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1.
Mar Drugs ; 22(1)2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38248664

RESUMO

This study aims to explore the potential inhibition effects of staurosporine isolated from a Streptomyces sp. SNC087 strain obtained from seawater on nasal polyps. Staurosporine possesses antimicrobial and antihypertensive activities. This research focuses on investigating the effects of staurosporine on suppressing the growth and development of nasal polyps and elucidating the underlying mechanisms involved. The experimental design includes in vitro and ex vivo evaluations to assess the inhibition activity and therapeutic potential of staurosporine against nasal polyps. Nasal polyp-derived fibroblasts (NPDFs) were stimulated with TGF-ß1 in the presence of staurosporine. The levels of α-smooth muscle actin (α-SMA), collagen type-I (Col-1), fibronectin, and phosphorylated (p)-Smad 2 were investigated using Western blotting. VEGF expression levels were analyzed in nasal polyp organ cultures treated with staurosporine. TGF-ß1 stimulated the production of Col-1, fibronectin, and α-SMA and was attenuated by staurosporine pretreatment. Furthermore, these inhibitory effects were mediated by modulation of the signaling pathway of Smad 2 in TGF-ß1-induced NPDFs. Staurosporine also inhibits the production of VEGF in ex vivo NP tissues. The findings from this study will contribute to a better understanding of staurosporine's role in nasal polyp management and provide insights into its mechanisms of action.


Assuntos
Pólipos Nasais , Streptomyces , Humanos , Fibronectinas , Pólipos Nasais/tratamento farmacológico , Estaurosporina/farmacologia , Fator de Crescimento Transformador beta1 , Fator A de Crescimento do Endotélio Vascular
2.
J Craniofac Surg ; 34(1): e88-e90, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35949023

RESUMO

Sinonasal hemangiomas are relatively rare among the hemangiomas that occur from the head and neck parts. According to their histopathologic findings, they are classified as capillary, cavernous, or venous type. Some cases of capillary or cavernous hemangioma that occur from the inferior turbinate have been reported. However, there was no reported case of venous hemangioma arising from the inferior turbinate. We present a case of 67-year-old male who has venous hemangioma of the left inferior turbinate whose initial symptoms were watery rhinorrhea and postnasal drip. With this study, although uncommon, venous hemangioma should be considered as a differential diagnosis in patient with mass lesion of the inferior turbinate.


Assuntos
Hemangioma Cavernoso , Hemangioma , Masculino , Humanos , Idoso , Conchas Nasais/diagnóstico por imagem , Conchas Nasais/cirurgia , Conchas Nasais/patologia , Hemangioma/diagnóstico por imagem , Hemangioma/cirurgia , Hemangioma Cavernoso/diagnóstico , Diagnóstico Diferencial
3.
J Craniofac Surg ; 34(5): e451-e452, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37010325

RESUMO

Hemangiomas, which originate in the sinonasal area, are not common among the various types of tumors from the head and neck region. Mechanisms for the formation of the tumor are yet to be discovered, and a few factors such as trauma, infection, oncogene, and some hormones are considered to take a role in the occurrence and growth of the tumor. Hemangiomas are classified for their histologic features as cavernous, capillary, and mixed types. There are a few reported cases of cavernous hemangiomas of the maxillary sinus, ethmoid sinus, middle and inferior nasal turbinate, and nasal septum. However, a case of cavernous hemangioma from the inferior nasal meatus, on the lateral wall to be precise, has never been reported. The authors are the first to report a case of a 69-year-old female patient who had cavernous hemangioma which was originated from the lateral wall of the inferior nasal meatus and successfully managed.


