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Vinson B, Fink C, Wargenau M, Talley NJ, Holtmann G. Double-blind, randomized, 8-week multicenter study of the efficacy and safety of STW 5-II versus placebo in functional dyspepsia. JGH Open 2024; 8:e13054. [PMID: 38699471 PMCID: PMC11064020 DOI: 10.1002/jgh3.13054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Revised: 02/09/2024] [Accepted: 03/02/2024] [Indexed: 05/05/2024]
Abstract
Background and Aim Herbal products are widely used to treat patients with disorders of gut brain interaction but clinical efficacy and safety data for treatments lasting >4 weeks are widely lacking. We evaluated the efficacy and safety of 8 weeks of treatment with the herbal combination product STW 5-II for patients with functional dyspepsia (FD) meeting Rome II criteria. We also conducted a post hoc analysis including patients meeting Rome IV criteria for FD and evaluated the effect of the G-protein beta 3 (GNB3) subunit polymorphism (C825T) on therapeutic response. Methods This multicenter, placebo-controlled, double-blind study included 272 FD patients meeting Rome II criteria in the intention-to-treat cohort and 266 meeting Rome IV criteria. We used the validated Gastrointestinal Symptom Score (GIS) to assess GI symptoms, defining response rate as the proportion of patients with ≥50% GIS improvement in at least three of four assessments. Results After 8 weeks, the response rate was significantly higher in the STW 5-II group versus placebo (61.2% vs 45.1%, P = 0.008). Mean GIS non-significantly improved with STW 5-II treatment (7.9 ± 4.41 vs 6.7 ± 4.91 with placebo; P = 0.07). In the Rome IV subgroup analysis, STW 5-II yielded a better response rate (P = 0.01) versus placebo and greater postprandial distress symptom improvement (P = 0.04) versus placebo. Safety parameters did not differ between groups, and GNB3 status was not linked with therapeutic response. Conclusion STW 5-II is efficacious, with no observed safety signals at up to 8 weeks of treatment in patients with FD meeting Rome II or IV criteria.
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Affiliation(s)
- Bettina Vinson
- Bayer Consumer Health, Steigerwald Arzneimittelwerk GmbHDarmstadtGermany
| | - Careen Fink
- Bayer Consumer Health, Steigerwald Arzneimittelwerk GmbHDarmstadtGermany
| | - Manfred Wargenau
- M.A.R.C.O. GmbH & Co. KG, Institute for Clinical Research and StatisticsDüsseldorfGermany
| | - Nicholas J Talley
- School of Medicine and Public Health, University of NewcastleCallaghanNew South WalesAustralia
| | - Gerald Holtmann
- University of Queensland and Department of Gastroenterology and HepatologyPrincess Alexandra HospitalWoolloongabbaQueenslandAustralia
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Šojat D, Volarić M, Keškić T, Volarić N, Cerovečki V, Trtica Majnarić L. Putting Functional Gastrointestinal Disorders within the Spectrum of Inflammatory Disorders Can Improve Classification and Diagnostics of These Disorders. Biomedicines 2024; 12:702. [PMID: 38540315 PMCID: PMC10967747 DOI: 10.3390/biomedicines12030702] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Revised: 03/17/2024] [Accepted: 03/19/2024] [Indexed: 01/03/2025] Open
Abstract
The spectrum, intensity, and overlap of symptoms between functional gastrointestinal disorders (FGIDs) and other gastrointestinal disorders characterize patients with FGIDs, who are incredibly different in their backgrounds. An additional challenge with regard to the diagnosis of FGID and the applicability of a given treatment is the ongoing expansion of the risk factors believed to be connected to these disorders. Many cytokines and inflammatory cells have been found to cause the continuous existence of a low level of inflammation, which is thought to be a basic pathophysiological process. The idea of the gut-brain axis has been created to offer a basic framework for the complex interactions that occur between the nervous system and the intestinal functions, including the involvement of gut bacteria. In this review paper, we intend to promote the hypothesis that FGIDs should be seen through the perspective of the network of the neuroendocrine, immunological, metabolic, and microbiome pathways. This hypothesis arises from an increased understanding of chronic inflammation as a systemic disorder, that is omnipresent in chronic health conditions. A better understanding of inflammation's role in the pathogenesis of FGIDs can be achieved by clustering markers of inflammation with data indicating symptoms, comorbidities, and psycho-social factors. Finding subclasses among related entities of FGIDs may reduce patient heterogeneity and help clarify the pathophysiology of this disease to allow for better treatment.
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Affiliation(s)
- Dunja Šojat
- Department of Family Medicine, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, 31000 Osijek, Croatia; (D.Š.); (M.V.)
| | - Mile Volarić
- Department of Family Medicine, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, 31000 Osijek, Croatia; (D.Š.); (M.V.)
- Department of Gastroenterology and Hepatology, University Clinical Hospital Mostar, Bijeli Brijeg bb, 88000 Mostar, Bosnia and Herzegovina
| | - Tanja Keškić
- Department Biomedicine, Technology and Food Safety, Laboratory of Chemistry and Microbiology, Institute for Animal Husbandry, Autoput Belgrade-Zagreb 16, 11080 Belgrade, Serbia;
| | - Nikola Volarić
- Department of Physiology and Immunology, Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, Crkvena ulica 21, 31000 Osijek, Croatia;
| | - Venija Cerovečki
- Department of Family Medicine, School of Medicine, University of Zagreb, Šalata 3, 10000 Zagreb, Croatia;
| | - Ljiljana Trtica Majnarić
- Department of Family Medicine, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, 31000 Osijek, Croatia; (D.Š.); (M.V.)
