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  1 / 1862 MEDLINE  
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[PMID]:29412224
[Au] Autor:El-Batal AI; Ahmed SF
[Ad] Endereço:National Centre for Radiation Research and Technology - NCRRT, Atomic Energy Authority, Drug Radiation Research Department, Nasr City, Cairo, Egypt.
[Ti] Título:Therapeutic effect of Aloe vera and silver nanoparticles on acid-induced oral ulcer in gamma-irradiated mice.
[So] Source:Braz Oral Res;32:e004, 2018 Feb 05.
[Is] ISSN:1807-3107
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:Radiation combined injury, a life-threatening condition, has higher mortality than simple radiation injury. The aim of the present study was to analyze the efficiency of Aloe vera and silver nanoparticles in improving the healing of ulcerated oral mucosa after irradiation. Thirty male Albino mice were divided into five groups: control, radiation, Aloe vera (AV), silver nanoparticles (NS), and AV+NS. The mice were exposed to whole body 6Gy gamma-radiation. After one hour, 20% acetic acid was injected into the submucosal layer of the lower lip for ulcer induction. The animals received topical treatment with the assigned substances for 5 days. Lip specimens were subjected to hematoxylin and eosin and anti alpha-smooth muscle actin immunohistochemical staining. Results demonstrated occurance of ulcer three days post irradiation in all groups except in the AV+NS group where only epithelial detachment was developed. After seven days, data revealed persistent ulcer in radiation group, and almost normal epithelium in the AV+NS group. A significant reduction of epithelial thickness was detected in all groups at the third day as compared to control. At the seventh day, only the AV+NS group restored the epithelial thickness. Area percent of alpha-smooth muscle actin expression was significantly decreased in radiation group at the third day followed by significant increase at the seventh day. However, all treatment groups showed significant increase in alpha-smooth muscle actin at the third day, which decreased to normal level at the seventh day. Our study demonstrated the efficiency of Aloe vera and silver nanoparticles in enhancing ulcer healing after irradiation.
[Mh] Termos MeSH primário: Aloe/química
Raios gama/efeitos adversos
Nanopartículas Metálicas/uso terapêutico
Úlceras Orais/tratamento farmacológico
Úlceras Orais/etiologia
Lesões Experimentais por Radiação/tratamento farmacológico
Prata/uso terapêutico
[Mh] Termos MeSH secundário: Ácido Acético
Actinas/análise
Administração Tópica
Animais
Células Epiteliais/efeitos dos fármacos
Células Epiteliais/efeitos da radiação
Fibroblastos/efeitos dos fármacos
Imuno-Histoquímica
Masculino
Camundongos
Microscopia Eletrônica de Transmissão
Úlceras Orais/patologia
Lesões Experimentais por Radiação/patologia
Valores de Referência
Reprodutibilidade dos Testes
Fatores de Tempo
Resultado do Tratamento
Cicatrização/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Actins); 0 (alpha-smooth muscle actin, mouse); 3M4G523W1G (Silver); Q40Q9N063P (Acetic Acid)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:D; IM
[Da] Data de entrada para processamento:180208
[St] Status:MEDLINE


  2 / 1862 MEDLINE  
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[PMID]:28449757
[Au] Autor:Brignardello-Petersen R
[Ti] Título:No evidence of an association between an allergy to dental materials and dental hygiene products and symptomatic oral lesions.
[So] Source:J Am Dent Assoc;148(5):e53, 2017 05.
[Is] ISSN:1943-4723
[Cp] País de publicação:England
[La] Idioma:eng
[Mh] Termos MeSH primário: Materiais Dentários
Higiene Bucal
[Mh] Termos MeSH secundário: Seres Humanos
Hipersensibilidade
Úlceras Orais
[Pt] Tipo de publicação:REVIEW; COMMENT
[Nm] Nome de substância:
0 (Dental Materials)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:D; IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE


  3 / 1862 MEDLINE  
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[PMID]:29224587
[Au] Autor:Madanat WY; Alawneh KM; Smadi MM; Saadeh SS; Omari MM; Bani Hani AB; Yazici H
[Ad] Endereço:Medical Department, Jordan's Friends of Behçet's Disease Patients Society, Amman, Jordan. wmadanat@orange.jo.