Assuntos
Hemangioma Cavernoso , Hemangioma , Feminino , Humanos , Idoso , Hemangioma Cavernoso/diagnóstico por imagem , Hemangioma Cavernoso/cirurgia , Cavidade Nasal/diagnóstico por imagem , Cavidade Nasal/patologia , Septo Nasal/diagnóstico por imagem , Septo Nasal/cirurgia , Septo Nasal/patologia , Seio Maxilar/patologia
4.
Curr Issues Mol Biol ; 44(11): 5815-5826, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36421679

RESUMO

Sargassum horneri is a seaweed species with diverse bioactivities. However, its antifibrotic effects during nasal polyp (NP) formation are not clearly understood. Therefore, we investigated the inhibitory effect of S. horneri on fibrosis progression in NP-derived fibroblasts (NPDFs) and NP tissues ex vivo. NPDFs were stimulated with TGF-ß1 in the presence or absence of S. horneri ethanol extract (SHE). The extracellular matrix (ECM) protein production levels, myofibroblast differentiation (α-smooth muscle actin, α-SMA), and phosphorylation of Smad 2/3 and -ERK in TGF-ß1-stimulated NPDFs were investigated using western blotting. Further, the contractile activity of SHE was assessed by performing a collagen gel contraction assay. The expression levels of collagen-1, fibronectin, and α-SMA were investigated in NP organ cultures treated with SHE. TGF-ß1 stimulated ECM protein expression, myofibroblast differentiation, and collagen contractile activity while these were attenuated by pretreatment with SHE. We also found antifibrotic effect of SHE on ex vivo NP tissues. The antifibrotic effects of SHE were modulated through the attenuation of Smad 2/3 and ERK signaling pathways in TGF-ß1-stimulated NPDFs. In conclusion, SHE inhibited ECM protein accumulation and myofibroblast differentiation during NP remodeling. Thus, SHE may be helpful as a treatment for NP recurrence after endoscopic sinus surgery.

5.
J Craniofac Surg ; 33(3): e298-e300, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34560754

RESUMO

ABSTRACT: Extranasopharyngeal angiofibroma which occurs in all head and neck regions is extremely rare. Unlike most angiofibromas which show nasal congestion and recurrent epistaxis as their symptoms, extranasopharyngeal angiofibromas (ENAF) may lead to various symptoms depending on their location. Nasal septum is the most frequent site of origin of ENAF. No study of ENAF originating in natural ostium of maxillary sinus has been reported. We present a case of 27-year-old male who has extranasophar- yngeal angiofibroma arising from the natural ostium of maxillary sinus in an adult patient whose symptom was right sided nasal obstruction. With this study, although uncommon, angiofibroma should be considered as a differential diagnosis in patient with mass lesion in the middle nasal meatus.


Assuntos
Angiofibroma , Neoplasias Nasais , Adulto , Angiofibroma/diagnóstico por imagem , Angiofibroma/cirurgia , Humanos , Masculino , Seio Maxilar/diagnóstico por imagem , Seio Maxilar/patologia , Seio Maxilar/cirurgia , Cavidade Nasal/patologia , Septo Nasal/patologia , Neoplasias Nasais/diagnóstico
6.
J Craniofac Surg ; 32(6): e545-e546, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-33534306

RESUMO

ABSTRACT: Isolated intraorbital mucocele without anatomical communication between the sinus and orbital cavity, and all orbital walls are intact is rare. It may lead to many orbital symptoms including proptosis, diplopia, orbital pain. Traditionally, many cases of typical paranasal sinus mucocele are successfully treated with endoscopic marsupialization. Most of the isolated intraorbital mucoceles were treated with complete removal of the mucocele via an external approach. However, there are many disadvantages of the external approach, and a case of isolated intraorbital mucocele in medial orbit treated by endoscopic intranasal marsupialization was reported. Here, the authors report a case of isolated orbital mucocele in inferior orbit treated by endoscopic intranasal marsupialization.


