RESUMEN
Twenty-five years ago, Helicobacter pylori was identified as the causative agent of gastric disorders,ranging from acute inflammation [...].
Asunto(s)
Infecciones por Helicobacter/complicaciones , Helicobacter pylori , Neoplasias Gástricas/etiología , Factores de Virulencia/metabolismo , Mucosa Gástrica/microbiología , Mucosa Gástrica/patología , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/patología , Helicobacter pylori/metabolismo , Helicobacter pylori/patogenicidad , Humanos , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/patologíaRESUMEN
Gastric cancer is a major health burden and is the fifth most common malignancy and the third most common cause of death from cancer worldwide. Development of gastric cancer involves several aspects, including host genetics, environmental factors, and Helicobacter pylori infection. There is increasing evidence from epidemiological studies of the association of H. pylori infection and specific virulence factors with gastric cancer. Studies in animal models indicate H. pylori is a primary factor in the development of gastric cancer. One major virulence factor in H. pylori is the cytotoxin-associated gene A (cagA), which encodes the CagA protein in the cag pathogenicity island (cag PAI). Meta-analysis of studies investigating CagA seropositivity irrespective of H. pylori status identified that CagA seropositivity increases the risk of gastric cancer (OR = 2.87, 95% CI: 1.95â»4.22) relative to the risk of H. pylori infection alone (OR = 2.31, 95% CI: 1.58â»3.39). Eradicating H. pylori is a strategy for reducing gastric cancer incidence. A meta-analysis of six randomised controlled trials (RCTs) suggests that searching for and eradicating H. pylori infection reduces the subsequent incidence of gastric cancer with a pooled relative risk of 0.66 (95% CI: 0.46â»0.95). The introduction in regions of high gastric cancer incidence of population-based H. pylori screening and treatment programmes, with a scientifically valid assessment of programme processes, feasibility, effectiveness and possible adverse consequences, would impact the incidence of H. pylori-induced gastric cancer. Given the recent molecular understanding of the oncogenic role of CagA, targeting H. pylori screening and treatment programmes in populations with a high prevalence of H. pylori CagA-positive strains, particularly the more oncogenic East Asian H. pylori CagA strains, may be worth further investigation to optimise the benefits of such strategies.
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Antígenos Bacterianos/genética , Proteínas Bacterianas/genética , Infecciones por Helicobacter/epidemiología , Helicobacter pylori/genética , Neoplasias Gástricas/epidemiología , Animales , Infecciones por Helicobacter/complicaciones , Humanos , Neoplasias Gástricas/etiologíaRESUMEN
Background: Sapovirus is one of the primary viral causes of acute gastroenteritis (AGE), especially where rotavirus vaccination has been implemented. The characteristics and impact of natural infection at the community level, however, have not been well documented. Methods: Stool samples were analyzed from 100 children randomly selected from a community-based birth cohort study in Peru. All diarrheal and 1 nondiarrheal stools collected trimonthly from children up to age 2 years (n = 1669) were tested for sapovirus detection. Viral shedding duration was determined by testing additional weekly samples (n = 440) collected before and after a sapovirus-positive sample. Results: The incidence of sapovirus infection in the first and second years of life was 4.3 and 11.1 per 100 child-months, respectively. By age 2 years, 82% of children had at least 1 sapovirus infection, and 64% had at least 1 sapovirus-associated diarrhea episode. The median shedding period was 18.5 days. In 112 of 175 infections, 14 genotypes from 4 genogroups (GI, GII, GIV, and GV) were determined. Among genogroups, GI were more frequently found in symptomatic infections than in asymptomatic infections (odds ratio, 3.1; 95% confidence interval, 1.3-7.4). Fifty-nine children had serial sapovirus infections, but only 3 had repeated infection of the same genotype. Conclusions: Sapovirus was frequently detected in children with AGE at the community level during the first 2 years of life. Serial sapovirus infections by multiple genotypes in a child suggest genotype-specific immunity from each infection, which needs to be taken into account for vaccine development.