[Ti] Título:The prevalence of Behçet's disease in the north of Jordan: a hospital-based epidemiological survey.
[So] Source:Clin Exp Rheumatol;35 Suppl 108(6):51-54, 2017 Nov-Dec.
[Is] ISSN:0392-856X
[Cp] País de publicação:Italy
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: To estimate the prevalence of Behçet's disease (BD) in Jordan, with the additional aim of comparing this prevalence among hospital workers in other geographical areas. METHODS: In the first stage of our survey, 2,569 employees from 6 hospitals in north Jordan were interviewed using a screening questionnaire to identify individuals with recurrent oral ulcers (ROU), a previous diagnosis of BD (PDBD) and/or any major symptom related to BD. In the second stage, all individuals with ROU or PDBD identified at stage 1, were examined by 2 rheumatologists for the presence/confirmation of BD according to the International Study Group (ISG) criteria. Pathergy test was performed according to recommendations. RESULTS: ROU were present in 210 (8.2%) individuals. BD was confirmed in 10 employees with PDBD. Seven more BD patients were found. Mean age of 17 BD patients was 38.6±10.7 (range 26-65 y). M: F was 2.4:1. Pathergy test was positive in 8/17. A family history of ROU or BD was noted in 9 (52%) and 3 (25.0%), respectively, compared to 227 (8.9%) and 62 (2.6%) in the whole group, excluding the BD patients (p<0.001 and 0.008, respectively). The prevalence rate of BD in the north of Jordan was estimated as 66:10.000 (95% CI 34.8 to 97.5:10000). CONCLUSIONS: The results of this first ever survey indicated that the prevalence of BD in the north of Jordan is among the highest in the world. This prevalence can now be compared to hospital workers in other geographical areas.
[Mh] Termos MeSH primário: Síndrome de Behçet/epidemiologia
Hospitais
Úlceras Orais/epidemiologia
Recursos Humanos em Hospital
[Mh] Termos MeSH secundário: Adulto
Idoso
Síndrome de Behçet/diagnóstico
Síndrome de Behçet/genética
Feminino
Predisposição Genética para Doença
Inquéritos Epidemiológicos
Hereditariedade
Seres Humanos
Jordânia/epidemiologia
Masculino
Meia-Idade
Úlceras Orais/diagnóstico
Úlceras Orais/genética
Linhagem
Prevalência
Recidiva
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171212
[St] Status:MEDLINE


  4 / 1862 MEDLINE  
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[PMID]:29188701
[Au] Autor:Malamos D; Scully C
[Ti] Título:Clinical Challenges Q&A 31. Painful Lip.
[So] Source:Dent Update;44(5):463, 2017 May.
[Is] ISSN:0305-5000
[Cp] País de publicação:England
[La] Idioma:eng
[Mh] Termos MeSH primário: Doenças Labiais/diagnóstico
Úlceras Orais/diagnóstico
[Mh] Termos MeSH secundário: Feminino
Seres Humanos
Doenças Labiais/complicações
Úlceras Orais/complicações
Dor/etiologia
Adulto Jovem
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180130
[Lr] Data última revisão:
180130
[Sb] Subgrupo de revista:D
[Da] Data de entrada para processamento:171201
[St] Status:MEDLINE


  5 / 1862 MEDLINE  
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[PMID]:29245353
[Au] Autor:Wang M; Sun W; Chen Z; Wang X; Lv J; Tan Q; Wang Y; Zhou J
[Ad] Endereço:aDepartment of Nephrology and Rheumatology, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, ChinabSingapore Thong Chai Medical Institution, Singapore.
[Ti] Título:Multiple aneurysms and gastrointestinal involvement in Behcet's disease: A case report.
