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1.
Sci Prog ; 106(3): 368504231199204, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37697808

RESUMO

BACKGROUND: Chronic otitis media with or without cholesteatoma progresses with various degrees of bone resorption and remodeling. Estrogen mediates osteoprotective effects through the receptor activator of NF-κB ligand (RANKL) pathway, which is mainly mediated by estrogen receptor-alpha (ER-α). OBJECTIVES: The present study investigated the expression patterns of receptor activator of NF-κB (RANK), osteoprotegerin (OPG), RANKL, and ER-α in pathological tissue from patients with chronic otitis media to determine the roles of those factors in osteolytic mechanisms underlying the pathogenesis of chronic otitis media. METHODS: Normal and pathological specimens from 18 patients with chronic otitis media were examined. RESULTS: There were no significant differences in RANK, OPG, RANKL, or ER-α mRNA expression between normal and pathological specimens of epithelial tissue. CONCLUSIONS: Our findings suggested that RANK, OPG, RANKL, and ER-α are not associated with the bone destruction in chronic otitis media; other cytokines may directly activate the osteoclasts in chronic otitis media.


Assuntos
Otite Média , Receptores de Estrogênio , Humanos , Receptor Ativador de Fator Nuclear kappa-B/genética , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Osteoprotegerina/genética , Osteoprotegerina/metabolismo , Otite Média/genética , Ligante RANK/genética , Ligante RANK/metabolismo
2.
Front Genet ; 13: 958540, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36437913

RESUMO

Otitis media (OM) is one of the largest public health problems of children and has devastating impacts in developing countries. The substantial medical and human costs involved have led to research to understand the disease and improve treatment. Animal models of OM have yielded critical information about the immune, inflammatory and genetic mechanisms of OM. However, it is important to link animal studies to human immune and inflammatory responses. In recent years, "humanized" mice have become a valuable tool to study the human immune system in an animal model. Here we describe the first use of humanized mice to study OM. We demonstrate that humanized mice with a sufficient degree of engraftment recapitulate a normal middle ear (ME) inflammatory response to bacterial infection, including the recruitment of human immune cells, and exhibit normal recovery. Moreover, these animals exhibit regulated expression of human-specific immune and inflammatory genes in the ME. In contrast, mice with insufficient engraftment fail to resolve OM. This model has many potential uses in OM research, including using hematopoietic stem cells from patients with differing degrees of OM susceptibility, to understand the role of human immune responses in proneness to this common childhood disease.

3.
Front Cell Infect Microbiol ; 11: 768815, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35004347

RESUMO

Background: Pathogens of otitis media (OM) induce inflammatory responses in the middle ear (ME), characterized by mucosal hyperplasia, leukocyte infiltration, and inflammatory mediators, including arachidonic acid metabolites. We studied the role of the eicosanoid leukotriene B4 (LTB4) in OM. Methods: Expression of LTB4-related genes was evaluated by gene array and single-cell RNA-Seq in MEs infected with nontypeable Haemophilus influenzae (NTHi). An inhibitor of LTB4 receptor 1 (i.e. U75302) was also used to block LTB4 responses. Results: ME expression of LTB4-related genes was observed by gene arrays and scRNA-Seq. However, not all genes involved in LTB4 generation occurred in any one specific cell type. Moreover, LTB4 receptor inhibition significantly reduced mucosal hyperplasia and virtually eliminated leukocyte infiltration. Conclusions: ME expression of LTB4-related genes suggest a functional role in OM disease. The fact that LTB4-generation is spread across different cell types is consistent with a transcellular pathway of eicosanoid biosynthesis involving cell-to-cell signaling as well as transfer of biosynthetic intermediates between cells. The dramatic reduction in ME leukocyte infiltration caused by U75302 indicates that LTB4 plays a major role in ME inflammatory cell recruitment, acting via the LTB4R1 receptor. Given that there are many other chemotactic factors that occur in the ME during OM, the ability of LTB4 to activate leukocytes and stimulate their extravasation may explain the effects of inhibition. Reduction in mucosal hyperplasia due to U75302 administration may be secondary to the reduction in leukocytes since LTB4R1 is not expressed by mucosal epithelial or stromal cells. The results suggest that LTB4 receptor antagonists could be useful in treating OM.


