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1.
Digestion ; 105(2): 99-106, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37963446

RESUMO

INTRODUCTION: The pathophysiology of irritable bowel syndrome (IBS) remains unknown. This study aimed to evaluate colonic motility and serotonin system response to restraint stress (RS) among adolescent rats who underwent neonatal maternal separation (NMS) to clarify the features of pathogenesis in adolescents with IBS. METHODS: Male rats were exposed to NMS as chronic stress, and a normally handled (NH) group was used as control. Four groups were created by adding RS as acute stress treatment to the NMS and NH groups. To realize the RS treatment, the subjects were restrained for 1 h at the age of 5 weeks, and hourly fecal pellet discharge was determined. After euthanization and proximal colon intestinal tissue collection, 5-hydroxytryptamine (5-HT) and 5-hydroxytryptamine receptor 3 (5-HT3R) concentrations, enterochromaffin (EC) cell density, and the expression of mRNA-encoding slc6a4 were examined. RESULTS: The amount of fecal pellet discharge during RS increased significantly in the RS and NMS+RS groups compared with that in the NH and NMS groups, respectively. The 5-HT concentration in the intestinal tissue of rats in the RS and NMS groups increased significantly compared with that of rats in the NH group. EC cell density also increased significantly in the NMS and NMS+RS groups compared with that in the NH and RS groups. However, combined stress did not result in any significant differences in the expression of 5-HT3R and mRNA-encoding slc6a4. CONCLUSIONS: The combination of juvenile and acute stress effectively induced increased 5-HT concentration or EC cell density via the 5-HT pathway in the proximal colon of adolescent rats.


Assuntos
Síndrome do Intestino Irritável , Humanos , Ratos , Animais , Masculino , Adolescente , Lactente , Síndrome do Intestino Irritável/etiologia , Colo , Serotonina/metabolismo , Serotonina/farmacologia , Ratos Sprague-Dawley , Privação Materna , Motilidade Gastrointestinal , RNA Mensageiro/metabolismo
2.
Pediatr Res ; 93(4): 1036-1040, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35906313

RESUMO

BACKGROUND: Iron deficiency anemia in children affects psychomotor development. We compared the accuracy and trend of a non-invasive transcutaneous spectrophotometric estimation of arterial hemoglobin (Hb) concentration (SpHb) by rainbow pulse CO-oximetry technology to the invasive blood Hb concentration measured by an automated clinical analyzer (Hb-Lab). METHODS: We measured the SpHb and Hb-Lab in 109 patients aged 1-5 years. Regression analysis was used to evaluate differences between the two methods. The bias, accuracy, precision, and limits of agreement of SpHb compared with Hb-Lab were calculated using the Bland-Altman method. RESULTS: Of the 109 enrolled subjects, 102 pairs of the SpHb and Hb-Lab datasets were collected. The average value of measured Hb was 12.9 ± 1.03 (standard deviation [SD]) g/dL for Hb-Lab. A significant correlation was observed between SpHb and Hb-Lab measurements (SpHb = 7.002 + 0.4722 Hb-Lab, correlation coefficient r = 0.548, 95% confidence interval = 0.329-0.615). Bland-Altman analysis showed good visual agreement, with a mean bias between SpHb and Hb-Lab of 0.188 ± 0.919 g/dL (mean ± SD). CONCLUSIONS: We concluded that non-invasive Hb measurement is useful for Hb estimation in children and provides new insights as a screening tool for anemia. IMPACT: Our results indicated a good correlation between non-invasive transcutaneous spectrophotometric estimation of arterial hemoglobin (Hb) concentration using a finger probe sensor by rainbow pulse CO-oximetry technology and invasive blood Hb concentration. Although previous studies have indicated that in patients with a worse condition, the bias between the two methods was large, this study, which was conducted on children with stable disease, showed a relatively small bias. Further studies using this non-invasive device might help to understand the current status of anemia in Japan and promote iron intake and nutritional management in children.


