RESUMO
Deficiencies in epithelial barrier integrity are involved in the pathogenesis of chronic rhinosinusitis (CRS). This study aimed to investigate the role of ephrinA1/ephA2 signaling on sinonasal epithelial permeability and rhinovirus-induced epithelial permeability. This role in the process of epithelial permeability was evaluated by stimulating ephA2 with ephrinA1 and inactivating ephA2 with ephA2 siRNA or inhibitor in cells exposed to rhinovirus infection. EphrinA1 treatment increased epithelial permeability, which was associated with decreased expression of ZO-1, ZO-2, and occludin. These effects of ephrinA1 were attenuated by blocking the action of ephA2 with ephA2 siRNA or inhibitor. Furthermore, rhinovirus infection upregulated the expression levels of ephrinA1 and ephA2, increasing epithelial permeability, which was suppressed in ephA2-deficient cells. These results suggest a novel role of ephrinA1/ephA2 signaling in epithelial barrier integrity in the sinonasal epithelium, suggesting their participation in rhinovirus-induced epithelial dysfunction.
Assuntos
Permeabilidade da Membrana Celular , Células Epiteliais , Receptor EphA1 , Receptor EphA2 , Humanos , Permeabilidade da Membrana Celular/genética , Permeabilidade da Membrana Celular/fisiologia , Células Epiteliais/metabolismo , Células Epiteliais/fisiologia , Infecções por Picornaviridae/metabolismo , Receptor EphA2/metabolismo , Rhinovirus/patogenicidade , RNA de Cadeia Dupla , RNA Interferente Pequeno/metabolismo , Transdução de Sinais/fisiologiaRESUMO
BACKGROUND: Little is known about the role of lymphotoxins (LTs) family in the sinonasal mucosa of patients with chronic rhinosinusitis (CRS). This study aims at investigating the expression of LIGHT, LTα, LTß, and their receptors, LTßR and HVEM in normal and inflammatory sinus mucosa, and the effect of LIGHT and LTalpha1beta2 on chemokine secretion in epithelial cells, epithelial permeability, and leukocyte migration. MATERIAL AND METHODS: The expression of LTs family in sinonasal mucosa was evaluated with real-time PCR, immunohistochemistry, and western blot. In LTßR, HVEM siRNA, or control siRNA-transfected epithelial cells treated with LIGHT or LTalpha1beta2, the expression of chemokines, the epithelial permeability, and the expression of junctional complex proteins were evaluated using real-time PCR, ELISA, western blot, confocal microscopy, and FITC-dextran. In cultured endothelial cells treated with LIGHT or LTalpha1beta2, the expression of ICAM-1 and VCAM-1, and leukocyte migration were elucidated. RESULTS: LTs family was expressed in normal mucosa and their levels were increased in inflammatory mucosa of CRS patients. Recombinant LIGHT and LTalpha1beta2 induced chemokine secretion, increased epithelial permeability, and promoted leukocyte migration. However, the activity of LIGHT and LTalpha1beta2 was attenuated in cells transfected with LTßR and HVEM siRNA. CONCLUSIONS: LIGHT and LTs may participate in the ongoing process of chronic inflammation, inducing chemokine secretion, leukocyte migration, and dysregulated epithelial barrier through LTßR and HVEM in sinonasal mucosa.