Assuntos
Leucotrieno B4 , Otite Média , Animais , Modelos Animais de Doenças , Haemophilus influenzae , Leucócitos
4.
Ren Fail ; 42(1): 98-106, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31906817

RESUMO

Purpose: Epidermal growth factor (EGF) has been found to be associated with the development and repair mechanisms of several renal diseases. In this study, we hypothesized that single nucleotide polymorphisms (SNPs) in EGF or its receptor genes might have an association with end-stage renal disease (ESRD) or acute renal allograft rejection (AR) in a Korean population.Methods: Three-hundred and forty seven recipients of the first renal transplants for ESRD, including 63 AR patients along with 289 healthy adults were included in the study. Five EGF gene SNPs (rs11568835, rs11568943, rs2237051, rs11569017, and rs3756261) and four EGFR gene SNPs (rs1140475, rs2293347, rs1050171, and rs6965469) were analyzed. The genotypes of these SNPs were analyzed using the AxiomTM genome-wide human assay. Statistical analysis was performed using SNPStats and Haploview version 4.2 software. Multiple logistic regression models (codominant, dominant, recessive, and Log-additive) were used to estimate the odds ratio (OR), 95% confidence interval (CI), and P value.Results: One SNP (rs11569017) in the EGF gene showed significant association with ESRD but not with AR. Another SNP (rs11568835) in the EGF gene showed significant association with susceptibility to AR but not with ESRD. One SNP (rs1050171) in the EGFR gene showed significant association with susceptibility to AR but not with ESRD.Conclusion: Our findings suggest that SNPs in the EGF and EGFR gene may be associated with the risk of ESRD and AR development in the Korean population.


Assuntos
Fator de Crescimento Epidérmico/genética , Rejeição de Enxerto/genética , Falência Renal Crônica/genética , Transplante de Rim/efeitos adversos , Adolescente , Adulto , Idoso , Criança , Receptores ErbB/genética , Feminino , Predisposição Genética para Doença , Rejeição de Enxerto/epidemiologia , Humanos , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/cirurgia , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , República da Coreia/epidemiologia , Transplante Homólogo/efeitos adversos , Adulto Jovem
5.
Int J Pediatr Otorhinolaryngol ; 116: 199-203, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30554699

RESUMO

OBJECTIVE: Recurrence rates following preauricular sinus (PAS) surgery vary. Few studies have investigated recurrence after primary PAS surgery in histopathological terms. We performed a histopathological analysis of the causes of revision surgery for PAS, with a view to reducing the recurrence rate after primary surgery. METHODS: We reviewed the medical records of patients who underwent revision surgery after primary excision of a PAS between 2002 and 2017. A pathologist reviewed the histopathology slides. RESULTS: In total, 24 patients underwent revision surgery; of those, histopathology slides were available for 18 patients (19 revisions). The mean interval between primary and revision surgery was 50.4 months. We detected lumen with stratified squamous epithelium in 14 of the 19 (73.7%) revisions. Cartilage tissue was attached to the epithelial lining of the lumen in 14 of the 17 (82.4%) slides containing lumen. Inflammatory changes were found in all slides, and granulation tissue was detected in 10 of 19 revision surgery slides. CONCLUSIONS: To prevent PAS recurrence after primary surgery, we recommend a wide local excision including the inflammatory soft tissue, with concomitant partial removal of the cartilage of the ascending helix adjacent to the PAS.


Assuntos
Anormalidades Craniofaciais/cirurgia , Procedimentos Cirúrgicos Otorrinolaringológicos/métodos , Reoperação/estatística & dados numéricos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Anormalidades Craniofaciais/patologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Otorrinolaringológicos/efeitos adversos , Complicações Pós-Operatórias/etiologia , Recidiva , Estudos Retrospectivos , Adulto Jovem
6.
Acta Otolaryngol ; 138(2): 116-121, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28990844

RESUMO

OBJECTIVES: We evaluated the relationship between pathological nasal conditions and pathological middle ear conditions on a large-scale epidemiological basis, conducted as a cross-sectional study at the population level using Korean National Health and Nutrition Examination Survey (KNHANES) data. STUDY DESIGN: A cross-sectional study. METHODS: In a retrospective cohort study, we analyzed data from the KNHANES (2008-2012), which used a stratified, multi-stage, probability-cluster sampling method in a rolling sampling survey of South Korean citizens. RESULTS: The prevalences of nasal and middle ear pathologies were evaluated. Chronic postnasal drip, chronic hypertrophic rhinitis, and nasal polyps were correlated with the presence of middle ear pathologies; allergic rhinitis was negatively correlated. The prevalences of chronic otitis media and septal deviation showed no relationship. Only nasal polyps showed a tendency to be associated with cholesteatomatous otitis media in patients with COM. CONCLUSIONS: Our results indicate the need for a nasal assessment when evaluating COM. Additionally, correction of nasal pathologies may be useful with the surgical treatment of COM to improve patient success rates and satisfaction.


