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1.
Am J Gastroenterol ; 119(6): 1167-1176, 2024 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-38235740

RESUMO

INTRODUCTION: There are limited data characterizing eating habits among pediatric patients with eosinophilic esophagitis (EoE). We compared eating behaviors in pediatric patients with EoE with healthy controls and assessed the degree of correlation with symptomatology, endoscopic and histologic findings, and esophageal distensibility. METHODS: We conducted a prospective, observational study where subjects consumed 4 food textures (puree, soft solid, chewable, and hard solid) and were scored for eating behaviors including number of chews per bite, sips of fluid per food, and consumption time. Symptomatic, endoscopic, histologic, and esophageal distensibility data were collected for case subjects. RESULTS: Twenty-seven case subjects and 25 healthy controls were enrolled in our study (mean age 11.0 years, 63.5% male). Compared with healthy controls, pediatric patients with EoE demonstrated more chews per bite with soft solid (13.6 vs 9.1, P = 0.031), chewable (14.7 vs 10.7, P = 0.047), and hard solid foods (19.0 vs 12.8, P = 0.037). Patients with EoE also demonstrated increased consumption time with soft solid (94.7 vs 58.3 seconds, P = 0.002), chewable (90.0 vs 65.1 seconds, P = 0.005), and hard solid foods (114.1 vs 76.4 seconds, P = 0.034) when compared with healthy controls. Subgroup analysis based on disease status showed no statistically significant differences in eating behaviors between active and inactive EoE. Total endoscopic reference score positively correlated with consumption time ( r = 0.53, P = 0.008) and number of chews ( r = 0.45, P = 0.027) for chewable foods and with number of chews ( r = 0.44, P = 0.043) for hard solid foods. Increased consumption time correlated with increased eosinophil count ( r = 0.42, P = 0.050) and decreased esophageal distensibility ( r = -0.82, P < 0.0001). DISCUSSION: Altered eating behaviors including increased chewing and increased consumption time can be seen in pediatric patients with EoE, can persist despite histologic remission, and may be driven by changes in esophageal distensibility.


Assuntos
Esofagite Eosinofílica , Esôfago , Comportamento Alimentar , Humanos , Esofagite Eosinofílica/fisiopatologia , Esofagite Eosinofílica/patologia , Masculino , Feminino , Estudos Prospectivos , Criança , Comportamento Alimentar/fisiologia , Estudos de Casos e Controles , Esôfago/patologia , Esôfago/fisiopatologia , Adolescente , Esofagoscopia
2.
J Pediatr ; 267: 113922, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38242317

RESUMO

OBJECTIVE: To develop and validate a set of static and animated gastroduodenal symptom pictograms for children. STUDY DESIGN: There were 3 study phases: 1: cocreation using experience design methods to develop pediatric gastroduodenal symptom pictograms (static and animated); 2: an online survey to assess acceptability, as well as face and content validity; and 3: a preference study. Phases 2 and 3 compared the novel pediatric pictograms with existing pictograms used with adult patients. RESULTS: Eight children aged 6-15 years (5 female) participated in phase 1, and 69 children in phase 2 (median age 13 years: IQR 9-15); an additional 49 participants were included in phase 3 (median age 15: IQR 12-17). Face and content validity were higher for the pediatric static and animated pictogram sets compared with pre-existing adult pictograms (78% vs 78% vs 61%). Participants with worse gastric symptoms had superior comprehension of the pediatric pictograms (χ2 [8, N = 118] P < .001). All participants preferred the pediatric static pictogram set was over both the animated and adult sets (χ2 [2, N = 118] P < .001). CONCLUSIONS: The cocreation phase resulted in the symptom concept confirmation and design of 10 acceptable static and animated gastroduodenal pictograms with high face and content validity when evaluated with children aged 6-18. Validity was superior when children reported more problematic symptoms. Therefore, these pictograms could be used in clinical and research practice to enable standardized symptom reporting for children with gastroduodenal disorders.