Assuntos
Exoftalmia , Mucocele , Doenças dos Seios Paranasais , Adulto , Endoscopia , Humanos , Masculino , Mucocele/diagnóstico por imagem , Mucocele/cirurgia , Órbita/diagnóstico por imagem , Órbita/cirurgia , Doenças dos Seios Paranasais/diagnóstico por imagem , Doenças dos Seios Paranasais/cirurgia
7.
Mar Drugs ; 16(9)2018 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-30201895

RESUMO

Nasal polyps (NPs) are a multifactorial disorder associated with a chronic inflammatory state of the nasal mucosa. Fucoxanthin (Fx) is a characteristic orange carotenoid obtained from brown algae and has diverse immunological properties. The present study investigated whether Fx inhibits fibrosis-related effects in nasal polyp-derived fibroblasts (NPDFs) and elucidated the molecular signaling pathways involved. The production of collagen type I (Col-1) was investigated in NP tissue via immunohistochemistry and western blot analysis. NPDFs were treated with transforming growth factor (TGF)-ß1 (1 ng/mL) in the presence or absence of Fx (5⁻30 µM). The levels of α-smooth muscle actin (α-SMA), Col-1, and phosphorylated (p)-Smad 2/3, signal protein-1 (SP-1), MAPKs (mitogen-activated protein kinases), and Akt were measured by western blot analysis. The expression of Col-1 was detected in NP tissues. TGF-ß1 stimulated the production of α-SMA and Col-1, and stimulated the contraction of collagen gel. However, pretreatment with Fx attenuated these effects. Furthermore, these inhibitory effects were mediated through modulation of both Smad 2/3 and Akt/SP-1 signaling pathways in TGF-ß1-induced NPDFs. The results from the present study suggest that Fx may be a novel anti-fibrotic agent for the treatment of NP formation.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Mucosa Nasal/patologia , Pólipos Nasais/patologia , Transdução de Sinais/efeitos dos fármacos , Xantofilas/farmacologia , Adulto , Células Cultivadas , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/fisiologia , Fibrose/prevenção & controle , Humanos , Masculino , Miofibroblastos/efeitos dos fármacos , Miofibroblastos/fisiologia , Mucosa Nasal/citologia , Mucosa Nasal/efeitos dos fármacos , Pólipos Nasais/tratamento farmacológico , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Fator de Transcrição Sp1/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Xantofilas/uso terapêutico
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.
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
10.
Biochem Biophys Res Commun ; 379(2): 255-60, 2009 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-19101504

RESUMO

We used an organ culture of nasal polyps (NP) to provide ex vivo model to study the expression of pro-angiogenic cytokines and the effect of glucocorticoids in the pathogenesis of NP. Glucocorticoids are the drugs of choice for clinical treatment of NP; however, their mechanism of action is not fully understood. The cell-cell and cell-matrix integrity is well maintained in cultured NP. Expression of IL-6, IL-8, bFGF, GRO, and MCP-1 was increased in cultured NP compared to pre-cultured NP. Expression levels of IL-6, bFGF, and GRO in cultured NP were downregulated by dexamethasone (DEX) treatment, while MCP-1 expression was not suppressed. Further, RT-PCR and immunohistochemical analysis showed that HIF-1alpha and VEGF were suppressed in DEX-treated NP compared to untreated NP. Taken together, these results suggest that ex vivo organ culture can be considered a useful model to study the pathogenesis and regulation of pro-angiogenic cytokines in nasal polypogenesis.


Assuntos
Citocinas/antagonistas & inibidores , Citocinas/biossíntese , Dexametasona/metabolismo , Modelos Biológicos , Pólipos Nasais/fisiopatologia , Neovascularização Patológica/metabolismo , Dexametasona/farmacologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Subunidade alfa do Fator 1 Induzível por Hipóxia/biossíntese , Pólipos Nasais/metabolismo , Pólipos Nasais/patologia , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , Técnicas de Cultura de Órgãos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/biossíntese
11.
Auris Nasus Larynx ; 35(3): 437-9, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17980991

RESUMO

Hamartoma in the nasopharynx of the children is especially rare. Most documented cases occurred in infants, with characteristic histologic features of a mixture of various mesenchymal tissues. We report a case arising in a 15-year-old male patient, who presented with a 1-month history of right-sided nasal obstruction. The mass was resected endoscopically and confirmed histologically as a lymphoid hamartoma. We report and discuss the pathological features of this rare nasopharyngeal hamartoma.