Assuntos
Colesteatoma/complicações , Pólipos Nasais/complicações , Otite Média com Derrame/complicações , Rinite/complicações , Adulto , Idoso , Doença Crônica , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/fisiopatologia , Rinite Alérgica/complicações
7.
Acta Otolaryngol ; 138(4): 357-362, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29130359

RESUMO

OBJECTIVES: The purpose of this study was to determine the prognostic potential of admission of a patient for idiopathic sudden sensorineural hearing loss (ISSNHL). STUDY DESIGN: Retrospective clinical study. METHODS: We conducted a retrospective study of 301 patients with ISSNHL. The patients were divided into a study (57 patients at out-patients department (OPD) based treatment, using systemic steroids and intra-tympanic (IT) steroid injection) and a control groups (301 patients at admission, using systemic steroids and IT steroid injection). We compared the success rate (15 dB cut off), Siegel's criteria and hearing gain decibels between two groups. RESULTS: The overall recovery rate of the OPD based treatment group (29.8%) was poor than that of the admission group (52.9%) (p = .002). The odd ratio of OPD based treatment factor was 2.035 when the OPD based treatment and poor prognostic factors were analyzed at logistic regression test (Duration of delayed treatment, 1.073; average hearing loss level, 0.972) (p = .041). CONCLUSION: Admission must be strongly recommended when the patients with ISSNHL asked about the necessity of admission. We hypothesized that resting, getting out of their social stress, and relief of anxiety might be helpful to their hearing recoveries.


Assuntos
Perda Auditiva Neurossensorial/terapia , Admissão do Paciente , Adulto , Idoso , Feminino , Perda Auditiva Neurossensorial/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
8.
J Craniofac Surg ; 28(3): 806-809, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28468172

RESUMO

OBJECTIVE: Methotrexate (MTX) is very effective when used to treat chronic inflammatory diseases, and also induces apoptosis in nasal polyps (NPs). Increasing evidence suggests that Fas-Fas ligand (FasL) interactions activate multiple pathways involved in the regulation of immune and inflammatory cell functions. The aim of the present study was to identify pathways activated by Fas signaling when NPs were treated with MTX. METHODS: Nasal polyps tissues were cultured using an air-liquid interface organ culture method. Cultures were maintained in the absence or presence of MTX (10 or 100 µM) for 24 hours. The authors used the reverse transcription-polymerase chain reaction method and Western blotting to identify pathways activated by Fas when NPs were treated with MTX. RESULTS: The Fas mRNA expression ratio was unchanged upon MTX treatment, but the FasL mRNA expression ratio was significantly higher in MTX-treated than nontreated polyps. In addition, the expression levels of the Fas and FasL proteins were significantly higher in polyps treated with both 10 and 100 µM MTX compared with nontreated polyps. CONCLUSIONS: Methotrexate induces apoptosis in NPs via the Fas pathway. Future studies should explore the topical use of MTX for NP control. Methotrexate may be a useful alternative steroid-sparing agent for the treatment of NPs.


Assuntos
Apoptose/efeitos dos fármacos , Proteína Ligante Fas/genética , Regulação da Expressão Gênica , Metotrexato/farmacologia , Pólipos Nasais/patologia , Técnicas de Cultura de Órgãos/métodos , RNA Mensageiro/genética , Apoptose/genética , Western Blotting , Proteína Ligante Fas/biossíntese , Humanos , Imunossupressores/uso terapêutico , Pólipos Nasais/tratamento farmacológico , Pólipos Nasais/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos
9.
Auris Nasus Larynx ; 44(5): 517-521, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27955869