Assuntos
Compreensão , Adulto , Humanos , Feminino , Criança , Adolescente , Inquéritos e Questionários
3.
J Allergy Clin Immunol ; 150(3): 649-656.e5, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35405206

RESUMO

BACKGROUND: Esophageal remodeling is a factor in disease progression and symptom severity for patients with eosinophilic esophagitis (EoE). Remodeling can begin early in children, resulting in stricture and food impaction. Detection of esophageal remodeling often depends on endoscopy and is appreciated only in its later stages. OBJECTIVE: We sought to determine whether luminal eosinophil-associated and remodeling proteins captured by the esophageal string test (EST) correlate with measures of esophageal remodeling and biomarkers of the epithelial-mesenchymal transition (EMT). METHODS: Patients with EoE (7-18 years old) were enrolled from 2 pediatric hospitals. Participants performed the EST and underwent endoscopy. Histology, distensibility measured by endoluminal functional lumen imaging probe, and symptoms were assessed. Protein quantitation by ELISA was performed on mucosal biopsy and EST samples. Tissue sections were evaluated for EMT. Outcome measures were summarized, and Spearman ρ was used to assess bivariate correlations. RESULTS: Forty patients (68% male) were enrolled (mean age, 12.5 years). Twenty-four (60%) had active disease (≥15 eosinophils per high-power field). EST-captured eotaxin-3, major basic protein 1, EDN, eosinophil peroxidase, and Charcot-Leyden crystal protein/galectin-10 showed significant correlations with peak eosinophils per high-power field (ρ 0.53-0.68, P < .001). Luminal proteins positively correlated with endoscopic features and markers of EMT, and negatively with esophageal distensibility. Periostin was captured by the EST and correlated with eosinophil density, basal zone hyperplasia, endoscopic appearance, and markers of EMT. CONCLUSION: Luminal markers of esophageal remodeling in addition to biomarkers of eosinophilic inflammation correlate with epithelial and functional remodeling in EoE.


Assuntos
Esofagite Eosinofílica , Adolescente , Biomarcadores/metabolismo , Criança , Enterite , Eosinofilia , Esofagite Eosinofílica/patologia , Eosinófilos/patologia , Feminino , Gastrite , Humanos , Inflamação/patologia , Masculino
4.
Immunity ; 39(6): 1158-70, 2013 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-24332033

RESUMO

Extramedullary hematopoiesis (EMH) refers to the differentiation of hematopoietic stem cells (HSCs) into effector cells that occurs in compartments outside of the bone marrow. Previous studies linked pattern-recognition receptor (PRR)-expressing HSCs, EMH, and immune responses to microbial stimuli. However, whether EMH operates in broader immune contexts remains unknown. Here, we demonstrate a previously unrecognized role for thymic stromal lymphopoietin (TSLP) in promoting the population expansion of progenitor cells in the periphery and identify that TSLP-elicited progenitors differentiated into effector cells including macrophages, dendritic cells, and granulocytes and that these cells contributed to type 2 cytokine responses. The frequency of circulating progenitor cells was also increased in allergic patients with a gain-of-function polymorphism in TSLP, suggesting the TSLP-EMH pathway might operate in human disease. These data identify that TSLP-induced EMH contributes to the development of allergic inflammation and indicate that EMH is a conserved mechanism of innate immunity.


Assuntos
Citocinas/metabolismo , Hematopoese Extramedular/imunologia , Hipersensibilidade/imunologia , Inflamação , Baço/imunologia , Animais , Citocinas/genética , Citocinas/imunologia , Modelos Animais de Doenças , Citometria de Fluxo , Perfilação da Expressão Gênica , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Polimorfismo Genético , Células Precursoras de Linfócitos B/citologia , Baço/citologia , Triquinelose/imunologia , Linfopoietina do Estroma do Timo
5.
Dis Esophagus ; 35(4)2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-34864928

RESUMO

BACKGROUND: Esophagogastric junction outflow obstruction (EGJOO) has a variable disease course. Currently, barium swallow (BaS) and manometric parameters are used to characterize clinically significant EGJOO. The esophagogastric junction distensibility index (EGJ-DI) measured via functional lumen imaging probe (FLIP) can provide complementary information. Our aim was to assess symptom response in patients with EGJOO and an abnormal EGJ-DI after botulinum toxin (BT) treatment. METHODS: A prospective cohort study of adults with idiopathic EGJOO was performed from September 2019 to March 2021. Patients with dysphagia underwent upper endoscopy with FLIP. If the EGJ-DI was abnormally low, BT was injected. Data examined included demographics, medical history, endoscopic and FLIP findings, BaS, manometry, and Eckardt score (ES). ES improvement was assessed via paired samples t-test. Pearson's chi-square tests were used to assess for associations. RESULTS: Of the 20 patients, 75% had an abnormal EGJ-DI and underwent BT injections. Mean ES for patients with abnormal EGJ-DIs significantly improved from baseline to 1, 3, and 6 month follow-up (P-values: 0.01, 0.05, and 0.02, respectively). There was a significant association between an abnormal EGJ-DI with delayed bolus transit and presence of rapid drink challenge panesophageal pressurization on manometry: P = 0.03 and P = 0.03. CONCLUSION: This prospective study revealed that an abnormal EGJ-DI can guide BT as assessed via symptomatic response. Additionally, abnormal EGJ-DI measurements were significantly associated with other parameters used previously to determine clinically relevant EGJOO. Larger follow-up studies are warranted to further elucidate guidance for therapy in EGJOO.