[So] Source:Medicine (Baltimore);96(49):e9131, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Behcet's disease (BD) is a rare systemic vasculitis disorder that can involve vessels of any size. PATIENT CONCERNS: A 60-year-old female had recurrent painful mouth ulcers about 30 years ago and recently presented with abdominal distension, conjunctival congestion, and chest pain in sequence. DIAGNOSES: The patient was diagnosed with BD according to the International Criteria for Behcet's Disease (ICBD). INTERVENTIONS: A therapy of glucocorticoids and cyclophosphamide was administered. OUTCOMES: After a 3-month treatment, follow-up examination showed a depression of the inflammation and a slight decrease of the arterial aneurysms. LESSONS: BD patients may get a delayed diagnosis because of the long duration between the first and subsequent manifestations. Suspect patients should be followed-up and the diagnosis of BD should be considered when multiple tissues or organs are involved.
[Mh] Termos MeSH primário: Aneurisma/etiologia
Síndrome de Behçet/complicações
Síndrome de Behçet/diagnóstico
Úlceras Orais/etiologia
[Mh] Termos MeSH secundário: Aneurisma/fisiopatologia
Síndrome de Behçet/tratamento farmacológico
Síndrome de Behçet/fisiopatologia
Feminino
Seres Humanos
Imunossupressores/uso terapêutico
Meia-Idade
Úlceras Orais/fisiopatologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Immunosuppressive Agents)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180105
[Lr] Data última revisão:
180105
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171217
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009131


  6 / 1862 MEDLINE  
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[PMID]:29191190
[Au] Autor:Xie L; Zhong X; Liu D; Liu L; Xia Z
[Ad] Endereço:College of Horticulture and Landscape Architecture, Hunan Agricultural University, Changsha, China.
[Ti] Título:The effects of freeze-dried Ganoderma lucidum mycelia on a recurrent oral ulceration rat model.
[So] Source:BMC Complement Altern Med;17(1):511, 2017 Dec 01.
[Is] ISSN:1472-6882
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Conventional scientific studies had supported the use of polysaccharides and ß-glucans from a number of fungi, including Ganoderma lucidum for the treatment of recurrent oral ulceration (ROU). Our aim of the present study was to evaluate whether freeze-dried powder from G. lucidum mycelia (FDPGLM) prevents ROU in rats. METHODS: A Sprague-Dawley (SD) rat model with ROU was established by autoantigen injection. The ROU rats were treated with three different dosages of FDPGLM and prednisone acetate (PA), and their effects were evaluated according to the clinical therapeutic evaluation indices of ROU. RESULTS: High-dose FDPGLM induced significantly prolonged total intervals and a reduction in the number of ulcers and ulcer areas, thereby indicating that the treatment was effective in preventing ROU. Enzyme-linked immunosorbent assay (ELISA) showed that high-dose FDPGLM significantly enhanced the serum transforming growth factor-ß1 (TGF-ß1) levels, whereas reduced those of interleukin-6 (IL-6) and interleukin-17 (IL-17). Flow cytometry (FCM) showed that the proportion of CD4 CD25 Foxp3 (forkhead box P3) regulatory T cells (Tregs) significantly increased by 1.5-fold in the high-dose FDPGLM group compared to that in the rat model group (P < 0.01). The application of middle- and high-dose FDPGLM also resulted in the upregulation of Foxp3 and downregulation of retinoid-related orphan receptor gamma t(RORγt) mRNA. CONCLUSION: High-dose FDPGLM possibly plays a role in ROU by promoting CD4 CD25 Foxp3 Treg and inhibiting T helper cell 17 differentiation. This study also shows that FDPGLM may be potentially used as a complementary and alternative medicine treatment scheme for ROU.