RESUMO

OBJECTIVE: Although fascia is widely used as the grafting material in tympanoplasty (TP), unsatisfactory outcomes can result in patients with poor prognostic factors. Recently, cartilage has emerged as a graft material in TP. This study examined the operative outcomes of type I TP using a cartilage shield graft (CSG) in patients with poor prognostic factors. METHODS: This study reviewed the medical records of patients who underwent type I TP using CSG performed by the same surgeon, with over 24 months of follow-up. RESULTS: There were 94 patients (mean age 46 years). Preoperatively, 39 patients had near-total perforation, 29 had a previous TP or myringoplasty, 14 had adhesive otitis media, and 12 had a marginal perforation covering ≥50% of the tympanic membrane area. The mean postoperative air-bone gap was significantly (p<0.0001) reduced compared to preoperative measurements. Postoperatively, tympanic membrane perforation occurred in 2.1% and otorrhea in 6.4%. There were no cases of retraction, adhesion, or lateralization. One subject complained of autophonia and ear fullness. CONCLUSION: Type I TP using CSG has excellent surgical results and minimal complications, even in patients with poor prognostic factors, and should thus be considered in those patients.


Assuntos
Cartilagem da Orelha/transplante , Perfuração da Membrana Timpânica/cirurgia , Timpanoplastia , Adolescente , Adulto , Idoso , Audiometria de Tons Puros , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miringoplastia , Otite Média/complicações , Otite Média/cirurgia , Complicações Pós-Operatórias , Prognóstico , Estudos Retrospectivos , Adulto Jovem
10.
Audiol Neurootol ; 21(3): 165-71, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27161899

RESUMO

OBJECTIVE: To investigate the time course of tinnitus changes in patients receiving cochlear implantation (CI) in a prospective, multicenter setting and to determine related factors. MATERIALS AND METHODS: A total of 79 adult patients who underwent CI were included in this study. We used the same questionnaires sequentially 5 times. The questionnaires included the Visual Analog Scale (VAS) for tinnitus severity, the Tinnitus Handicap Inventory (THI), Beck's Depression Index (BDI), and the Brief Encounter Psychosocial Instrument (BEPSI) for stress assessment. RESULTS: Tinnitus was present in 59 (74.7%) of the 79 study subjects. After CI, tinnitus was eliminated in 10 patients (25%) and improved in 16 patients (40%) of the 40 patients who completed the final questionnaires, and most of the tinnitus reduction occurred in the early period of CI use. In an analysis of psychological functioning with CI, BDI was reduced significantly after CI. Multiple linear regression analysis revealed that preoperative auditory steady-state response (ASSR), THI, and final BDI score were significantly associated with the changes in tinnitus after CI. CONCLUSIONS: Most of the tinnitus reduction occurred within 1 month after CI use, and the changes were significantly associated with THI, ASSR, and BDI scores 6 months after CI. CI is a valuable therapeutic modality in tinnitus of a deafened ear.


Assuntos
Implante Coclear , Surdez/reabilitação , Depressão/psicologia , Zumbido/fisiopatologia , Adulto , Idoso , Surdez/complicações , Surdez/fisiopatologia , Surdez/psicologia , Depressão/complicações , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários , Zumbido/complicações , Zumbido/psicologia , Resultado do Tratamento
11.
Int J Pediatr Otorhinolaryngol ; 78(11): 1843-8, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25190621

RESUMO

OBJECTIVE: Although most preauricular sinuses are located near the anterior limb of the ascending helix, some are located in unusual areas around the auricle, as shown previously in limited reports. This study analyzed the clinical manifestations of congenital periauricular fistulas with unusual fistula locations and the possible relationship with the classical preauricular sinus. METHODS: We reviewed the medical records of patients who underwent congenital periauricular sinus excision by three surgeons and followed them for more than 6 months. Clinical manifestations were compared between classical preauricular sinus (classical group) and congenital periauricular fistula (variant group) patients. RESULTS: The classical and variant groups included 192 and 20 ears each, respectively. In the variant group, the fistula locations were in the ascending helix crus (15 ears, most common), infra-auricular area (3 ears), supra-auricular area (1 ear), and anterior to tragus (1 ear). In ears with fistulas in the ascending helix crus, the fistulous tract most often showed a medial direction (9 ears). There were 4 ears in the variant group with fistulous tracts running toward the postauricular area. CONCLUSIONS: Congenital periauricular fistulas can be located anywhere around the auricle, and also considered the variant of preauricular sinus because the whole tracts were limited to lateral side of temporalis muscle and parotid gland as well as not associated with external auditory canal and facial nerve. Among them, the most common variant was a fistula on the ascending helix crus with short fistulous tract directed medially.