Assuntos
Toxinas Botulínicas , Transtornos de Deglutição , Acalasia Esofágica , Transtornos da Motilidade Esofágica , Gastropatias , Adulto , Transtornos da Motilidade Esofágica/diagnóstico , Junção Esofagogástrica , Humanos , Manometria/métodos , Estudos Prospectivos , Gastropatias/complicações
6.
Clin Gastroenterol Hepatol ; 18(7): 1475-1482.e1, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31499251

RESUMO

BACKGROUND & AIMS: Although eosinophil count is the standard used to monitor disease activity in patients with eosinophilic esophagitis (EoE), there are often disparities between patient-reported symptoms and eosinophil counts. We examined the prevalence of epithelial alterations, namely basal cell hyperplasia (BCH) and spongiosis, among patients with inactive EoE (eosinophil counts below 15 following therapy) and aimed to determine whether maintenance of these changes in epithelial morphology are associated with persistent clinical findings. METHODS: Esophageal biopsies of 243 patients (mean age, 16.9 years) undergoing routine endoscopy at the University of Pennsylvania were evaluated for epithelial BCH and spongiosis. Univariable analysis was used to calculate the association between epithelial changes and symptoms as well as endoscopic findings and peak eosinophil count. We validated our findings using data from a cohort of patients at the University of North Carolina. RESULTS: The discovery and validation cohorts each included patients with inactive EoE, based on histologic factors, but ongoing BCH and spongiosis. Ongoing BCH, but not spongiosis, in patients with inactive EoE was associated with symptoms (odds ratio, 2.14; 95% CI, 1.03-4.42; P = .041) and endoscopic findings (odds ratio, 7.10; 95% CI, 3.12-16.18; P < .001). CONCLUSIONS: In patients with EoE, the presence of BCH might indicate ongoing disease activity, independent of eosinophil count. This might account for the persistent symptoms in patients who are considered to be in remission based on histologic factors.


Assuntos
Esofagite Eosinofílica , Adolescente , Esofagite Eosinofílica/patologia , Eosinófilos/patologia , Humanos , Hiperplasia/patologia , Contagem de Leucócitos
7.
J Allergy Clin Immunol ; 144(1): 171-182, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30578874

RESUMO

BACKGROUND: Fibrosis and stricture are major comorbidities in patients with eosinophilic esophagitis (EoE). Lysyl oxidase (LOX), a collagen cross-linking enzyme, has not been investigated in the context of EoE. OBJECTIVE: We investigated regulation of epithelial LOX expression as a novel biomarker and functional effector of fibrostenotic disease conditions associated with EoE. METHODS: LOX expression was analyzed by using RNA-sequencing, PCR assays, and immunostaining in patients with EoE; cytokine-stimulated esophageal 3-dimensional organoids; and fibroblast-epithelial cell coculture, the latter coupled with fluorescence-activated cell sorting. RESULTS: Gene ontology and pathway analyses linked TNF-α and LOX expression in patients with EoE, which was validated in independent sets of patients with fibrostenotic conditions. TNF-α-mediated epithelial LOX upregulation was recapitulated in 3-dimensional organoids and coculture experiments. We find that fibroblast-derived TNF-α stimulates epithelial LOX expression through activation of nuclear factor κB and TGF-ß-mediated signaling. In patients receiver operating characteristic analyses suggested that LOX upregulation indicates disease complications and fibrostenotic conditions in patients with EoE. CONCLUSIONS: There is a novel positive feedback mechanism in epithelial LOX induction through fibroblast-derived TNF-α secretion. Esophageal epithelial LOX might have a role in the development of fibrosis with substantial translational implications.