Assuntos
Anemia Ferropriva , Anemia , Humanos , Pré-Escolar , Hemoglobinometria/métodos , Oximetria/métodos , Hemoglobinas/análise , Anemia Ferropriva/diagnóstico
3.
Helicobacter ; 28(3): e12976, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36951390

RESUMO

Many studies in adults have suggested an association between Helicobacter pylori (H. pylori) infection and chronic immune thrombocytopenia (ITP). In adults with ITP and H. pylori infection, eradicating H. pylori is recommended as the first-line therapy. However, the association between ITP and H. pylori in children remains controversial. Diagnosing thrombocytopenia in pregnant women is challenging but crucial because maternal ITP causes neonatal ITP through transplacental transfer of immunoglobulin G, also known as passive ITP. Herein, we report a case of neonatal passive ITP due to maternal H. pylori-associated ITP. A boy was born at term with neonatal thrombocytopenia to a mother tentatively diagnosed with gestational thrombocytopenia. However, further examination suggested that maternal thrombocytopenia was associated with H. pylori, and neonatal thrombocytopenia was diagnosed as ITP due to maternal ITP. The newborn received intravenous immunoglobulin treatment, and the thrombocytopenia did not recur. The mother was examined using esophagogastroduodenoscopy, and her rapid urease test using gastric mucosa tissue samples was positive. Subsequently, she was diagnosed with H. pylori infection and received H. pylori eradication therapy, after which her platelet count remained normal. To our knowledge, this is the first reported case of neonatal passive ITP secondary to maternal H. pylori-associated ITP. This case suggests that maternal H. pylori infection can lead to the production of platelet autoantibodies, which can destroy antibody-sensitized platelets in the mother and neonate. To summarize, H. pylori infection can also cause ITP in children. Therefore, pregnant women diagnosed with H. pylori-associated ITP should receive H. pylori eradication therapy to prevent their neonates from developing passive ITP.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Púrpura Trombocitopênica Idiopática , Trombocitopenia Neonatal Aloimune , Humanos , Gravidez , Adulto , Masculino , Criança , Recém-Nascido , Feminino , Púrpura Trombocitopênica Idiopática/complicações , Púrpura Trombocitopênica Idiopática/diagnóstico , Infecções por Helicobacter/complicações , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Plaquetas
4.
Medicina (Kaunas) ; 59(4)2023 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-37109684

RESUMO

The frequency of split cord malformation (SCM) is approximately 1 in 5000 births; however, patients are rarely diagnosed with SCM in the neonatal period. Moreover, there have been no reports of SCM with hypoplasia of the lower extremities at birth. A 3-day-old girl was transferred to our hospital for a thorough examination of hypoplasia of the left lower extremity and lumbosacral abnormalities detected after birth. The spinal magnetic resonance imaging (MRI) revealed a split spinal cord in a single dural tube. Based on the MRI findings, the patient was diagnosed with SCM type II. Following discussions with the parents, pediatricians, neurosurgeons, psychologists, and social workers, we decided to perform untethering to prevent further neurological impairment after achieving a sufficient body weight. The patient was discharged on day 25 of life. Early diagnosis and intervention may improve the neurological prognosis in terms of motor function, bladder and bowel function, and superficial sensation; thus, clinicians should report infrequent findings that may lead to SCM diagnosis. SCM should be differentiated in patients with left-right differences in the appearance of the lower extremity, particularly in those with lumbosacral abnormalities.


Assuntos
Defeitos do Tubo Neural , Medula Espinal , Recém-Nascido , Feminino , Humanos , Medula Espinal/anormalidades , Defeitos do Tubo Neural/complicações , Defeitos do Tubo Neural/diagnóstico , Coluna Vertebral , Imageamento por Ressonância Magnética , Extremidade Inferior
5.
Digestion ; 103(2): 150-158, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34718239