Assuntos
Pavilhão Auricular/anormalidades , Fístula/cirurgia , Adolescente , Pré-Escolar , Pavilhão Auricular/cirurgia , Feminino , Seguimentos , Humanos , Masculino
12.
Ann Otol Rhinol Laryngol ; 123(1): 47-52, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24574423

RESUMO

OBJECTIVES: Surgical procedures for chronic ear disease can be grossly divided into two tympanoplasty procedures: canal wall-up and canal wall-down (CWD) mastoidectomies. The choice depends on the surgeon's preference. Epitympanoplasty with mastoid obliteration (EMO) has shown postoperative results similar to those of CWD mastoidectomy with long-term follow-up. In this study, we compared the outcomes of EMO and CWD mastoidectomy in preoperatively sclerotic mastoid cavities with cholesteatoma, chronic otitis media with poor eustachian tube function, or adhesive otitis media. The operations were performed by the same surgeons in order to eliminate any effect of surgeon preference on the surgical outcomes. METHODS: We reviewed the medical records of patients who underwent tympanoplasty with EMO (EMO group) or CWD mastoidectomy (CWD group) and followed them for more than 28 months. The postoperative outcomes were analyzed and compared. RESULTS: The EMO and CWD groups comprised 132 and 110 ears, respectively. In both groups, the air-bone gaps were significantly reduced after operation. The relapse rates of the groups were similar. Cavity problems were the most common complication in the CWD group. The overall complication rate in the EMO group was significantly lower than that in the CWD group (p = 0.044). CONCLUSIONS: Epitympanoplasty with mastoid obliteration can be considered an alternative procedure to CWD mastoidectomy in patients with preoperatively sclerotic mastoid cavities. It gives similar surgical results and has fewer complications.


Assuntos
Colesteatoma da Orelha Média/cirurgia , Meato Acústico Externo/cirurgia , Processo Mastoide/cirurgia , Timpanoplastia/métodos , Adolescente , Adulto , Idoso , Criança , Colesteatoma da Orelha Média/patologia , Feminino , Seguimentos , Humanos , Masculino , Processo Mastoide/patologia , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Otológicos/métodos , Estudos Retrospectivos , Esclerose , Resultado do Tratamento
13.
Int Forum Allergy Rhinol ; 4(5): 353-6, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24431189

RESUMO

BACKGROUND: Cells of the innate immune system that are implicated in allergy and immunity bind to chitin during tissue infiltration in a process negatively regulated by vertebrate chitinases. Both acidic mammalian chitinase (AMCase) and chitotriosidase (ChT) exert chitinolytic activity. The levels of activities of these enzymes in nasal polyps (NPs) of subjects who smoke or who suffer from allergies are unknown. In the present work, we measured the activities of AMCase and ChT in NPs of smokers and allergic subjects. METHODS: We report a prospective cohort study in a tertiary care facility. AMCase and ChT activities of NPs were measured in buffers of several pH values using the fluorogenic substrate 4-methylumbelliferyl-ß-d-N,N',N″-triacetyl-chitotriose. RESULTS: The activities of AMCase and ChT in NPs did not differ significantly among smokers, nonsmokers, and ex-smokers. AMCase and ChT activities were significantly higher in NPs of allergic subjects than in NPs of those who did not suffer from allergy. CONCLUSION: Increased levels of chitinolytic activities in NPs were associated with the allergic rhinitis. We suggest that control of such rhinitis may help to prevent the development and growth of NPs.


Assuntos
Quitinases/metabolismo , Hexosaminidases/metabolismo , Pólipos Nasais/diagnóstico , Rinite Alérgica/diagnóstico , Fumar , Adulto , Quitina/metabolismo , Estudos de Coortes , Feminino , Corantes Fluorescentes , Humanos , Imunidade Inata , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/enzimologia , Estudos Prospectivos , Rinite Alérgica/enzimologia , Fumar/efeitos adversos , Atenção Terciária à Saúde , Trissacarídeos , Umbeliferonas
14.
Am J Rhinol Allergy ; 27(1): e26-31, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23406595