Assuntos
Biomarcadores/metabolismo , Esofagite Eosinofílica/genética , Células Epiteliais/fisiologia , Esôfago/patologia , Fibroblastos/fisiologia , Proteína-Lisina 6-Oxidase/genética , Fator de Necrose Tumoral alfa/metabolismo , Adolescente , Adulto , Idoso , Células Cultivadas , Criança , Pré-Escolar , Técnicas de Cocultura , Constrição Patológica , Esofagite Eosinofílica/diagnóstico , Feminino , Fibrose , Ontologia Genética , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Proteína-Lisina 6-Oxidase/metabolismo , Regulação para Cima , Adulto Jovem
8.
Gut ; 66(7): 1197-1207, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-26884425

RESUMO

OBJECTIVE: The influence of eosinophilic oesophagitis (EoE)-associated inflammation upon oesophageal epithelial biology remains poorly understood. We investigated the functional role of autophagy in oesophageal epithelial cells (keratinocytes) exposed to the inflammatory EoE milieu. DESIGN: Functional consequences of genetic or pharmacological autophagy inhibition were assessed in endoscopic oesophageal biopsies, human oesophageal keratinocytes, single cell-derived ex vivo murine oesophageal organoids as well as a murine model recapitulating EoE-like inflammation and basal cell hyperplasia. Gene expression, morphological and functional characterisation of autophagy and oxidative stress were performed by transmission electron microscopy, immunostaining, immunoblotting, live cell imaging and flow cytometry. RESULTS: EoE-relevant inflammatory conditions promoted autophagy and basal cell hyperplasia in three independent murine EoE models and oesophageal organoids. Inhibition of autophagic flux via chloroquine treatment augmented basal cell hyperplasia in these model systems. Oesophageal keratinocytes stimulated with EoE-relevant cytokines, including tumour necrosis factor-α and interleukin-13 exhibited activation of autophagic flux in a reactive oxygen species-dependent manner. Autophagy inhibition via chloroquine treatment or depletion of Beclin-1 or ATG-7, augmented oxidative stress induced by EoE-relevant stimuli in murine EoE, oesophageal organoids and human oesophageal keratinocytes. Oesophageal epithelia of paediatric EoE patients with active inflammation displayed increased autophagic vesicle content compared with normal and EoE remission subjects. Functional flow cytometric analysis revealed autophagic flux in human oesophageal biopsies. CONCLUSIONS: Our findings reveal for the first time that autophagy may function as a cytoprotective mechanism to maintain epithelial redox balance and homeostasis under EoE inflammation-associated stress, providing mechanistic insights into the role of autophagy in EoE pathogenesis.


Assuntos
Autofagia/fisiologia , Esofagite Eosinofílica/metabolismo , Animais , Autofagia/efeitos dos fármacos , Cloroquina/farmacologia , Citocinas/farmacologia , Esofagite Eosinofílica/patologia , Eosinófilos/metabolismo , Epitélio/metabolismo , Esofagoscopia , Esôfago/patologia , Humanos , Queratinócitos/metabolismo , Queratinócitos/patologia , Camundongos , Modelos Animais , Estresse Oxidativo
9.
Am J Gastroenterol ; 112(9): 1466-1473, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28508868

RESUMO

OBJECTIVES: Sequelae of eosinophilic esophagitis (EoE) include food impaction and esophageal stricture. Duration of inflammation is a predicted risk factor; however, complications remain unpredictable. Studies using the functional lumen imaging probe (FLIP) have demonstrated decreased distensibility of the esophagus in adult patients with EoE. As the impact of inflammation on the developing esophagus is unknown, we investigated esophageal distensibility in a pediatric cohort to determine the effect of age, ongoing inflammation, and fibrotic features on distensibility. METHODS: We conducted a prospective observational study at two tertiary pediatric institutions. Subjects underwent FLIP evaluation during endoscopy to determine distensibility of the esophagus. During stepwise distension, simultaneous intrabag pressure and 16 channels of cross-sectional areas were measured. The minimal diameter at maximal esophageal distention at an intrabag pressure of 40 mm Hg was identified. Distensibility was compared between EoE and non-EoE subjects and between clinical variables within the EoE cohort. Potential confounding variables were identified. RESULTS: Forty-four non-EoE and 88 EoE subjects aged 3-18 years were evaluated. Age positively correlated with esophageal distensibility in the non-EoE cohort, but this trend was not observed in the EoE population. Subjects with EoE had reduced distensibility even after adjusting for age. Active inflammation (eosinophils >15 eos/high-power field), histological lamina propria fibrosis, and various features of a fibrotic phenotype (stricture, food impaction, circumferential rings on endoscopy) were associated with decreased distensibility within the EoE cohort. FLIP was safe, feasible, and well tolerated. CONCLUSIONS: These findings suggest that remodeling occurs in the pediatric EoE population, warranting early diagnosis and initiation of therapy prior to the onset of disease complications.