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Infecciones por Caliciviridae/epidemiología , Diarrea/virología , Gastroenteritis/epidemiología , Gastroenteritis/virología , Sapovirus/aislamiento & purificación , Estudios de Cohortes , Diarrea/epidemiología , Heces/virología , Femenino , Genotipo , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Perú/epidemiología , Filogenia , Salud Pública , Esparcimiento de VirusRESUMEN
Persistent infections with the human pathogen and class-I carcinogen Helicobacter pylori (H. pylori) are closely associated with the development of acute and chronic gastritis, ulceration, gastric adenocarcinoma and lymphoma of the mucosa-associated lymphoid tissue (MALT) system. Disruption and depolarization of the epithelium is a hallmark of H. pylori-associated disorders and requires extensive modulation of epithelial cell surface structures. Hence, the complex network of controlled proteolysis which facilitates tissue homeostasis in healthy individuals is deregulated and crucially contributes to the induction and progression of gastric cancer through processing of extracellular matrix (ECM) proteins, cell surface receptors, membrane-bound cytokines, and lateral adhesion molecules. Here, we summarize the recent reports on mechanisms how H. pylori utilizes a variety of extracellular proteases, involving the proteases Hp0169 and high temperature requirement A (HtrA) of bacterial origin, and host matrix-metalloproteinases (MMPs), a disintegrin and metalloproteinases (ADAMs) and tissue inhibitors of metalloproteinases (TIMPs). H. pylori-regulated proteases represent predictive biomarkers and attractive targets for therapeutic interventions in gastric cancer.
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Infecciones por Helicobacter/complicaciones , Helicobacter pylori/metabolismo , Péptido Hidrolasas/metabolismo , Neoplasias Gástricas/etiología , Animales , Humanos , Mucosa Intestinal , ProteolisisRESUMEN
Human sapovirus has been shown to be one of the most important etiologies in pediatric patients with acute diarrhea. However, very limited data are available about the causative roles and epidemiology of sapovirus in community settings. A nested matched case-control study within a birth cohort study of acute diarrhea in a peri-urban community in Peru from 2007 to 2010 was conducted to investigate the attributable fraction (AF) and genetic diversity of sapovirus. By quantitative reverse transcription-real-time PCR (qPCR) sapovirus was detected in 12.4% (37/299) of diarrheal and 5.7% (17/300) of nondiarrheal stools (P = 0.004). The sapovirus AF (7.1%) was higher in the second year (13.2%) than in the first year (1.4%) of life of children. Ten known genotypes and one novel cluster (n = 5) within four genogroups (GI, GII, GIV, and GV) were identified by phylogenetic analysis of a partial VP1 gene. Further sequence analysis of the full VP1 gene revealed a possible novel genotype, tentatively named GII.8. Notably, symptomatic reinfections with different genotypes within the same (n = 3) or different (n = 5) genogroups were observed in eight children. Sapovirus exhibited a high attributable burden for acute gastroenteritis, especially in the second year of life, of children in a Peruvian community. Further large-scale studies are needed to understand better the global burden, genetic diversity, and repeated infections of sapovirus.
Asunto(s)
Infecciones por Caliciviridae/epidemiología , Infecciones por Caliciviridae/virología , Gastroenteritis/epidemiología , Gastroenteritis/virología , Sapovirus/aislamiento & purificación , Estudios de Casos y Controles , Estudios de Cohortes , Diarrea/epidemiología , Diarrea/virología , Femenino , Genotipo , Humanos , Lactante , Recién Nacido , Masculino , Perú/epidemiología , Filogenia , Prevalencia , Reacción en Cadena en Tiempo Real de la Polimerasa , Recurrencia , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sapovirus/clasificación , Sapovirus/genética , Análisis de Secuencia de ADN , Población SuburbanaRESUMEN
BACKGROUND: Childhood growth is a cornerstone of pediatric research. Statistical models need to consider individual trajectories to adequately describe growth outcomes. Specifically, well-defined longitudinal models are essential to characterize both population and subject-specific growth. Linear mixed-effect models with cubic regression splines can account for the nonlinearity of growth curves and provide reasonable estimators of population and subject-specific growth, velocity and acceleration. METHODS: We provide a stepwise approach that builds from simple to complex models, and account for the intrinsic complexity of the data. We start with standard cubic splines regression models and build up to a model that includes subject-specific random intercepts and slopes and residual autocorrelation. We then compared cubic regression splines vis-à-vis linear piecewise splines, and with varying number of knots and positions. Statistical code is provided to ensure reproducibility and improve dissemination of methods. Models are applied to longitudinal height measurements in a cohort of 215 Peruvian children followed from birth until