RESUMO

INTRODUCTION: Long-term disease duration of ulcerative colitis (UC) is known to increase the risk of developing colorectal cancer in adults; however, this association has not been genetically analyzed in children with UC. Herein, we examined the expression of cancer-related genes in the colonic mucosa of pediatric UC patients and their risk of developing colorectal cancer. METHODS: Microarray analysis of cancer-related gene expression was conducted on rectal mucosa biopsy specimens randomly selected from pediatric cases, including 4 active-phase UC cases, 3 remission-phase UC cases, and 3 irritable bowel syndrome control cases. The subject pool was then expanded to 10 active-phase cases, 10 remission-phase cases, and 10 controls, which were analyzed by real-time polymerase chain reaction (PCR) and immunohistochemical staining. RESULTS: The microarray results indicated significantly higher expression levels of cancer-related genes PIM2 and SPI1 in the active group than in the remission and control groups (p < 0.05). Real-time PCR confirmed that PIM2 and SPI1 expression levels were significantly higher, whereas TP53 and APC expression levels were significantly lower, in the active-phase group than in the remission and control groups (p < 0.05). Immunohistochemical staining for PIM2, SPI1, TP53, and APC proteins supported the real-time PCR results. CONCLUSIONS: Expression levels of previously unreported cancer-related genes in adult UC patients were significantly higher in pediatric UC patients than in controls. Inflammation of the gastrointestinal mucosa increased the expression levels of cancer-related genes even in childhood-onset UC cases, suggesting that chronic inflammation from childhood may increase the risk of colorectal cancer development.


Assuntos
Colite Ulcerativa , Síndrome do Intestino Irritável , Adulto , Criança , Colite Ulcerativa/patologia , Humanos , Mucosa Intestinal/patologia , Síndrome do Intestino Irritável/patologia
6.
Helicobacter ; 26(1): e12764, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33073418

RESUMO

BACKGROUND: Helicobacter pylori (H. pylori) infection causes chronic gastritis, duodenal and to a lesser extent, gastric ulcers, and gastric cancer. Most H. pylori infections are acquired in childhood, and effective treatment of childhood infection is very important. Esophagogastroduodenoscopy (EGD) is useful for endoscopic diagnosis, mucosal tissue biopsy, and culture examination for H. pylori in children and adults. In this paper, we report results of susceptibility tests and eradication rates in H. pylori-positive children who underwent EGD over a 12-year period. MATERIALS AND METHODS: The subjects were H. pylori-positive pediatric patients who had gastrointestinal symptoms and underwent EGD in the Department of Pediatrics, Juntendo University Hospital (January 2007-December 2018). Patients underwent serum IgG antibody tests, fecal antigen tests, or urea breath tests, and subsequently, culture tests by gastric mucosal biopsy during EGD. H. pylori positivity was defined as a positive result on both tests. Patients received triple therapy for 14 days using our regimen, and eradication was assessed at 2, 6, and 12 months after therapy. RESULTS: Forty-five patients were H. pylori-positive, and the overall clarithromycin (CAM) resistance rate was 71.1 % (32/45). The CAM resistance rate for the 2013-2018 period was significantly higher than the 2007-2012 period (52.6% vs. 84.6%, P < 0.05). According to the results of the antimicrobial susceptibility test, we prescribed effective antibiotics, and this resulted in a primary eradication rate of 97.7%. CONCLUSIONS: We suggest that antimicrobial susceptibility testing can significantly improve rates of primary eradication of H. pylori infection.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Infecções por Helicobacter , Testes de Sensibilidade Microbiana , Antibacterianos/uso terapêutico , Testes Respiratórios , Criança , Claritromicina/uso terapêutico , Quimioterapia Combinada , Mucosa Gástrica , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Humanos
7.
Digestion ; 102(5): 783-788, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33477162

RESUMO

INTRODUCTION: Anal fistulae have a significant impact on the quality of life of patients with Crohn's disease (CD). In this cross-sectional study, we aimed to determine whether biological agents were effective in treating anal fistulae in patients with CD. METHODS: Fifty-three patients diagnosed with CD were retrospectively enrolled. Their data regarding symptoms, treatments, and disease progression from January 2007 to December 2016 were reviewed from the medical records. Fifteen (28%) patients with CD were complicated by anal fistulae. RESULTS: The male-to-female ratio was 13:2, and the mean age at onset was 11 years and 6 months. Among the 15 patients, 14 (93%) had anal fistulae as an initial symptom. Almost all patients were treated by providing elemental diet, 5-aminosalicylic acid, and steroids as induction therapy. Biological agents were used in 8 patients (53.3%), and fistula closure was confirmed in all of them. Among the 7 patients not treated with biological agents, 1 (14.3%) had a recurrent anal fistula, while another had incomplete fistula closure. Regarding surgical management, 2 patients were treated using the seton method, and no patients required a colostomy. CONCLUSION: Treatment with biological agents is highly effective concerning the closure of anal fistulae in patients with CD, and reducing pain may improve their quality of life.


