RESUMO
OBJECTIVE: We aimed to examine the effect of remission status on thiol-disulfide homeostasis in celiac patients and thus to indirectly determine the effect of oxidative stress and inflammation caused by non-compliance with the diet. METHODS: Between February 2019 and December 2021, 117 patients diagnosed with celiac disease were included in this prospective randomized and controlled study. In addition to routine tests of celiac patients, thiol and disulfide measurements were made from the blood both at the beginning of the study and at the end of the first year. RESULTS: While 52 of the patients (44.4%) were in remission, 65 patients (55.6%) were not. There was an evident increase in native thiol levels of the patients who were initially not in remission but went into at the end of the first year (347.4±46.7 µmol/L vs. 365.3±44.0 µmol/L; p=0.001). Mean plasma disulfide levels of patients with celiac going into remission became reduced in the first year from the level of 14.5±5.1 µmol/L down to 8.9±4.2 µmol/L (p<0.001). In celiac patients who entered remission, disulfide and anti-tissue transglutaminase immunoglobulin A levels decreased in a correlation (r=0.526; p<0.001). CONCLUSION: Not being in remission in celiac disease leads to increased oxidative stress, and thiol-disulfide homeostasis is an indirect indicator of this. Additionally, providing remission in celiac patients reduces oxidative stress.
Assuntos
Doença Celíaca , Dieta Livre de Glúten , Dissulfetos , Estresse Oxidativo , Cooperação do Paciente , Compostos de Sulfidrila , Humanos , Doença Celíaca/dietoterapia , Doença Celíaca/sangue , Estresse Oxidativo/fisiologia , Feminino , Masculino , Dissulfetos/sangue , Estudos Prospectivos , Compostos de Sulfidrila/sangue , Adulto , Indução de Remissão , Adulto Jovem , Adolescente , Pessoa de Meia-Idade , Imunoglobulina A/sangue , Transglutaminases/sangueRESUMO
Current screening guidelines in North America for celiac disease recommend additional IgG based testing for younger children. Our multicenter retrospective study showed that the anti-tissue transglutaminase IgA antibody test should be the recommended initial test in all children, including those ≤24 months of age.
Assuntos
Doença Celíaca/sangue , Proteínas de Ligação ao GTP/sangue , Transglutaminases/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Doença Celíaca/diagnóstico , Feminino , Humanos , Deficiência de IgA/sangue , Imunoglobulina A/sangue , Lactente , Masculino , Proteína 2 Glutamina gama-Glutamiltransferase , Estudos RetrospectivosRESUMO
OBJECTIVE: To study the optimal cut-off value for anti-tissue transglutaminase type 2 IgA antibodies (TG2A) in serum to select for diagnostic small bowel biopsies for celiac disease in children with type 1 diabetes mellitus. STUDY DESIGN: Children with type 1 diabetes mellitus with elevated TG2A titers and duodenal biopsies performed during the course of their diabetes treatment were included. Anti-endomysial antibodies were recorded if present. The optimal TG2A cut-off value, expressed as the ratio between obtained value and upper limit of normal (ULN), was determined using receiver operating characteristic curve analysis and compared with the cut-off value used in the European Society for Pediatric Gastroenterology, Hepatology and Nutrition guidelines in terms of sensitivity, specificity, positive and negative predictive value. RESULTS: We included 63 children. The optimal cut-off value for performing biopsies is demonstrated to be 11 times the ULN. Raising the cut-off value from 3 times the ULN to 11 times the ULN changed sensitivity from 96% to 87% and increased specificity from 36% to 73%, increased the positive predictive value from 88% to 94% and lowered negative predictive value from 67% to 53%. The percentage of normal histology was decreased from 12% to 6%. CONCLUSIONS: Increasing the TG2A cut-off value for performing duodenal biopsies in children with type 1 diabetes mellitus and suspected celiac disease leads to a substantial reduction of unnecessary biopsies. We advocate to adapt the European Society for Pediatric Gastroenterology, Hepatology and Nutrition 2012 guidelines for this group of children, including monitoring patients with TG2A levels of less than 11 times the ULN over time.