RESUMO

BACKGROUND: Methotrexate (MTX) is a very effective treatment for chronic inflammatory diseases that induces apoptosis in nasal polyps (NPs). However, the precise apoptotic pathway in NPs remains unclear. The aim of this study was to identify the apoptotic signaling pathways activated by MTX in NPs. METHODS: NP tissues were organ cultured using an air-liquid interface method. Cultures were maintained in the presence or absence of MTX (10 or 100 µM) for 24 hours. To investigate apoptotic signaling in NPs, we performed reverse transcription-polymerase chain reaction and Western blotting. RESULTS: MTX-treated NPs contained significantly increased amounts of the active forms of caspase 8, caspase 9, and caspase 3 and displayed increased cleavage of poly(ADP-ribose) polymerase. Expression of the proapoptotic molecules Bax and Bad at the mRNA and protein levels and of the activated molecules p-Bad and tBid was significantly higher in MTX-treated NPs than in nontreated NPs. In contrast, expression of the antiapoptotic molecule Bcl-2 at the mRNA and protein levels was significantly lower in MTX-treated NPs than in nontreated NPs. Expression of the phosphorylated forms of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) was significantly higher in MTX-treated NPs than in nontreated NPs. In contrast, expression of the phosphorylated form of Akt was significantly lower in MTX-treated NPs than in nontreated NPs. CONCLUSION: MTX induces apoptosis in NPs via caspase cascades and both mitochondria-mediated and p38 MAPK/JNK pathways. We suggest that MTX can be used to treat NPs.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Metotrexato/uso terapêutico , Mitocôndrias/metabolismo , Pólipos Nasais/tratamento farmacológico , Seios Paranasais/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Caspases/metabolismo , Células Cultivadas , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Mitocôndrias/efeitos dos fármacos , Pólipos Nasais/patologia , Técnicas de Cultura de Órgãos , Seios Paranasais/patologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , Proteína de Morte Celular Associada a bcl/genética , Proteína de Morte Celular Associada a bcl/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
15.
Biochem Biophys Res Commun ; 411(2): 259-64, 2011 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-21723260

RESUMO

Galectin-9 exhibited potent and selective eosinophil chemoattractant activity and attracted eosinophils in vitro and in vivo. Nasal polyposis is a chronic inflammatory disease of the upper airway characterized by the marked presence of inflammatory cells, particularly eosinophils. Thus, galectin-9 may be implicated in the pathogenesis of nasal polyposis. The study was designed to investigate whether interferon-gamma (IFN-γ) can induce the augmentation of galectin-9 expression and induce the expression of galectin-9 in nasal polyps. We examined the correlation between galectin-9 expression and eosinophil infiltration in nasal polyps. In addition, we identified the signaling pathways involved in the elevation of galectin-9 expression in response to IFN-γ. Our data demonstrate that the involvement of mitogen-activated protein kinases (MAPKs), phosphatidylinositol 3 phosphate kinase (PI3K), and Janus kinase/signal transducer and activator of transcription (JAK/STAT) may play important roles in the selective recruitment of eosinophils in nasal polyp tissues through the production of galectin-9. These findings suggest that galectin-9 expression is associated with eosinophil infiltration in polyps of patients with nasal polyposis.


Assuntos
Eosinófilos/imunologia , Galectinas/biossíntese , Interferon gama/imunologia , Janus Quinases/metabolismo , Pólipos Nasais/imunologia , Células Cultivadas , Eosinófilos/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibroblastos/imunologia , Humanos , Interferon gama/farmacologia , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fatores de Transcrição STAT/metabolismo
16.
Am J Rhinol Allergy ; 25(1): 12-4, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21711963

RESUMO

BACKGROUND: Chitin is a recognition element for tissue infiltration by innate cells implicated in allergy and immunity. This process can be negatively regulated by vertebrate chitinases. Both acidic mammalian chitinase (AMCase) and chitotriosidase (ChT) have chitinolytic activity. This study aimed to determine the activities of AMCase and ChT in nasal polyps (NPs), as well as their in situ localization in NP tissue. METHODS: AMCase and ChT activities in NPs were compared with those in inferior turbinate tissue samples. Tissue samples were measured for AMCase and ChT activities at a range of pHs using the fluorogenic substrate 4-methylumbelliferyl-beta-d-N,N',N''-triacetyl-chitotriose. Double immunofluorescent staining for the localization of both AMCase and ChT was performed using NP cryosections. RESULTS: Both AMCase and ChT displayed markedly increased chitinolytic activity in all NPs, compared with inferior turbinate tissues. Double immunofluorescent staining revealed that CD68 highlighted monocytes in the submucosa of NP and these cells disclosed coexpression of AMCase and ChT. CD31 detected capillary endothelial cells, but did not express any AMCase and ChT. CONCLUSION: The increased chitinolytic activities of AMCase and ChT in NPs may be important in NP pathogenesis, suggesting that inhibition of chitinolytic activity may be a novel therapeutic strategy for the treatment of NPs.