Assuntos
Doença de Crohn , Fístula Retal , Fatores Biológicos , Criança , Doença de Crohn/complicações , Doença de Crohn/tratamento farmacológico , Estudos Transversais , Feminino , Humanos , Masculino , Qualidade de Vida , Fístula Retal/tratamento farmacológico , Fístula Retal/etiologia , Fístula Retal/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
8.
Curr Top Microbiol Immunol ; 421: 1-19, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31123883

RESUMO

It has been over 30 years since a link was established between H. pylori infection of the gastric mucosa and the development of chronic gastric diseases. Research in rodent models supported by data from human tissue demonstrated that the host immune response to H. pylori is limited by host regulatory T cells. Immunization has been shown to induce a potent Th1- and Th17-mediated immune response capable of eradicating or at least significantly reducing the bacterial load of H. pylori in the stomach in small animal models. These results have not translated well to humans. Clinical trials employing many of the strategies used in rodents for oral immunization including the use of a mucosal adjuvant such as Escherichia coli LT or delivery by attenuated enteric bacteria have failed to limit H. pylori infection and have highlighted the potential toxicity of exotoxin-based mucosal adjuvants. A recent study, however, utilizing a recombinant fusion protein of H. pylori urease and the subunit B of E. coli LT, was performed on over 4000 children. Efficacy of over 70% was demonstrated against naturally acquired infection compared to control volunteers one year post-immunization. Efficacy was reduced, but still above 50% at three years. This study provided new insight into the strategies for developing an improved vaccine for widespread use in countries with high infection rates and where gastric cancer (GC) remains one of the most common causes of death due to cancer.


Assuntos
Vacinas Bacterianas/imunologia , Mucosa Gástrica/microbiologia , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/patologia , Helicobacter pylori/imunologia , Helicobacter pylori/patogenicidade , Animais , Anticorpos Antibacterianos/imunologia , Vacinas Bacterianas/química , Escherichia coli/imunologia , Mucosa Gástrica/imunologia , Mucosa Gástrica/patologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/prevenção & controle , Humanos , Inflamação/imunologia , Inflamação/microbiologia , Inflamação/patologia
10.
Dig Endosc ; 31(4): 372-377, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30549318

RESUMO

Colonoscopy has been shown to reduce the risk of colon cancer by enabling the removal of precancerous lesions. Although cold snare and hot snare polypectomy have similar retrieval rates and complete resection rates, rates of delayed bleeding tend to be lower with cold snare polypectomy than with hot snare polypectomy, especially for patients taking antithrombotic agents. However, among cold snares there may be differences in terms of the completeness of polyp excision, as complete removal appears more likely with thin-wire dedicated cold snares compared to the traditional, thick-wire cold snares. Cold snare polypectomy may be especially well suited for use in patients taking antithrombotic agents, due to its minimal risk of delayed bleeding. Histological analyses suggest that cold snare polypectomy causes less damage to blood vessels in the submucosal layers, which results in a reduced incidence of hemorrhage compared to hot snare polypectomy. However, cold snare removal of small polyps may result in fragmentation of small specimens during collection and concerns as to whether the resection is complete. An endoscopy biomarker of effective cold snare polypectomy technique is needed to ensure complete removal of non-pedunculated colorectal polyps ≤10 mm. Future uses of cold snare polypectomy may include piecemeal removal of sessile serrated adenoma/polyp lesions >10 mm. Currently, cold snare polypectomy should be considered a primary method for colorectal polyps of less than 10 mm, especially those in the 4- to 10-mm range.