their fourth year of life. RESULTS: Unexplained variability, as measured by the variance of the regression model, was reduced from 7.34 when using ordinary least squares to 0.81 (p < 0.001) when using a linear mixed-effect models with random slopes and a first order continuous autoregressive error term. There was substantial heterogeneity in both the intercept (p < 0.001) and slopes (p < 0.001) of the individual growth trajectories. We also identified important serial correlation within the structure of the data (ρ = 0.66; 95 % CI 0.64 to 0.68; p < 0.001), which we modeled with a first order continuous autoregressive error term as evidenced by the variogram of the residuals and by a lack of association among residuals. The final model provides a parametric linear regression equation for both estimation and prediction of population- and individual-level growth in height. We show that cubic regression splines are superior to linear regression splines for the case of a small number of knots in both estimation and prediction with the full linear mixed effect model (AIC 19,352 vs. 19,598, respectively). While the regression parameters are more complex to interpret in the former, we argue that inference for any problem depends more on the estimated curve or differences in curves rather than the coefficients. Moreover, use of cubic regression splines provides biological meaningful growth velocity and acceleration curves despite increased complexity in coefficient interpretation. CONCLUSIONS: Through this stepwise approach, we provide a set of tools to model longitudinal childhood data for non-statisticians using linear mixed-effect models.
RESUMEN
BACKGROUND: Helicobacter pylori infection has been associated with an imbalance of iron homeostasis. IL-1ß has been related with iron absorption disturbances through a variety of mechanisms. The aim of this study was to evaluate the presence of polymorphic variants for IL-1ß cluster and gastric IL1ß mRNA expression in H. pylori-infected children and their relationship with hypochlorhydria and iron deficiency (ID). PATIENTS AND METHODS: Prospective study of 123 symptomatic children. At endoscopy, antral biopsies were taken for urease test, pathology and culture and blood for analysis of ferritin, transferrin, serum iron, and total iron-binding capacity. Polymorphisms in the IL-1ß cluster (positions -511, -31, +3954, ILRN) were determined by PCR-RFLP. Gastric mucosal expression of IL-1ß mRNA was determined by RT-PCR. RESULTS: After exclusions, of 105 patients, 33 (31.4%) were H. pylori positive. Nine (8.6%) children were classified as iron deficient (ID). Helicobacter pylori positivity was associated with ID (OR: 5.1; 95% CI: 1.2-21.9) (p = .04). No significant differences were found in allele frequency for IL1ß gene cluster polymorphisms between infected and uninfected children. Helicobacter pylori-infected children with ID had significantly increased gastric IL1ß mRNA in comparison with infected children without ID. In addition, a significant positive correlation was observed between mucosal IL-1ß mRNA and fasting gastric juice pH. Gastric pH values were significantly increased in H. pylori-infected patients with ID compared to uninfected children. CONCLUSIONS: The established association between H. pylori infection and ID in children may be mediated by increased gastric mucosal IL-1ß.
Asunto(s)
Perfilación de la Expresión Génica , Infecciones por Helicobacter/complicaciones , Interleucina-1beta/biosíntesis , Interleucina-1beta/genética , Deficiencias de Hierro , Polimorfismo Genético , Aclorhidria/epidemiología , Adolescente , Biopsia , Niño , Endoscopía Gastrointestinal , Femenino , Mucosa Gástrica/patología , Humanos , Concentración de Iones de Hidrógeno , Masculino , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Estudios Prospectivos , ARN Mensajero/análisis , ARN Mensajero/genéticaRESUMEN
Helicobacter pylori transactivates the epidermal growth factor receptor (EGFR) on gastric epithelial cells via a signalling cascade involving a disintegrin and metalloprotease 17 (ADAM17) cleavage of membrane bound heparin binding-epidermal growth factor (HB-EGF). The effects of H. pylori on ADAM17 C-terminus in epithelial cells have been examined. Total cellular ADAM17 and surface expression of ADAM17 were significantly increased by H. pylori in AGS gastric epithelial cells. These changes were associated with ADAM17 C-terminal phosphorylation at T375 and S791. AGS cells lacking the ADAM17 C-terminal domain induced significantly attenuated cleavage of HB-EGF and were also unable to upregulate HB-EGF and EGFR transcripts to the same extent as cells expressing full length ADAM17. In mitotic unstimulated AGS and ADAM17 over-expressing AGS cells, ADAM17 was highly T735 phosphorylated indicating ADAM17 T735 phosphorylation is modified during the cell cycle. In conclusion, H. pylori induced ADAM17 C-terminal T735 and/or S791 phosphorylation in gastric epithelial cells are likely to be an important trigger inducing ADAM17 activation and shedding of HB-EGF leading to EGFR transactivation. ADAM17 over-expression in gastric cancer represents a potential target for therapeutic intervention.