Assuntos
Quitinases/metabolismo , Hexosaminidases/metabolismo , Monócitos/metabolismo , Pólipos Nasais/enzimologia , Peptídeo Hidrolases/metabolismo , Rinite/enzimologia , Sinusite/enzimologia , Conchas Nasais/enzimologia , Antígenos CD/biossíntese , Antígenos de Diferenciação Mielomonocítica/biossíntese , Quitina/imunologia , Quitina/metabolismo , Doença Crônica , Humanos , Monócitos/imunologia , Monócitos/patologia , Pólipos Nasais/patologia , Rinite/imunologia , Rinite/fisiopatologia , Sinusite/imunologia , Sinusite/fisiopatologia , Conchas Nasais/patologia
17.
Otolaryngol Head Neck Surg ; 145(4): 660-5, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21613625

RESUMO

OBJECTIVES/HYPOTHESIS: Chronic rhinosinusitis (CRS), otitis media with effusion (OME), and allergic rhinitis (AR) are common conditions that have been associated with hypertrophied adenoids in children, and adenoidectomy is clinically recommended. The investigators assayed the expression level and site of acidic mammalian chitinase (AMCase) and chitotriosidase (ChT) in hypertrophied adenoids of children to determine the expression levels of 2 chitinases in relation to CRS, OME, and AR. STUDY DESIGN: A prospective cohort study. SETTING: A tertiary care facility. METHODS: Hypertrophied adenoids from 41 children were harvested during adenoidectomy. Medical records were reviewed and the subjects were grouped according to the presence of CRS, OME, and AR. Messenger RNA (mRNA) and protein expression of AMCase and ChT in adenoid tissues was assessed by reverse transcription polymerase chain reaction and Western blotting. Immunohistochemical staining revealed the sites of AMCase and ChT expression. RESULTS: mRNA and protein of AMCase and ChT were present in adenoids of all subjects. CRS was a significant variable in AMCase mRNA and protein expression. CRS, OME, and AR were significant variables in ChT mRNA and protein expression. Both AMCase and ChT were expressed in histiocytes and vascular endothelial cells of adenoid tissues. CONCLUSIONS: The findings suggest that chitin-containing pathogens or dysregulated immune responses to them in the hypertrophied adenoids of children could be factors contributing to CRS, OME, and AR via AMCase or ChT overexpression.


Assuntos
Tonsila Faríngea/metabolismo , Tonsila Faríngea/patologia , Quitinases/metabolismo , Hexosaminidases/metabolismo , Adolescente , Western Blotting , Criança , Pré-Escolar , Doença Crônica , Eletroforese em Gel de Poliacrilamida , Feminino , Humanos , Hipertrofia , Imuno-Histoquímica , Masculino , Otite Média com Derrame/metabolismo , Otite Média com Derrame/patologia , Estudos Prospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Rinite/metabolismo , Rinite/patologia , Sinusite/metabolismo , Sinusite/patologia
18.
Otolaryngol Head Neck Surg ; 141(4): 462-6, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19786213

RESUMO

OBJECTIVE: Chitin is a recognition element for tissue infiltration by innate cells implicated in allergy and helminth immunity, and this process can be negatively regulated by vertebrate chitinases. Acidic mammalian chitinase (AMCase) and chitotriosidase (ChT) have chitinolytic activity, but little is known about their roles in nasal polyps. STUDY DESIGN: A prospective controlled study. SETTING: A tertiary referral center. SUBJECTS AND METHODS: Nineteen subjects with nasal polyps and 12 subjects with deviated nasal septums were recruited to obtain inferior turbinate mucosa samples. The expression levels of AMCase and ChT were compared in nasal polyp and inferior turbinate tissue samples. The tissue samples were analyzed by reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemical staining. RESULTS: AMCase and ChT were detected in all nasal polyps and inferior turbinate tissues. AMCase and ChT messenger RNA and protein expression were significantly higher in nasal polyps than in inferior turbinate tissues. In nasal polyps, AMCase-positive and ChT-positive cells were detected in the epithelium, inflammatory cells, and submucosal gland. CONCLUSIONS: AMCase and ChT may be important mediators in the pathogenesis of nasal polyps. Nasal polyps appear to have elevated levels of chitinases, and the presence or growth of chitin-containing pathogens might enhance chitinase expression, resulting in nasal polyp formation and growth in susceptible individuals.


