacorresistência Bacteriana Múltipla , Imobilização , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Dióxido de Silício/química
6.
Arq Gastroenterol ; 56(4): 361-366, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31721972

RESUMO

BACKGROUND: Helicobacter pylori infection in Chile remains as a public and private health-care system's challenge, with a prevalence of the infection over 70%. Nowadays, antibiotic treatment of the infection is mandatory to prevent the arising of severe associated diseases but failures in the eradication therapy mainly due to clarithromycin resistance has been observed worldwide and first line eradication therapy seems to be not effective anymore in several geographical areas. Thus, health-care systems are committed to maintain an epidemiological surveillance upon the evolution of the antibiotic resistance of this priority 2 pathogen. OBJECTIVE: This work reports a 10 years surveillance of the primary antibiotic resistance of H. pylori clinical isolates at the Biobío region-Chile, and the evolution of resistance toward amoxicillin, clarithromycin, levofloxacin, metronidazole, and tetracycline among the species. METHODS: H. pylori strains were investigated during the periods 2005-2007 (1435 patients analysed) and 2015-2017 (220 patients analysed) by inoculating a saline homogenate biopsy onto the surface of Columbia agar (Oxoid, Basingstoke, UK) - supplemented with 7% horse red blood cells plus DENT inhibitor (Oxoid, Basingstoke, UK) - following by incubation at 37ºC under 10% CO2 atmosphere for five days. Antibiotic resistance pattern of the isolates was assessed using the disk diffusion test in Müeller-Hinton agar supplemented with 7% horse red blood cells followed by incubation for further three days under 10% CO2 atmosphere. Statistical analysis was done using the SPSS v22 software and P values <0.05 were considered statistically significant. RESULTS: A total of 41% of 1435 patients were detected to be infected with H. pylori by bacteriological culture in 2005-2007 period, meanwhile 32.7% from 220 patients were also infected in 2015-2017 period. The clinical isolates of H. pylori are mostly susceptible to amoxicillin and tetracycline (both over 98% of strains), but less susceptible to levofloxacin in both periods analysed (over 79% of the strains). On the other hand, metronidazole continuous showing the highest score of resistant isolates (over 40% of resistant strains), although an 18% fewer resistant strains were observed in 2015-2017 period. Clarithromycin, the key antibiotic in eradication therapies, has an increased frequency of resistant strain isolated in the decade (22.5% in 2005-2007 and 29.2% in 2015-2017). Multidrug resistant strains (two, three and four antibiotics) were also detected in both periods with the highest scores for simultaneous resistance to clarithromycin-metronidazole (18%) and clarithromycin-metronidazole-levofloxacin (12.5%) resistant strains. According to gender, the isolates resistant to amoxicillin, clarithromycin and metronidazole were more frequent in female, with a specific increment in amoxicillin and clarithromycin resistance. CONCLUSION: The frequency of clarithromycin resistance (29.2%) detected in 2015-2017 suggests that conventional triple therapy is no longer effective in this region.


Assuntos
Antibacterianos/farmacologia , Helicobacter pylori/efeitos dos fármacos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Amoxicilina/farmacologia , Chile , Claritromicina/farmacologia , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Farmacorresistência Bacteriana Múltipla , Feminino , Infecções por Helicobacter/microbiologia , Humanos , Levofloxacino/farmacologia , Masculino , Metronidazol/farmacologia , Pessoa de Meia-Idade , Vigilância da População , Tetraciclina/farmacologia , Adulto Jovem
7.
Rev Med Suisse ; 15(667): 1854-1858, 2019 Oct 16.
Artigo em Francês | MEDLINE | ID: mdl-31617972

RESUMO

Helicobacter pylori infection is associated with chronic gastric inflammation, peptic ulcer and an increased risk of gastric cancer. Helicobacter eradication traditionally consists of an empirical therapy combining clarithromycine, amoxicillin and proton pump inhibitors. However, this classic therapy needs to be reassessed because of the raising prevalence of clarithromycine resistance. Various alternative eradication treatments have been studied. This article aims to review the recommended alternatives and the different factors to guide the most appropriate first line eradication therapy.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Amoxicilina/farmacologia , Amoxicilina/uso terapêutico , Antibacterianos/farmacologia , Claritromicina/farmacologia , Claritromicina/uso terapêutico , Farmacorresistência Bacteriana/efeitos dos fármacos , Quimioterapia Combinada , Humanos , Inibidores da Bomba de Prótons/farmacologia , Inibidores da Bomba de Prótons/uso terapêutico
8.
BMC Infect Dis ; 19(1): 880, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31640588