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Proteínas ADAM/metabolismo , Células Epiteliales/fisiología , Helicobacter pylori/fisiología , Treonina/metabolismo , Proteína ADAM17 , Línea Celular Tumoral , Células Epiteliales/inmunología , Helicobacter pylori/patogenicidad , Humanos , Fosforilación/inmunología , Neoplasias Gástricas/etiología , Neoplasias Gástricas/genética , Regulación hacia Arriba/inmunologíaRESUMEN
BACKGROUND & AIMS: Helicobacter pylori infection is a risk factor for gastric cancer. To explore the genetic basis of gastric cancer that develops in inflamed gastric mucosa, we investigated genetic aberrations that latently accumulate in nontumorous gastric epithelium with H pylori infection. METHODS: We performed whole-exome sequencing of gastric tumors, noncancerous tissues with gastritis, and peripheral lymphocytes from 5 patients. We performed additional deep-sequencing analyses of selected tumor-related genes using 34 gastritis mucosal samples from patients with or without gastric cancer. We also performed deep sequencing analyses of gastric mucosal tissues from mice that express transgenic human TP53 and constitutively express activation-induced cytidine deaminase (AICDA or AID) (human TP53 knock-in/AID-transgenic mice). RESULTS: Whole-exome sequencing revealed that somatic mutations accumulated in various genes in inflamed gastric tissues. Additional deep-sequencing analyses of tissues from regions of gastritis confirmed nonsynonymous low-abundance mutations in TP53 in 15 cases (44.1%) and ARID1A in 5 cases (14.7%). The mutations that accumulated in gastric mucosal tissues with H pylori-induced gastritis, as well as gastric tumors, were predominantly C:G>T:A transitions in GpCpX motifs-a marker of cytidine deamination induced by AID. Constitutive expression of AID in the gastric mucosa of mice led to mutations in the human TP53, at amino acid coding positions identical to those detected in human gastric cancers. CONCLUSIONS: Studies of gastric tumors and tissues from humans and mice indicate that somatic mutations accumulate in various genes in gastric mucosal tissues with H pylori infection. Increased cytidine deaminase activity in these tissues appears to promote the accumulation of these mutations and might promote gastric carcinogenesis in patients with H pylori infection.