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Kumar A, Selim A, Gowri V, Ahmad A, Vyawahare A, Nadeem A, Siddiqui N, Raza SS, Jayamurugan G, Khan R. Cellulose-Conjugated Copper-Oxide Nanoparticles for the Treatment of Ethanol-Induced Gastric Ulcers in Wistar Rats. ACS Biomater Sci Eng 2022; 8:2636-2643. [PMID: 35513890 DOI: 10.1021/acsbiomaterials.2c00090] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Gastric ulcer (GU) is the most common and chronic inflammatory condition mediated by multiple immune cells like neutrophils, macrophages, and lymphocytes with multiple pro-inflammatory cytokine interleukins such as IL-8, IL-10, IL-β, and interferon-γ (IFN-γ). Copper (Cu) is one of the essential micronutrients mainly found in the liver and brain. It plays a major role in metabolism, enzyme conversion, free radical scavenging, trafficking agents, and many others. Due to its various roles in the biological system, it can also be used as a therapeutic agent in many diseases like colon cancer, bone fracture healing, angiogenesis, as an antibacterial, wound-healing and radiotherapeutic agents. In this study, we used thiol-functionalized cellulose-conjugated copper-oxide nanoparticles (CuI/IIO NPs) synthesized under environmentally friendly conditions. We have evaluated the effects of cellulose-conjugated CuI/IIO NPs against ethanol-induced gastric ulcer in Wistar rats. The cellulose-conjugated CuI/IIO NPs were evaluated against different physical, histochemical, and inflammatory parameters. The NPs promoted mucosal healing by ameliorating ulcerative damage, restoring the histoarchitecture of gastric mucosa, and inhibiting pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β), and other inflammatory biomarkers such as myeloperoxidase (MPO) activity and nitric oxide (NO) levels. The current study's findings suggest that cellulose-conjugated CuI/IIO NPs exerted antiulcer effects on the preclinical rat model and have promising potential as a novel therapeutic agent for the treatment of gastric ulcers.
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Affiliation(s)
- Ajay Kumar
- Chemical Biology Unit, Institute of Nano Science and Technology (INST), Knowledge City, Sector 81, Mohali, Punjab 140306, India
| | - Abdul Selim
- Energy and Environment Unit, Institute of Nano Science and Technology (INST), Knowledge City, Sector 81, Mohali, Punjab 140306, India
| | - Vijayendran Gowri
- Energy and Environment Unit, Institute of Nano Science and Technology (INST), Knowledge City, Sector 81, Mohali, Punjab 140306, India
| | - Anas Ahmad
- Julia McFarlane Diabetes Research Centre (JMDRC) and Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases and Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada
| | - Akshay Vyawahare
- Chemical Biology Unit, Institute of Nano Science and Technology (INST), Knowledge City, Sector 81, Mohali, Punjab 140306, India
| | - Ahmed Nadeem
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
| | - Nahid Siddiqui
- Amity Institute of Biotechnology, Amity University, Sector-125, Noida 201303, Uttar Pradesh, India
| | - Syed Shadab Raza
- Laboratory for Stem Cell & Restorative Neurology, Department of Biotechnology, Era's Lucknow Medical College and Hospital, Sarfarazganj, Lucknow 226003, Uttar Pradesh, India
| | - Govindasamy Jayamurugan
- Energy and Environment Unit, Institute of Nano Science and Technology (INST), Knowledge City, Sector 81, Mohali, Punjab 140306, India
| | - Rehan Khan
- Chemical Biology Unit, Institute of Nano Science and Technology (INST), Knowledge City, Sector 81, Mohali, Punjab 140306, India
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Abstract
The aim of the review is to examine the role of growth factors and cytokines in the management of Diabetic Foot Ulcers, such as platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and Insulin like growth factor (IGF). Taking this a step further, the role of Hypoxia-inducible factors (HIFs), Transforming growth factor beta 1 (TGF-β-1) and other growth factors have also been examined, with regard to the treatment of diabetic foot ulcers. The roles of these above-mentioned growth cytokines have been analyzed by studying various scholastic articles. The complete process of wound healing is implemented and regulated by numerous cytokines and human growth factors. The findings of the study indicate that wound healing of diabetic foot ulcers is a complex and extremely challenging biological and molecular process that involves coordinated efforts of multiple cell types. The therapeutic effects of various growth factors in the clinical management of wounds are chronic venous ulcers, pressure ulcers, and diabetic foot ulcers. It has been concluded that altercations of various cytokines are found in patients enduring diabetic foot ulcers. In a similar way, changes in the level of cytokines are also found in patients suffering from other diabetic complications such as diabetic nephropathy, retinopathy, and neuropathy. Subsequently, the diabetic wound healing process can be accelerated by regulating the levels of the cytokines.
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Affiliation(s)
- Mohammad Zubair
- Department of Medical Microbiology, Faculty of Medicine, University of Tabuk, Tabuk, 71491, Kingdom of Saudi Arabia.
| | - Jamal Ahmad
- Rajiv Gandhi Centre for Diabetes and Endocrinology, Faculty of Medicine, J.N. Medical College, Aligarh Muslim University, Aligarh, 202002, India
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A modified pectic polysaccharide from turmeric (Curcuma longa) with antiulcer effects via anti–secretary, mucoprotective and IL–10 mediated anti–inflammatory mechanisms. Int J Biol Macromol 2018; 118:864-880. [PMID: 29924982 DOI: 10.1016/j.ijbiomac.2018.06.053] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Revised: 06/03/2018] [Accepted: 06/11/2018] [Indexed: 12/15/2022]
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Arunachalam K, Balogun SO, Pavan E, de Almeida GVB, de Oliveira RG, Wagner T, Cechinel Filho V, de Oliveira Martins DT. Chemical characterization, toxicology and mechanism of gastric antiulcer action of essential oil from Gallesia integrifolia (Spreng.) Harms in the in vitro and in vivo experimental models. Biomed Pharmacother 2017; 94:292-306. [PMID: 28763752 DOI: 10.1016/j.biopha.2017.07.064] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2017] [Revised: 07/01/2017] [Accepted: 07/14/2017] [Indexed: 12/12/2022] Open
Abstract
Gallesia integrifolia is a Brazilian Amazon tree whose bark decoction is popularly used to treat peptic ulcer. The essential oil from the inner stem bark of G. integrifolia (EOGi) was chemically characterized by GC/MS. The in vitro cytotoxicity and genotoxicity were evaluated in CHO-K1 cells, while the in vivo oral acute toxicity was performed in mice. The gastroprotective effect of EOGi was assessed in acidified ethanol and piroxicam and ulcer healing on acetic acid -induced ulcer models in rodents. Anti-secretory, mucus, K+-ATP channels, prostaglandins (PGs), nitric oxide (NO), TNF-α, IL-1β, IL-10, catalase (CAT) and myeloperoxidase (MPO) activities and in vitro Helicobacter pylori action by EOGi were evaluated. EOGi exhibited cytotoxic effects only at 72h and no acute toxicity. EOGi showed gastroprotective and ulcer healing effects. EOGi gastroprotection was attenuated by indomethacin pre-treatment. Gastric volume and total acidity were reduced, while gastric pH was elevated. EOGi increased mucus and NO productions and CAT activity, and inhibited MPO activity, TNF-α and IL-1β concentrations and augmented IL-10. EOGi was not active against H. pylori. These results indicated that EOGi is safe and exerts preventive and curative gastric ulcer effects by multitarget actions. Twenty compounds were identified and (-)-alpha-santalene was the main compound.