Assuntos
Linfotoxina-alfa/metabolismo , Mucosa Nasal/metabolismo , Pólipos Nasais/metabolismo , Rinite/metabolismo , Sinusite/metabolismo , Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo , Adulto , Permeabilidade da Membrana Celular , Quimiocinas/metabolismo , Doença Crônica , Impedância Elétrica , Células Epiteliais/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Leucócitos/patologia , Masculino , Mucosa Nasal/patologia , Pólipos Nasais/genética , Pólipos Nasais/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Membro 14 de Receptores do Fator de Necrose Tumoral/metabolismo , Rinite/genética , Rinite/patologia , Sinusite/genética , Sinusite/patologia , Migração Transendotelial e Transepitelial , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismoRESUMO
Chronic rhinosinusitis (CRS) is a chronic inflammatory condition of the nasal and paranasal sinus mucosa that affects up to 10% of the population worldwide. CRS is the most representative disease of the upper respiratory tract where airway remodeling occurs, including epithelial damage, thickening of the basement membrane, fibrosis, goblet cell hyperplasia, subepithelial edema, and osteitis. CRS is divided into two phenotypes according to the presence or absence of nasal polyps: CRS with nasal polyp (CRSwNP) and CRS without nasal polyps (CRSsNP). Based on the underlying pathophysiologic mechanism, CRS is also classified as eosinophilic CRS and non-eosinophilic CRS, owing to Type 2 T helper (Th2)-based inflammation and Type 1 T helper (Th1)/Type 17 T helper (Th17) skewed immune response, respectively. Differences in tissue remodeling in CRS are suggested to be based on the clinical phenotype and endotypes; this is because fibrosis is prominent in CRSsNP, whereas edematous changes occur in CRSwNP, especially in the eosinophilic type. This review aims to summarize the latest information on the different mechanisms of airway remodeling in CRS according to distinct endotypes.
Assuntos
Remodelação das Vias Aéreas/genética , Inflamação/imunologia , Pólipos Nasais/imunologia , Rinite/imunologia , Remodelação das Vias Aéreas/imunologia , Remodelação das Vias Aéreas/fisiologia , Doença Crônica/epidemiologia , Fibrose , Células Caliciformes/classificação , Células Caliciformes/imunologia , Humanos , Inflamação/patologia , Pólipos Nasais/genética , Pólipos Nasais/patologia , Rinite/genética , Rinite/patologia , Sinusite , Células Th1/classificação , Células Th1/imunologia , Células Th17/classificação , Células Th17/imunologia , Células Th2/classificação , Células Th2/imunologiaRESUMO
BACKGROUND: IL-36 family, a recently reported member of the IL-1 cytokine family, plays an essential role in nonspecific innate immune response to infection. This study aims at investigating the expression of IL-36 family members (α, ß, and γ) in normal and inflammatory sinus mucosa of patients with chronic rhinosinusitis (CRS), their effects on chemokine secretion and on the barrier function of epithelial and endothelial cells, and the effect of Toll-like receptors on the expression of IL-36 in epithelial cells. MATERIAL AND METHODS: The expression of IL-36 family in normal and inflammatory sinus mucosa, the production of chemokines or the expression levels of IL-36 family in epithelial cells treated with IL-36 family members or stimulated with TLR3, TLR4, TLR5, or TLR7/8 agonists were measured with real time PCR, ELISA, immunohistochemistry, or Western blot. The epithelial and endothelial permeability, and transendothelial leukocyte migration were investigated using cultured epithelial and endothelial cells. RESULTS: IL-36α, IL-36ß, and IL-36γ were localized in epithelial cells of sinonasal mucosa. Their levels increased in inflammatory mucosa of CRS patients and are up-regulated by TLR3, TLR4, or TLR5 agonists. IL-36α, or IL-36γ induced CXCL1, CXCL2, and CXCL3 production. Epithelial and endothelial permeability, transendothelial leukocyte migration were increased in cells treated with IL-36α, IL-36ß, or IL-36γ. CONCLUSIONS: These results suggest that IL-36α, IL-36ß, and IL-36γ localized in superficial epithelium may act as a responder to microbial and nonmicrobial elements through TLR and subsequently produce CXC chemokines, playing an interplay between innate and adaptive immune response.
