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Mahmud AR, Ema TI, Siddiquee MFR, Shahriar A, Ahmed H, Mosfeq-Ul-Hasan M, Rahman N, Islam R, Uddin MR, Mizan MFR. Natural flavonols: actions, mechanisms, and potential therapeutic utility for various diseases. BENI-SUEF UNIVERSITY JOURNAL OF BASIC AND APPLIED SCIENCES 2023; 12:47. [PMID: 37216013 PMCID: PMC10183303 DOI: 10.1186/s43088-023-00387-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Accepted: 05/07/2023] [Indexed: 05/24/2023] Open
Abstract
Background Flavonols are phytoconstituents of biological and medicinal importance. In addition to functioning as antioxidants, flavonols may play a role in antagonizing diabetes, cancer, cardiovascular disease, and viral and bacterial diseases. Quercetin, myricetin, kaempferol, and fisetin are the major dietary flavonols. Quercetin is a potent scavenger of free radicals, providing protection from free radical damage and oxidation-associated diseases. Main body of the abstract An extensive literature review of specific databases (e.g., Pubmed, google scholar, science direct) were conducted using the keywords "flavonol," "quercetin," "antidiabetic," "antiviral," "anticancer," and "myricetin." Some studies concluded that quercetin is a promising antioxidant agent while kaempferol could be effective against human gastric cancer. In addition, kaempferol prevents apoptosis of pancreatic beta-cells via boosting the function and survival rate of the beta-cells, leading to increased insulin secretion. Flavonols also show potential as alternatives to conventional antibiotics, restricting viral infection by antagonizing the envelope proteins to block viral entry. Short conclusion There is substantial scientific evidence that high consumption of flavonols is associated with reduced risk of cancer and coronary diseases, free radical damage alleviation, tumor growth prevention, and insulin secretion improvement, among other diverse health benefits. Nevertheless, more studies are required to determine the appropriate dietary concentration, dose, and type of flavonol for a particular condition to prevent any adverse side effects.
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Affiliation(s)
- Aar Rafi Mahmud
- Department of Biochemistry and Molecular Biology, Mawlana Bhashani Science and Technology University, Santosh, Tangail, 1902 Bangladesh
| | - Tanzila Ismail Ema
- Department of Biochemistry and Microbiology, North South University, Dhaka, 1229 Bangladesh
| | | | - Asif Shahriar
- Department of Microbiology, Stamford University Bangladesh, 51 Siddeswari Road, Dhaka, 1217 Bangladesh
| | - Hossain Ahmed
- Department of Biotechnology and Genetic Engineering, University of Development Alternative (UODA), Dhaka, 1208 Bangladesh
| | - Md. Mosfeq-Ul-Hasan
- Hajee Mohammad Danesh Science and Technology University, Dinajpur, 5200 Bangladesh
| | - Nova Rahman
- Department of Biochemistry and Molecular Biology, Jahangirnagar University, Savar, Dhaka, 1342 Bangladesh
| | - Rahatul Islam
- Department of Genetic Engineering and Biotechnology, Shahjalal University of Science and Technology, Sylhet, Bangladesh
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Taghizadeh S, Falsafi T, Kermanshahi RK, Ramezani R. Antagonistic and Immunomodulant Effects of Two Probiotic Strains of Lactobacillus on Clinical Strains of Helicobacter pylori. Galen Med J 2021; 9:e1794. [PMID: 34466594 PMCID: PMC8343775 DOI: 10.31661/gmj.v9i0.1794] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Revised: 01/05/2020] [Accepted: 01/18/2020] [Indexed: 12/11/2022] Open
Abstract
Background:
The present study aimed to evaluate the in vitro and in situ antagonistic effects of Lactobacillus probiotic strains on clinical strains of Helicobacter pylori. Also to investigate their immunomodulation effects on a macrophage cell model.
Materials and Methods:
Anti-microbial effects of probiotic lactobacilli against H. pylori was assessed using the well and disk diffusion methods. Effects of lactobacilli probiotics strains, as well as their cell-free supernatant on adhesion of H. pylori to MKN-45 gastric epithelial cells, were examined in their presence and absence. Immunomodulation effects of probiotic lactobacilli were performed using the U937 macrophage cell model. Incubation of host cells with probiotics and their cell-free supernatants with cultured host cells was performed in different optimized conditions. The supernatant of host cells cultured in their presence and absence was used for cytokines measurement.
Results:
Two probiotics,Lactobacillus acidophilus ATCC4356, and Lactobacillus rhamnosus PTCC1607, could inhibit the growth of clinical H. pylori in vitro. They could also inhibit attachment of H. pylori to MKN-45 cells. Cell-free supernatant of L. acidophilus had a stimulating effect on the production of Interferon-gamma (IFN-γ) by U937 cells.