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Affiliation(s)
- Karuppusamy Arunachalam
- Área de Farmacologia, Departamento de Ciências Básicas em Saúde, Faculdade de Medicina, Universidade Federal de Mato Grosso (UFMT), Cuiabá, Brazil
| | - Sikiru Olaitan Balogun
- Área de Farmacologia, Departamento de Ciências Básicas em Saúde, Faculdade de Medicina, Universidade Federal de Mato Grosso (UFMT), Cuiabá, Brazil; Curso de Farmácia, Faculdade Noroeste do Mato Grosso, Associação Juinense de Ensino Superior (AJES), Juína, Mato Grosso, Brazil
| | - Eduarda Pavan
- Área de Farmacologia, Departamento de Ciências Básicas em Saúde, Faculdade de Medicina, Universidade Federal de Mato Grosso (UFMT), Cuiabá, Brazil
| | - Guilherme Vieira Botelho de Almeida
- Área de Farmacologia, Departamento de Ciências Básicas em Saúde, Faculdade de Medicina, Universidade Federal de Mato Grosso (UFMT), Cuiabá, Brazil
| | - Ruberlei Godinho de Oliveira
- Área de Farmacologia, Departamento de Ciências Básicas em Saúde, Faculdade de Medicina, Universidade Federal de Mato Grosso (UFMT), Cuiabá, Brazil
| | - Theodoro Wagner
- Programa de Pós-Graduação em Ciências Farmacêuticas e Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí, Itajaí, Santa Catarina, Brazil
| | - Valdir Cechinel Filho
- Programa de Pós-Graduação em Ciências Farmacêuticas e Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí, Itajaí, Santa Catarina, Brazil
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Singh R, Ghoshal UC, Kumar S, Mittal B. Genetic variants of immune-related genes IL17F and IL10 are associated with functional dyspepsia: A case-control study. Indian J Gastroenterol 2017; 36:343-352. [PMID: 28965252 DOI: 10.1007/s12664-017-0788-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2017] [Accepted: 09/11/2017] [Indexed: 02/04/2023]
Abstract
BACKGROUND Low-grade inflammation may play an important role in pathogenesis of functional dyspepsia (FD). Since cytokines may influence gastric mucosal inflammation, which is associated with FD, we evaluated singe nucleotide polymorphisms (SNPs) of pro-inflammatory IL17F and anti-inflammatory IL10 cytokine genes in patients with FD and healthy subjects (HS). METHODS Two hundred and thirty-seven consecutive patients with FD (Rome III) and 250 HS were genotyped for IL17F (rs2397084: A/G, rs763780: T/C) and IL10 (rs1800896: G/A, rs1800871: C/T) (PCR-RFLP). RESULTS Patients with FD [173 (73%) men, age 38.4±12 years] were comparable with HS [195 (78%) men, age 37.3±12 years] with respect to age and gender. Out of 237 patients, 26 (11%) had epigastric pain, 55 (23.2%) had post-prandial distress syndromes (EPS, PDS), and 156 (65.8%) had EPS-PDS overlap. Among 237 patients with FD, GG (variant) genotype of IL17F (rs2397084) was more common than HS [15 (6.3%) vs. 4 (1.6%), p=0.015, odds ratio (OR)=4.0, 95% confidence interval (CI)=1.3-12.3]. IL17F (rs763780) and IL10 (rs1800896) were comparable among patients and HS (p=0.56, 0.28), respectively. However, TT (variant) genotype of IL10 (rs1800871) was more common among patients than HS [39 (16.5%) vs. 32 (12.8%), p=0.06, OR=1.7, 95% CI=0.98-2.98]. SNPs of IL17F and IL10 (rs2397084, rs763780, rs1800896 and rs1800871) were comparable among patients among sub-types of FD (p=0.80 and 0.44). CONCLUSION SNPs of IL17F (rs2397084) and IL10 (rs1800871) genes are associated with FD.
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Affiliation(s)
- Rajan Singh
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Uday C Ghoshal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India.
| | - Sushil Kumar
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Balraj Mittal
- Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India
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Paediatric Rome III Criteria-Related Abdominal Pain Is Associated With Helicobacter pylori and Not With Calprotectin. J Pediatr Gastroenterol Nutr 2016; 63:417-22. [PMID: 26913755 DOI: 10.1097/mpg.0000000000001172] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
OBJECTIVES Abdominal pain-related functional gastrointestinal disorders in children include functional dyspepsia, functional abdominal pain, irritable bowel syndrome, and abdominal migraine. We aimed to evaluate a possible association between functional abdominal pain disorders and Helicobacter pylori infection and faecal calprotectin level. METHODS Prospective observational study including consecutive children with functional gastrointestinal disorders fulfilling Rome III criteria (cases) and age/sex-matched healthy controls. H pylori has been detected by biopsy-based tests and stool-antigen detection, faecal calprotectin by enzyme-linked immunosorbent assay. RESULTS A total of 56 cases (27 with functional dyspepsia) and 56 controls were enrolled. H pylori being detected in 17 of 56 cases (30.4%) and 4 of 56 controls (7.1%, odds ratio: 5.7; 95% confidence interval [CI]: 1.8-18.2, P = 0.003). H pylori was detected significantly more frequently in cases with functional dyspepsia (14/27, 51.9% odds ratio: 14.0; 95% CI: 3.9-49.7, P = 0.00001) than in controls and not in cases with other well-recognized functional gastrointestinal complaints (3/29, 10.3%). The median faecal calprotectin level was similar in cases (7.8 μg/g, 95% CI: 7.8-8.4) including those with gastritis, and controls (9.1 μg/g, 95% CI: 7.8-11.3). Gastritis features were more frequent in H pylori-infected and noninfected cases with functional dyspepsia (27/27, 100%) than in cases with other abdominal functional complaints (15/29, 51.7%, P = 0.007). CONCLUSIONS H pylori gastritis and noninfectious gastritis were associated with functional dyspepsia in children referred for abdominal pain-related functional gastrointestinal disorders while faecal calprotectin is not a predictor of gastritis and is similar in children with functional abdominal pain symptoms and in controls.