Assuntos
Hamartoma/diagnóstico , Doenças Nasofaríngeas/diagnóstico , Adolescente , Diagnóstico Diferencial , Endoscopia , Hamartoma/patologia , Hamartoma/cirurgia , Humanos , Masculino , Obstrução Nasal/etiologia , Obstrução Nasal/patologia , Obstrução Nasal/cirurgia , Doenças Nasofaríngeas/patologia , Doenças Nasofaríngeas/cirurgia , Nasofaringe/patologia , Nasofaringe/cirurgia , Tomografia Computadorizada por Raios X
12.
Int J Mol Med ; 42(4): 2213-2220, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30015862

RESUMO

Phlorotannins (PTNs), a group of phenolic compounds from seaweeds, have diverse bioactivities. However, there has been no report on their antifibrotic effects during nasal polyp (NP) formation. In the present study, the effect of PTNs on transforming growth factor (TGF)­ß1­induced profibrotic responses in nasal polyp­derived fibroblasts (NPDFs) were determined and the relevant signaling pathways were investigated. The expression levels of collagen type­1 (Col­1) and fibronectin in NP tissues were measured by western blot analysis and immunohistochemistry. The NPDFs were treated with TGF­ß1 (1 ng/ml) in the presence or absence of PTNs (5­30 µg/ml). The expression levels of α­smooth muscle actin (α­SMA), Col­1, fibronectin, and phosphorylated­small mothers against decapentaplegic (Smad)2/3 in NPDFs were measured by western blot analysis. The contractile activity of the NPDFs was determined by a collagen gel contraction assay. Col­1 and fibronectin proteins were found to be expressed in NP tissues. PTNs had no significant cytotoxic effect on TGF­ß1­induced NPDFs. TGF­ß1 induced the expression α­SMA, Col­1 and fibronectin, and stimulated fibroblast­mediated contraction of collagen gel. However, pre­treatment with PTNs inhibited the expression of these proteins. The inhibitory effects were mediated through the suppression of Smad2/3 signaling pathways in TGF­ß1­induced NPDFs. These resulted suggested that PTNs may be important in inhibiting myofibroblast differentiation and extracellular matrix protein accumulation in NP formation through the Smad2/3 signaling pathway.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Proteínas da Matriz Extracelular/biossíntese , Regulação da Expressão Gênica/efeitos dos fármacos , Miofibroblastos/metabolismo , Pólipos Nasais/metabolismo , Taninos/farmacologia , Fator de Crescimento Transformador beta1/metabolismo , Feminino , Humanos , Masculino , Miofibroblastos/patologia , Pólipos Nasais/patologia , Alga Marinha/química , Taninos/química
13.
Int J Mol Med ; 40(6): 1950-1956, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29039451

RESUMO

Marine algae are rich sources of biologically active compounds that may present useful leads in the development of pharmaceuticals, nutraceuticals, and functional foods. The main aim of this study was to identify the possible anti-inflammatory effects of Distromium decumbens in nasal polyp-derived fibroblasts (NPDFs) and its associated mechanism of action. NPDFs were stimulated by Pseudomonas aeruginosa lipopolysaccharide (PA-LPS) and treated with an ethanolic extract of Distromium decumbens (DDE). The production of interleukin-6 (IL-6) and IL-8 in the supernatant, the phosphorylation of mitogen-activated protein kinase (MAPK) molecules [extracellular signal-related kinase 1/2 (ERK1/2), c-Jun N-terminal kinase and p38 MAPK] and Akt, and the activation of nuclear factor-κB (NF-κB) were assayed in the PA-LPS-stimulated NPDFs untreated or treated with DDE. The expression levels of IL-6 and IL-8 in PA-LPS-exposed NPDFs were detected using enzyme-linked immunosorbent assays. The mechanisms by which DDE regulates cellular signaling cascades were investigated using electrophoretic mobility shift assays and western blot analysis. Functional validation was performed by measuring the inhibitory effects of DDE on neutrophil migration in vitro. DDE reduced the expression of IL-6 and IL-8 stimulated by PA-LPS in NPDFs. The activation of ERK1/2, Akt and NF-κB by PA-LPS was inhibited by DDE. Inhibitors of ERK1/2, Akt and NF-κB inhibited the expression of IL-6 and IL-8. In addition, DDE significantly attenuated PA-LPS-induced migration of differentiated HL-60 cells. The present findings suggest that DDE potently inhibits inflammation through the ERK1/2, Akt and NF-κB signaling pathways in NPDFs.