Conclusion:
The present study demonstrates that, L. acidophilus ATCC4356 and L. rhamnosus PTCC1607 probiotic strains can inhibit the growth of clinical H. pylori in vitro. Treatment of U937 with alive H. pylori plus cell-free supernatant of L. acidophilus, have a significantly higher capacity to stimulate IFN-γ production than H. pylori alone. So, the metabolite (s) of this probiotic may have an immunomodulatory effect in immune response versus H. pylori.
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Affiliation(s)
- Somayyeh Taghizadeh
- Microbiology Department, Faculty of Biological Sciences, Alzahra University, Tehran, Iran
| | - Tahereh Falsafi
- Microbiology Department, Faculty of Biological Sciences, Alzahra University, Tehran, Iran
- Correspondence to: Tahereh Falsafi, Microbiology Department, Faculty of Biological Sciences, Alzahra University, Tehran, Iran Telephone Number: +989127095294 Email Address:
| | | | - Reihaneh Ramezani
- Department of Biomedical Sciences, Woman Research Center, Alzahra University, Tehran, Iran
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Hebel-Gerber S, García-Cancino A, Urbina A, Simirgiotis MJ, Echeverría J, Bustamante-Salazar L, Sáez-Carrillo K, Alarcón J, Pastene-Navarrete E. Chilean Rhubarb, Gunnera tinctoria (Molina) Mirb. (Gunneraceae): UHPLC-ESI-Orbitrap-MS Profiling of Aqueous Extract and its Anti- Helicobacter pylori Activity. Front Pharmacol 2021; 11:583961. [PMID: 33708110 PMCID: PMC7941271 DOI: 10.3389/fphar.2020.583961] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 11/12/2020] [Indexed: 01/10/2023] Open
Abstract
The full UHPLC-MS metabolome fingerprinting and anti-Helicobacter pylori effect of Gunnera tinctoria (Molina) Mirb. (Nalca) total extract (GTE) and fractions prepared from its edible fresh petioles were evaluated. The activity of G. tinctoria against H. pylori strains ATCC 45504 and J99 was assessed in vitro by means of agar diffusion assay, Minimum Inhibition Concentration (MIC), and Minimum Bactericidal Concentration (MBC), while killing curve and transmission electronic microscopy (TEM) were conducted in order to determine the effect of the plant extract on bacterial growth and ultrastructure. Additionally, the inhibitory effect upon urease was evaluated using both the Jack Bean and H. pylori enzymes. To determine which molecules could be responsible for the antibacterial effects, tentative identification was done by ultra-high performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-Q-Orbitrap®-HR-MS). Furthermore, the total G. tinctoria extract was fractionated using centrifugal partition chromatography (CPC), giving four active fractions (1-4). It was determined that the crude extract and centrifugal partition chromatography fractions of G. tinctoria have a bactericidal effect being the lowest MIC and MBC = 32 μg/ml. In the killing curves, fraction one acts faster than control amoxicillin. In the urease assay, F3 exhibited the lowest IC50 value of 13.5 μg/ml. Transmission electronic microscopy showed that crude G. tinctoria extract promotes disruption and separation of the cellular wall and outer membrane detachment on H. pylori causing bacterial cell death.
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Affiliation(s)
- Sonja Hebel-Gerber
- Laboratorio de Farmacognosia, Departamento de Farmacia, Facultad de Farmacia, Universidad de Concepción, Concepción, Chile
- Laboratorio de Patogenicidad Bacteriana, Departamento de Microbiología, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción, Chile
| | - Apolinaria García-Cancino
- Laboratorio de Patogenicidad Bacteriana, Departamento de Microbiología, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción, Chile
| | - Angélica Urbina
- Departamento de Producción Vegetal, Facultad de Agronomía, Universidad de Concepción, Chillán, Chile
| | - Mario J. Simirgiotis
- Instituto de Farmacia, Facultad de Ciencias, Universidad Austral de Chile, Campus Isla Teja, Valdivia, Chile
| | - Javier Echeverría
- Departamento de Ciencias del Ambiente, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago, Chile
| | - Luis Bustamante-Salazar
- Departamento de Análisis Instrumental, Facultad de Farmacia, Universidad de Concepción, Concepción, Chile
| | - Katia Sáez-Carrillo
- Facultad de Ciencias Físicas y Matemáticas, Universidad de Concepción, Concepción, Chile
| | - Julio Alarcón
- Laboratorio de Síntesis y Biotransformación de Productos Naturales, Departamento de Ciencias Básicas, Universidad de Bío-Bío, Chillán, Chile
| | - Edgar Pastene-Navarrete
- Laboratorio de Farmacognosia, Departamento de Farmacia, Facultad de Farmacia, Universidad de Concepción, Concepción, Chile
- Laboratorio de Síntesis y Biotransformación de Productos Naturales, Departamento de Ciencias Básicas, Universidad de Bío-Bío, Chillán, Chile
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Liu W, Zeng Z, Luo S, Hu C, Xu N, Huang A, Zheng L, Sundberg EJ, Xi T, Xing Y. Gastric Subserous Vaccination With Helicobacter pylori Vaccine: An Attempt to Establish Tissue-Resident CD4+ Memory T Cells and Induce Prolonged Protection. Front Immunol 2019; 10:1115. [PMID: 31156652 PMCID: PMC6533896 DOI: 10.3389/fimmu.2019.01115] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Accepted: 05/01/2019] [Indexed: 12/22/2022] Open
Abstract