RESUMO

BACKGROUND: Antibiotic resistance is a leading cause of treatment failure in Helicobacter pylori infection. In Africa, there are very little data concerning the susceptibility of Helicobacter pylori isolates to antibiotics. The purpose of this study was to evaluate the resistance prevalence of Helicobacter pylori strains circulating in Cameroon, and to assess overexpression of efflux pump as a possible multi-drug resistance mechanisms. METHODS: A total of 140 H. pylori isolates were recovered from gastric biopsies of dyspeptic patients in two reference hospitals in Cameroon and analyzed for their antimicrobial susceptibility to amoxicillin, co-amoxiclav, ampicillin, penicillin, imipenem, metronidazole, rifabutin, erythromycin, clarithromycin, azithromycin, levofloxacin, ciprofloxacin, norfloxacin, tetracycline, doxycycline and minocycline. Antibiotic sensitivity was tested by disk diffusion method. Phe-Arg-naphthylamide (PAßN) was used as efflux pump inhibitor. INT broth microdilution method in supplemented Brain Heart Infusion broth was used to determine the MIC of ampicillin, amoxicillin, metronidazole, erythromycin, clarithromycin and doxycycline in the absence and the presence of PAßN against 32 selected MDR isolates. RESULTS: Overall H. pylori resistance rate was 100% to ampicillin, penicillin and co-amoxiclav; 97.14% to amoxicillin, 97.85% to metronidazole, 47.85% to erythromycin, 13.57% to clarithromycin; 5, 2.86 and 0.71% to doxycycline, tetracycline and minocycline respectively. No resistance to azithromycin, rifabutin, imipenem, ciprofloxacin, norfloxacin and levofloxacin was detected among H. pylori isolates. Seventy percent (70%) of the tested isolates elicited a multiple drugs resistance pattern; 42.57% double, 15.71% triple and 5.71% quadruple drugs resistance. Metronidazole and amoxicillin were more concerned with double resistance pattern (86.76%). The spectrum of activity recorded with metronidazole, doxycycline, clarithromycin and erythromycin ranged from 0 to 100% in the absence to the presence of PAßN against the tested MDR isolates. An 8 to 128-fold increase in potency was also noticed with these antibiotics in the presence of PAßN. CONCLUSION: With regard to the high resistance rate to both amoxicillin and metronidazole, these drugs should be avoided as components of triple therapy in our milieu. In contrast, ciprofloxacin, norfloxacin, levofloxacin and tetracyclines could be used to achieve a better eradication rate and to reduce the risk of selection of H. pylori resistant strains.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Dispepsia/microbiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Adulto , Antibacterianos/uso terapêutico , Biópsia , Camarões , Estudos Transversais , Dipeptídeos/farmacologia , Feminino , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Testes de Sensibilidade Microbiana
9.
Gastroenterol. hepatol. (Ed. impr.) ; 42(8): 476-485, oct. 2019. graf, tab
Artigo em Inglês | IBECS | ID: ibc-183883

RESUMO

Objective: Helicobacter pylori resistance to antimicrobial agents is on the rise and it is thus imperative to be aware of local resistance rates. The main objective of the present study was to describe the evolution of primary antimicrobial resistance in H. pylori, analysing its antibiotic susceptibility over a 13-year period in a region of northern Spain, as well as host-related factors. Patients and methods: Between 2004 and 2016 a total of 3426 patients who met the H. pylori eradication criteria underwent gastroscopy. The gastric biopsies were processed and those testing positive for H. pylori were identified and tested for clarithromycin, metronidazole and levofloxacin susceptibility using E-test. Results: H. pylori was isolated in 1604 (47%) patients, ranging from 63% (133/212) in 2004 to 39% (137/347) in 2016. Primary resistances to clarithromycin, metronidazole and levofloxacin were on average 19% (278/1116), 40% (572/865) and 17% (137/669), respectively. Clarithromycin resistance was 24% (167/686) in females and 15% (11/753) in males (p=0.0002); metronidazole resistance was 29% (72/246) in patients over 70 years compared to 42% (499/1190) in younger patients (p=0.0396); levofloxacin resistance increased with age, being 13% (57/439) in patients ≤55 years, 19% (46/236) for those between 56 and 70, and 26% (34/130) in patients >70 years (p=0.0087). Discussion: A decline in the prevalence of H. pylori infection was observed over the years, along with relatively high rates of primary resistance to clarithromycin, metronidazole and levofloxacin. Variations in resistance rates were found with sex and age