Assuntos
Inflamação/tratamento farmacológico , Pólipos Nasais/tratamento farmacológico , Phaeophyceae/química , Animais , Diferenciação Celular/efeitos dos fármacos , Citocinas/genética , Fibroblastos/efeitos dos fármacos , Humanos , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/microbiologia , Lipopolissacarídeos/toxicidade , Camundongos , Pólipos Nasais/induzido quimicamente , Pólipos Nasais/genética , Pólipos Nasais/patologia , Fosforilação , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/patogenicidade , Transdução de Sinais/efeitos dos fármacos
14.
Otolaryngol Head Neck Surg ; 135(6): 928-32, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17141086

RESUMO

OBJECTIVE: To evaluate expression of cyclooxygenase (COX)-2 and 5-lipoxygenase (5-LO) associated with interleukin (IL)-4 promoter polymorphism -590 in nasal polyp tissues. STUDY DESIGN AND SETTING: A prospective controlled study. A venous blood sample was taken to determine the genotype in 61 nasal polyp subjects. The C-590T variant was determined by the polymerase chain reaction-restriction fragment length polymorphism method. The expression of 5-LO and COX-2 was determined with immunohistochemical staining in 37 nasal polyp tissues associated with genotype. RESULTS: The genotype frequencies at position -590 of the IL-4 gene in the patients with nasal polyp were C/C (8.20%), C/T (40.98%), and T/T (50.82%). There was no significantly increased expression of COX-2 among genotypes. The 5-LO expression was significantly increased in C/C compared with C/T and T/T. CONCLUSION: We suggested that the IL-4 promoter polymorphism -590 C/C is associated with the expression of 5-LO in the patients with nasal polyp.


Assuntos
Araquidonato 5-Lipoxigenase/metabolismo , Ciclo-Oxigenase 2/metabolismo , Interleucina-4/genética , Pólipos Nasais/genética , Regiões Promotoras Genéticas , Estudos de Casos e Controles , Genótipo , Humanos , Imuno-Histoquímica , Pólipos Nasais/metabolismo , Polimorfismo Genético , Estudos Prospectivos
15.
Acta Otolaryngol ; 126(12): 1339-41, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17101598

RESUMO

Mucormycosis of the nasal cavity and paranasal sinuses is an uncommon opportunistic fungal infection, which often has an aggressive, life-threatening course. Patients who have this condition are generally diabetic or immunosuppressed. However, mucormycosis can also occur in immunocompetent individuals. The most effective treatment consists of reversal of the source of immunocompromise, immediate surgical debridement and administration of systemic amphotericin B. No consensus has been reached regarding the appropriate surgical treatment or the total dose of amphotericin B. We present the case of a patient suffering from localized bilateral paranasal mucormycosis who was treated by means of endoscopic sinus surgery and administration of systemic amphotericin B. We suggest that endoscopic sinus surgery is the choice of treatment for localized paranasal mucormycosis in an immunocompetent patient, and that the total dose of amphotericin B can be determined by the extent of disease and the postoperative endoscopic findings.