Assuntos
Doença Celíaca/diagnóstico , Diabetes Mellitus Tipo 1/complicações , Proteínas de Ligação ao GTP/sangue , Transglutaminases/sangue , Adolescente , Anticorpos , Biópsia/efeitos adversos , Doença Celíaca/sangue , Doença Celíaca/etiologia , Criança , Pré-Escolar , Feminino , Humanos , Intestino Delgado/imunologia , Masculino , Proteína 2 Glutamina gama-Glutamiltransferase , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Procedimentos DesnecessáriosRESUMO
BACKGROUND: Celiac disease is an enteropathy caused by dietary gluten. The combination of serologic, genetic and histologic data has led to description of other categories of this disease. OBJECTIVE: There are a number of patients with iron deficiency anemia (IDA) that do not respond to iron treatment and may be repeated for many times, Therefore, we aimed to investigate celiac disease in this group. METHODS: In this cross sectional transverse prospective study from August 2011 to February 2013, in a Pediatric care clinic affiliated to Shiraz University of Medical Sciences, 184 children including 92 IDA patients who responded to treatment using iron supplement, 45 non-responding iron deficient patients, and 47 healthy individuals, with the maximum age of 18 years, with written consent from their parents, participated in serologic screening (with Anti-TTG antibody and anti-Endomysial antibody) for celiac disease. Patients with at least one positive serology test underwent multiple mucosal biopsy from bulb and duodenum. RESULTS: Among 184 participants, 19 (10.3%) subjects had positive serologic test for celiac disease, including 13 (28.9%) patients in the group with refractory IDA, 5 (5.4%) patients in the group with treated IDA, and 1 patient in the healthy group. The frequency of positive serologic test in the group with IDA resistant to treatment was prominently higher than the other two groups (P<0.001). Among the patients with positive serologic celiac test who underwent endoscopy and biopsy, no histologic evidence of celiac disease was seen. They were diagnosed as potential celiac disease. CONCLUSION: Frequency of potential celiac disease in patients with refractory IDA was higher than control the subjects. Therefore, we recommend serologic screening for early detection and minimizing the complications of celiac disease and repeated iron therapy for this group.
Assuntos
Anemia Ferropriva/sangue , Doença Celíaca/sangue , Doença Celíaca/diagnóstico , Adolescente , Anemia Ferropriva/complicações , Anemia Ferropriva/terapia , Autoanticorpos/sangue , Biomarcadores/sangue , Biópsia , Doença Celíaca/imunologia , Doença Celíaca/patologia , Criança , Pré-Escolar , Estudos Transversais , Duodeno/patologia , Feminino , Humanos , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Testes Sorológicos/métodos , Transglutaminases/sangueRESUMO
ABSTRACT BACKGROUND: Celiac disease is an enteropathy caused by dietary gluten. The combination of serologic, genetic and histologic data has led to description of other categories of this disease. OBJECTIVE: There are a number of patients with iron deficiency anemia (IDA) that do not respond to iron treatment and may be repeated for many times, Therefore, we aimed to investigate celiac disease in this group. METHODS: In this cross sectional transverse prospective study from August 2011 to February 2013, in a Pediatric care clinic affiliated to Shiraz University of Medical Sciences, 184 children including 92 IDA patients who responded to treatment using iron supplement, 45 non-responding iron deficient patients, and 47 healthy individuals, with the maximum age of 18 years, with written consent from their parents, participated in serologic screening (with Anti-TTG antibody and anti-Endomysial antibody) for celiac disease. Patients with at least one positive serology test underwent multiple mucosal biopsy from bulb and duodenum. RESULTS: Among 184 participants, 19 (10.3%) subjects had positive serologic test for celiac disease, including 13 (28.9%) patients in the group with refractory IDA, 5 (5.4%) patients in the group with treated IDA, and 1 patient in the healthy group. The frequency of positive serologic test in the group with IDA resistant to treatment was prominently higher than the other two groups (P<0.001). Among the patients with positive serologic celiac test who underwent endoscopy and biopsy, no histologic evidence of celiac disease was seen. They were diagnosed as potential celiac disease. CONCLUSION: Frequency of potential celiac disease in patients with refractory IDA was higher than control the subjects. Therefore, we recommend serologic screening for early detection and minimizing the complications of celiac disease and repeated iron therapy for this group.