Assuntos
Quimiocinas/metabolismo , Células Endoteliais/metabolismo , Células Epiteliais/metabolismo , Interleucina-1/metabolismo , Interleucina-1/farmacologia , Sinusite/metabolismo , Receptores Toll-Like/agonistas , Adolescente , Adulto , Movimento Celular/efeitos dos fármacos , Doença Crônica , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/fisiologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/fisiologia , Flagelina/farmacologia , Humanos , Imuno-Histoquímica , Inflamação/genética , Inflamação/metabolismo , Interleucina-1/genética , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Lipopolissacarídeos/farmacologia , Pessoa de Meia-Idade , Mucosa Nasal/metabolismo , Permeabilidade , Reação em Cadeia da Polimerase em Tempo Real , Sinusite/genética , Receptor 3 Toll-Like/agonistas , Receptor 3 Toll-Like/metabolismo , Receptor 4 Toll-Like/agonistas , Receptor 4 Toll-Like/metabolismo , Receptor 5 Toll-Like/agonistas , Receptor 5 Toll-Like/metabolismo , Receptor 7 Toll-Like/agonistas , Receptor 7 Toll-Like/metabolismo , Receptor 8 Toll-Like/agonistas , Receptor 8 Toll-Like/metabolismo , Receptores Toll-Like/metabolismoRESUMO
With the advancement of the Internet of Medical Things technology, many vital sign-sensing devices are being developed. Among the diverse healthcare devices, portable electrocardiogram (ECG) measuring devices are being developed most actively with the recent development of sensor technology. These ECG measuring devices use different sampling rates according to the hardware conditions, which is the first variable to consider in the development of ECG analysis technology. Herein, we propose an R-point detection method using an adaptive median filter based on the sampling rate and analyze major arrhythmias using the signal characteristics. First, the sliding window and median filter size are determined according to the set sampling rate, and a wider median filter is applied to the QRS section with high variance within the sliding window. Then, the R point is detected by subtracting the filtered signal from the original signal. Methods for detecting major arrhythmias using the detected R point are proposed. Different types of ECG signals were used for a simulation, including ECG signals from the MIT-BIH arrhythmia database and MIT-BIH atrial fibrillation database, signals generated by a simulator, and actual measured signals with different sampling rates. The experimental results indicated the effectiveness of the proposed R-point detection method and arrhythmia analysis technique.
Assuntos
Algoritmos , Arritmias Cardíacas/diagnóstico , Eletrocardiografia , Processamento de Sinais Assistido por Computador , Simulação por Computador , Bases de Dados Factuais , HumanosRESUMO
BACKGROUND: Little is known about antiviral responses in the sinonasal mucosal tissue of patients with chronic rhinosinusitis (CRS). OBJECTIVE: we investigated the presence of virus and the expression of Toll-like receptor (TLR) 3, TLR7, and interferon and interferon-stimulated genes (ISGs) in healthy mucosal tissue of control subjects and the inflammatory sinus mucosal tissue of CRS patients, and evaluated whether levels of interferons and ISGs might be affected by CRS-related cytokines and by treatment with macrolides, dexamethasone, or TLR3 and TLR7 agonists. METHODS: The presence of virus in the sinonasal mucosa was evaluated with real-time PCR. The expression of interferons and ISGs in the sinonasal mucosa and in cultured epithelial cells treated with TH1 and TH2 cytokines, macrolides, dexamethasone, or TLR3 and TLR7 agonists were evaluated with real-time PCR and Western blotting. The expression of TLR3 and TLR7 in the sinonasal mucosa were evaluated with immunohistochemistry. RESULTS: Respiratory viruses were detected in 15% of samples. Interferons and ISGs are expressed in normal mucosa, but their levels were decreased in patients with CRS. Interferon and ISG levels were upregulated in cells treated with macrolides, dexamethasone, or TLR3 agonist, but some were decreased in cytokine-treated cells. TLR3 and TLR7 levels showed no significant difference between normal and inflammatory sinus mucosal tissue. CONCLUSION: These results suggest that decreased levels of interferons and ISGs in patients with CRS might contribute to impairment of the antiviral innate response in inflammatory sinonasal epithelial cells. Macrolides and glucocorticoids might provide positive effects on the treatment of CRS by upregulating interferon and ISG expression.