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Transformación Celular Neoplásica/genética , Mucosa Gástrica/microbiología , Gastritis/genética , Infecciones por Helicobacter/genética , Helicobacter pylori/patogenicidad , Mutación , Lesiones Precancerosas/genética , Neoplasias Gástricas/genética , Proteína p53 Supresora de Tumor/genética , Animales , Análisis Mutacional de ADN , Proteínas de Unión al ADN , Exoma , Gastritis/diagnóstico , Gastritis/microbiología , Regulación Neoplásica de la Expresión Génica , Predisposición Genética a la Enfermedad , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/microbiología , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Ratones , Ratones de la Cepa 129 , Ratones Transgénicos , Proteínas Nucleares/genética , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/microbiología , Factores de Riesgo , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/microbiología , Factores de Transcripción/genéticaRESUMEN
BACKGROUND: In endemic settings, Helicobacter pylori infection can occur shortly after birth and may be associated with a reduction in childhood growth. MATERIALS AND METHODS: This study investigated what factors promote earlier age of first H. pylori infection and evaluated the role of H. pylori infection in infancy (6-11 months) versus early childhood (12-23 months) on height. We included 183 children near birth from a peri-urban shanty town outside of Lima, Peru. Field-workers collected data on socioeconomic status (SES), daily diarrheal and breast-feeding history, antibiotic use, anthropometrics, and H. pylori status via carbon 13-labeled urea breath test up to 24 months after birth. We used a proportional hazards model to assess risk factors for earlier age at first detected infection and linear mixed-effects models to evaluate the association of first detected H. pylori infection during infancy on attained height. RESULTS: One hundred and forty (77%) were infected before 12 months of age. Lower SES was associated with earlier age at first detected H. pylori infection (low vs middle-to-high SES Hazard ratio (HR) 1.59, 95% CI 1.16, 2.19; p = .004), and greater exclusive breast-feeding was associated with reduced likelihood (HR 0.63, 95% CI 0.40, 0.98, p = .04). H. pylori infection in infancy was not independently associated with growth deficits (p = .58). However, children who had their first detected H. pylori infection in infancy (6-11 months) versus early childhood (12-23 months) and who had an average number of diarrhea episodes per year (3.4) were significantly shorter at 24 months (-0.37 cm, 95% CI, -0.60, -0.15 cm; p = .001). DISCUSSION: Lower SES was associated with a higher risk of first detected H. pylori infection during infancy, which in turn augmented the adverse association of diarrheal disease on linear growth.
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Desarrollo Infantil , Discapacidades del Desarrollo/epidemiología , Diarrea/complicaciones , Infecciones por Helicobacter/complicaciones , Helicobacter pylori/aislamiento & purificación , Animales , Pruebas Respiratorias , Preescolar , Discapacidades del Desarrollo/etiología , Diarrea/epidemiología , Femenino , Infecciones por Helicobacter/epidemiología , Humanos , Lactante , Recién Nacido , Masculino , Perú/epidemiología , Embarazo , Factores de Riesgo , Clase Social , Población Suburbana , Urea/análisisRESUMEN
BACKGROUND: Human noroviruses are among the most common enteropathogens globally, and are a leading cause of infant diarrhea in developing countries. However, data measuring the impact of norovirus at the community level are sparse. METHODS: We followed a birth cohort of children to estimate norovirus infection and diarrhea incidence in a Peruvian community. Stool samples from diarrheal episodes and randomly selected nondiarrheal samples were tested by polymerase chain reaction for norovirus genogroup and genotype. Excretion duration and rotavirus coinfection were evaluated in a subset of episodes. RESULTS: Two hundred twenty and 189 children were followed to 1 and 2 years of age, respectively. By 1 year, 80% (95% confidence interval [CI], 75%-85%) experienced at least 1 norovirus infection and by 2 years, 71% (95% CI, 65%-77%) had at least 1 episode of norovirus-associated diarrhea. Genogroup II (GII) infections were 3 times more frequent than genogroup 1 (GI) infections. Eighteen genotypes were found; GII genotype 4 accounted for 41%. Median excretion duration was 34.5 days for GII vs 8.5 days for GI infection (P = .0006). Repeat infections by the same genogroup were common, but repeat infections by the same genotype were rare. Mean length-for-age z score at 12 months was lower among children with prior norovirus infection compared to uninfected children (coefficient: -0.33 [95% CI, -.65 to -.01]; P = .04); the effect persisted at 24 months. CONCLUSIONS: Norovirus infection occurs early in life and children experience serial infections with multiple genotypes, suggesting genotype-specific immunity. An effective vaccine would have a substantial impact on morbidity, but may need to target multiple genotypes.