Tissue-resident memory T (Trm) cells are enriched at the sites of previous infection and required for enhanced protective immunity. However, the emergence of Trm cells and their roles in providing protection are unclear in the field of Helicobacter pylori (H. pylori) vaccinology. Here, our results suggest that conventional vaccine strategies are unable to establish a measurable antigen (Ag)-specific memory cell pool in stomach; in comparison, gastric subserous injection of mice with micro-dose of Alum-based H. pylori vaccine can induce a pool of local CD4+ Trm cells. Regional recruitment of Ag-specific CD4+ T cells depends on the engagement of Ag and adjuvant-induced inflammation. Prior subcutaneous vaccination enhanced this recruitment. A stable pool of Ag-specific CD4+ T cells can be detected for 240 days. Two weeks of FTY720 administration in immune mice suggests that these cells do not experience the recirculation. Immunohistochemistry results show that close to the vaccination site, abundant CD4+T cells locate on epithelial niches, independent of lymphocyte cluster. Paradigmatically, Ag-specific CD4+ T cells with a phenotype of CD69+CD103- are preferential on lymphocytes isolated from epithelium. Upon Helicobacter infection, CD4+ Trm cells orchestrate a swift recall response with the recruitment of circulating antigen-specific Th1/Th17 cells to trigger a tissue-wide pathogen clearance. This study investigates the vaccine-induced gastric CD4+ Trm cells in a mice model, and highlights the need for designing a vaccine strategy against H. pylori by establishing the protective CD4+ Trm cells.
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Affiliation(s)
- Wei Liu
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.,Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, China
| | - Zhiqin Zeng
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.,Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, China
| | - Shuanghui Luo
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.,Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, China
| | - Chupeng Hu
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.,Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, China
| | - Ningyin Xu
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.,Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, China
| | - An Huang
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.,Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, China
| | - Lufeng Zheng
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.,Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, China
| | - Eric J Sundberg
- Institute of Human Virology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, United States.,Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, United States
| | - Tao Xi
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.,Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, China
| | - Yingying Xing
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.,Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, China
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Park HS, Wijerathne CUB, Jeong HY, Seo CS, Ha H, Kwun HJ. Gastroprotective effects of Hwanglyeonhaedok-tang against Helicobacter pylori-induced gastric cell injury. JOURNAL OF ETHNOPHARMACOLOGY 2018; 216:239-250. [PMID: 29410309 DOI: 10.1016/j.jep.2018.01.025] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/22/2017] [Revised: 01/18/2018] [Accepted: 01/19/2018] [Indexed: 06/07/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Helicobacter pylori, which is found in the stomachs of approximately half of the world's population, has been associated with the development of chronic gastritis and gastric cancer. Hwanglyeonhaedok-tang (HHT) is a popular traditional medicine for the therapies of gastric ulcers and gastritis. AIM OF THE STUDY The emerging resistance of H. pylori to antibiotics arouses requirement on alternative nonantibiotic-based therapies. In the present study, we investigated the anti-inflammatory activity and anti-microbial activity of HHT against H. pylori in vitro and in an H. pylori-infected mouse model. MATERIALS AND METHODS H. pylori were treated with various concentrations of HHT and then incubated with human gastric carcinoma AGS cells. For the in vivo study, mice were orally infected with H. pylori three times over the course of 1 week, and then subjected to daily administration of HHT (120 or 600 mg/kg) for 4 weeks or standard triple therapy for 1 week. At the scheduled termination of the experiment, all mice were killed and their stomachs were collected for histological examination, quantitative real-time PCR, and Western blot analysis. RESULTS Our in vitro studies showed that HHT treatment inhibited the adhesion of H. pylori to AGS cells and suppressed the H. pylori-induced increases of inflammatory regulators, such as interleukin (IL)-8, cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS). In the mouse model, HHT treatment significantly reduced H. pylori colonization, inflammation, and the levels of IL-1β, IL-6, C-X-C motif chemokine ligand 1 (CXCL1), tumor necrosis factor alpha (TNF-α), COX-2, and iNOS in gastric mucosa. Further investigation showed that HHT treatment reduced the H. pylori-induced phosphorylations of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK), and nuclear factor-kappa B (NF-κB). CONCLUSIONS Our findings collectively suggest that HHT has anti-inflammatory activity and antibacterial activity against H. pylori and could be an alternative to antibiotics for preventing H. pylori infection.