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Siregar G, Halim S, Sitepu R. Serum IL-10, MMP-7, MMP-9 Levels in Helicobacter pylori Infection and Correlation with Degree of Gastritis. Open Access Maced J Med Sci 2016; 4:359-363. [PMID: 27703556 PMCID: PMC5042616 DOI: 10.3889/oamjms.2016.099] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2016] [Revised: 08/22/2016] [Accepted: 08/24/2016] [Indexed: 12/12/2022] Open
Abstract
AIM Helicobacter pylori causes gastric mucosal inflammation and immune reaction. However, the increase of IL-10, MMP-7, and MMP-7 levels in the serum is still controversial. The objective of this study was to investigate the serum levels of IL-10, MMP-7 & MMP-9 in gastritis patients with H. pylori infection. MATERIALS AND METHODS A cross-sectional study was done on seventy gastritis patients that consecutive admitted to endoscopy units. The diagnosis of gastritis was made based on histopathology and diagnosis of H. pylori infection was based on rapid urease test. Serum samples were obtained to determine to circulate IL-10, MMP-7, and MMP-9 level. Univariate and bivariate analysis were done by SPSS version 22. RESULTS Forthy percentages of the patients were infected with H. pylori. The IL-10 level was significantly higher in H. pylori-infected patients compared to non-infected patients. However, there were no differences between serum levels of MMP-7 and MMP-9 in infected and non-infected H. pylori patients. CONCLUSIONS The immune response to H. pylori promotes systemic inflammation, which was reflected by the increased levels of serum IL-10. However, there were no significant differences in MMP-7 and MMP-9 serum levels between positive and negative infected H. pylori patients.
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Affiliation(s)
- Gontar Siregar
- University of Sumatera Utara, Gastroentero-Hepatology, Komp. Tasbi YY No 203, Medan, Sumatera Utara 20122, Indonesia
| | - Sahat Halim
- University of Sumatera Utara, Internal Medicine, Medan, Sumatera Utara, Indonesia
| | - Ricky Sitepu
- University of Sumatera Utara, Internal Medicine, Medan, Sumatera Utara, Indonesia
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Kourikou A, Karamanolis GP, Dimitriadis GD, Triantafyllou K. Gene polymorphisms associated with functional dyspepsia. World J Gastroenterol 2015; 21:7672-7682. [PMID: 26167069 PMCID: PMC4491956 DOI: 10.3748/wjg.v21.i25.7672] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2015] [Revised: 04/07/2015] [Accepted: 05/21/2015] [Indexed: 02/06/2023] Open
Abstract
Functional dyspepsia (FD) is a constellation of functional upper abdominal complaints with poorly elucidated pathophysiology. However, there is increasing evidence that susceptibility to FD is influenced by hereditary factors. Genetic association studies in FD have examined genotypes related to gastrointestinal motility or sensation, as well as those related to inflammation or immune response. G-protein b3 subunit gene polymorphisms were first reported as being associated with FD. Thereafter, several gene polymorphisms including serotonin transporter promoter, interlukin-17F, migration inhibitory factor, cholecystocynine-1 intron 1, cyclooxygenase-1, catechol-o-methyltransferase, transient receptor potential vanilloid 1 receptor, regulated upon activation normal T cell expressed and secreted, p22PHOX, Toll like receptor 2, SCN10A, CD14 and adrenoreceptors have been investigated in relation to FD; however, the results are contradictory. Several limitations underscore the value of current studies. Among others, inconsistencies in the definitions of FD and controls, subject composition differences regarding FD subtypes, inadequate samples, geographical and ethnical differences, as well as unadjusted environmental factors. Further well-designed studies are necessary to determine how targeted genes polymorphisms, influence the clinical manifestations and potentially the therapeutic response in FD.
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Balogun SO, Damazo AS, de Oliveira Martins DT. Helicteres sacarolha A. St.- Hil. et al.: gastroprotective and possible mechanism of actions in experimental animals. JOURNAL OF ETHNOPHARMACOLOGY 2015; 166:176-184. [PMID: 25792014 DOI: 10.1016/j.jep.2015.03.021] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/14/2014] [Revised: 02/10/2015] [Accepted: 03/08/2015] [Indexed: 06/04/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Helicteres sacarolha A. St.- Hil. et al. popularly known in Brazil as 'semente-de-macaco', is widely employed in the popular medicine in many of parts of Brazil in the alleviation of symptoms of ailments such as peptic ulcer and inflammation. Up to the present, there is no study addressing the gastroprotective activity of the hydroethanolic extract of H. sacarolha and its possible mechanism of actions. MATERIALS AND METHODS The hydroethanolic (70%) extract of H. sacarolha (HEHs) was obtained by maceration. The gastroprotective activity was assessed using gastric ulcer models induced by acidified ethanol, piroxicam, and water restraint stress in mice and rats at doses of 20, 50 and 250mg/kg p.o. Mechanistic studies involved the antisecretory assay evaluated with pylorus ligation in rats and pre-treatments with appropriate antagonists/inhibitors such as yohimbine, glibenclamide, indomethacin and l-NAME, effect on catalase and myeloperoxidase activities and gastric mucus determination using acidified ethanol- induced ulcer in mice. RESULTS HEHs at all doses tested demonstrated potent gastroprotective activities in the acute ulcer models. The gastroprotective activity of HEHs was attenuated by pre-treatments with yohimbine, glibenclamide, indomethacin and l-NAME. HEHs effectively reduced basal gastric juice production without any effect on the free and total acidity. The gastroprotective action of HEHs involved increasing the antioxidant enzyme catalase and mucus secretion and inhibition of neutrophyl infiltration as reflected by the reduction in the myeloperoxidase activity. CONCLUSION The results of this study gave a scientific support for the popular use of the leaves of H. sacarolha in the treatment of gastric ulcers and that it has a multi-targeted action.