Assuntos
Esofagite Eosinofílica/fisiopatologia , Estenose Esofágica/fisiopatologia , Adolescente , Fatores Etários , Criança , Serviços de Saúde da Criança , Pré-Escolar , Estudos de Coortes , Colorado , Esofagoscopia , Feminino , Humanos , Masculino , Pennsylvania , Estudos Prospectivos
10.
Water Sci Technol ; 75(5-6): 1351-1361, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28333051

RESUMO

The complex non-linear behavior presented in the biological treatment of wastewater requires an accurate model to predict the system performance. This study evaluates the effectiveness of an artificial intelligence (AI) model, based on the combination of artificial neural networks (ANNs) and genetic algorithms (GAs), to find the optimum performance of an up-flow anaerobic sludge blanket reactor (UASB) for saline wastewater treatment. Chemical oxygen demand (COD) removal was predicted using conductivity, organic loading rate (OLR) and temperature as input variables. The ANN model was built from experimental data and performance was assessed through the maximum mean absolute percentage error (= 9.226%) computed from the measured and model predicted values of the COD. Accordingly, the ANN model was used as a fitness function in a GA to find the best operational condition. In the worst case scenario (low energy requirements, high OLR usage and high salinity) this model guaranteed COD removal efficiency values above 70%. This result is consistent and was validated experimentally, confirming that this ANN-GA model can be used as a tool to achieve the best performance of a UASB reactor with the minimum requirement of energy for saline wastewater treatment.


Assuntos
Inteligência Artificial , Análise da Demanda Biológica de Oxigênio , Reatores Biológicos , Modelos Teóricos , Esgotos/química , Águas Residuárias/química , Purificação da Água/métodos , Algoritmos , Anaerobiose , Simulação por Computador , Redes Neurais de Computação , Oxigênio/análise , Soluções , Temperatura
12.
J Pediatr Gastroenterol Nutr ; 63(2): 200-9, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26727658

RESUMO

OBJECTIVES: Eosinophilic esophagitis (EoE) is an immune-mediated allergic disease characterized by progressive esophageal dysmotility and fibrotic stricture associated with chronic esophageal fibroblast activation. It remains unknown how esophageal fibroblasts respond to EoE-relevant matrix stiffness or inflammatory cytokines. METHODS: Immunofluorescence was used to evaluate α-smooth muscle actin (α-SMA) expression in endoscopic esophageal biopsies. Primary esophageal fibroblasts from adult and pediatric patients with or without EoE were exposed to transforming growth factor (TGF)ß to determine gene expression, collagen-matrix contractility, and cytoskeletal organization. The influence of matrix stiffness upon fibroblast behavior was assessed on the engineered surface of polyacrylamide gels with varying stiffness. Fibroblast traction forces were measured using microfabricated-post-array-detectors. RESULTS: EoE esophageal fibroblasts had enhanced α-SMA expression. TGFß not only stimulated enhanced fibroblast-specific gene expression but also promoted fibroblast-mediated collagen-matrix contraction, despite disease state or age of patients as the origin of cells. Unlike conventional monolayer cell, culture conditions using plastic surface (1 GPa) that activates fibroblasts constitutively, our engineered platforms recapitulating physiologically relevant stiffness (1-20 kPa) revealed that matrix stiffness defines the extent of α-SMA expression, intracellular collagen fibril organization, SMAD3 phosphorylation, and fibroblast traction force. CONCLUSIONS: Matrix stiffness may critically influence TGFß-mediated gene expression and functions of esophageal fibroblasts ex vivo independent of age and disease conditions. These findings provide a novel insight into the pathogenesis of fibrostenotic disease in EoE.


Assuntos
Microambiente Celular/fisiologia , Esofagite Eosinofílica/fisiopatologia , Esôfago/fisiopatologia , Fibroblastos/fisiologia , Actinas/metabolismo , Adulto , Biomarcadores/metabolismo , Western Blotting , Células Cultivadas , Criança , Citocinas/metabolismo , Esofagite Eosinofílica/genética , Esofagite Eosinofílica/metabolismo , Esofagite Eosinofílica/patologia , Esôfago/metabolismo , Esôfago/patologia , Matriz Extracelular/fisiologia , Feminino , Fibroblastos/metabolismo , Fibroblastos/patologia , Imunofluorescência , Regulação da Expressão Gênica , Humanos , Masculino , Reação em Cadeia da Polimerase em Tempo Real , Fator de Crescimento Transformador beta/metabolismo
13.
Exp Cell Res ; 330(1): 102-10, 2015 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-25183431