Assuntos
Regulação para Baixo/imunologia , Fatores Reguladores de Interferon/imunologia , Interferon beta/imunologia , Interferons/imunologia , Pólipos Nasais/imunologia , Rinite/imunologia , Sinusite/imunologia , Adulto , Doença Crônica , Humanos , Masculino , Mucosa Nasal/imunologia , Mucosa Nasal/patologia , Pólipos Nasais/patologia , Reação em Cadeia da Polimerase em Tempo Real , Rinite/patologia , Sinusite/patologia , Células Th1/imunologia , Células Th1/patologia , Células Th2/imunologia , Células Th2/patologia , Receptor 3 Toll-Like/imunologia , Receptor 7 Toll-Like/imunologiaRESUMO
Prostaglandins (PGs) are a family of lipid compounds that are derived from arachidonic acid via the cyclooxygenase pathway, and consist of PGD2, PGI2, PGE2, PGF2, and thromboxane B2. PGs signal through G-protein coupled receptors, and individual PGs affect allergic inflammation through different mechanisms according to the receptors with which they are associated. In this review article, we have focused on the metabolism of the cyclooxygenase pathway, and the distinct biological effect of each PG type on various cell types involved in allergic airway diseases, including asthma, allergic rhinitis, nasal polyposis, and aspirin-exacerbated respiratory disease.
Assuntos
Asma/metabolismo , Prostaglandinas/metabolismo , Animais , Asma/patologia , Humanos , Hipersensibilidade/metabolismo , Hipersensibilidade/patologia , Rinite Alérgica/metabolismo , Rinite Alérgica/patologia , Tromboxano B2/metabolismoRESUMO
BACKGROUND: Neutrophil extracellular traps (NETs) participate in innate immunity by trapping microorganisms. Their pathophysiological implications have not been defined in chronic rhinosinusitis (CRS). OBJECTIVE: We investigated the presence of NETs in nasal secretion of patients with stable or exacerbated CRS and evaluated whether NETs participate in the secretion of chemokines in sinonasal epithelial cells, the epithelial permeability, and transendothelial leucocyte migration, and elucidate whether NETs are released by macrolides and dexamethasone. METHODS: The presence of NETs in nasal secretion and the release of NETs from neutrophils stimulated with macrolides or dexamethasone were evaluated by dsDNA Assay kit and fluorescence microscope. The chemokine secretion, epithelial permeability, and transendothelial leucocyte migration were measured in cultured cells incubated with NETs, the supernatant of unstimulated neutrophils (unstim), NETs inhibitor (DPI), or H3Cit, where the expression of junctional complex proteins and ICAM-1 was evaluated by real-time PCR, Western blots, and confocal microscope. RESULTS: The amount of NETs and NETs-forming neutrophils in nasal secretion increased in exacerbated CRS. Epithelial cells treated with NETs or H3Cit secreted chemokines and showed decreased permeability associated with up-regulated junctional complex proteins. Increased transendothelial leucocyte migration associated with up-regulated ICAM-1 was noted in endothelial cells treated with NETs or H3Cit. These findings were not found in cells treated with unstim, or DPI. NETs were released by macrolides, but not by dexamethasone. CONCLUSIONS AND CLINICAL RELEVANCE: NETs formation increased in exacerbated CRS, inducing chemokine secretion, strengthening the epithelial barrier, and promoting the neutrophils infiltration. Therefore, the release of NETs in CRS might be beneficial or detrimental to CRS patients.