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Affiliation(s)
- Sikiru Olaitan Balogun
- Postgraduate Studies in Health Sciences, Faculty of Medicine, Federal University of Mato Grosso (UFMT), 78060-900 Cuiabá, MT, Brazil
| | - Amilcar Sabino Damazo
- Postgraduate Studies in Health Sciences, Faculty of Medicine, Federal University of Mato Grosso (UFMT), 78060-900 Cuiabá, MT, Brazil; Department of Basic Health Sciences, Faculty of Medicine, Federal University of Mato Grosso (UFMT), 78060-900 Cuiabá, MT, Brazil
| | - Domingos Tabajara de Oliveira Martins
- Postgraduate Studies in Health Sciences, Faculty of Medicine, Federal University of Mato Grosso (UFMT), 78060-900 Cuiabá, MT, Brazil; Department of Basic Health Sciences, Faculty of Medicine, Federal University of Mato Grosso (UFMT), 78060-900 Cuiabá, MT, Brazil.
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Chmiela M, Gajewski A, Rudnicka K. Helicobacter pylori vs coronary heart disease - searching for connections. World J Cardiol 2015; 7:187-203. [PMID: 25914788 PMCID: PMC4404374 DOI: 10.4330/wjc.v7.i4.187] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2014] [Revised: 01/16/2015] [Accepted: 02/09/2015] [Indexed: 02/07/2023] Open
Abstract
In this review, we discussed the findings and concepts underlying the potential role of Helicobacter pylori (H. pylori) infections in the initiation, development or persistence of atherosclerosis and coronary heart disease (CHD). This Gram-negative bacterium was described by Marshall and Warren in 1984. The majority of infected subjects carries and transmits H. pylori with no symptoms; however, in some individuals these bacteria may cause peptic ulcers, and even gastric cancers. The widespread prevalence of H. pylori infections and the fact that frequently they remain asymptomatic may suggest that, similarly to intestinal microflora, H. pylori may deliver antigens that stimulate not only local, but also systemic inflammatory response. Recently, possible association between H. pylori infection and extragastric disorders has been suggested. Knowledge on the etiology of atherosclerosis together with current findings in the area of H. pylori infections constitute the background for the newly proposed hypothesis that those two processes may be related. Many research studies confirm the indirect association between the prevalence of H. pylori and the occurrence of CHD. According to majority of findings the involvement of H. pylori in this process is based on the chronic inflammation which might facilitate the CHD-related pathologies. It needs to be elucidated, if the infection initiates or just accelerates the formation of atheromatous plaque.
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Lagunes-Servin H, Torres J, Maldonado-Bernal C, Pérez-Rodríguez M, Huerta-Yépez S, Madrazo de la Garza A, Muñoz-Pérez L, Flores-Luna L, Ramón-García G, Camorlinga-Ponce M. Toll-like receptors and cytokines are upregulated during Helicobacter pylori infection in children. Helicobacter 2013; 18:423-32. [PMID: 23869400 DOI: 10.1111/hel.12067] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIM Helicobacter pylori infection is mainly acquired during childhood, and establishes a chronic infection that may lead to peptic ulcer or gastric cancer during adulthood. Toll-like receptors (TLRs) are expressed by distinct cell types throughout the gastrointestinal tract, and play an important role in regulation of the innate immune response. Few works have addressed TLRs expression in gastric epithelia of adults, and scarce studies have done it in children. The aim of this work was to analyze the expression of TLR2, TLR4, TLR5, TLR9, and IL-8, IL-10 and TNF-α in the gastric mucosa of children with and without H. pylori infection. METHODS Gastric biopsies were collected by endoscopy from 50 children with recurrent abdominal pain, 25 with H. pylori infection and 25 without infection. In the gastric biopsies the expression of TLRs and cytokines was studied by immunohistochemistry, and the degree of mucosal inflammation was determined using the Sydney system. RESULTS We found that H. pylori infection was associated with a significant increased expression of TLRs 2, 4, 5 and 9, although expression varied between surface epithelia and glands. Epithelial cells expressing IL-8, IL-10 and TNF-α were increased in gastric mucosa of children with H. pylori infection. CONCLUSION This study shows the gastric epithelia of children respond to H. pylori infection by increasing the expression of TLR2, TLR4, TLR5, TLR9 and the cytokines IL-8, IL-10 and TNF-α.
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Affiliation(s)
- Hugo Lagunes-Servin
- Unidad de Investigación Médica en Enfermedades Infecciosas, Centro Médico Nacional Siglo XXI, IMSS, Mexico City, México
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Overexpression of IFITM1 has clinicopathologic effects on gastric cancer and is regulated by an epigenetic mechanism. THE AMERICAN JOURNAL OF PATHOLOGY 2012; 181:43-52. [PMID: 22609115 DOI: 10.1016/j.ajpath.2012.03.027] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/17/2011] [Revised: 01/10/2012] [Accepted: 03/15/2012] [Indexed: 12/12/2022]
Abstract
In an effort to identify novel genes related to the prognosis of gastric cancer, we performed gene expression profiling and found overexpressed levels of human interferon-induced transmembrane protein 1 (IFITM1). We validated the gastric cancer-specific up-regulation of IFITM1 and its association with cancer progression. We also studied its epigenetic regulation and tumorigenesis-related functions. Expression of IFITM1 was evaluated in various human gastric cancer cells and in 35 patient tumor tissues by quantitative RT-PCR and Western blot analyses. The results showed highly up-regulated IFITM1 in cancer cell lines and tissues. Furthermore, IHC studies were performed on 151 patient tissues, and a significant correlation was revealed between higher IFITM1 expression and Lauren's intestinal type (P = 0.007) and differentiated adenocarcinoma (P = 0.025). Quantitative studies of DNA methylation for 27 CpG sites in the regulatory region showed hypermethylation in cells expressing low levels of IFITM1. Methylation-dependent IFITM1 expression was confirmed further by in vitro demethylation using 5-aza-2'-deoxycytidine and luciferase assays. The functional analysis of IFITM1 by silencing of its expression with small-interfering RNA showed decreased migration and invasiveness of cancer cells, whereas its overexpression exhibited the opposite results. In this study, we demonstrated gastric cancer-specific overexpression of IFITM1 regulated by promoter methylation and the role of IFITM1 in cancer prognosis.