RESUMO CONTEXTO: A doença celíaca é uma enteropatia causada pelo glúten na dieta. A combinação de dados sorológicos, genéticos e histológicos proporcionou a descrição de outras categorias desta doença. OBJETIVO: Há pacientes com anemia por deficiência de ferro que não respondem ao tratamento com ferro mesmo que repetido por muitas vezes. O objetivo deste trabalho foi investigar a presença de doença celíaca nestes indivíduos. MÉTODOS: Realizado estudo prospectivo com cruzamento secional transversal, de agosto de 2011 a fevereiro de 2013, em uma clínica de cuidados pediátricos afiliados a Shiraz University Medical Sciences, com 184 crianças incluindo 92 pacientes com anemia por deficiência de ferro que responderam ao tratamento com ferro suplementar, 45 não respondedores e 47 indivíduos sadios, com idade máxima de 18 anos, todos com consentimento informado dos pais. Todos participaram da triagem sorológica (com anticorpos anti-TTG e anticorpo antiendomísio) para doença celíaca. Pacientes com pelo menos um teste de sorologia positiva foram submetidos a biópsia da mucosa múltipla do bulbo e duodeno. RESULTADOS: Entre os 184 participantes, 19 (10,3%) tinham teste sorológico positivo para doença celíaca, incluindo 13 (28,9%) pacientes no grupo com a anemia por deficiência de ferro refratária, 5 (5,4%) pacientes no grupo com anemia por deficiência de ferro tratados e respondedores e 1 paciente do grupo saudável. A frequência de teste sorológico positivo no grupo com anemia por deficiência de ferro resistente ao tratamento foi destacadamente maior do que os outros dois grupos (P<0,001). Entre os pacientes com teste sorológico positivo para doença celíaca submetidos a endoscopia e biópsia, não foi vista nenhuma evidência histológica de doença celíaca. Foram diagnosticados como potencial doença celíaca. CONCLUSÃO: Potencial frequência de doença celíaca em pacientes com anemia por deficiência de ferro refratária foi maior do que nos controles. Portanto, recomendamos testes sorológicos de triagem para a detecção precoce, minimizando as complicações da terapia de ferro repetidas para este grupo.
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Doença Celíaca/diagnóstico , Doença Celíaca/sangue , Anemia Ferropriva/sangue , Autoanticorpos/sangue , Biópsia , Testes Sorológicos/métodos , Biomarcadores/sangue , Doença Celíaca/imunologia , Doença Celíaca/patologia , Transglutaminases/sangue , Estudos Transversais , Estudos Prospectivos , Anemia Ferropriva/complicações , Anemia Ferropriva/terapia , Duodeno/patologia , Mucosa Intestinal/patologia , Pessoa de Meia-IdadeRESUMO
ABSTRACT BACKGROUND Celiac disease is a glutten induced enteropathy. Some authors recommended screening celiac in children with constipation. There are studies to evaluate celiac disease in children with constipation. But most of them included children regardless to treatment failure. OBJECTIVE The aim of this study was to evaluate frequency of elevated anti TTG in children with constipation after failure to improve during 6 week of appropriate treatment of constipation. METHODS In this cross sectional study, 550 children with prolonged constipation were included. Place of study was Pediatric Gastroenterology clinic of Abuzar children's hospital. Prolonged constipation was defined as a constipation which failed to resolved after 6 weeks of appropriate treatment. Constipation was defined according to ROME III criteria. After parental agreement, 5 mL of blood was obtained. Serum anti TTG level was measure using ELISA method by Orientec kit. Anti TTG>10 was considered positive if IgA was normal. SPSS version 16.0 (Chicago, IL, USA) was used for data analysis. Chi square, t-test, and Mann Whitney test used for data analysis. RESULTS In this study 550 children (m=277, f=273) were included. Mean age of the cases was 6.8±2.9 year. Anti TTG antibody level was 5.8±2.8 unit/mL. Of these case, 42 (7.6%) had positive anti-TTG antibody. Celiac disease was confirmed in 40 cases after histopathology examination. CONCLUSION Anti-TTG was positive in 7.6% children with chronic constipation who failed to respond after 6 week of treatment. Another multicenter study with longer follow up period is recommended.