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Affiliation(s)
- Hee-Seon Park
- Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea..
| | - Charith U B Wijerathne
- Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea..
| | - Hye-Yun Jeong
- Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea..
| | - Chang-Seob Seo
- K-herb Research Center, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea..
| | - Hyekyung Ha
- K-herb Research Center, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea..
| | - Hyo-Jung Kwun
- Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea..
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Sequential versus concomitant therapy for treatment of Helicobacter pylori infection: an updated systematic review and meta-analysis. Eur J Clin Pharmacol 2017; 74:1-13. [DOI: 10.1007/s00228-017-2347-7] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2017] [Accepted: 09/29/2017] [Indexed: 02/06/2023]
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Xu YF, Lian DW, Chen YQ, Cai YF, Zheng YF, Fan PL, Ren WK, Fu LJ, Li YC, Xie JH, Cao HY, Tan B, Su ZR, Huang P. In Vitro and In Vivo Antibacterial Activities of Patchouli Alcohol, a Naturally Occurring Tricyclic Sesquiterpene, against Helicobacter pylori Infection. Antimicrob Agents Chemother 2017; 61:e00122-17. [PMID: 28320722 PMCID: PMC5444145 DOI: 10.1128/aac.00122-17] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2017] [Accepted: 03/10/2017] [Indexed: 12/12/2022] Open
Abstract
This study further evaluated the in vitro and in vivo anti-Helicobacter pylori activities and potential underlying mechanism of patchouli alcohol (PA), a tricyclic sesquiterpene. In the in vitro assay, the capacities of PA to inhibit and kill H. pylori were tested on three standard strains at different pH values and on 12 clinical isolates. The effects of PA on H. pylori adhesion (and its alpA, alpB, and babA genes), motility (and its flaA and flaB genes), ultrastructure, and flagellation were investigated. Moreover, the H. pylori resistance to and postantibiotic effect (PAE) of PA were determined. Furthermore, the in vivo effects of PA on H. pylori eradication and gastritis were examined. Results showed that MICs of PA against three standard strains (pH 5.3 to 9) and 12 clinical isolates were 25 to 75 and 12.5 to 50 μg/ml, respectively. The killing kinetics of PA were time and concentration dependent, and its minimal bactericidal concentrations (MBCs) were 25 to 75 μg/ml. In addition, H. pylori adhesion, motility, ultrastructure, and flagellation were significantly suppressed. PA also remarkably inhibited the expression of adhesion genes (alpA and alpB) and motility genes (flaA and flaB). Furthermore, PA treatment caused a longer PAE and less bacterial resistance than clarithromycin and metronidazole. The in vivo study showed that PA can effectively eradicate H. pylori, inhibit gastritis, and suppress the expression of inflammatory mediators (COX-2, interleukin 1β, tumor necrosis factor alpha, and inducible nitric oxide synthase [iNOS]). In conclusion, PA can efficiently kill H. pylori, interfere with its infection process, and attenuate gastritis with less bacterial resistance, making it a potential candidate for new drug development.
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Affiliation(s)
- Y F Xu
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China
| | - D W Lian
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China
| | - Y Q Chen
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China
| | - Y F Cai
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China
| | - Y F Zheng
- Department of Mammary Disease, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China
| | - P L Fan
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China
| | - W K Ren
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China
| | - L J Fu
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China
| | - Y C Li
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China
| | - J H Xie
- Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China
| | - H Y Cao
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China
| | - B Tan
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China
| | - Z R Su
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China
- Dongguan Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Dongguan, People's Republic of China
| | - P Huang
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China
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Tan Z, Liu W, Liu H, Li C, Zhang Y, Meng X, Tang T, Xi T, Xing Y. Oral Helicobacter pylori vaccine-encapsulated acid-resistant HP55/PLGA nanoparticles promote immune protection. Eur J Pharm Biopharm 2017; 111:33-43. [DOI: 10.1016/j.ejpb.2016.11.007] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2016] [Accepted: 11/02/2016] [Indexed: 12/19/2022]
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Hassan STS, Šudomová M. The Development of Urease Inhibitors: What Opportunities Exist for Better Treatment of Helicobacter pylori Infection in Children? CHILDREN-BASEL 2017; 4:children4010002. [PMID: 28054971 PMCID: PMC5296663 DOI: 10.3390/children4010002] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/17/2016] [Revised: 12/25/2016] [Accepted: 12/27/2016] [Indexed: 12/12/2022]
Abstract
Stomach infection with Helicobacter pylori (H. pylori) causes severe gastroduodenal diseases in a large number of patients worldwide. The H. pylori infection breaks up in early childhood, persists lifelong if not treated, and is associated with chronic gastritis and an increased risk of peptic ulcers and gastric cancer. In recent years, the problem of drug-resistant strains has become a global concern that makes the treatment more complicated and the infection persistent at higher levels when the antibiotic treatment is stopped. Such problems have led to the development of new strategies to eradicate an H. pylori infection. Currently, one of the most important strategies for the treatment of H. pylori infection is the use of urease inhibitors. Despite the fact that large numbers of molecules have been shown to exert potent inhibitory activity against H. pylori urease, most of them were prevented from being used in vivo and in clinical trials due to their hydrolytic instability, toxicity, and appearance of undesirable side effects. Therefore, it is crucial to focus attention on the available opportunities for the development of urease inhibitors with suitable pharmacokinetics, high hydrolytic stability, and free toxicological profiles. In this commentary, we aim to afford an outline on the current status of the use of urease inhibitors in the treatment of an H. pylori infection, and to discuss the possibility of their development as effective drugs in clinical trials.