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Varbanova M, Malfertheiner P. Bacterial load and degree of gastric mucosal inflammation in Helicobacter pylori infection. Dig Dis 2011; 29:592-9. [PMID: 22179216 DOI: 10.1159/000333260] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Helicobacter pylori induces an inflammatory immune response in the gastric mucosa. The degree of gastric mucosal inflammation and its topographic distribution are key factors in the diversity of H. pylori-related complications. Here we summarize substantial evidence reported in the literature concerning the impact of H. pylori density on gastric inflammation, the development of severe complications, and its relation to H. pylori suppression therapy. Most studies demonstrate a significant correlation between H. pylori density and the grade of acute and chronic inflammation, taking into account the limitations of each method for density assessment. Overall, high bacterial loads are associated with increased acute mucosal damage and long-term changes in the gastric mucosa. The influence of H. pylori density reduction on the improvement of gastric mucosal changes was observed in studies using 'clearance' therapies. Mucosal agents provoke a significant, but not persistent, reduction in gastritis activity. Treatments suppressing the density and virulence of H. pylori could become strategies to prevent H. pylori-associated disease in the future.
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Affiliation(s)
- M Varbanova
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto von Guericke University, Magdeburg, Germany
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Tahara T, Arisawa T, Shibata T, Nakamura M, Wang F, Yoshioka D, Okubo M, Maruyama N, Kamiya Y, Nakamura M, Fujita H, Nagasaka M, Iwata M, Takahama K, Watanabe M, Hirata I, Nakano H. A Genetic Variant of the CD14 C-159T in Patients with Functional Dyspepsia (FD) in Japanese Subjects. J Clin Biochem Nutr 2011; 42:104-10. [PMID: 18385826 PMCID: PMC2266053 DOI: 10.3164/jcbn.2008015] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2007] [Accepted: 08/27/2007] [Indexed: 12/22/2022] Open
Abstract
Inflammatory changes in the gastric mucosa are commonly observed in Japanese patients with functional dyspepsia (FD). However, detailed data regarding the relationship between the genetic regulatory factors of inflammation and FD are not available. CD14 is an important mediator of the inflammatory response in the first line of host defense by recognition of Lipopolysaccharide (LPS). We aimed to investigate the association between CD14 promoter C-159T polymorphism and FD in a Japanese population. 108 patients with FD and 99 non-dyspeptic subjects enrolled in this study. Dyspeptic symptoms were divided according to Rome III criteria. CD14 gene C-159T polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism. In the non-dyspeptics, the CD14 genotype distribution was 28CC (28.3%), 51CT (51.5%), 21TT (21.2%). Meanwhile, the CD14 genotype distribution in FD was 31CC (28.4%), 56CT (51.4%), 22TT (20.2%). The genotype distribution was not significantly different. There was no significant difference between two groups in the genotype distribution. We did not found any association between CD14 genotypes and dyspeptic patients in different gender and Helicobacter pylori infection status. No significant association was also found between CD14 polymorphism and any of different subtypes of FD according to Rome III while there was a weak correlation between TT genotype and PDS in male subjects (TT vs others, OR = 3.18, 95% CI = 0.98−10.26, p = 0.06). In conclusion, our results suggest that CD14 polymorphism is unlikely to associate with susceptibility of dyspeptic symptoms. The role of inflammation related-gene polymorphisms to the development of dyspepsia needs to further evaluation.
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Affiliation(s)
- Tomomitsu Tahara
- Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan
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Helmin-Basa A, Michalkiewicz J, Gackowska L, Kubiszewska I, Eljaszewicz A, Mierzwa G, Bala G, Czerwionka-Szaflarska M, Prokurat A, Marszalek A. Pediatric Helicobacter pylori infection and circulating T-lymphocyte activation and differentiation. Helicobacter 2011; 16:27-35. [PMID: 21241409 DOI: 10.1111/j.1523-5378.2010.00809.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND In this study, H. pylori-infected and noninfected children with gastritis were compared to a control group with respect to circulating CD4(+) and CD8(+) T lymphocytes expressing activation and differentiation markers. Additionally, the lymphocyte phenotypes of children with gastritis were correlated with the gastric inflammation scores. MATERIALS AND METHODS H. pylori infection status was assessed based on [¹³C]urea breath test, rapid urease test, and histology. Analysis of the lymphocyte surface molecule expression was carried out by triple-color flow cytometry. RESULTS The group of H. pylori-infected children showed an elevated proportion of peripheral B cells with CD19(low) , along with a twofold increase in the percentage of memory (CD45RO(+)) CD4(+) and CD8(+) T-cell subsets (p < .05). Moreover, a positive correlation between the age and the percentage of these subsets was seen (r = .38, p = .04 and r = .56, p < .01, respectively). Children with gastritis but without infection had a slightly increased percentage of CD8(+) T cells and CD56(+) NK cells, CD3(high) T cells and CD45RO(high) CD4(+) T-cell subsets (p < .05). Both H. pylori-infected and noninfected children with gastritis were characterized by an increased percentage of memory/effector CD4(+) T cells, the presence of NK cells with CD56(high), memory T-cell subset with CD4(high), and naive, memory, memory/effector, and effector T-cell subsets with CD8(high) (p < .05). Gastric inflammation scores correlated positively with the percentage of CD4(+) T lymphocytes in H. pylori-infected children (r = .42, p = .03). In noninfected children, gastric inflammation scores correlated positively with the percentage of B cells (r = .45, p = .04). CONCLUSION In H. pylori-negative children, gastritis was associated with an increased percentage of activated NK and T cells, and intermediate-differentiated peripheral blood CD4(+) T cells, which was more pronounced in H. pylori-positive children who also showed an increased B-cell response. However, increased inflammation was only associated with the elevation of CD4(+) T-cell percentage in H. pylori-positive children as well as B-cell percentage in H. pylori-negative children with gastritis.
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Affiliation(s)
- Anna Helmin-Basa
- Department of Immunology, Collegium Medicum Nicolaus Copernicus University, Bydgoszcz, Poland.