Assuntos
Pólipos Adenomatosos/cirurgia , Pólipos do Colo/cirurgia , Colonoscopia , Neoplasias Colorretais/cirurgia , Lesões Pré-Cancerosas/cirurgia , Previsões , Humanos , Complicações Pós-Operatórias , Instrumentos Cirúrgicos
11.
Pediatr Int ; 60(5): 446-454, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29415337

RESUMO

BACKGROUND: Chronic Helicobacter pylori infection in children induces lymphoid hyperplasia called nodular gastritis (NG) at the antral gastric mucosa. The aim of this study was to evaluate genes in gastric biopsy on microarray analysis, to identify molecules associated with NG on comparison with NG-negative pediatric corpus tissue and with H. pylori-infected adult tissue with atrophic gastritis (AG). METHODS: Eight pediatric and six adult H. pylori-infected patients, as well as six pediatric and six adult uninfected patients were evaluated. All infected adults had AG. NG was observed in the antrum of all eight pediatric patients and in the corpus of three patients. Adult and uninfected patients were free of NG; that is, only pediatric H. pylori-infected patients had NG. Total RNA was purified from gastric biopsy, and microarray analysis was performed to compare gene expression between groups. The three infected children with NG in both the antrum and corpus were excluded from analysis of corpus samples. RESULTS: The number of genes significantly up- or downregulated (fold change >3, P < 0.01) compared with uninfected controls varied widely: 72 in pediatric antrum, 45 in pediatric corpus, 103 in adult antrum and 71 in adult corpus. Nineteen genes had significantly altered expression in the antrum of NG tissue compared with NG-negative pediatric corpus tissue and adult AG tissue. The CD20 B-cell specific differentiation antigen had the most pronounced increase. Previously described regulators of NG development were not predominantly upregulated in the NG mucosa. CONCLUSIONS: CD20 overexpression may play an important role in lymphoid follicle enlargement and NG.


Assuntos
Gastrite/genética , Infecções por Helicobacter/complicações , Estômago/patologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Gastrite/complicações , Predisposição Genética para Doença , Helicobacter pylori , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos/métodos
12.
Pediatr Int ; 60(8): 719-726, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29804317

RESUMO

BACKGROUND: Shwachman-Diamond syndrome (SDS) is a rare multisystem disorder associated with exocrine pancreatic insufficiency. The present study reports the results of a nationwide survey and a systematic review on SDS to develop consensus guidelines for intractable diarrhea including SDS. METHODS: Questionnaires were sent to 616 departments of pediatrics or of pediatric surgery in Japan in a nationwide survey. A second questionnaire was sent to doctors who had treated SDS patients and included questions on clinical information. Additionally, a systematic review was performed using digital literature databases to assess the influence of medical (i.e. non-surgical) treatment on SDS prognosis. RESULTS: Answers were received from 529 institutions (85.9%), which included information on 24 patients with SDS (median age, 10.4 years; male, n = 15) treated from January 2005 to December 2014. Although 75% of patients received pancreatic enzyme replacement therapy, there was no significant association between treatment and prognosis. Systematic review identified one clinical practice guideline, two case series, eight case reports and 26 reviews. Patient information from those studies was insufficient for meta-analysis. CONCLUSIONS: The rarity of SDS makes it difficult to establish evidence-based treatment for SDS. According to the limited information from patients and published reports, medical treatment for malabsorption due to SDS should be performed to improve fat absorption and stool condition, but it is not clear whether this treatment improves the prognosis of malabsorption.


Assuntos
Doenças da Medula Óssea/terapia , Insuficiência Pancreática Exócrina/terapia , Lipomatose/terapia , Adolescente , Adulto , Doenças da Medula Óssea/diagnóstico , Criança , Pré-Escolar , Insuficiência Pancreática Exócrina/diagnóstico , Feminino , Humanos , Lactente , Japão , Lipomatose/diagnóstico , Masculino , Prognóstico , Síndrome de Shwachman-Diamond , Inquéritos e Questionários , Adulto Jovem
13.
Helicobacter ; 21(2): 114-23, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26140656