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Infecciones por Caliciviridae/epidemiología , Infecciones por Caliciviridae/virología , Diarrea/epidemiología , Diarrea/virología , Norovirus/clasificación , Norovirus/aislamiento & purificación , Adulto , Preescolar , Estudios de Cohortes , Coinfección/epidemiología , Coinfección/virología , Heces/virología , Femenino , Genotipo , Técnicas de Genotipaje , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Epidemiología Molecular , Norovirus/genética , Perú/epidemiología , Reacción en Cadena de la Polimerasa , Embarazo , ARN Viral/genética , ARN Viral/aislamiento & purificación , Rotavirus/aislamiento & purificación , Población SuburbanaRESUMEN
Accurate noninvasive tests for diagnosing Helicobacter pylori infection in very young children are strongly required. We investigated the agreement between the [(13)C]urea breath test ([(13)C]UBT) and a monoclonal ELISA (HpSA) for detection of H. pylori antigen in stool. From October 2007 to July 2011, we enrolled 414 infants (123 from Brazil and 291 from Peru) of ages 6 to 30 months. Breath and stool samples were obtained at intervals of at least 3 months from Brazilian (n = 415) and Peruvian (n = 908) infants. [(13)C]UBT and stool test results concurred with each other in 1,255 (94.86%) cases (kappa coefficient = 0.90; 95% confidence interval [CI] = 0.87 to 0.92). In the H. pylori-positive group, delta-over-baseline (DOB) and optical density (OD) values were positively correlated (r = 0.62; P < 0.001). The positivity of the tests was higher (P < 0.001; odds ratio [OR] = 6.01; 95% CI = 4.50 to 8.04) in Peru (546/878; 62.2%) than in Brazil (81/377; 21.5%) and increased with increasing age in Brazil (P = 0.02), whereas in Peru it decreased with increasing age (P < 0.001). The disagreement between the test results was associated with birth in Brazil and female gender but not with age and diarrhea. Our results suggest that both [(13)C]UBT and the stool monoclonal test are reliable for diagnosing H. pylori infection in very young children, which will facilitate robust epidemiological studies in infants and toddlers.
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Pruebas Respiratorias/métodos , Técnicas de Laboratorio Clínico/métodos , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/microbiología , Helicobacter pylori/aislamiento & purificación , Antígenos Bacterianos/análisis , Brasil/epidemiología , Preescolar , Ensayo de Inmunoadsorción Enzimática/métodos , Heces/microbiología , Femenino , Humanos , Lactante , Masculino , Perú/epidemiología , Prevalencia , Ureasa/análisisRESUMEN
Helicobacter pylori infection is predominantly acquired early in life. The prevalence of the infection in childhood is low in developed countries, whereas in developing countries most children are infected by 10 y of age. In poor resource settings, where malnutrition, parasitic/enteropathogen and H. pylori infection co-exist in young children, H. pylori might have potentially more diverse clinical outcomes. This paper reviews the impact of childhood H. pylori infection in developing countries that should now be the urgent focus of future research. The extra-gastric manifestations in early H. pylori infection in infants in poor resource settings might be a consequence of the infection associated initial hypochlorhydria. The potential role of H. pylori infection on iron deficiency, growth impairment, diarrheal disease, malabsorption and cognitive function is discussed in this review.
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Anemia Ferropénica/epidemiología , Diarrea/epidemiología , Trastornos del Crecimiento/epidemiología , Infecciones por Helicobacter/epidemiología , Anemia Ferropénica/complicaciones , Niño , Preescolar , Países en Desarrollo , Diarrea/complicaciones , Trastornos del Crecimiento/complicaciones , Infecciones por Helicobacter/complicaciones , Helicobacter pylori , Humanos , Lactante , Síndromes de Malabsorción/complicaciones , Síndromes de Malabsorción/epidemiología , Prevalencia , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
OBJECTIVE: Iron deficiency (ID) and iron deficiency anaemia (IDA) are global major public health problems, particularly in developing countries. Whilst an association between H. pylori infection and ID/IDA has been proposed in the literature, currently there is no consensus. We studied the effects of H. pylori infection on ID/IDA in a cohort of children undergoing upper gastrointestinal endoscopy for upper abdominal pain in two developing and one developed country. METHODS: In total 311 children (mean age 10.7±3.2 years) from Latin America--Belo Horizonte/Brazil (nâ=â125), Santiago/Chile (nâ=â105)--and London/UK (nâ=â81), were studied. Gastric and duodenal biopsies were obtained for evaluation of histology and H. pylori status and blood samples for parameters of ID/IDA. RESULTS: The prevalence of H. pylori infection was 27.7% being significantly higher (p<0.001) in Latin America (35%) than in UK (7%). Multiple linear regression models revealed H. pylori infection as a significant predictor of low ferritin and haemoglobin concentrations in children from Latin-America. A negative correlation was observed between MCV (râ=â-0.26; pâ=â0.01) and MCH (râ=â-0.27; pâ=â0.01) values and the degree of antral chronic inflammation, and between MCH and the degree of corpus chronic (râ=â-0.29, pâ=â0.008) and active (râ=â-0.27, pâ=â0.002) inflammation. CONCLUSIONS: This study demonstrates that H. pylori infection in children influences the serum ferritin and haemoglobin concentrations, markers of early depletion of iron stores and anaemia respectively.