Objetivo: El aumento de la resistencia de Helicobacter pylori a los antibióticos hace indispensable conocer las tasas de resistencia locales. El principal objetivo de este estudio fue describir la evolución de la resistencia primaria de H. pylori a los antibióticos, analizando su sensibilidad durante un período de tiempo de 13 años en una región del norte de España, así como los factores asociados del huésped. Pacientes y métodos: Entre 2004 y 2016 se realizaron gastroscopias a 3.426 pacientes que cumplían criterios de erradicación de la infección por H. pylori. En las biopsias gástricas en las que se detectó crecimiento compatible con H. pylori se identificó este microorganismo y se testó la sensibilidad a claritromicina, metronidazol y levofloxacino mediante Etest(R). Resultados: Se aisló H. pylori en 1.604 (47%) pacientes, desde el 63% (133/212) en 2004 hasta el 39% (137/347) en 2016. Las resistencias primarias a claritromicina, metronidazol y levofloxacino fueron del 19% (278/1.116), 40% (572/865) y 17% (137/669), respectivamente. La resistencia a claritromicina fue mayor en mujeres: 24% (167/686) vs. 15% (11/753) (p=0,0002); la resistencia a metronidazol fue mayor en jóvenes: 29% (72/246) en >70 años vs. 42% (499/1.190) en ≤70 años (p=0,0396); la resistencia a levofloxacino aumentó con la edad de los pacientes: 13% (57/439) en <55 años, 19% (46/236) entre 56 y 70 años y 26% (34/130) en >70 años (p=0,0087). Discusión: Se observa una disminución en la prevalencia de la infección por H. pylori a lo largo de los años, con tasas relativamente altas de resistencia primaria a claritromicina, metronidazol y levofloxacino. Se encuentran variaciones en estas tasas de resistencia en función del sexo y de la edad de los pacientes


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Resistência Microbiana a Medicamentos , Helicobacter pylori/efeitos dos fármacos , Infecções por Helicobacter/epidemiologia , Espanha/epidemiologia , Antibacterianos , Estudos Retrospectivos , Testes de Sensibilidade Microbiana/estatística & dados numéricos , Sensibilidade e Especificidade , Claritromicina , Metronidazol , Levofloxacino
11.
Comput Biol Chem ; 83: 107126, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31557645

RESUMO

The cascade of complications by Helicobacter pylori including extra-gastric and peptic ulcers to gastric cancer imposes a salient cause of cancer death globally. Adverse drug reactions and burgeoned genetically diverse resistant strains create a big barrier in the treatment, thereby demanding novel proof-of-concept ligands and breakthrough medicines. Hence, as a follow-up of the previous proteomics study against 53 H. pylori strains, KdsB was identified as a vital conserved-target enzyme. Herein, the rational therapeutic-design strategies exploiting for such a hidden cryptic inhibitor were utilized in lead-optimization campaigns through shape screening, the powerful scaffold-hopping, rigid-receptor, quantum-polarized ligand and induced-fit docking techniques coupled with estimating molecular-mechanics energies (ΔGbind) through generalized-Born and surface-area-continuum solvation. Variable-dielectric-Surface-Generalized Born, a novel energy model and physics-based corrections for bond-interactions and ADME/Tox predictions led to yield improved eight therapeutic chemical entities with positive synthesizability scores (0-1). Long-range molecular dynamics (300 ns) simulations revealed stability of leads. Significant computational findings with better competitive binding-strengths than experimental ligands could pave the best choice for selecting better leads as it warrants and filter false-positives based on the consensus of scaffolds interactions and suggesting that designed novel class of KdsB-antagonist molecules may dysfunction the target and stimulate new insights for developing effectual medical interventions.