RESUMO

BACKGROUND: Although Helicobacter pylori infection among adults is a major risk factor for the development of gastric cancer and initial infection with H. pylori may occur before 5 years of age, the direct effects of H. pylori infection since childhood on gastric mucosa are unknown. The aim of this study was to evaluate gene expression in the H. pylori-infected gastric mucosa of children. METHODS: Gastric mucosal samples were obtained from 24 patients (12 adults and 12 children) who had undergone endoscopic evaluation of chronic abdominal complaints and were examined by the adult and pediatric gastroenterologists at Juntendo University Hospital. Six adult and pediatric patients with and six without H. pylori infection were enrolled. Their gastric mucosal samples obtained from the antrum and corpus were used for microarray, real-time polymerase chain reaction, and immunohistochemical analyses to examine the expression of inflammatory carcinogenic molecules. RESULTS: The expression of inflammatory molecules was upregulated in the H. pylori-infected gastric mucosa from both adults and children. The expression of olfactomedin-4 was only upregulated in adult patients, while that of pim-2, regenerating islet-derived 3 alpha, lipocalin-2, and C-X-C motif chemokine ligand 13 was equally upregulated in the infected gastric mucosa of both adults and children. CONCLUSIONS: Because several carcinogenic molecules are upregulated in H. pylori-infected gastric mucosa even in children, early eradication therapy from childhood may be beneficial to decrease the incidence of gastric cancer. Although increased expression of olfactomedin-4 can be important in suppressing gastric cancer in adults, the increase was not detected in children.


Assuntos
Mucosa Gástrica/patologia , Perfilação da Expressão Gênica , Infecções por Helicobacter/patologia , Adolescente , Adulto , Biópsia , Criança , Pré-Escolar , Endoscopia Gastrointestinal , Feminino , Humanos , Imuno-Histoquímica , Japão , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real
14.
J Pediatr Gastroenterol Nutr ; 63(5): 512-515, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27352080

RESUMO

OBJECTIVES: The prevalence of ulcerative colitis (UC) differs by country, which is likely due to differences in genetic factors among ethnicities. Moreover, the prevalence of pediatric UC with a family history (FH) is 4.1% in Japanese patients; its clinical course begins at an early age and is more severe. Recently, a genome-wide association study identified 3 new susceptibility loci for adult Japanese patients with UC. METHODS: To assess the effects of FH in patients with UC, 60 children were enrolled. Age at diagnosis, clinical features of the initial symptoms, and family structure were assessed in patients with and without an FH. The 3 new loci were examined in patients who provided informed consent. RESULTS: Of the patients with UC, 10 (16.7%) had an FH involving first-degree relatives, including 7 mothers, 1 father, and 2 sisters. There was a trend toward a younger age at onset in the positive FH group. There were, however, no significant differences in the clinical characteristics of the patients regardless of FH. From the genomic analyses, there were significant differences in the polymorphisms of the solute carrier family 26, member 3 (SLC26A3) between those with and without an FH. CONCLUSIONS: Although the etiology of UC remains unknown, there were no observed relation between clinical symptoms and FH. SLC26A3 may, however, contribute to the pathogenesis of UC in Japanese individuals with an FH.


Assuntos
Colite Ulcerativa/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Colite Ulcerativa/genética , Família , Feminino , Loci Gênicos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Japão , Masculino , Polimorfismo de Nucleotídeo Único , Adulto Jovem
15.
Pediatr Int ; 56(6): 873-883, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24750209

RESUMO

BACKGROUND: Although pediatric inflammatory bowel disease (IBD) is characterized by extensive intestinal involvement and rapid early progression, the precise cause and specific factors involved in disease aggravation have not been well established. The aim of this study was to investigate the pathogenesis of pediatric IBD. METHODS: The expression of inflammatory molecules in colon samples taken from active ulcerative colitis (UC) and Crohn's disease (CD) patients was compared with those of controls. Three children each with UC and CD in both the active and remission phase and their controls were enrolled, and the inflammatory gene expression in the mucosa was examined by microarray. Additionally, six children from each group were further enrolled in a real-time reverse transcription polymerase chain reaction and an immunohistochemical study to examine the expression of CXCL9, 10, 11, CXCR3, matrix metalloproteinase (MMP)-1, -3, -7, and -10. RESULTS: The microarray analysis revealed enhanced expression of the CXCL9, 10, and 11 genes in the active phase of CD. The expression of MMP-1, -3, -7, and -10 was significantly enhanced in the active phase of UC. These changes were also confirmed by real-time reverse transcription polymerase chain reaction. Immunohistochemical analysis revealed enhanced expression of CXCL9, 10, and 11 in both the lamina propria and epithelial cells in these patients. CXCR3-positive cells were also confirmed in the lamina propria. The expression of MMP-1, -3, -7, and -10 was also enhanced in the mucosal epithelial cells and the lamina propria in both CD and UC patients. CONCLUSIONS: These findings suggest that CXCR3 axis components and MMP play an important role in the mucosal damage in pediatric IBD.