RESUMO

BACKGROUND AND AIMS: Eosinophilic esophagitis (EoE) is an allergic inflammatory disease that leads to esophageal fibrosis and stricture. We have recently shown that in EoE, esophageal epithelial cells undergo an epithelial to mesenchymal transition (EMT), characterized by gain of mesenchymal markers and loss of epithelial gene expression. Whether epithelial cells exposed to profibrotic cytokines can also acquire the functional characteristics of activated myofibroblasts, including migration, contraction, and extracellular matrix deposition, is relevant to our understanding and treatment of EoE-associated fibrogenesis. In the current study, we characterize cell migration, contraction, and collagen production by esophageal epithelial cells that have undergone cytokine-induced EMT in vitro. METHODS AND RESULTS: Stimulation of human non-transformed immortalized esophageal epithelial cells (EPC2-hTERT) with profibrotic cytokines TNFα, TGFß, and IL1ß for three weeks led to acquisition of mesenchymal αSMA and vimentin, and loss of epithelial E-cadherin expression. Upon removal of the profibrotic stimulus, epithelial characteristics were partially rescued. TGFß stimulation had a robust effect upon epithelial collagen production. Surprisingly, TNFα stimulation had the most potent effect upon cell migration and contraction, exceeding the effects of the prototypical profibrotic cytokine TGFß. IL1ß stimulation alone had minimal effect upon esophageal epithelial migration, contraction, and collagen production. CONCLUSIONS: Esophageal epithelial cells that have undergone EMT acquire functional characteristics of activated myofibroblasts in vitro. Profibrotic cytokines exert differential effects upon esophageal epithelial cells, underscoring complexities of fibrogenesis in EoE, and implicating esophageal epithelial cells as effector cells in EoE-associated fibrogenesis.


Assuntos
Células Epiteliais/metabolismo , Transição Epitelial-Mesenquimal , Miofibroblastos/metabolismo , Actinas/metabolismo , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular , Movimento Celular , Colágeno/genética , Colágeno/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/fisiologia , Esôfago/citologia , Humanos , Interleucina-1beta/farmacologia , Miofibroblastos/efeitos dos fármacos , Miofibroblastos/fisiologia , Fator de Crescimento Transformador beta/farmacologia , Fator de Necrose Tumoral alfa/farmacologia
14.
Am J Physiol Gastrointest Liver Physiol ; 307(8): G803-12, 2014 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-25147232

RESUMO

The incidence of eosinophilic esophagitis (EoE) has increased in the past several years, yet our understanding of its pathogenesis remains limited. To test the hypothesis that microRNAs (miRNAs) are altered in children with EoE, miRNAs were profiled in esophageal mucosa biopsies obtained from patients with active disease (n = 5) and healthy control subjects (n = 6). Fourteen miRNAs were significantly altered between groups; four of these miRNAs were decreased in EoE patients. A panel of five miRNAs (miR-203, miR-375, miR-21, miR-223, and miR-142-3p) were selected for validation in an independent set of samples from control (n = 22), active disease (n = 22), inactive disease (n = 22), and gastroesophageal reflux disease (n = 6) patients. Each panel miRNA was significantly altered among groups. miRNA changes in esophageal biopsies were not reflected in the circulating RNA pool, as no differences in panel miRNA levels were observed in sera collected from the four patient groups. In addition, in contrast to previous studies, no change in esophageal miRNA levels was detected following treatment that resolved esophageal eosinophilia. In an effort to identify the ramifications of reduced esophageal miR-203, miR-203 activity was inhibited in cultured epithelial cells via expression of a tough decoy miRNA inhibitor. Luciferase reporter assays demonstrated that miR-203 does not directly regulate human IL-15 through targeting of the IL-15 3'-untranslated region. From these experiments, it is concluded that miRNAs are perturbed in the esophageal mucosa, but not the serum, of pediatric EoE patients. Further investigation is required to decipher pathologically relevant consequences of miRNA perturbation in this context.