RESUMO CONTEXTO A doença celíaca é uma enteropatia glúten-induzida. Alguns autores recomendam a triagem de doença celíaca em crianças com constipação. Há estudos para avaliar a doença celíaca em crianças com constipação, mas a maioria inclue crianças independentemente do insucesso do tratamento. OBJETIVO O objetivo deste estudo foi avaliar a frequência de anti-TTG elevado em crianças com constipação após 6 semanas de tratamento adequado e sem sucesso. MÉTODOS Através de cruzamento seccional, 550 crianças com constipação prolongada foram incluídas. O local de estudo foi o ambulatório de Gastroenterologia Pediátrica do Hospital Infantil de Abuzar. Constipação prolongada foi definida como uma constipação, cuja resolução falhou após 6 semanas de tratamento adequado. Constipação foi definida de acordo com critérios de Roma III. Após o consentimento informado dos pais, obteve-se 5 mL de sangue. O nível de anti TTG no soro foi medido usando-se o método ELISA pelo Orientec kit. O anti-TTG >10 foi considerado positivo se IgA estivesse normal. Os dados foram analisados através de testes do Chi-quadrado, t-teste e teste de Mann Whitney utilizando-se o SPSS versão 16.0 (Chicago, IL, EUA). RESULTADOS Um total de 550 crianças (m=277, f=273) foi incluído neste estudo. A média de idade dos pacientes foi 6,8±2,9 anos. O nível de anticorpo anti-TTG foi de 5,8±2,8 unidades/mL. Do total, 42 (7,6%) indivíduos tinham anticorpos anti-TTG positivo. A doença celíaca foi confirmada em 40 casos após exame de histopatologia. CONCLUSÃO O Anti-TTG foi positivo em 7,6% crianças com constipação crônica que não conseguiram responder após 6 semanas de tratamento. Outro estudo multicêntrico, com acompanhamento mais longo período é recomendado.
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Autoanticorpos/sangue , Doença Celíaca/diagnóstico , Transglutaminases/sangue , Constipação Intestinal/diagnóstico , Proteínas de Ligação ao GTP/sangue , Ensaio de Imunoadsorção Enzimática , Doença Celíaca/complicações , Transglutaminases/imunologia , Estudos Transversais , Falha de Tratamento , Constipação Intestinal/etiologia , Constipação Intestinal/terapia , Proteínas de Ligação ao GTP/imunologiaRESUMO
BACKGROUND: Cigarette smoking plays a major role in cardiovascular diseases. The acute effects of cigarette smoking produce central nervous system-mediated activation of the sympathetic nervous system. The overactive sympathetic nervous system stimulates the secretion of serotonin (5-HT) and catecholamine into blood at supraphysiological levels. The correlation between these pathological conditions induced by smoking and the increased risk of thrombosis has not been thoroughly investigated. The goal of our study was to explore cigarette smoking-associated changes in platelet biology mediated by elevated 5-HT and catecholamine levels in blood plasma. METHODS AND RESULTS: Using blood samples collected from healthy nonsmokers and smokers (15 minutes after smoking), we determined that cigarette smoking increased the plasma 5-HT/catecholamine concentration by several fold and the percent aggregation of platelets 2-fold. Liquid chromatography-tandem mass spectrometry analysis of proteins eluted from platelet plasma membranes of smokers and nonsmokers demonstrated that GTPase-activating proteins and proteins participating in the actin cytoskeletal network were differentially and significantly elevated in smokers' platelet membranes compared with those of nonsmokers. Interestingly, Matrix-assisted laser desorption/ionization-mass spectrometry analyses of the glycans eluted from platelet plasma membranes of the smokers demonstrated that the level and structures of glycans are different from the nonsmokers' platelet surface glycans. Pharmacological blockade of 5-HT or catecholamine receptors counteracted the 5-HT/catecholamine-mediated aggregation and altered the level and composition of glycan on platelet surfaces. CONCLUSIONS: Based on our findings, we propose that smoking-associated 5-HT/catecholamine signaling accelerates the trafficking dynamics of platelets, and this remodels the surface proteins and glycans and predisposes platelets to hyperactive levels. Smokers' platelets also had correspondingly higher resting concentrations of intracellular calcium and transglutaminase activity. These findings suggest a link among smoking, platelet 5-HT, catecholamine signaling, and their downstream effectors-including phospholipase C and inositol-1,4,5-triphosphate pathways-resulting in an increased tonic level of platelet activation in smokers.