Assuntos
Quimiocinas CXC/metabolismo , Doenças Inflamatórias Intestinais/metabolismo , Metaloproteinases da Matriz/metabolismo , Receptores CXCR3/metabolismo , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Doenças Inflamatórias Intestinais/etiologia , Doenças Inflamatórias Intestinais/patologia , Masculino
16.
Pediatr Int ; 55(6): 753-6, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23773416

RESUMO

BACKGROUND: Although it is recognized that the Th1 and Th17 cytokines are directly involved in the pathogenesis of Crohn's disease (CD), the precise cause of pediatric CD in the Japanese population has not been well established. In the present study, we examined the expression of pro-inflammatory cytokines and their signaling molecules in the intestinal mucosa of Japanese children with acute- and remission-phase CD. METHODS: A total of 11 children with acute-phase CD (mean age 10.32 ± 6.02 years) and 20 children with remission-phase CD (mean age 11.87 ± 4.29 years) provided samples for a serum cytokine assay. Among these children, seven with acute-phase CD (mean age 13.63 ± 1.94 years), six with remission-phase CD (mean age 9.93 ± 4.33 years), and six healthy controls (mean age 9.90 ± 4.88 years) provided samples for a signaling assay. Among this group, the expression of Th1, Th2, Th17, and regulatory T-cell signaling molecules were examined by real-time polymerase chain reaction. RESULTS: A significant elevation in the serum level of interleukin-6 and tumor necrosis factor-α was confirmed in pediatric patients with acute-phase CD compared to patients with remission-phase CD (P < 0.01 and 0.05, respectively). The mucosal expression of interferon-γ, signal transducer and activator of transcription 4, and transforming growth factor-ß1 were significantly enhanced in pediatric patients with acute-phase CD compared to patients with remission-phase CD or those with normal mucosa. CONCLUSIONS: These results suggest the possible involvement of Th1 and Th17 signaling in the pathogenesis of CD in Japanese children.


Assuntos
Doença de Crohn/imunologia , Citocinas/imunologia , Povo Asiático , Criança , Feminino , Humanos , Masculino
17.
Pediatr Res ; 71(1): 46-53, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22289850

RESUMO

INTRODUCTION: To examine the immune-modulatory effects of probiotics during early infancy, Bifidobacterium breve M-16V (B. breve) was administered to rat pups during the newborn or weaning period, and the expression of inflammatory genes was investigated using a cDNA microarray and real-time PCR. RESULTS: After B. breve administration, significant increases in the numbers of Bifidobacterium in both the cecum and colon were confirmed during the newborn period. The numbers of upregulated and downregulated genes were greater during the weaning period than in the newborn period and were greatest in the colon, with fewer genes altered in the small intestine and the fewest in the spleen. The expression of inflammation-related genes, including lipoprotein lipase (Lpl), glutathione peroxidase 2 (Gpx2), and lipopolysaccharide-binding protein (Lbp), was significantly reduced in the colon during the newborn period. In weaning rat pups, the expression of CD3d, a cell surface receptor-linked signaling molecule, was significantly enhanced in the colon; however, the expression of co-stimulatory molecules was not enhanced. DISCUSSION: Our findings support a possible role for B. breve in mediating anti-inflammatory and antiallergic reactions by modulating the expression of inflammatory molecules during the newborn period and by regulating the expression of co-stimulatory molecules during the weaning period. METHODS: Gene expression in the intestine was investigated after feeding 5 × 10(8) cfu of B. breve every day to the F344/Du rat from days 1 to 14 (newborn group) and from days 21 to 34 (weaning group). mRNA was extracted from intestine, and the expression of inflammatory gene was analyzed by microarray and real-time PCR.


