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2.
Acta Biomater ; 91: 209-219, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31029828

RESUMO

Oral cavity wound healing occurs in an environment that sustains ongoing physical trauma and is rich in bacteria. Despite this, injuries to the mucosal surface often heal faster than cutaneous wounds and leave less noticeable scars. Patients undergoing cleft palate repair have a high degree of wound healing complications with up to 60% experiencing oronasal fistula (ONF) formation. In this study, we developed a mouse model of hard palate mucosal injury, to study the endogenous injury response during oral cavity wound healing and ONF formation. Immunophenotyping of the inflammatory infiltrate following hard palate injury showed delayed recruitment of non-classical LY6Clo monocytes and failure to resolve inflammation. To induce a pro-regenerative inflammatory response, delivery of FTY720 nanofiber scaffolds following hard palate mucosal injury promoted complete ONF healing and was associated with increased LY6Clo monocytes and pro-regenerative M2 macrophages. Alteration in gene expression with FTY720 delivery included increased Sox2 expression, reduction in pro-inflammatory IL-1, IL-4 and IL-6 and increased pro-regenerative IL-10 expression. Increased keratinocyte proliferation during ONF healing was observed at day 5 following FTY720 delivery. Our results show that local delivery of FTY720 from nanofiber scaffolds in the oral cavity enhances healing of ONF, occurring through multiple immunomodulatory mechanisms. STATEMENT OF SIGNIFICANCE: Wound healing complications occur in up to 60% of patients undergoing cleft palate repair where an oronasal fistula (ONF) develops, allowing food and air to escape from the nose. Using a mouse model of palate mucosal injury, we explored the role of immune cell infiltration during ONF formation. Delivery of FTY720, an immunomodulatory drug, using a nanofiber scaffold into the ONF was able to attract anti-inflammatory immune cells following injury that enhanced the reepithelization process. ONF healing at day 5 following FTY720 delivery was associated with altered inflammatory and epithelial transcriptional gene expression, increased anti-inflammatory immune cell infiltration, and increased proliferation. These findings demonstrate the potential efficacy of immunoregenerative therapies to improve oral cavity wound healing.


Assuntos
Cloridrato de Fingolimode , Imunomodulação/efeitos dos fármacos , Palato Duro , Cicatrização , Animais , Citocinas/imunologia , Cloridrato de Fingolimode/química , Cloridrato de Fingolimode/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/imunologia , Macrófagos/imunologia , Macrófagos/patologia , Camundongos , Nanofibras/química , Nanofibras/uso terapêutico , Palato Duro/imunologia , Palato Duro/lesões , Palato Duro/patologia , Fatores de Transcrição SOXB1/imunologia , Cicatrização/efeitos dos fármacos , Cicatrização/imunologia
3.
J Pediatric Infect Dis Soc ; 8(1): 73-76, 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-29415165

RESUMO

Single gene defects that impair lymphocyte cytotoxicity can predispose to severe viral infection that normally remains subclinical. The classic severe presentation is hemophagocytic lymphohistiocytosis. Here, we report the case of a neonate who presented with cytomegalovirus palatal ulceration and bocavirus pneumonitis secondary to impaired cytotoxicity caused by biallelic mutations in the UNC13D gene.


Assuntos
Infecções por Citomegalovirus/imunologia , Citotoxicidade Imunológica , Bocavirus Humano/isolamento & purificação , Linfócitos/imunologia , Proteínas de Membrana/genética , Palato Duro/imunologia , Infecções por Parvoviridae/imunologia , Pneumonia Viral/imunologia , Úlcera/imunologia , Infecções por Citomegalovirus/patologia , Humanos , Recém-Nascido , Masculino , Mutação , Palato Duro/patologia , Palato Duro/virologia , Infecções por Parvoviridae/genética , Infecções por Parvoviridae/patologia , Pneumonia Viral/genética , Pneumonia Viral/patologia , Úlcera/patologia , Úlcera/virologia
4.
Oral Dis ; 14(1): 73-81, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18173452

RESUMO

AIM: Hyperimmunoglobulin-E syndrome (HIES) is a primary immunodeficiency characterized by eczema, recurrent skin and lung infections with pneumatocoele formation, and extremely elevated serum immunoglobulin-E. The precise immunologic defect and genetic etiology remain unknown. Non-immunologic findings include characteristic facial features (prominent forehead, fleshy nasal tip, and increased interalar distance); skeletal involvement (pathological fractures, scoliosis, and craniosynostosis); and retention of primary teeth. This study aims to characterize intraoral soft tissue findings in HIES patients. METHODS: Sixty HIES patients (4-54 years, 27 males, 33 females) received intraoral and radiographic evaluations. Chronological dental development was also assessed. RESULTS: Lesions of the hard palate and dorsal tongue were found in 55% and 60% of patients, respectively. Palatal lesions ranged from a generalized surface keratosis to a midline sagittal fibrotic bridge. Tongue lesions consisted of multiple fissures and a midline cleft. On the lip and buccal mucosa, keratotic plaques and/or surface fissures were found in 8% and 23% of patients, respectively. Manifested in 76.7% of patients, the intraoral lesions were significantly more prevalent than the characteristic facial traits (P=0.0013). CONCLUSIONS: Alterations in oral mucosa and gingiva were present in the majority of HIES patients. These novel intraoral findings may facilitate the diagnosis of HIES.


Assuntos
Hipergamaglobulinemia/imunologia , Imunoglobulina E/imunologia , Doenças da Boca/imunologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Fibrose , Humanos , Leucoplasia Oral/imunologia , Doenças Labiais/imunologia , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/imunologia , Odontogênese/imunologia , Palato Duro/imunologia , Fenótipo , Síndrome , Língua/anormalidades , Doenças da Língua/imunologia
5.
Artigo em Inglês | MEDLINE | ID: mdl-15735372

RESUMO

Non-Hodgkin lymphomas of the sinonasal region have been the subject of numerous studies. Previous reports have suggested that nasal lymphomas occurring in Orientals are mostly of the natural killer cell (NK)/T-cell phenotype which contrasts with the preponderance of the B-cell type in western populations. Recent studies indicated that NK/T-cell lymphoma constitutes the clinical condition of lethal midline granuloma. These reports led us to question whether all NK/T lymphomas are always lethal midline granuloma. We have investigated a series of 15 cases of non-Hodgkin lymphomas in the nasal and/or paranasal sinuses clinically, immunohistochemically and for the presence of Epstein-Barr virus (EBV). This study showed that the presence of EBV was common in nasal NK/T lymphoma, and this type of lymphoma was clearly highly frequent in other types of nasal lymphoma in our department. Moreover, in 4 cases of NK/T-cell lymphomas, the clinical features of lethal midline granuloma did not appear, indicating that NK/T lymphomas are not always lethal midline granuloma.


Assuntos
Neoplasias Ósseas/patologia , Neoplasias Ósseas/radioterapia , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/radioterapia , Palato Duro/patologia , Palato Duro/efeitos da radiação , Neoplasias dos Seios Paranasais/patologia , Neoplasias dos Seios Paranasais/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD20/imunologia , Neoplasias Ósseas/imunologia , Complexo CD3/imunologia , Antígeno CD56/imunologia , Feminino , Humanos , Imuno-Histoquímica , Hibridização In Situ , Japão , Linfoma não Hodgkin/imunologia , Masculino , Pessoa de Meia-Idade , Palato Duro/imunologia , Neoplasias dos Seios Paranasais/imunologia , Dosagem Radioterapêutica
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