Assuntos
Plaquetas/metabolismo , Membrana Celular/metabolismo , Epinefrina/sangue , Ativação Plaquetária , Serotonina/sangue , Transdução de Sinais , Fumar/sangue , Antagonistas Adrenérgicos beta/farmacologia , Adulto , Plaquetas/efeitos dos fármacos , Cálcio/sangue , Estudos de Casos e Controles , Membrana Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Humanos , Masculino , Ativação Plaquetária/efeitos dos fármacos , Agregação Plaquetária , Inibidores da Agregação Plaquetária/farmacologia , Polissacarídeos/sangue , Transporte Proteico , Antagonistas do Receptor 5-HT2 de Serotonina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Fumar/efeitos adversos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectrometria de Massas em Tandem , Fatores de Tempo , Transglutaminases/sangue , Regulação para CimaRESUMO
BACKGROUND: Celiac disease is a glutten induced enteropathy. Some authors recommended screening celiac in children with constipation. There are studies to evaluate celiac disease in children with constipation. But most of them included children regardless to treatment failure. OBJECTIVE: The aim of this study was to evaluate frequency of elevated anti TTG in children with constipation after failure to improve during 6 week of appropriate treatment of constipation. METHODS: In this cross sectional study, 550 children with prolonged constipation were included. Place of study was Pediatric Gastroenterology clinic of Abuzar children's hospital. Prolonged constipation was defined as a constipation which failed to resolved after 6 weeks of appropriate treatment. Constipation was defined according to ROME III criteria. After parental agreement, 5 mL of blood was obtained. Serum anti TTG level was measure using ELISA method by Orientec kit. Anti TTG>10 was considered positive if IgA was normal. SPSS version 16.0 (Chicago, IL, USA) was used for data analysis. Chi square, t-test, and Mann Whitney test used for data analysis. RESULTS: In this study 550 children (m=277, f=273) were included. Mean age of the cases was 6.8±2.9 year. Anti TTG antibody level was 5.8±2.8 unit/mL. Of these case, 42 (7.6%) had positive anti-TTG antibody. Celiac disease was confirmed in 40 cases after histopathology examination. CONCLUSION: Anti-TTG was positive in 7.6% children with chronic constipation who failed to respond after 6 week of treatment. Another multicenter study with longer follow up period is recommended.
Assuntos
Autoanticorpos/sangue , Doença Celíaca/diagnóstico , Constipação Intestinal/diagnóstico , Proteínas de Ligação ao GTP/sangue , Transglutaminases/sangue , Adolescente , Doença Celíaca/complicações , Criança , Pré-Escolar , Constipação Intestinal/etiologia , Constipação Intestinal/terapia , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Proteínas de Ligação ao GTP/imunologia , Humanos , Masculino , Proteína 2 Glutamina gama-Glutamiltransferase , Transglutaminases/imunologia , Falha de TratamentoRESUMO
The prevalence of Celiac disease in the general population is approximately 1% and remains undiagnosed in a significant proportion of individuals. Its clinical presentation includes the classical malabsorption syndrome, unspecific and extra-intestinal manifestations, and silent celiac disease. The serologic diagnosis has an elevated sensitivity and specificity and, at least in adult population, it must be confirmed by biopsy in every case. Diagnosis in subjects already on gluten free diet includes HLA typing and gluten challenge with posterior serologic and histologic evaluation. The core of the treatment is the gluten free diet, which must be supervised by an expert nutritionist. Monitoring must be performed with serology beginning at 3-6 months, and with histology two years after the diagnosis, unless the clinical response is poor. Poor disease control is associated with complications such as lymphoma and small bowel adenocarcinoma. In the future, it is likely that new pharmacologic therapies will be available for the management of celiac disease.
Assuntos
Autoanticorpos/sangue , Doença Celíaca , Imunoglobulina A/sangue , Transglutaminases/sangue , Biomarcadores/sangue , Biópsia , Doença Celíaca/sangue , Doença Celíaca/diagnóstico , Doença Celíaca/etiologia , Doença Celíaca/terapia , Humanos , Imunoglobulina A/imunologia , Sensibilidade e Especificidade , Transglutaminases/imunologiaRESUMO
The prevalence of Celiac disease in the general population is approximately 1% and remains undiagnosed in a significant proportion of individuals. Its clinical presentation includes the classical malabsorption syndrome, unspecific and extra-intestinal manifestations, and silent celiac disease. The serologic diagnosis has an elevated sensitivity and specificity and, at least in adult population, it must be confirmed by biopsy in every case. Diagnosis in subjects already on gluten free diet includes HLA typing and gluten challenge with posterior serologic and histologic evaluation. The core of the treatment is the gluten free diet, which must be supervised by an expert nutritionist. Monitoring must be performed with serology beginning at 3-6 months, and with histology two years after the diagnosis, unless the clinical response is poor. Poor disease control is associated with complications such as lymphoma and small bowel adenocarcinoma. In the future, it is likely that new pharmacologic therapies will be available for the management of celiac disease.