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Affiliation(s)
- Sherif T S Hassan
- Department of Natural Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Palackého tř. 1946/1, 61242 Brno, Czech Republic.
- Department of Applied Ecology, Faculty of Environmental Sciences, Czech University of Life Sciences Prague, Kamýcká 129, 165 21 Praha 6-Suchdol, Czech Republic.
| | - Miroslava Šudomová
- Museum of the Brno Region, Museum of Literature in Moravia, Porta Coeli 1001, 66602 Předklášteří, Czech Republic.
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Hassan STS, Berchová K, Majerová M, Pokorná M, Švajdlenka E. In vitro synergistic effect of Hibiscus sabdariffa aqueous extract in combination with standard antibiotics against Helicobacter pylori clinical isolates. PHARMACEUTICAL BIOLOGY 2016; 54:1736-40. [PMID: 26731378 DOI: 10.3109/13880209.2015.1126618] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/23/2015] [Revised: 10/07/2015] [Accepted: 11/27/2015] [Indexed: 05/27/2023]
Abstract
Context The increasing problem of drug-resistant strains has led to the failure of current treatment regimens of Helicobacter pylori (HP) infection. Recently, a new treatment strategy has been developed to overcome the problem by using natural products in combination with antibiotics to enhance the treatment efficacy. Objective The antimicrobial combinatory effect of the aqueous extract of Hibiscus sabdariffa L. (Malvaceae) (AEHS) with antibiotics (clarithromycin, CLA; amoxicillin, AMX; metronidazole, MTZ) has been evaluated in vitro against HP strains. Materials and methods Hibiscus calyces (35 g) were brewed in 250 mL of boiled water for 30 min, and minimum inhibitory concentrations (MICs) were determined by agar dilution method. The checkerboard assay was used to evaluate the antimicrobial combinatory effect according to the sum of fractional inhibitory concentration (∑FIC) indices. Results In this study, AEHS exerted remarkable bacteriostatic effect against all HP strains tested with MICs values ranging from 9.18 to 16.68 μg/mL. Synergy effect of AEHS with CLA or MTZ was obtained against four of seven HP strains tested with ∑FIC ranging from 0.21 to 0.39. The additive effect of AEHS with AMX was obtained against five of seven HP strains tested with ∑FIC ranging from 0.61 to 0.91. Conclusion This study presents AEHS as a potent therapeutic candidate alone, or in combination with antibiotics for the treatment of HP infection.
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Affiliation(s)
- Sherif T S Hassan
- a Department of Natural Drugs , Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno , Brno , Czech Republic
- b Department of Applied Ecology , Faculty of Environmental Sciences, Czech University of Life Sciences Prague , Praha , Suchdol , Czech Republic
| | - Kateřina Berchová
- b Department of Applied Ecology , Faculty of Environmental Sciences, Czech University of Life Sciences Prague , Praha , Suchdol , Czech Republic
| | - Michaela Majerová
- a Department of Natural Drugs , Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno , Brno , Czech Republic
| | - Marie Pokorná
- a Department of Natural Drugs , Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno , Brno , Czech Republic
| | - Emil Švajdlenka
- a Department of Natural Drugs , Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno , Brno , Czech Republic
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Anti-Helicobacter pylori activity of crude N-acetylneuraminic acid isolated from glycomacropeptide of whey. Lab Anim Res 2016; 32:99-104. [PMID: 27382378 PMCID: PMC4931043 DOI: 10.5625/lar.2016.32.2.99] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2016] [Revised: 06/01/2016] [Accepted: 06/06/2016] [Indexed: 12/15/2022] Open
Abstract
Helicobacter pylori colonizes the gastric mucosa of about half of the world's population, causing chronic gastritis and gastric cancer. An increasing emergence of antibiotic-resistant H. pylori arouses demand on alternative non-antibiotic-based therapies. In this study, we freshly prepared crude N-acetylneuraminic acid obtained from glycomacropeptide (G-NANA) of whey through a neuraminidase-mediated reaction and evaluated its antibacterial ability against H. pylori and H. felis. Overnight cultures of the H. pylori were diluted with fresh media and different concentrations (1-150 mg/mL) of crude G-NANA were added directly to the culture tube. Bacterial growth was evaluated by measuring the optical density of the culture medium and the number of viable bacteria was determined by a direct count of the colony forming units (CFU) on agar plates. For the in vivo study, mice were orally infected with 100 µL (5×10(8) cfu/mL) of H. felis four times at a day's interval, accompanied by a daily administration of crude G-NANA or vehicle. A day after the last infection, the mice were daily administered the crude G-NANA (0, 75, and 300 mg/mL) for 10 days and euthanized. Their stomachs were collected and bacterial colonization was determined by quantitative real-time PCR. Crude G-NANA inhibited H. pylori's growth and reduced the number of viable bacteria in a dose-dependent manner. Furthermore, crude G-NANA inhibited bacterial colonization in the mice. These results showed that crude G-NANA has antibacterial activity against Helicobacter and demonstrated its therapeutic potential for the prevention of chronic gastritis and gastric carcinogenesis induced by Helicobacter infection in humans.