Assuntos
Quimiocinas/imunologia , Armadilhas Extracelulares/imunologia , Mucosa Nasal/imunologia , Neutrófilos/imunologia , Rinite/imunologia , Sinusite/imunologia , Adolescente , Adulto , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/patologia , Neutrófilos/patologia , Sinusite/patologiaAssuntos
AMP Cíclico , Células Th2 , Quimiocina CCL2 , Células Dendríticas , Humanos , Imunidade , Células Th1RESUMO
BACKGROUND: It has been suggested that glucocorticoids might act in target tissues to increase their own intracellular availability in response to inflammatory stimuli. These mechanisms depend on the local metabolism of glucocorticoids catalyzed by 11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1) and 11ß-hydroxysteroid dehydrogenase 2 (11ß-HSD2). OBJECTIVE: This study is to investigate the effect of chronic rhinosinusitis (CRS) on expression of 11ß-HSD1, 11ß-HSD2, steroidogenic enzymes (cytochrome P450, family 11, subfamily B, polypeptide 1 [CYP11B1] and cytochrome P450, family 11, subfamily A, polypeptide 1 [CYP11A1]), and endogenous cortisol levels in human sinus mucosa. Expression levels were compared with those of healthy control subjects. METHODS: The expression levels of 11ß-HSD1, 11ß-HSD2, CYP11B1, CYP11A1, and cortisol were measured in healthy control subjects, patients with CRS with nasal polyps, and patients with CRS without nasal polyps by using real-time PCR, Western blotting, immunohistochemistry, and ELISA. Expression levels of 11ß-HSD1, 11ß-HSD2, CYP11B1, CYP11A1, and cortisol were determined in cultured epithelial cells treated with CRS-relevant cytokines. The conversion ratio of cortisone to cortisol was evaluated by using the small interfering RNA technique, 11ß-HSD1 inhibitor, and measurement of 11ß-HSD1 activity. RESULTS: 11ß-HSD1, CYP11B1, and cortisol levels increased in patients with CRS with nasal polyps and those with CRS without nasal polyps, but 11ß-HSD2 expression decreased. In cultured epithelial cells treated with IL-4, IL-5, IL-13, IL-1ß, TNF-α, and TGF-ß1, 11ß-HSD1 expression and activity increased in parallel with expression levels of CYP11B1 and cortisol, but the production of 11ß-HSD2 decreased. The small interfering RNA technique or the measurement of 11ß-HSD1 activity showed that the sinus epithelium activates cortisone to cortisol in an 11ß-HSD-dependent manner. CONCLUSION: These results indicate that CRS-relevant cytokines can modulate the expression of 11ß-HSD1, 11ß-HSD2, and CYP11B1 in the sinus mucosa, resulting in increasing intracellular concentrations of bioactive glucocorticoids.
Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , 11-beta-Hidroxiesteroide Desidrogenase Tipo 2/metabolismo , Células Epiteliais/imunologia , Mucosa Nasal/imunologia , Pólipos Nasais/imunologia , Rinite/imunologia , Sinusite/imunologia , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/genética , 11-beta-Hidroxiesteroide Desidrogenase Tipo 2/genética , Células Cultivadas , Enzima de Clivagem da Cadeia Lateral do Colesterol/genética , Enzima de Clivagem da Cadeia Lateral do Colesterol/metabolismo , Doença Crônica , Citocinas/imunologia , Regulação da Expressão Gênica , Glucocorticoides/metabolismo , Humanos , Hidrocortisona/genética , Hidrocortisona/metabolismo , RNA Interferente Pequeno/genéticaRESUMO
Nasal polyps are chronic inflammatory conditions characterized by myofibroblast differentiation and extracelluar matrix accumulation. The major catechin from green tea is (-)-epigallocatechin-3-gallate (EGCG), which has garnered attention for its potential to prevent oxidative stress-related diseases. The purpose of this study was twofold: (i) to determine the effect of EGCG on fibroblast differentiation into myofibroblasts and extracellular matrix accumulation in transforming growth factor (TGF)-ß1-induced nasal polyp-derived fibroblasts (NPDFs) and (ii) to determine if the antioxidative effect of EGCG on reactive oxygen species (ROS) production in TGF-ß1-induced NPDFs is involved in the aforementioned processes. TGF-ß1-induced NPDFs were treated with or without EGCG. α-smooth muscle actin (α-SMA) and collagen type I mRNA were analyzed by reverse transcription-polymerase chain reaction. α-SMA protein was also detected using immunofluorescent staining. The amount of total soluble collagen was analyzed by Sircol collagen assay. ROS activity was measured by the nitroblue tetrazolium reduction assay and visualized by fluorescent microscopy. EGCG significantly inhibited expressions of α-SMA and collagen type I mRNA and reduced α-SMA and collagen protein levels at concentrations of 10-20 µg/mL. EGCG also inhibited TGF-ß1-induced ROS production at the same concentrations. These results suggest the possibility that EGCG may be effective at inhibiting the development of nasal polyps through an anti-oxidant effect.