Assuntos
Antibacterianos/farmacologia , Helicobacter pylori/efeitos dos fármacos , Simulação de Dinâmica Molecular , Teoria Quântica , Antibacterianos/química , Sítios de Ligação , Testes de Sensibilidade Microbiana
12.
J Enzyme Inhib Med Chem ; 34(1): 1660-1667, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31530039

RESUMO

Ethoxzolamide (EZA), acetazolamide, and methazolamide are clinically used sulphonamide drugs designed to treat non-bacteria-related illnesses (e.g. glaucoma), but they also show antimicrobial activity against the gastric pathogen Helicobacter pylori. EZA showed the highest activity, and was effective against clinical isolates resistant to metronidazole, clarithromycin, and/or amoxicillin, suggesting that EZA kills H. pylori via mechanisms different from that of these antibiotics. The frequency of single-step spontaneous resistance acquisition by H. pylori was less than 5 × 10-9, showing that resistance to EZA does not develop easily. Resistance was associated with mutations in three genes, including the one that encodes undecaprenyl pyrophosphate synthase, a known target of sulphonamides. The data indicate that EZA impacts multiple targets in killing H. pylori. Our findings suggest that developing the approved anti-glaucoma drug EZA into a more effective anti-H. pylori agent may offer a faster and cost-effective route towards new antimicrobials with a novel mechanism of action.


Assuntos
Antibacterianos/farmacologia , Etoxzolamida/farmacologia , Helicobacter pylori/efeitos dos fármacos , Antibacterianos/síntese química , Antibacterianos/química , Relação Dose-Resposta a Droga , Etoxzolamida/síntese química , Etoxzolamida/química , Helicobacter pylori/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade
13.
Int J Mol Sci ; 20(18)2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31500233

RESUMO

Helicobacter pylori colonises the human stomach and has tropism for the gastric mucin, MUC5AC. The majority of organisms live in the adherent mucus layer within their preferred location, close to the epithelial surface where the pH is near neutral. Trefoil factor 1 (TFF1) is a small trefoil protein co-expressed with the gastric mucin MUC5AC in surface foveolar cells and co-secreted with MUC5AC into gastric mucus. Helicobacter pylori binds with greater avidity to TFF1 dimer, which is present in gastric mucus, than to TFF1 monomer. Binding of H. pylori to TFF1 is mediated by the core oligosaccharide subunit of H. pylori lipopolysaccharide at pH 5.0-6.0. Treatment of H. pylori lipopolysaccharide with mannosidase or glucosidase inhibits its interaction with TFF1. Both TFF1 and H. pylori have a propensity for binding to mucins with terminal non-reducing α- or ß-linked N-acetyl-d-glucosamine or α-(2,3) linked sialic acid or Gal-3-SO42-. These findings are strong evidence that TFF1 has carbohydrate-binding properties that may involve a conserved patch of aromatic hydrophobic residues on the surface of its trefoil domain. The pH-dependent lectin properties of TFF1 may serve to locate H. pylori deep in the gastric mucus layer close to the epithelium rather than at the epithelial surface. This restricted localisation could limit the interaction of H. pylori with epithelial cells and the subsequent host signalling events that promote inflammation.


Assuntos
Helicobacter pylori/fisiologia , Lipopolissacarídeos/metabolismo , Estômago/microbiologia , Fator Trefoil-1/metabolismo , Mucinas Gástricas/metabolismo , Glucosidases/farmacologia , Helicobacter pylori/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Lipopolissacarídeos/química , Manosidases/farmacologia , Mucina-5AC/metabolismo , Polissacarídeos Bacterianos/química , Polissacarídeos Bacterianos/metabolismo , Ligação Proteica/efeitos dos fármacos , Multimerização Proteica , Fator Trefoil-1/química , Tropismo
14.
Helicobacter ; 24 Suppl 1: e12640, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31486235