[Mh] Termos MeSH primário: Produtos Biológicos/uso terapêutico
Ganoderma/química
Micélio/química
Úlceras Orais/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Produtos Biológicos/química
Produtos Biológicos/farmacologia
Citocinas/sangue
Modelos Animais de Doenças
Fatores de Transcrição Forkhead/genética
Fatores de Transcrição Forkhead/metabolismo
Liofilização
Mucosa Bucal/química
Mucosa Bucal/patologia
Prednisona/farmacologia
Prednisona/uso terapêutico
Ratos
Ratos Sprague-Dawley
Recidiva
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biological Products); 0 (Cytokines); 0 (Forkhead Transcription Factors); 0 (Foxp3 protein, rat); VB0R961HZT (Prednisone)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171220
[Lr] Data última revisão:
171220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171202
[St] Status:MEDLINE
[do] DOI:10.1186/s12906-017-2021-8


  7 / 1862 MEDLINE  
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[PMID]:28968732
[Au] Autor:Ishido T; Horita N; Takeuchi M; Kawagoe T; Shibuya E; Yamane T; Hayashi T; Meguro A; Ishido M; Minegishi K; Yoshimi R; Kirino Y; Kato S; Arimoto J; Ishigatsubo Y; Takeno M; Kurosawa M; Kaneko T; Mizuki N
[Ad] Endereço:Department of Ophthalmology and Visual Science.
[Ti] Título:Clinical manifestations of Behçet's disease depending on sex and age: results from Japanese nationwide registration.
[So] Source:Rheumatology (Oxford);56(11):1918-1927, 2017 Nov 01.
[Is] ISSN:1462-0332
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Objective: This report aimed to scrutinize the prevalence of Behçet's disease (BD)-related clinical manifestations based on age- and sex-specific subgroups using a Japanese nationwide registration database. Methods: The database of newly registered BD was obtained from the Japanese Ministry of Health, Labour and Welfare. Patients who met the International Criteria for Behçet's Disease were selected and analysed. Results: Among 6627 International Criteria for Behçet's Disease cases, 2651 (40.0%) were men and 3976 (60.0%) were women with a median age of 39 years (interquartile range: 31-50 years). Ocular lesion was more common in male [odds ratio (male: female) 2.64 (95% CI: 2.35, 2.95, P < 0.001)] and genital ulceration was more common in female (odds ratio = 0.29, 95% CI: 0.25, 0.32, P < 0.001). Ocular lesion (P < 0.001), arthritis (P < 0.001) and vascular lesions (P < 0.001) were more frequently observed in elderly registered patients. Contrarily, genital ulceration (P < 0.001), epididymitis of males (P = 0.023) and oral ulceration (P = 0.003) were more common in younger patients. Simultaneous assessment of sex and age revealed that male predominance of ocular involvement was found in the young adult generation, but not in patients over 70 year of age. A female predominance of genital ulcer was prominently observed in patients 20-59 year of age; however, the sex difference was not found in patients over 60 years of age. Sensitivity analysis using International Study Group criteria replicated the results. Conclusion: We showed that clinical phenotype in early phase of BD was different depending on onset age and sex.
[Mh] Termos MeSH primário: Síndrome de Behçet/fisiopatologia
Sistema de Registros
[Mh] Termos MeSH secundário: Adolescente
Adulto
Fatores Etários
Idoso
Artrite/etiologia
Artrite/fisiopatologia
Síndrome de Behçet/complicações
Síndrome de Behçet/genética
Criança
Bases de Dados Factuais
Epididimite/etiologia
Epididimite/fisiopatologia
Oftalmopatias/etiologia
Oftalmopatias/fisiopatologia
Feminino
Gastroenteropatias/etiologia
Gastroenteropatias/fisiopatologia
Doenças dos Genitais Femininos/etiologia
Doenças dos Genitais Femininos/fisiopatologia
Doenças dos Genitais Masculinos/etiologia
Doenças dos Genitais Masculinos/fisiopatologia
Antígeno HLA-B51/genética
Seres Humanos
Japão
Masculino
Meia-Idade
Doenças do Sistema Nervoso/etiologia
Doenças do Sistema Nervoso/fisiopatologia
Razão de Chances
Úlceras Orais/etiologia
Úlceras Orais/fisiopatologia
Fenótipo
Fatores Sexuais
Úlcera Cutânea/etiologia
Úlcera Cutânea/fisiopatologia
Doenças Vasculares/etiologia
Doenças Vasculares/fisiopatologia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HLA-B51 Antigen)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171003
[St] Status:MEDLINE
[do] DOI:10.1093/rheumatology/kex285


  8 / 1862 MEDLINE  
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Rados, Pantelis Varvaki
Lameira, Osmar Alves
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[PMID]:28635033
[Au] Autor:Wagner VP; Webber LP; Ortiz L; Rados PV; Meurer L; Lameira OA; Lima RR; Martins MD
[Ad] Endereço:Department of Oral Pathology, School of Dentistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, 90035-003, Brazil.