Assuntos
Mucormicose , Sinusite/microbiologia , Idoso , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Endoscopia , Humanos , Imunocompetência , Masculino , Mucormicose/diagnóstico , Mucormicose/terapia , Sinusite/terapia
16.
Acta Otolaryngol ; 126(9): 910-5, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16864486

RESUMO

CONCLUSION: The lipopolysaccharide (LPS)-induced chinchilla otitis media (OM) model was proven useful in screening anti-inflammatory agents for topical use. Both 1% rimexolone and 1% dexamethasone are effective in reducing the volume of middle ear effusion and mucosal thickness compared with control groups. Topical corticosteroid therapy was efficacious in reducing middle ear mucosal inflammation. OBJECTIVE: OM is one of the most common diseases in the pediatric population. Our previous studies have shown that treatment with systemic antibiotics and corticosteroids was more efficacious than antibiotics alone. The purpose of this study was to determine the effectiveness of topically applied corticosteroids on the outcome of OM. The long-term goal of this study was to develop a better method of OM treatment by demonstrating effectiveness of topically applied anti-inflammatory agents, such as corticosteroids, avoiding systemic side effects. MATERIALS AND METHODS: Three experimental groups were studied in chinchillas. OM with effusion was induced in all groups by injecting LPS. Group 1 consisted of controls in three subgroups as follows. Control-LPS alone, vehicle of dexamethasone (control-dexa), vehicle of rimexolone (control-rimex). Group 2 was treated with dexamethasone and included subgroups of separate concentrations of dexamethasone: 0.1% and 1% suspensions. Group 3 was treated with rimexolone and included subgroups of separate concentrations of rimexolone: 0.1% and 1% suspensions. A total of 58 animals were used: 18 for controls and 40 for experimental groups. All test substances (saline, control-dexa, control-rimex, dexamethasone and rimexolone, 200 microl) were injected at -2, 48 and 60 h; LPS was injected at 0 h. Animals were monitored by daily otomicroscopy. After 4 days, samples of middle ear effusion (MEE) were collected for analysis and temporal bones were harvested for histopathological studies. RESULTS: At the end of 4 days, only in five ears (3/20 with 1% dexamethasone, 1/20 with 1% rimexolone, and 1/20 with 0.1% rimexolone) had the fluid diminished to the point of being unobservable. The volume of MEE, thickness of mucoperiosteum, and the degree of inflammation of middle ear mucosa with 1% dexamethasone and 1% rimexolone was significantly less compared with other groups.


Assuntos
Dexametasona/farmacologia , Glucocorticoides/farmacologia , Otite Média com Derrame/tratamento farmacológico , Pregnadienos/farmacologia , Administração Tópica , Animais , Chinchila , Modelos Animais de Doenças , Feminino , Masculino , Microscopia , Mucosa/efeitos dos fármacos , Mucosa/patologia , Otite Média com Derrame/patologia , Periósteo/efeitos dos fármacos , Periósteo/patologia , Distribuição Aleatória , Osso Temporal/patologia
17.
Int Forum Allergy Rhinol ; 6(7): 731-6, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27012683

RESUMO

BACKGROUND: The "a disintegrin and metalloproteases" (ADAMs) are a multifunctional gene family that contribute to the homeostasis of the extracellular matrix, transduction of specific intracellular signals, organogenesis, inflammation, tissue remodeling, adhesion, and cell migration. ADAM17 is the best-characterized of the "sheddases," and its putative substrates are widespread, including various inflammatory modulators. ADAM10 is the most similar to ADAM17 in terms of protein sequence and the structural properties of their catalytic domains. The objective of this work was to assess the roles of ADAM17 and ADAM10 in nasal polyps (NPs) by measuring their expression. METHODS: The expression of ADAM10 and 17 was investigated in NPs at endonasal sinus surgery (n = 15) and compared with that in inferior turbinate mucosa samples obtained from nonallergic hypertrophic rhinitis patients (n = 15). Tissue samples were analyzed by real-time polymerase chain reaction (PCR), Western blotting, and immunohistochemical staining. RESULTS: The ADAM17 messenger RNA (mRNA) and protein levels were significantly higher in the inferior turbinate than in NPs (p < 0.05). The ADAM10 mRNA and protein levels did not differ significantly between NPs and inferior turbinates (p > 0.05). ADAM10 and ADAM17 were expressed primarily in inflammatory cells, submucosal glandular cells, and lining epithelial cells. CONCLUSION: ADAM17 may contribute to the development of NPs in contrast to ADAM10, based on their expression patterns. It may be important to discover the role of ADAM17 in the development of NP and helpful to examine the specific mechanism of the development of NPs.