RESUMO

This review summarizes important studies regarding Helicobacter pylori therapy published from May 2018 to May 2019. The main themes that emerge involve studies assessing the efficacy of bismuth-based regimens. While in recent years the efficacy of bismuth-based quadruple therapy as a second-line therapy has been clearly established, there is now substantial evidence that it is the best performing first-line therapy. Antibiotic resistance was again intensely studied this year, and a clear and dramatic increase in resistance is noted for clarithromycin and levofloxacin; most notably, it may not be possible to support these therapies in most regions of the world much longer without testing. The utility of vonoprazan as an alternative to proton-pump inhibitor therapy, especially in resistant and difficult to treat groups, has also been considered in greater detail this year, as well as means of supporting and enhancing adherence to therapy. Several studies showed that the diversity of gut microbiota was significantly altered shortly after H pylori eradication. However, the diversity was restored to pre-treatment state after 2 months in patients treated with triple therapy. More studies are warranted to assess the long-term changes of gut microbiota after H pylori eradication.


Assuntos
Antibacterianos/uso terapêutico , Quimioterapia Combinada/métodos , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Inibidores da Bomba de Prótons/uso terapêutico , Farmacorresistência Bacteriana , Humanos , Resultado do Tratamento
15.
Phytochemistry ; 167: 112111, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31491684

RESUMO

A C20-diterpenoid alkaloid with an unprecedented carbon skeleton, acoapetaludine A, together with ten undescribed aconitine-type C19-diterpenoid alkaloids, acoapetaludines B-K, were isolated from the whole plants of Aconitum apetalum (Huth) B. Fedtsch. (Ranunculaceae). The structures were elucidated based on a comprehensive spectroscopic data analysis. The absolute configuration of acoapetaludine A was determined by quantum ECD calculation. Acoapetaludines D and E exhibited weak anti-Helicobacter pylori activity at a minimum inhibitory concentration (MIC) of 100 and 50 µg/mL, respectively.


Assuntos
Aconitum/química , Alcaloides/química , Alcaloides/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Diterpenos/química , Helicobacter pylori/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Conformação Molecular
17.
Orv Hetil ; 160(34): 1340-1345, 2019 Aug.
Artigo em Húngaro | MEDLINE | ID: mdl-31423829

RESUMO

Introduction and aim: As the efficacy of the first-line traditional treatment used to eradicate Helicobacter pylori (H. p.) decreased below 75% in Hungary, a new protocol had to be created. Method: Supposing the success rate of the traditional therapy (14-day double dose of proton pump inhibitor [PPI], 1000 mg amoxicillin b.i.d., 500 mg clarithromycin b.i.d. [PAC]) to be 75% and the efficacy of the new protocol (10-day 120 mg bismuth dicitrate q.i.d., double dose PPI b.i.d., 500 mg tetracycline q.i.d. and 500 mg tinidazole b.i.d. [BQT]) to be 90%, we calculated 109 patients on each arm. Patients were recruited after upper gastrointestinal endoscopy from 5 endoscopic units in Vas county. The heterogeneity of groups, success rate and side effects of both therapies were evaluated by Fisher exact test; p<0.05 was considered significant. Results: 110 patients were included in the BQT and 109 patients in the PAC group. There was no heterogeneity between the two groups in age, gender and indication of eradication. H. p. eradication was successful in 103/110 (93.6%) in the BQT and 81/109 (74.3%) in the PAC group (p<0.001). The odds ratio in the BQT group for successful eradication was 5.05 (95% confidence interval: 2.02-14.42) as compared to the PAC group (p<0.001). The side effects of the two groups were similar, in the BQT group the frequency was 34.5%. Conclusion: 10 day-long BQT containing double dose PPI with 120 mg bismuth dicitrate q.i.d., 500 mg tetracycline q.i.d. and 500 mg tinidazole b.i.d. is recommended as the first-line treatment for the eradication of H. p. because of its high efficacy and tolerable side effects. Orv Hetil. 2019; 160(34): 1340-1345.