Assuntos
Esofagite Eosinofílica/metabolismo , Esôfago/metabolismo , MicroRNAs/metabolismo , Adolescente , Estudos de Casos e Controles , Células Cultivadas , Criança , Pré-Escolar , Esofagite Eosinofílica/sangue , Células Epiteliais/metabolismo , Esôfago/patologia , Feminino , Refluxo Gastroesofágico/sangue , Refluxo Gastroesofágico/metabolismo , Humanos , Masculino , MicroRNAs/sangue , MicroRNAs/genética
15.
Exp Cell Res ; 319(6): 850-9, 2013 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-23237990

RESUMO

BACKGROUND: Esophageal fibrosis is a complication of eosinophilic esophagitis (EoE) which has been attributed to both subepithelial fibrosis and to epithelial to mesenchymal transition (EMT), a process by which epithelial cells acquire mesenchymal features. Common to both causes of EoE-fibrosis is the notion that granulocyte-derived TGF-ß, induces myofibroblast differentiation of the target cell. To date, the role of esophageal epithelial cells as effector cells in esophageal fibrosis has never been explored. Herein, we investigated consequences of cross-talk between esophageal epithelial cells and fibroblasts, and identified profibrotic cytokines which influence the development of EMT in vitro. METHODS AND RESULTS: Stimulation of primary fetal esophageal fibroblasts (FEF3) with conditioned media (CEM) from esophageal epithelial cells (EPC2-hTERT), primed FEF3 cells to secrete IL-1ß and TNFα, but not TGFß. To determine whether these cytokines signaled in a paracrine fashion to esophageal epithelial cells, FEF3 cells were stimulated with CEM, followed by transfer of this fibroblast conditioned media (FCM) to EPC2-hTERT cells. Epithelial FCM stimulation increased expression of mesenchymal markers and reduced E-cadherin expression, features of EMT which were TNFα and IL-1ß-dependent. Using organotypic culture models, primary EoE epithelial cells exhibited features of EMT compared to non-EoE cells, corresponding to patterns of EMT in native biopsies. CONCLUSIONS: Esophageal epithelial cell and fibroblast cross-talk contributes to esophageal fibrosis. Our results suggest that features of EMT can develop independent of TGF-ß and granulocytes, which may have important implications in treatment of EoE.


Assuntos
Comunicação Celular , Esofagite Eosinofílica/patologia , Células Epiteliais/citologia , Transição Epitelial-Mesenquimal , Esôfago/citologia , Adolescente , Biópsia , Caderinas/metabolismo , Diferenciação Celular , Células Cultivadas , Criança , Meios de Cultivo Condicionados/metabolismo , Meios de Cultivo Condicionados/farmacologia , Esofagite Eosinofílica/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Esôfago/efeitos dos fármacos , Esôfago/metabolismo , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Granulócitos/metabolismo , Humanos , Interleucina-1beta/metabolismo , Interleucina-1beta/farmacologia , Masculino , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologia , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/farmacologia
16.
Clin Transl Gastroenterol ; 14(4): e00564, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36603149

RESUMO

INTRODUCTION: Inflammation in eosinophilic esophagitis (EoE) often leads to esophageal strictures. Evaluating esophageal narrowing is clinically challenging. We evaluated esophageal distensibility as related to disease activity, fibrosis, and dysphagia. METHODS: Adult patients with and without EoE underwent endoscopy and distensibility measurements. Histology, distensibility, and symptoms were analyzed. RESULTS: Patients with EoE had significantly lower distensibilities than controls. We found a cohort with esophageal diameter under 15 mm despite lack of dysphagia. DISCUSSION: This study raises concern that current assessments of fibrostenosis are suboptimal. We describe a cohort with unrecognized slender esophagus that were identified through impedance planimetry measurements. This tool provides additional information beyond symptomatic, histologic, and endoscopic assessments.


Assuntos
Transtornos de Deglutição , Esofagite Eosinofílica , Estenose Esofágica , Adulto , Humanos , Esofagite Eosinofílica/complicações , Esofagite Eosinofílica/diagnóstico , Esofagite Eosinofílica/patologia , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/etiologia , Estenose Esofágica/diagnóstico , Estenose Esofágica/etiologia , Estenose Esofágica/patologia , Endoscopia Gastrointestinal
17.
J Child Health Care ; 27(3): 374-385, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-34978212

RESUMO

Children with eosinophilic esophagitis (EoE) are faced with ongoing treatments that can impact their wellbeing. There are no evidence-based resources that families can implement independently to cope with EoE-related stressors. This study aimed to examine acceptability, feasibility, and preliminary outcomes of the newly developed Cellie Coping Kit for Children with EoE intervention. Forty child-caregiver dyads completed a baseline assessment (T1) and initiated the intervention; 30 (75%) child participants and 33 (82.5%) caregivers were retained to follow-up (T2). Of those who completed the T2 assessment, most reported that the intervention was easy to use (>90%) and would recommend the intervention to others (>90%). The intervention was feasible: >70% used the kit, and most indicated they would use it again (>75%). More than half of families reported learning new information and/or coping strategies. No statistically significant changes were identified in comparing T1 and T2 coping and health-related quality of life. These findings suggest that the Cellie Coping Kit for Children with EoE is a promising intervention in that it was well accepted, feasible, and helped many families learn novel strategies on how to manage EoE challenges. Future research should examine how to strengthen the intervention to achieve longer-term targeted outcomes.