Assuntos
Bifidobacterium/fisiologia , Regulação da Expressão Gênica , Inflamação/fisiopatologia , Intestinos/microbiologia , Intestinos/patologia , Intestinos/fisiologia , Desmame , Animais , Animais Recém-Nascidos , Perfilação da Expressão Gênica , Humanos , Análise em Microsséries , Ratos
18.
Pediatr Int ; 54(3): 319-24, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22320455

RESUMO

BACKGROUND: Although initial infection with Helicobacter pylori may occur before 5 years of age, the pediatric mucosal immune response against H. pylori is not clear. The aim of the present study was to evaluate immune responses in the H. pylori-infected gastric mucosa of children using microarray and real-time polymerase chain reaction (PCR) analysis of pediatric gastric samples. METHODS: Gastric samples were obtained from 12 patients undergoing routine endoscopy of chronic abdominal complaints. Six patients (three boys, three girls) aged 10.1-14.6 years had evidence of H. pylori infection, and the remaining six (three boys, three girls) aged 10.3-15.5 years had no evidence of infection and presented no histological changes associated with gastritis. Microarray and real-time PCR analyses were performed, and the changes in gene expression-related immune response were also analyzed. RESULTS: Using microarray analysis, the total number of significantly upregulated and downregulated genes (fold change >5, P < 0.01) was 21 in the antrum and 16 in the corpus when comparing patients with or without infection. Using real-time PCR, the expression of lipocalin-2 (Lcn2), C-C motif chemokine ligand (CCL) 18, C-X-C motif chemokine ligand (CXCL) 9 and CXCL11 was upregulated, while the expression of pepsinogen (PG) I and PGII was downregulated when comparing patients with or without infection. CONCLUSIONS: Lcn2, CCL18, CXCL9, CXCL11, PGI and PGII play important roles in childhood H. pylori infection.


Assuntos
Infecções por Helicobacter/diagnóstico , Helicobacter pylori , Adolescente , Criança , Feminino , Mucosa Gástrica , Humanos , Masculino , Análise em Microsséries , Reação em Cadeia da Polimerase em Tempo Real
19.
Juntendo Iji Zasshi ; 68(3): 271-281, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-39021725

RESUMO

Objectives: The correlation between altered small intestinal motility and irritable bowel syndrome is not well evaluated. This study aimed to assess the small intestinal and colonic transits in an adolescent irritable bowel syndrome rat model with restraint stress and determine the role of small intestinal motility in the irritable bowel syndrome pathophysiology. Materials: Restraint stress was utilized to prepare adolescent irritable bowel syndrome rat models that were evaluated for clinical signs, including stool frequency and diarrhea. The small intestinal motility and transit rate were also evaluated. Methods: The amounts of mRNA encoding corticotropin-releasing hormone, mast cell, and serotonin (5-Hydroxytryptamine) receptor 3a were quantified using real-time polymerase chain reaction; the 5-Hydroxytryptamine expression was evaluated using immunostaining. Results: Restraint stress significantly increased the number of fecal pellet outputs, stool water content, and small intestinal motility in the adolescent irritable bowel syndrome rat models. There was no difference in real-time polymerase chain reaction results; however, immunostaining analysis revealed that 5-Hydroxytryptamine expression in the small intestine was significantly increased in the adolescent irritable bowel syndrome rat models. Conclusions: In the rat model of adolescent irritable bowel syndrome with restraint stress, we observed an increase in small intestinal and colonic motility. In the small intestine, enhanced 5-Hydroxytryptamine secretion in the distal portion may be involved in increasing the small intestinal motility. Although the present study focused on 5-Hydroxytryptamine, further investigation of other factors that regulate intestinal peristalsis may lead to the establishment of more effective treatment methods for adolescent irritable bowel syndrome.

20.
Hum Genome Var ; 9(1): 24, 2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35688819

RESUMO

A 2-day-old neonate presented with seizures, multiple intracranial hemorrhages, and bilateral congenital cataracts. Targeted next-generation sequencing of the collagen type IV alpha 1 chain (COL4A1) gene revealed a heterozygous de novo missense variant (NM_001845.6:c.2291G>A/p.Gly764Asp). This missense variant adds to the compendium of COL4A1 variants and is associated with a COL4A1-related disorder.

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