Assuntos
Quitinases/metabolismo , Hexosaminidases/metabolismo , Mucosa Nasal/enzimologia , Pólipos Nasais/enzimologia , Quitinases/genética , Hexosaminidases/genética , Humanos , Imuno-Histoquímica , Septo Nasal/enzimologia , RNA Mensageiro/análise
19.
Auris Nasus Larynx ; 36(4): 487-90, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19135324

RESUMO

Lymphoepithelial carcinoma (LEC) of the maxillary sinus is a very rare neoplasm that shares some characteristics with nasopharyngeal carcinoma. Epstein-Barr virus (EBV) has been reported to be associated with LEC located outside of the nasopharynx in Asian populations. A case report of a 64-year-old Asian female with right-sided cheek mass which was diagnosed preoperatively as a maxillary mass by paranasal sinus computed tomography scan is presented. Because maxillary sinus cancer with orbital invasion was considered, she underwent surgical removal of a mass. Final pathology revealed LEC, which is presented in our report. However, in situ hybridization assays returned negative results for Epstein-Barr virus. The patient underwent postoperative chemoradiotherapy, and has remained disease-free during 3-year follow-up. Although a few cases in the maxillary LEC have been reported, this is the first report describing the diagnosis and treatment of LEC occurred in the maxillary sinus. Surgical removal and adjuvant chemoradiotherapy may be useful in the treatment of more advanced maxillary LEC.


Assuntos
Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Neoplasias do Seio Maxilar/diagnóstico por imagem , Neoplasias do Seio Maxilar/patologia , Órbita/diagnóstico por imagem , Órbita/patologia , Tomografia Computadorizada por Raios X , Carcinoma de Células Escamosas/cirurgia , Quimioterapia Adjuvante , Face/patologia , Feminino , Humanos , Neoplasias do Seio Maxilar/cirurgia , Pessoa de Meia-Idade , Invasividade Neoplásica , Radioterapia Adjuvante , Tela Subcutânea/patologia
20.
Am J Rhinol ; 22(5): 533-6, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18954516

RESUMO

BACKGROUND: The transsphenoidal approach (TSA) is the procedure of choice for the vast majority of pituitary neoplasms. Sinusitis is considered a contraindication to TSA because of possible transcranial spread of infection. This study was performed to determine if TSA for pituitary tumors could be extended to patients with pituitary adenoma and chronic rhinosinusitis (CRS). METHODS: Medical records, including rhinologic outcomes, were retrospectively assessed in 11 consecutive patients who underwent concurrent TSA and endoscopic sinus surgery (ESS) because of pituitary adenoma and CRS between May 2004 and October 2007. RESULTS: The 11 patients consisted of 5 men and 6 women, with a mean age of 55 years (range, 31-69 years) and average follow-up of 24.4 months (range, 6-44 months). Preoperatively, all patients had symptoms of CRS, but none had acute exacerbation of rhinosinusitis. All patients had CRS and two had nasal polyps. TSA was via the transcolumellar transseptal approach in seven patients and the transnasal approach in four patients. No postoperative complications due to ESS were observed. Two patients, including one with sphenoid aspergillosis, had preoperative unilateral sphenoid sinusitis, which was managed by ESS on the involved side, with TSA performed concurrently through the contralateral healthy sphenoid sinus. There was one case of postoperative sphenoid sinusitis and one case of septal perforation due to TSA. There were no postoperative intracranial complications, including meningitis and brain abscess. CONCLUSION: Concurrent TSA and ESS can be performed in selected patients with CRS and pituitary adenoma. Future studies should involve more patients and longer follow-ups.


Assuntos
Procedimentos Cirúrgicos Otorrinolaringológicos/métodos , Neoplasias Hipofisárias/cirurgia , Rinite/cirurgia , Sinusite/cirurgia , Adulto , Idoso , Doença Crônica , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/diagnóstico , Complicações Pós-Operatórias , Estudos Retrospectivos , Rinite/complicações , Rinite/diagnóstico , Sinusite/complicações , Sinusite/diagnóstico , Osso Esfenoide/cirurgia , Resultado do Tratamento
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