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Talebi Bezmin Abadi A. Vaccine against Helicobacter pylori: Inevitable approach. World J Gastroenterol 2016; 22:3150-3157. [PMID: 27003991 PMCID: PMC4789989 DOI: 10.3748/wjg.v22.i11.3150] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2015] [Revised: 01/05/2016] [Accepted: 01/30/2016] [Indexed: 02/06/2023] Open
Abstract
Over three decades have passed since the discovery of Helicobacter pylori (H. pylori), and yet many questions about its treatment remain unanswered. For example, there is no certainty regarding continued use of current antibiotic therapy against H. pylori. The bad news is that even combined regimens are also unable to eradicate bacterial colonization. The worst problem with H. pylori chemotherapy is that even if we identify the most successful regimen, it cannot eliminate the risk of re-infection. This problem is further complicated by the fact that clinicians have no information as to whether probiotics are useful or not. Moreover, to date, we have no large scale produced vaccine effective against H. pylori. Due to the relatively rapid and abundant dissemination of guidelines globally reported concerning management of gastric cancer prevention and therapeutic regimens, clinicians may choose a vaccine as better effective weapon against H. pylori. Therefore, a radical shift in adopted strategies is needed to guide ultimate decisions regarding H. pylori management. In light of failures in vaccine projects, we should identify better vaccine design targeting conserved/essential genes. The unique character and persistence of H. pylori pose obstacles to making an effective vaccine. Preferably, in developing countries, the best reasonable and logical approach is to recommend prophylactic H. pylori vaccine among children as an obligatory national program to limit primary colonization. Trying to produce a therapeutic vaccine would be postponed until later. In reality, we should not forget to prescribe narrow spectrum antibiotics. In the current review, I draw a route to define the best adopted strategy against this rogue bacterium.
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Di Giulio M, Di Campli E, Di Bartolomeo S, Cataldi V, Marzio L, Grossi L, Ciccaglione AF, Nostro A, Cellini L. In vitro antimicrobial susceptibility of Helicobacter pylori to nine antibiotics currently used in Central Italy. Scand J Gastroenterol 2016; 51:263-9. [PMID: 26554617 DOI: 10.3109/00365521.2015.1092577] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Helicobacter pylori expresses an increased resistance in respect to antimicrobials currently used in therapy. The aim of this study was to evaluate the antimicrobial profiles of H. pylori isolates to nine conventional antibiotics used in a Central Region (Abruzzo) of Italy. MATERIALS AND METHODS Biopsies were taken from antrum and fundus of 112 adult and 3 children with Urea Breath Test positive with dyspeptic symptoms and analyzed for H. pylori culture and antibacterial activity. Antimicrobial susceptibility tests were performed for clarithromycin, metronidazole, levofloxacin, moxifloxacin, ciprofloxacin, tetracycline, amoxicillin, ampicillin, and rifabutin by a modified agar dilution susceptibility test. RESULTS Bacterial culture was successful in 100 out of 115 patients. Helicobacter pylori strains were isolated from 98 antrum and 83 fundus samples. The rate of recovery of H. pylori strains was 90.50% (181/200). The percentages of resistance were as follows: clarithromycin 72.44% antrum, 72.28% fundus; metronidazole 34.69% antrum, 42.16% fundus; levofloxacin 42.85% antrum, 53.01% fundus; moxifloxacin 37.35% antrum, 46.57% fundus; ciprofloxacin 39.47% antrum, 44.28% fundus; tetracycline 2.63% antrum, 2.85% fundus; amoxicillin 1.02% antrum, 1.20% fundus; ampicillin 0% antrum and fundus and rifabutin 0% antrum, 1.20% fundus. A total of 35 subjects harbored multi-resistant strains. CONCLUSIONS This study underlines the high rate of resistance to clarithromycin, metronidazole and quinolones, which may reflect an overuse of them. Culture and susceptibility test, should be performed to prevent the emergence of multi-resistance and to assess an efficacious regimen.