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Dolor Abdominal/sangre , Anemia Ferropénica/sangre , Ferritinas/metabolismo , Infecciones por Helicobacter/sangre , Hemoglobinas/metabolismo , Hierro/sangre , Dolor Abdominal/complicaciones , Dolor Abdominal/microbiología , Dolor Abdominal/patología , Adolescente , Anemia Ferropénica/complicaciones , Anemia Ferropénica/microbiología , Anemia Ferropénica/patología , Biopsia , Brasil/epidemiología , Niño , Chile/epidemiología , Duodenoscopía , Duodeno/metabolismo , Duodeno/microbiología , Duodeno/patología , Femenino , Mucosa Gástrica/metabolismo , Gastroscopía , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/patología , Helicobacter pylori/aislamiento & purificación , Helicobacter pylori/metabolismo , Humanos , Londres/epidemiología , Masculino , Prevalencia , Estómago/microbiología , Estómago/patologíaRESUMEN
The O-chain polysaccharide of Helicobacter pylori is important for colonization and generation of chronic gastritis in mice. There are marked host differences in the development of H. pylori-induced gastric pathology in mice and gerbils. To investigate the role of the O-chain polysaccharide of H. pylori in colonization and gastritis in Mongolian gerbils, inoculation by oral gavage with H. pylori strain SS1 and its corresponding O-chain polysaccharide-deficient mutant SS1 HP0826::Kan was undertaken. Infection with both strains resulted in corpus atrophy, loss of parietal cells, and extensive mucous metaplasia at both 18 and 30 weeks postinfection. Contrary to previous results in splenocyte recipient severe combined immunodeficiency (SCID) mice, no difference was found in the grade of chronic gastritis, polymorphonuclear cell infiltration, atrophy, and mucous metaplasia in gerbils infected with the wild-type SS1 strain or SS1 HP0826::Kan strain. Examination of the effects of gerbil passage on LPS profiles of output SS1 HP0826::Kan isolates by SDS-PAGE, sugar, and methylation analyses revealed significant differences in LPS profiles of SS1 HP0826::Kan cells recovered from infected gerbils as compared to input bacteria. Specifically, the presence of a novel homopolymer of d-galactan, as well as an extended polymer of d-riban, was detected. These data provide evidence for the role of H. pylori LPS in bacterial adaption to promote colonization and pathology.
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Gastritis/patología , Gerbillinae/microbiología , Infecciones por Helicobacter/patología , Helicobacter pylori/patogenicidad , Mutación , Antígenos O , Animales , Secuencia de Carbohidratos , Electroforesis en Gel de Poliacrilamida , Mucosa Gástrica/microbiología , Mucosa Gástrica/patología , Gastritis/complicaciones , Gastritis/microbiología , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/microbiología , Helicobacter pylori/química , Helicobacter pylori/genética , Masculino , Antígenos O/química , Estómago/patologíaRESUMEN
Association between H. pylori infection, iron deficiency and iron deficiency anaemia has been described, but the mechanisms involved have not been established. We hypothesized that in H. pylori infected children increased gastric concentrations of IL-1ß and/or TNF-α, both potent inhibitors of gastric acid secretion that is essential for iron absorption, are predictors for low blood concentrations of ferritin and haemoglobin, markers of early depletion of iron stores and anaemia, respectively. We evaluated 125 children undergoing endoscopy to clarify the origin of gastrointestinal symptoms. Gastric specimens were obtained for H. pylori status and cytokine evaluation and blood samples for determination of iron deficiency/iron deficiency anaemia parameters and IL1 cluster and TNFA polymorphisms that are associated with increased cytokine secretions. Higher IL-1ß and TNF-α gastric concentrations were observed in H. pylori-positive (nâ=â47) than in -negative (nâ=â78) children. Multiple linear regression models revealed gastric IL-1ß, but not TNF-α, as a significant predictor of low ferritin and haemoglobin concentrations; results were reproduced in young children in whom IL1RN polymorphic genotypes associated with higher gastric IL-1ß expression and lower blood ferritin and haemoglobin concentrations. In conclusion, high gastric levels of IL-1ß can be the link between H. pylori infection and iron deficiency/iron deficiency anaemia in childhood.