Assuntos
Proteína ADAM10/metabolismo , Proteína ADAM17/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Proteínas de Membrana/metabolismo , Pólipos Nasais/metabolismo , Proteína ADAM10/genética , Proteína ADAM17/genética , Secretases da Proteína Precursora do Amiloide/genética , Humanos , Proteínas de Membrana/genética , Pólipos Nasais/genética , Pólipos Nasais/cirurgia , Seios Paranasais/metabolismo , Seios Paranasais/cirurgia , RNA Mensageiro/metabolismo
18.
Otolaryngol Head Neck Surg ; 132(4): 532-6, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15806040

RESUMO

OBJECTIVE: To describe and evaluate the mediolateral graft tympanoplasty for the reconstruction of anterior or subtotal tympanic membrane (TM) perforation. STUDY DESIGN AND SETTING: Retrospective study of 100 patients who underwent the mediolateral graft tympanoplasty at community and tertiary care centers from 1995 to 2001. All patients underwent preoperative and postoperative audiograms. Posterior tympanomeatal flap is elevated same as in the medial (underlay) graft tympanoplasty. Anterior-medial canal skin is elevated down to the annulus. At the annulus, only squamous epithelial layer of TM is elevated up to anterior half of the TM perforation. Temporalis fascia is grafted medial (underlay) to the posterior half of the perforation and lateral (overlay) to the anterior half of the de-epithelialized TM perforation, up to the annulus. Anterior canal skin is rotated to cover the fascia graft and TM perforation as a second-layer closure. Patients were followed for at least 6 months. Outcome was considered successful if the TM is intact. RESULTS: There were 3 failures (97% success rate), attributable to a postoperative infection, anterior blunting, and recurrent cholesteatoma, respectively. There was no significant postoperative hearing loss compared with preoperative hearing. More than 70% of the operated ears had hearing improvement of 0-40 dB (0-10 dB in 19% of ears, 11-20 dB in 44%, 21-30 dB in 7%, and 31-40 dB in 4%) even without ossiculoplasty. With ossiculoplasty using either partial ossicular replacement prosthesis (PORP, 15%) or total ossicular replacement prosthesis (TORP, 11%), there were various degree of hearing improvement from 11 to 30 dB. CONCLUSION AND SIGNIFICANCE: The mediolateral graft method is superior to the traditional medial or lateral graft technique for the reconstruction of large anterior or subtotal TM perforation. This new method should help otologic surgeons to improve outcome of tympanoplasty for anterior or total TM perforation. EBM RATING: C-1.


Assuntos
Retalhos Cirúrgicos , Perfuração da Membrana Timpânica/cirurgia , Timpanoplastia/métodos , Audiometria de Tons Puros , Limiar Auditivo , Colesteatoma da Orelha Média/cirurgia , Seguimentos , Humanos , Processo Mastoide/cirurgia , Prótese Ossicular , Complicações Pós-Operatórias/diagnóstico , Desenho de Prótese , Recidiva , Estudos Retrospectivos , Fatores de Risco
19.
Int Forum Allergy Rhinol ; 5(11): 1036-41, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26250527