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Affiliation(s)
- Mara Di Giulio
- a Department of Pharmacy , University "G. d'Annunzio" Chieti-Pescara , Chieti , Italy
| | - Emanuela Di Campli
- a Department of Pharmacy , University "G. d'Annunzio" Chieti-Pescara , Chieti , Italy
| | - Soraya Di Bartolomeo
- a Department of Pharmacy , University "G. d'Annunzio" Chieti-Pescara , Chieti , Italy
| | - Valentina Cataldi
- a Department of Pharmacy , University "G. d'Annunzio" Chieti-Pescara , Chieti , Italy
| | - Leonardo Marzio
- b Digestive Physiopathology Unit, University "G. d'Annunzio" Chieti-Pescara, Pescara Civic Hospital , Italy
| | - Laurino Grossi
- b Digestive Physiopathology Unit, University "G. d'Annunzio" Chieti-Pescara, Pescara Civic Hospital , Italy
| | | | - Antonia Nostro
- c Department of Pharmaceutical Sciences and Health Products , University of Messina , Messina , Italy
| | - Luigina Cellini
- a Department of Pharmacy , University "G. d'Annunzio" Chieti-Pescara , Chieti , Italy
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A Biotin Biosynthesis Gene Restricted to Helicobacter. Sci Rep 2016; 6:21162. [PMID: 26868423 PMCID: PMC4751477 DOI: 10.1038/srep21162] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2015] [Accepted: 01/12/2016] [Indexed: 02/07/2023] Open
Abstract
In most bacteria the last step in synthesis of the pimelate moiety of biotin is cleavage of the ester bond of pimeloyl-acyl carrier protein (ACP) methyl ester. The paradigm cleavage enzyme is Escherichia coli BioH which together with the BioC methyltransferase allows synthesis of the pimelate moiety by a modified fatty acid biosynthetic pathway. Analyses of the extant bacterial genomes showed that bioH is absent from many bioC-containing bacteria and is replaced by other genes. Helicobacter pylori lacks a gene encoding a homologue of the known pimeloyl-ACP methyl ester cleavage enzymes suggesting that it encodes a novel enzyme that cleaves this intermediate. We isolated the H. pylori gene encoding this enzyme, bioV, by complementation of an E. coli bioH deletion strain. Purified BioV cleaved the physiological substrate, pimeloyl-ACP methyl ester to pimeloyl-ACP by use of a catalytic triad, each member of which was essential for activity. The role of BioV in biotin biosynthesis was demonstrated using a reconstituted in vitro desthiobiotin synthesis system. BioV homologues seem the sole pimeloyl-ACP methyl ester esterase present in the Helicobacter species and their occurrence only in H. pylori and close relatives provide a target for development of drugs to specifically treat Helicobacter infections.
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Yee JKC. Helicobacter pylori colonization of the oral cavity: A milestone discovery. World J Gastroenterol 2016; 22:641-648. [PMID: 26811613 PMCID: PMC4716065 DOI: 10.3748/wjg.v22.i2.641] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2015] [Accepted: 10/13/2015] [Indexed: 02/06/2023] Open
Abstract
Over the past several years, the severity of Helicobacter pylori (H. pylori) infections has not significantly diminished. After successful eradication, the annual H. pylori recurrence rate is approximately 13% due to oral H. pylori infection. Established clinical diagnostic techniques do not identify an oral etiologic basis of H. pylori prior to gastric infection. There has been disagreement as to whether oral infection of H. pylori exists or not, with no definite conclusion. In medical practice, negative results with the urea breath test suggest that the stomach infection of H. pylori is cured in these patients. In fact, patients can present negative urea breath test results and yet exhibit H. pylori infection due to oral infection. The present paper provides evidence that H. pylori oral infection is nonetheless present, and the oral cavity represents a secondary site for H. pylori colonization.
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Espinosa-Rivero J, Rendón-Huerta E, Romero I. Inhibition of Helicobacter pylori growth and its colonization factors by Parthenium hysterophorus extracts. JOURNAL OF ETHNOPHARMACOLOGY 2015; 174:253-260. [PMID: 26297842 DOI: 10.1016/j.jep.2015.08.021] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/27/2015] [Revised: 07/30/2015] [Accepted: 08/18/2015] [Indexed: 06/04/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Parthenium hysterophorus (Asteraceae) is a traditional medicinal plant used to treat gastrointestinal disorders, such as gastritis. Helicobacter pylori have been described as the etiological agent of gastritis, peptic ulcer, as well as gastric adenocarcinoma. 50% of the world's population is infected with this bacterium and the current therapy fails due to the increment in antibiotic resistance; therefore, it is necessary to find new approaches to control H. pylori infection, either by its eradication or by preventing the bacterial colonization. AIM OF THE STUDY To investigate the effect of P. hysterophorus extracts on H. pylori growth and upon its colonization-related factors. MATERIALS AND METHODS Five different polarity extracts from roots and aerial parts of P. hysterophorus were evaluated in vitro against H. pylori growth by the broth dilution method. Anti-colonization activities were determined as follows: motility in soft agar plates, urease activity by ammonia colorimetrical quantification, and adherence of FITC labeled H. pylori to AGS cells by fluorometrical measurement. RESULTS Organic extracts inhibited H. pylori growth. Particularly, the dichloromethane extract from roots showed a MIC of 15.6 µg/ml while the aqueous extracts showed low or null activity. There is a direct correlation between antibacterial activity and inhibition of motility. Urease activity was partially inhibited by organic extracts, at best 46%, except for the roots dichloromethane extract which reached 74% of inhibition with 500 µg/ml (IC50=136.4 µg/ml). Plant extracts inhibited adherence in different ranges but the dichloromethane-methanol ones possessed the highest effect, with a 70% maximal inhibition at 1mg/ml. CONCLUSION The results indicate that some P. hysterophorus extracts have various biological activities that could act synergistically against H. pylori. This work contributes to the ethnomedical knowledge of this species and underlines the potential of some organic extracts as a good source for the isolation of bioactive compounds.