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Kushch IG, Korenev NM, Kamarchuk LV, Pospelov AP, Alexandrov YL, Kamarchuk GV. Sensors for Breath Analysis: An Advanced Approach to Express Diagnostics and Monitoring of Human Diseases. BIODEFENCE 2011. [DOI: 10.1007/978-94-007-0217-2_7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
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Sadeghian S, Neyestani TR, Shirazi MH, Ranjbarian P. Bacteriostatic effect of dill, fennel, caraway and cinnamon extracts againstHelicobacter pylori. ACTA ACUST UNITED AC 2009. [DOI: 10.1080/13590840500535313] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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20
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Kindlund B, Sjöling A, Hansson M, Edebo A, Hansson LE, Sjövall H, Svennerholm AM, Lundin BS. FOXP3-expressing CD4(+) T-cell numbers increase in areas of duodenal gastric metaplasia and are associated to CD4(+) T-cell aggregates in the duodenum of Helicobacter pylori-infected duodenal ulcer patients. Helicobacter 2009; 14:192-201. [PMID: 19702849 DOI: 10.1111/j.1523-5378.2009.00673.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND We have previously demonstrated that Helicobacter pylori infection is associated with an increased number of CD4(+)CD25(high) regulatory T cells in the gastric and duodenal mucosa. In this study, we determined the number and localization of CD4(+) cells expressing the regulatory T-cell-specific transcription factor FOXP3 in the antrum and duodenum of duodenal ulcer patients, asymptomatic carriers, and uninfected individuals. We also determined gene expression levels of FOXP3 as well as anti- and proinflammatory cytokines before and after H. pylori eradication. METHODS Cellular FOXP3 expression was studied by immunofluorescence and flow cytometry, and transcription levels of FOXP3, interleukin (IL)-10, transforming growth factor-beta, CD4, and interferon-gamma were analyzed by real-time reverse transcription-polymerase chain reaction. RESULTS We found an increased (6-fold) frequency of CD4(+)FOXP3(+) T cells in H. pylori-infected gastric mucosa; interestingly 26% of these cells did not co-express CD25. The increase of FOXP3-expressing T cells in the antrum of infected individuals was dependent on the presence of H. pylori, since eradication therapy resulted in 4-fold lower levels of FOXP3 and IL-10 mRNA in the antrum. Furthermore, higher numbers of CD4(+)FOXP3(+) T cells were found in areas of duodenal gastric metaplasia in the duodenum of duodenal ulcer patients compared to duodenal gastric metaplasia of asymptomatic individuals and healthy mucosa in both patient groups. In duodenal ulcer patients, the CD4(+)FOXP3(+) T cells were more highly associated to aggregates in the duodenal mucosa. CONCLUSION The numbers of CD4(+)FOXP3(+) T cells are increased and localized in CD4(+) T-cell aggregates in areas of duodenal gastric metaplasia in duodenal ulcer patients.
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Affiliation(s)
- Bert Kindlund
- Department of Microbiology and Immunology, Sahlgrenska Academy, University of Gothenburg and Mucosal Immunobiology and Vaccine Center, Gothenburg, Sweden.
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Nakata M, Itou T, Sakai T. Molecular cloning and phylogenetic analysis of inflammatory cytokines of the ferret (Mustela putorius furo). J Vet Med Sci 2008; 70:543-50. [PMID: 18628593 DOI: 10.1292/jvms.70.543] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
The present study determined the cDNA and deduced amino acid sequences of ferret (Mustela putorius furo) inflammatory cytokines, interferon (IFN)-gamma, interleukin (IL)-1beta, IL-6, IL-8 and tumor necrosis factor (TNF)-alpha. The homologies of the nucleotide sequences of IFN-gamma, IL-1beta, IL-6, IL-8 and TNF-alpha of the ferret to those from other mammalian species ranged from 64.3-92.9%, 73.0-83.9, 58.1-84.8%, 58.1-89.7% and 79.0-95.0%, respectively. As distinctive amino acid residues constituting various motifs and ligand-binding sites and cysteine residues were highly conserved in ferret inflammatory cytokine proteins, ferret cytokines may have fundamentally similar functions to those of other mammals. Phylogenetic analyses based on the deduced amino acid sequences revealed that all ferret inflammatory cytokines were more closely related to those of the Carnivora order, specifically dog and cat, than to other species.
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Affiliation(s)
- Makoto Nakata
- Nihon University Veterinary Research Center, Kanagawa, Japan
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Enhanced gastric IL-18 mRNA expression in Helicobacter pylori-infected children is associated with macrophage infiltration, IL-8, and IL-1 beta mRNA expression. Eur J Gastroenterol Hepatol 2008; 20:314-9. [PMID: 18334875 DOI: 10.1097/meg.0b013e3282f340da] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
OBJECTIVE To investigate IL-18 mRNA expression in the gastric mucosa in Helicobacter pylori-infected children and its association with macrophage infiltration, IL-8, and IL-1 beta mRNA expression. METHODS From 39 children, blood samples were taken for IL-1 beta gene polymorphism analysis and antral biopsies were obtained for histology (including macrophage immunostaining), culture and semiquantitative analysis of IL-18, IL-8, IL-1 beta, and CD14 mRNA expression by reverse transcription-PCR (RT-PCR). RT-PCR was used for H. pylori ureA and cagA mRNA detection in gastric tissue. RESULTS H. pylori-infected patients had significantly higher IL-18, IL-8, and IL-1 beta transcript levels and macrophage numbers in the antral mucosa than H. pylori-negative children. IL-1 beta-511/31 gene polymorphism had no impact on gastric IL-1 beta mRNA levels. IL-18 mRNA expression correlated with mRNA expression of IL-8 and IL-1 beta, and transcript levels of all three cytokines were associated with macrophage infiltration and CD14 mRNA expression in the gastric tissue. Significant correlation was also observed between macrophage numbers and histological parameters of gastritis. CONCLUSION These results suggest that interleukin(IL)-18 and macrophages may have an important function in gastric inflammatory response to H. pylori infection in children. IL-18, and possibly CD14 receptor signalling pathway, may be involved in macrophage activation and subsequent IL-8 and IL-1 beta release.