[Ti] Título:Effects of Copaiba Oil Topical Administration on Oral Wound Healing.
[So] Source:Phytother Res;31(8):1283-1288, 2017 Aug.
[Is] ISSN:1099-1573
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The effects of topical copaiba oil extract and topical corticosteroid were assessed on oral wound healing in an in vivo model using 96 male Wistar rats. Traumatic ulcers were caused in the dorsum of the tongue using a 3-mm punch tool. The animals were divided into: Control; Corticosteroid; Placebo and Copaiba oil Group. The animals received two daily applications of the products. The control group received only daily handling. Six rats in each group were euthanized at days 3, 5, 10 and 14. The animals were monitored daily to determine wound status. The weigh was assessed at day 0 and euthanasia day. The percentage of repair was calculated, and histopathological aspects were analyzed. The Kruskal-Wallis test was used to compare the results between groups and times of evaluation. Closing time was assessed through the log-rank test. The corticosteroid group lost more weight at days 10 and 14 than the control group (p < 0.05). Moreover, the healing time of corticosteroid group was longer than the control group (p = 0.007). No differences were observed between the copaiba oil group and the control group. We concluded that topical copaiba oil, in spite of being safe, did not accelerate the process of oral wound healing. Copyright © 2017 John Wiley & Sons, Ltd.
[Mh] Termos MeSH primário: Fabaceae/química
Úlceras Orais/tratamento farmacológico
Óleos Vegetais/farmacologia
Cicatrização/efeitos dos fármacos
[Mh] Termos MeSH secundário: Administração Tópica
Corticosteroides/farmacologia
Animais
Masculino
Distribuição Aleatória
Ratos
Ratos Wistar
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adrenal Cortex Hormones); 0 (Plant Oils)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170622
[St] Status:MEDLINE
[do] DOI:10.1002/ptr.5845


  9 / 1862 MEDLINE  
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[PMID]:28619306
[Au] Autor:Lee YC; Wang TH; Chen SY; Lin HL; Tsai MY
[Ad] Endereço:Department of Chinese Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
[Ti] Título:Management of viral oral ulcers in children using Chinese herbal medicine: A report of two cases.
[So] Source:Complement Ther Med;32:61-65, 2017 Jun.
[Is] ISSN:1873-6963
[Cp] País de publicação:Scotland
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Viral oral ulcers are common presentations in pediatric clinics. Although self-limiting, painful ulcerative lesions and inflamed mucosa can decrease oral intake and lead to dehydration. Despite the widespread use of Chinese herbal medicine (CHM) for pediatric upper respiratory disease in Taiwan, there is little evidence for its effectiveness as an antipyretic or in aiding ulcer healing for children with viral oral ulcers. We report two cases of children who presented with viral oral ulcers to illustrate the potential efficacy of CHM treatment in recovery from herpangina (HA) and herpetic gingivostomatitis (HGS). CLINICAL FEATURES AND OUTCOME: A 10-year-old girl with HA presented with an acute febrile illness associated with small vesicular or ulcerative lesions on the posterior oropharyngeal structures. The family refused western medicine due to a prior anaphylactic skin rash when she had taken sulfa drugs. The other patient was a 4-year-old boy with complaints of painful ulcers and hemorrhagic crusts on the lips. He was diagnosed with HGS and had received ibuprofen and supportive treatments such as hydration and local anesthesia spray for days, characterized by fever, anorexia, and nausea to no effect. Because the patients were suffering from the damp-heat syndrome according to Traditional Chinese Medicine (TCM) differentiation, both were treated using the same herbal formulas powder prescription, named Liang Ge San (LGS) and Gan Lu Xiao Du Dan (GLXDD). After several days of CHM treatment, the oral ulcers were in regression. Follow-up of the frontal view in both patients showed satisfactory disappearance of the sick furred tongue. CONCLUSIONS: The results of these case reports show that the early prescription of CHM is an effective modality of alternative treatment for viral oral ulcers. To our knowledge, this is the first report of CHM treatment hastening the recovery from febrile disease with viral oral ulcers in Taiwan. Future experimental studies to determine the definitive mechanism and clinical trials are warranted.