RESUMO

BACKGROUND: A disintegrin and metalloprotease (ADAM) is a multifunctional gene family that contributes to the homeostasis of the extracellular matrix, transduction of specific intracellular signals, organogenesis, inflammation, tissue remodeling, adhesion, and cell migration. ADAM17 is the best characterized sheddase, with widespread putative substrates, including various inflammatory modulators. ADAM10 is the most similar ADAM to ADAM17 in terms of both protein sequence and the structural properties of their catalytic domains. The objective of this work was to assess the expression of ADAM10 and ADAM17 in allergic rhinitis to gain insight into their respective roles. METHODS: The expression of ADAM10 and ADAM17 was investigated in the nasal mucosa under allergic and nonallergic conditions. Tissue samples were evaluated by reverse-transcription polymerase chain reaction (RT-PCR) and Western blotting, and data were analyzed semiquantitatively with densitometry. RESULTS: The ADAM17 messenger RNA (mRNA) level was significantly (p < 0.001) lower in the allergic nasal mucosa than in the nonallergic nasal mucosa, whereas the ADAM10 mRNA level was significantly (p < 0.001) lower in the nonallergic nasal mucosa. The ADAM17 protein levels were also significantly (p < 0.001) lower in the allergic nasal mucosa, whereas the ADAM10 protein levels were lower in the nonallergic nasal mucosa (p = 0.002). CONCLUSION: Decreased expression of ADAM17 and increased expression of ADAM10 may contribute to the development of allergic rhinitis through unknown pathways. We suggest that understanding the expression profile of ADAM17 and ADAM10 might help to elucidate the mechanism of allergic rhinitis.


Assuntos
Proteínas ADAM/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Inflamação/imunologia , Proteínas de Membrana/metabolismo , Mucosa Nasal/fisiologia , Rinite Alérgica/imunologia , Proteínas ADAM/genética , Proteína ADAM10 , Proteína ADAM17 , Secretases da Proteína Precursora do Amiloide/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Proteínas de Membrana/genética
20.
Laryngoscope ; 114(4): 768-71, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15064639

RESUMO

OBJECTIVES: Otic drops are commonly used not only for otitis externa but also for otorrhea in the presence of tympanic membrane perforation or tympanostomy tube. Many studies demonstrated the ototoxicity of aminoglycoside. In our previous study, we observed that gentamicin (GM), when activated with liver extract, demonstrated significant cytotoxicity. The purpose of this study was to assess the protective effect of corticosteroid against the cytotoxicity of GM and tobramycin drops using isolated cochlear outer hair cells (OHCs) in vitro with liver extract. METHODS: OHCs from adult chinchilla cochleae were exposed to standard bathing solution, liver extract alone, and aminoglycoside otic drops with and without corticosteroid and liver extract. All experiments were performed at an osmolality of 305 +/- 5 mOsm, at room temperature, and for up to 60 minutes. The images of OHCs were recorded using an inverted microscope and analyzed on the Image Pro-Plus 3.0 program. Time to cell death and change of cell length were measured and analyzed. RESULTS: The time to cell death and percent change in cell length observed was significantly longer in the GM + liver extract + dexamethasone group than the GM + liver extract group (P <.05). The Tobradex + liver extract group showed an insignificant increase in percent change of cell length (P >.05) and significantly increased time to cell death than the tobramycin + liver extract group (P <.05). CONCLUSION: This study demonstrated that dexamethasone significantly reduced aminoglycoside cytotoxicity.


Assuntos
Aminoglicosídeos/efeitos adversos , Anti-Inflamatórios/uso terapêutico , Otorreia de Líquido Cefalorraquidiano/tratamento farmacológico , Dexametasona/uso terapêutico , Células Ciliadas Auditivas Externas/efeitos dos fármacos , Tobramicina/efeitos adversos , Perfuração da Membrana Timpânica/tratamento farmacológico , Aminoglicosídeos/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Morte Celular/efeitos dos fármacos , Chinchila , Dexametasona/farmacologia , Quimioterapia Combinada , Tobramicina/metabolismo
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