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Yom HW, Seo JW. Gastric mucosal immune response of Helicobacter pylori-infected children. KOREAN JOURNAL OF PEDIATRICS 2008. [DOI: 10.3345/kjp.2008.51.5.492] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Affiliation(s)
- Hye Won Yom
- Department of Pediatrics, Ewha Womans University School of Medicine, Seoul, Korea
| | - Jeong Wan Seo
- Department of Pediatrics, Ewha Womans University School of Medicine, Seoul, Korea
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Andersen LP, Holck S, Kupcinskas L, Kiudelis G, Jonaitis L, Janciauskas D, Permin H, Wadström T. Gastric inflammatory markers and interleukins in patients with functional dyspepsia treated with astaxanthin. FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY 2007; 50:244-248. [PMID: 17521392 DOI: 10.1111/j.1574-695x.2007.00257.x] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
The chronic active inflammation caused by Helicobacter pylori is dominated by neutrophils, macrophages, lymphocytes and plasma cells. Several interleukins are involved in the inflammatory process. The aim of this study was to investigate the effect of astaxanthin on gastric inflammation in patients with functional dyspepsia. Forty-four consecutive patients were included, and biopsies were examined for IL-4, IL-6, IL-8, IL-10, interferon-gamma, CD4, CD8, CD14, CD19, CD25 and CD30. Patients were randomized: 21 patients were treated with 40 mg of astaxanthin daily, and 23 patients were treated with a placebo. There was a significant decrease in gastric inflammation in H. pylori-positive patients from both groups. There were no significant changes in the density of H. pylori or in any of the interleukins during or after treatment. There was a significant up-regulation of CD4 and down-regulation of CD8 in patients with H. pylori treated with astaxanthin. Astaxanthin had an effect on the inflammation and on the density of H. pylori in mice in a study where the diet could be standardized without antioxidants (Bennedsen et al., 1999). These dietary conditions are impossible in studies involving humans, and may be due to the minor effect when the host have access to antioxidants in their diet.
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Affiliation(s)
- Leif Percival Andersen
- Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
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Wang SK, Zhu HF, He BS, Zhang ZY, Chen ZT, Wang ZZ, Wu GL. CagA+ H pylori infection is associated with polarization of T helper cell immune responses in gastric carcinogenesis. World J Gastroenterol 2007; 13:2923-31. [PMID: 17589941 PMCID: PMC4171143 DOI: 10.3748/wjg.v13.i21.2923] [Citation(s) in RCA: 58] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
AIM: To characterize the immune responses including local and systemic immunity induced by infection with H pylori, especially with CagA+ H pylori strains and the underlying immunopathogenesis.
METHODS: A total of 711 patients with different gastric lesions were recruited to determine the presence of H pylori infection and cytotoxin associated protein A (CagA), the presence of T helper (Th) cells and regulatory T (Treg) cells in peripheral blood mononuclear cells (PBMCs), expression of plasma cytokines, and RNA and protein expression of IFN-γ and IL-4 in gastric biopsies and PBMCs were determined by rapid urease test, urea [14C] breath test, immunoblotting test, flow cytometry , real time RT-PCR and immunohistochemistry.
RESULTS: Of the patients, 629 (88.47%) were infected with H pylori; 506 (71.16%) with CagA+ and 123 (17.30%) with CagA- strains. Among patients infected with CagA+ H pylori strains, Th1-mediated cellular immunity was associated with earlier stages of gastric carcinogenesis, while Th2-mediated humoral immunity dominated the advanced stages and was negatively associated with an abundance of Treg cells. However, there was no such tendency in Th1/Th2 polarization in patients infected with CagA- H pylori strains and those without H pylori infection.
CONCLUSION: Polarization of Th cell immune responses occurs in patients with CagA+ H pylori infection, which is associated with the stage and severity of gastric pathology during the progression of gastric carcinogenesis. This finding provides further evidence for a causal role of CagA+ H pylori infection in the immunopathogenesis of gastric cancer.
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Affiliation(s)
- Shu-Kui Wang
- Department of Pathogen Biology, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, Jiangsu Province, China
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Panos GZ, Xirouchakis E, Tzias V, Charatsis G, Bliziotis IA, Doulgeroglou V, Margetis N, Falagas ME. Helicobacter pylori infection in symptomatic HIV-seropositive and -seronegative patients: a case-control study. AIDS Res Hum Retroviruses 2007; 23:709-12. [PMID: 17530997 DOI: 10.1089/aid.2006.0174] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
We conducted a case-control study in a Greek hospital to evaluate the prevalence and morbidity of Helicobacter pylori in HIV-infected patients. HIV-seropositive patients were infected by H. pylori less often than HIV-seronegative controls [12/58 (20.7%) versus 38/58 (65.5%),p < 0.001]. The mean CD4 count was lower for H. pylori-negative than H. pylori-positive HIV-infected patients (p < 0.007). Also, among HIV patients, prior use of antibiotics or proton pump inhibitors was more common in those without H. pylori infection, however, this difference was not statistically significant (p = 0.06). The grading of the density of H. pylori infection and the grading of the histomorphological findings according to the Sydney classification were similar between HIV-seropositive and -seronegative patients with H. pylori infection.
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Kato I, Canzian F, Plummer M, Franceschi S, van Doorn LJ, Vivas J, Lopez G, Lu Y, Gioia-Patricola L, Severson RK, Schwartz AG, Muñoz N. Polymorphisms in genes related to bacterial lipopolysaccharide/peptidoglycan signaling and gastric precancerous lesions in a population at high risk for gastric cancer. Dig Dis Sci 2007; 52:254-61. [PMID: 17171451 DOI: 10.1007/s10620-006-9303-1] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2005] [Accepted: 03/05/2006] [Indexed: 12/13/2022]
Abstract
As Helicobacter pylori (HP) is a Gram-negative bacterium, we investigated the associations between several functional polymorphisms in genes involved in lipopolysaccharide (LPS) signaling and the prevalence of various stages of gastric premalignant lesions in a Venezuelan population. The two NOD2 polymorphisms, del3020insC and Gly908Arg, were too infrequent to study their associations with gastric lesions. The risk of intestinal metaplasia (IM) was significantly increased among subjects with the CD14 T-260 allele compared to those without this allele. A similar, but nonsignificant increase in risk for dysplasia was observed among homozygotes of this allele. There was no association between TLR4 Asp299Gly polymorphism and any type of lesions, except for a slight nonsignificant increase in risk of IM associated with the AA genotype among subjects with a higher histological HP score. These results suggest that genetic polymorphisms in HP LPS signaling may be implicated in the development of intermediate stages of gastric premalignant lesions.
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Affiliation(s)
- Ikuko Kato
- Karmanos Cancer Institute, 110 East Warren Avenue, Detroit, Michigan 48201, USA.
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