Assuntos
Esofagite Eosinofílica , Humanos , Esofagite Eosinofílica/terapia , Qualidade de Vida , Estudos de Viabilidade , Adaptação Psicológica , Aprendizagem
19.
Chemosphere ; 267: 129234, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33352363

RESUMO

In this study, known combinations of Advanced Oxidation Processes (AOPs, namely Electro-Fenton (EF), Photo-Electro-Fenton (PEF), Electro-Oxidation (EO), and EO/Ozone (O3) were compared for the discoloration of tannery industry azo dye Brown HT (BHT). The different AOPs were tested in a 0.160 L batch electrochemical stirred thank reactor using Boron Doped Diamond (BDD) electrodes. The influence of parameters such as the current density (j) and the initial BHT concentration were to exanimated on the efficiency of all the tested processes. The oxidation tendency of EF, and PEF were compared with those of EO and O3, based on their efficiency for BHT discoloration, which resulted as PEF > EF > EO > O3. The AOPs showing the best oxidation performance was PEF which, using Na2SO4 (0.05 M) electrolyte solution and Fe2+ (0.5 mM), pH 3.0, j = 71 mA cm-2, and 500 rpm process, achieved 100% discoloration and 80% chemical oxygen demand (COD) abatement after 60 min of treatment for two initial BHT concentrations (50 and 80 mg L-1). The process accounted for a current efficiency of 30% and energy consumption 2.25 kWh (g COD)-1 through the discoloration test. The azo dye gradually degraded, yielding non-toxic oxalic, oxamic, and glyoxylic acid, whose Fe(III) complexes were quickly photolyzed.


Assuntos
Compostos Férricos , Poluentes Químicos da Água , Compostos Azo , Diamante , Eletrodos , Peróxido de Hidrogênio , Oxirredução
20.
Neurogastroenterol Motil ; 33(12): e14133, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33871917

RESUMO

BACKGROUND: Achalasia is an esophageal motility disorder characterized by esophagogastric junction (EGJ) dysfunction and impaired esophageal peristalsis with significant impact on quality of life. While the functional luminal imaging probe (FLIP) has been used to assess EGJ distensibility in achalasia, its clinical utility in pediatrics is limited due to absence of normative values and correlations with clinical outcomes in children. Thus, we sought to evaluate FLIP's use in a pediatric achalasia cohort undergoing dilations and non-achalasia controls. METHODS: We conducted a retrospective study of pediatric patients with achalasia who underwent FLIP before and immediately after balloon dilations and compared to a non-achalasia cohort. KEY RESULTS: Thirty patients with achalasia (mean age, 15.2 years; 40% female), including fourteen treatment-naïve and thirteen controls (mean age, 7.9 years; 61% female) were identified. Median EGJ distensibility index (EGJ-DI) 2.07 mm2  mmHg-1 and diameter (9.23 mm) in treatment-naïve patients were significantly lower compared to controls (EGJ-DI 6.8 mm2  mmHg-1 ; diameter 18.61 mm; (p < 0.001). Balloon dilations resulted in a significant increase in EGJ-DI immediately after the dilation, particularly in treatment-naïve patients (p < 0.001), and a significant improvement in Eckardt scores (p < 0.001). CONCLUSIONS & INFERENCES: Functional luminal imaging probe measurements of EGJ-DI in pediatric patients with achalasia are mostly consistent with adult findings. However, normal EGJ-DI is seen in symptomatic patients, including treatment-naive, highlighting the need for pediatric reference data. Balloon dilations achieve a significant increase in EGJ-DI with improvement in Eckardt scores, confirming the therapeutic value of dilations in achalasia management.


Assuntos
Endoscopia/métodos , Acalasia Esofágica/diagnóstico , Junção Esofagogástrica/fisiopatologia , Adolescente , Criança , Pré-Escolar , Dilatação , Acalasia Esofágica/fisiopatologia , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos
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