Assuntos
Antiácidos/administração & dosagem , Antibacterianos/administração & dosagem , Bismuto/administração & dosagem , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Inibidores da Bomba de Prótons/administração & dosagem , Adulto , Idoso , Amoxicilina/administração & dosagem , Amoxicilina/uso terapêutico , Antiácidos/uso terapêutico , Antibacterianos/uso terapêutico , Bismuto/uso terapêutico , Claritromicina/administração & dosagem , Claritromicina/uso terapêutico , Esquema de Medicação , Farmacorresistência Bacteriana , Quimioterapia Combinada , Endoscopia Gastrointestinal , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/isolamento & purificação , Humanos , Hungria , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons/uso terapêutico , Tetraciclina/administração & dosagem , Tetraciclina/uso terapêutico , Tinidazol/administração & dosagem , Tinidazol/uso terapêutico , Resultado do Tratamento
18.
Expert Rev Clin Pharmacol ; 12(9): 909-915, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31424296

RESUMO

Introduction: Helicobacter pylori antibiotic resistance has increased worldwide and multidrug resistance (MDR), which seriously hampers eradication success of the frequent chronic infection, has often been reported. Areas covered: H. pylori MDR rates are discussed, mostly from recent articles published since 2015. Present approaches and future directions to counteract the MDR are outlined. Expert opinion: Alarming presence of triple, quadruple and, in some studies, quintuple and sextuple resistance was detected. Primary MDR rates ranged from <10% in most European countries to >40% in Peru. Post-treatment or overall MDR rates were >23-36% in about half of the studies. MDR prevalence has varied both among and within the countries. Factors linked to the MDR are national antibiotic consumption, antibiotic misuse, treatment failures and bacterial factors such as mutations, efflux pumps, and biofilms. Important directions to counteract the MDR increase can be optimization of present and new eradication regimens, wider use of bismuth-containing regimens, assessment of benefit of vonoprazan, new antibiotics such as newer fluoroquinolones and oxazolidinone analogues, adjuvants involving N-acetylcysteine and probiotics, anti-biofilm approaches using anti-biofilm peptides and rhamnolipid and development of vaccines and non-invasive tests for resistance detection. However, more efforts and studies are required. Strain susceptibility testing is increasingly important.


Assuntos
Antibacterianos/administração & dosagem , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla , Quimioterapia Combinada , Saúde Global , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/isolamento & purificação , Humanos , Testes de Sensibilidade Microbiana
20.
Chem Pharm Bull (Tokyo) ; 67(8): 810-815, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31366830

RESUMO

Helicobacter pylori (H. pylori) infection is common and can result in gastric and duodenal ulcers, and in some cases, gastric lymphoma and cancer. Omeprazole (OMP)-in combination with clarithromycin (CLR), amoxicillin (AMX), tinidazole (TND), or metronidazole (MET)-is used in double or triple combination therapy for eradication of H. pylori. However, the roles of the drugs other than OMP are not clearly understood. Therefore, in the present study, we aimed to investigate any effects of these drugs on OMP metabolism by wild-type CYP2C19 using spectroscopy and enzyme kinetics. The dissociation constants (Kd) for CYP2C19 with OMP, CLR, AMX, TND, and MET were 8.6, 126, 156, 174, and 249 µM, respectively. The intrinsic clearance of OMP was determined to be 355 mL/min/µmol of CYP2C19. Metabolism of OMP was significantly inhibited by 69, 66, 28, and 40% in the presence of CLR, TND, AMX, and MET, respectively. Moreover, the combination of CLR and TND resulted in 76% inhibition of OMP metabolism, while the combination of AMX and MET resulted in 48% inhibition of OMP metabolism. Both combinations of drugs not only have antibacterial effects, but also enhance the effect of OMP by inhibiting its metabolism by CYP2C19. These results indicate that drug-drug interactions of co-administered drugs can cause complex effects, providing a basis for OMP dose adjustment when used in combination therapy for H. pylori eradication.


Assuntos
Antibacterianos/farmacologia , Citocromo P-450 CYP2C19/metabolismo , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Omeprazol/farmacologia , Amoxicilina/química , Amoxicilina/farmacologia , Antibacterianos/química , Antibacterianos/metabolismo , Cromatografia Líquida de Alta Pressão , Claritromicina/química , Claritromicina/farmacologia , Citocromo P-450 CYP2C19/química , Combinação de Medicamentos , Humanos , Metronidazol/química , Metronidazol/farmacologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Omeprazol/antagonistas & inibidores , Omeprazol/metabolismo , Tinidazol/química , Tinidazol/farmacologia
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