[Mh] Termos MeSH primário: Medicamentos de Ervas Chinesas
Úlceras Orais
Viroses
[Mh] Termos MeSH secundário: Criança
Pré-Escolar
Medicamentos de Ervas Chinesas/administração & dosagem
Medicamentos de Ervas Chinesas/uso terapêutico
Feminino
Seres Humanos
Masculino
Boca/patologia
Úlceras Orais/tratamento farmacológico
Úlceras Orais/patologia
Úlceras Orais/virologia
Viroses/tratamento farmacológico
Viroses/patologia
Viroses/virologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drugs, Chinese Herbal)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170627
[Lr] Data última revisão:
170627
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170617
[St] Status:MEDLINE


  10 / 1862 MEDLINE  
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[PMID]:28600438
[Au] Autor:Badran YR; Dedeoglu F; Leyva Castillo JM; Bainter W; Ohsumi TK; Bousvaros A; Goldsmith JD; Geha RS; Chou J
[Ad] Endereço:Division of Immunology, Boston Children's Hospital, Boston, MA.
[Ti] Título:Human haploinsufficiency results in autosomal-dominant chronic mucocutaneous ulceration.
[So] Source:J Exp Med;214(7):1937-1947, 2017 Jul 03.
[Is] ISSN:1540-9538
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The treatment of chronic mucocutaneous ulceration is challenging, and only some patients respond selectively to inhibitors of tumor necrosis factor-α (TNF). TNF activates opposing pathways leading to caspase-8-mediated apoptosis as well as nuclear factor κB (NF-κB)-dependent cell survival. We investigated the etiology of autosomal-dominant, mucocutaneous ulceration in a family whose proband was dependent on anti-TNF therapy for sustained remission. A heterozygous mutation in , encoding the NF-κB subunit RelA, segregated with the disease phenotype and resulted in RelA haploinsufficiency. The patients' fibroblasts exhibited increased apoptosis in response to TNF, impaired NF-κB activation, and defective expression of NF-κB-dependent antiapoptotic genes. mice have similarly impaired NF-κB activation, develop cutaneous ulceration from TNF exposure, and exhibit severe dextran sodium sulfate-induced colitis, ameliorated by TNF inhibition. These findings demonstrate an essential contribution of biallelic expression in protecting stromal cells from TNF-mediated cell death, thus delineating the mechanisms driving the effectiveness of TNF inhibition in this disease.
[Mh] Termos MeSH primário: Genes Dominantes/genética
Haploinsuficiência
Úlceras Orais/genética
Úlcera Cutânea/genética
Fator de Transcrição RelA/genética
[Mh] Termos MeSH secundário: Animais
Sequência de Bases
Células Cultivadas
Doença Crônica
Colite/induzido quimicamente
Colite/genética
Sulfato de Dextrana
Exoma/genética
Feminino
Fibroblastos/metabolismo
Perfilação da Expressão Gênica/métodos
Seres Humanos
Masculino
Camundongos Knockout
NF-kappa B/metabolismo
Linhagem
Análise de Sequência de DNA/métodos
Fator de Transcrição RelA/metabolismo
Fator de Necrose Tumoral alfa/metabolismo
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (NF-kappa B); 0 (RELA protein, human); 0 (Transcription Factor RelA); 0 (Tumor Necrosis Factor-alpha); 9042-14-2 (Dextran Sulfate)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171006
[Lr] Data última revisão:
171006
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170611
[St] Status:MEDLINE
[do] DOI:10.1084/jem.20160724



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