Asunto(s)
Anemia Ferropénica/microbiología , Mucosa Gástrica/metabolismo , Infecciones por Helicobacter/metabolismo , Helicobacter pylori/aislamiento & purificación , Interleucina-1beta/metabolismo , Hierro/metabolismo , Estómago/microbiología , Adolescente , Anemia Ferropénica/genética , Anemia Ferropénica/metabolismo , Niño , Preescolar , Endoscopía/métodos , Femenino , Ferritinas/genética , Ferritinas/metabolismo , Genotipo , Infecciones por Helicobacter/sangre , Infecciones por Helicobacter/genética , Infecciones por Helicobacter/microbiología , Humanos , Proteína Antagonista del Receptor de Interleucina 1/genética , Proteína Antagonista del Receptor de Interleucina 1/metabolismo , Interleucina-1beta/genética , Hierro/sangre , Masculino , Polimorfismo Genético , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Helicobacter pylori transactivates the Epidermal Growth Factor Receptor (EGFR) and predisposes to gastric cancer development in humans and animal models. To examine the importance of EGFR signalling to gastric pathology, this study investigated whether treatment of Mongolian gerbils with a selective EGFR tyrosine kinase inhibitor, EKB-569, altered gastric pathology in chronic H. pylori infection. Gerbils were infected with H. pylori and six weeks later received either EKB-569-supplemented, or control diet, for 32 weeks prior to sacrifice. EKB-569-treated H. pylori-infected gerbils had no difference in H. pylori colonisation or inflammation scores compared to infected animals on control diet, but showed significantly less corpus atrophy, mucous metaplasia and submucosal glandular herniations along with markedly reduced antral and corpus epithelial proliferation to apoptosis ratios. EKB-569-treated infected gerbils had significantly decreased abundance of Cox-2, Adam17 and Egfr gastric transcripts relative to infected animals on control diet. EGFR inhibition by EKB-569 therefore reduced the severity of pre-neoplastic gastric pathology in chronically H. pylori-infected gerbils. EKB-569 increased gastric epithelial apoptosis in H. pylori-infected gerbils which counteracted some of the consequences of increased gastric epithelial cell proliferation. Similar chemopreventative strategies may be useful in humans who are at high risk of developing H.pylori-induced gastric adenocarcinoma.
RESUMEN
AIMS: Acute Helicobacter pylori infection is associated with transient hypochlorhydria. In H pylori-associated atrophy, hypochlorhydria has a role in iron deficiency (ID) through changes in the physiology of iron-complex absorption. The aims were to evaluate the association between H pylori-associated hypochlorhydria and ID in children. METHODS: Symptomatic children (n=123) were prospectively enrolled. Blood, gastric juice and gastric biopsies were taken, respectively, for haematological analyses, pH assessment and H pylori determination, and duodenal biopsies for exclusion of coeliac disease. Stool samples were collected for parasitology/microbiology. Thirteen children were excluded following parasitology and duodenal histopathology, and five due to impaired blood analysis. RESULTS: Ten children were hypochlorhydric (pH>4) and 33 were H pylori positive. In H pylori-positive children with pH>4 (n=6) serum iron and transferrin saturation levels % were significantly lower (p<0.01) than H pylori-positive children with pH≤4. No differences in ferritin, or total iron binding capacity, were observed. In H pylori-negative children with pH>4, iron and transferrin saturation were not significantly different from children with pH≤4. CONCLUSIONS: Low serum iron and transferrin in childhood H pylori infection is associated with hypochlorhydria. In uninfected children, hypochlorhydria was not associated with altered serum iron parameters, indicating a combination of H pylori infection and/or inflammation, and hypochlorhydria has a role in the aetiology of ID. Although H pylori-associated hypochlorhydria is transient during acute gastritis, this alters iron homeostasis with clinical impact in developing countries with a high H pylori prevalence.