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Affiliation(s)
- Jazmín Espinosa-Rivero
- Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad Universitaria, C.P. 04510 México, D.F., Mexico
| | - Erika Rendón-Huerta
- Laboratorio Inmunobiología, Departamento de Biología Celular y Tisular, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad Universitaria, C.P. 04510 México, D.F., Mexico
| | - Irma Romero
- Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad Universitaria, C.P. 04510 México, D.F., Mexico.
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Dore MP, Goni E, Di Mario F. Is There a Role for Probiotics in Helicobacter pylori Therapy? Gastroenterol Clin North Am 2015; 44:565-75. [PMID: 26314668 DOI: 10.1016/j.gtc.2015.05.005] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The role of probiotics in Helicobacter pylori therapy remains unclear. Lactobacilli can be shown to inhibit H pylori in vitro. Some strains of Lactobacilli may exert specific antimicrobial effects. There is no strong evidence of a benefit on eradication rate when probiotics are added to a regimen. Despite promising results obtained using compounds of L reuteri and S boulardii, high-quality trials are needed to define the role of probiotics as adjuvant therapy. Variables that remain to be studied with L reuteri, currently the most promising strain, include dosage, frequency of administration, administration in relation to meals, and duration of therapy.
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Affiliation(s)
- Maria P Dore
- Dipartimento di Medicina Clinica e Sperimentale, University of Sassari, Viale San Pietro n 8, Sassari 07100, Italy; Department of Medicine, Michael E. DeBakey VAMC, Baylor College of Medicine, 2002 Holcombe Boulevard, Houston, TX 77030, USA
| | - Elisabetta Goni
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg 39106, Germany
| | - Francesco Di Mario
- Department of Clinical and Experimental Medicine, University of Parma, School of Medicine, Via Gramsci 14, Parma 43125, Italy.
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A novel chimeric flagellum fused with the multi-epitope vaccine CTB-UE prevents Helicobacter pylori-induced gastric cancer in a BALB/c mouse model. Appl Microbiol Biotechnol 2015; 99:9495-502. [DOI: 10.1007/s00253-015-6705-z] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2015] [Revised: 05/13/2015] [Accepted: 05/17/2015] [Indexed: 12/16/2022]
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Standard Triple Therapy versus Sequential Therapy in Helicobacter pylori Eradication: A Double-Blind, Randomized, and Controlled Trial. Gastroenterol Res Pract 2015; 2015:818043. [PMID: 26064098 PMCID: PMC4434224 DOI: 10.1155/2015/818043] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2015] [Accepted: 04/22/2015] [Indexed: 12/12/2022] Open
Abstract
Aim. To compare 10-day standard triple therapy versus sequential therapy as first-line treatment in patients infected with H. pylori. Methods. One hundred H. pylori positive patients (diagnosed by rapid urease test and histology), with average age of 47.2, M/F = 28/72, were randomized to receive either standard triple treatment (TT) as follows: lansoprazole 30 mg, clarithromycin 500 mg, and amoxicillin 1 g, b.i.d. for ten days, or sequential treatment (ST) as follows: lansoprazole 30 mg, amoxicillin and placebo 1.0 g b.i.d for the first five days, followed by lansoprazole 30 mg, clarithromycin 500 mg, and tinidazole 500 mg b.i.d, for the remaining five days. Eradication rates were determined 60 days after treatment by urease, histology, or 13C-urea breath test. Results. In intention to treat (ITT) analysis, the rate of H. pylori eradication in the TT and ST groups was the same for both regimens as follows: 86% (43/50), 95% CI 93,3 to 73.4%. In Per protocol (PP) analysis, the rate of H. pylori eradication in the TT and ST groups was 87.8% (43/49), 95% CI 94,5 to 75.3% and 89.6% (43/48), 95% CI 95,8 to 77.3%, respectively. Conclusions. In Brazil, standard triple therapy is as equally effective as sequential therapy in eradicating Helicobacter pylori patients. This study was registered under Clinical Trials with number ISRCTN62400496.
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