Assuntos
Catequina/análogos & derivados , Colágeno Tipo I/biossíntese , Fibroblastos/efeitos dos fármacos , Pólipos Nasais/patologia , Actinas/metabolismo , Adulto , Antioxidantes/metabolismo , Catequina/farmacologia , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Matriz Extracelular/metabolismo , Feminino , Fibroblastos/metabolismo , Humanos , Masculino , Miofibroblastos/citologia , Pólipos Nasais/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator de Crescimento Transformador beta1/farmacologiaAssuntos
Regulação da Expressão Gênica , Mucosa Nasal/metabolismo , Canais de Potássio de Domínios Poros em Tandem/biossíntese , Rinite/metabolismo , Sinusite/metabolismo , Doença Crônica , Humanos , Mucosa Nasal/imunologia , Rinite/imunologia , Rinite/patologia , Sinusite/imunologia , Sinusite/patologiaRESUMO
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) or without nasal polyps (CRSsNP) is associated with expression of various cytokines. Suppressors of cytokine signaling (SOCS) regulate cytokine activity in a variety of cells, modulating inflammatory responses. OBJECTIVE: We analyzed the expression and distribution pattern of SOCS1 and SOCS3 in CRSwNP and CRSsNP, and their cytokine-driven expression regulation in sinus mucosa. In addition, the expression levels of various cytokines were evaluated in CRSwNP and CRSsNP. METHODS: The expression levels of SOCS1 and SOCS3 in CRSwNP and CRSsNP and in control samples were assessed by using real-time PCR, Western blot, and immunohistochemistry. Nasal epithelial cell culture was used to elucidate the effect of IL-4, IL-5, IL-6, IL-10, IL-13, IFN-γ, TNF-α, and TGF-ß1 on SOCS1 and SOCS3 expression in sinus mucosa. The expression levels of these cytokines were also evaluated in normal and inflammatory sinus mucosa by using real-time PCR and Western blot. RESULTS: The expression levels of SOCS1 and SOCS3 were increased in CRS, irrespective of the presence of nasal polyp, and they were distributed in superficial epithelium, submucosal glands, and vascular endothelium in sinus mucosa. SOCS1 was induced by IL-4, IL-13, IFN-γ, and TNF-α, while SOCS3 expression was upregulated by IL-6, IL-13, IFN-γ, and TNF-α. IL-4 and IL-13 levels were increased in CRSwNP, while IL-4, IFN-γ, TNF-α, and TGF-ß1 levels were increased in CRSsNP. CONCLUSION: SOCS1 and SOCS3 are increased in CRS, irrespective of nasal polyp presence. This may be a response to elevated levels of various cytokines increasingly expressed in inflammatory sinus mucosa.
Assuntos
Pólipos Nasais/metabolismo , Rinite/metabolismo , Sinusite/metabolismo , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Adolescente , Adulto , Células Cultivadas , Citocinas/genética , Citocinas/metabolismo , Células Epiteliais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/metabolismo , Pólipos Nasais/etiologia , RNA Mensageiro/metabolismo , Rinite/complicações , Sinusite/complicações , Proteína 1 Supressora da Sinalização de Citocina , Proteína 3 Supressora da Sinalização de Citocinas , Proteínas Supressoras da Sinalização de Citocina/genética , Adulto JovemRESUMO
OBJECTIVES: The aims of the present study were twofold. We sought to compare two methods of titrating the level of continuous positive airway pressure (CPAP) - auto-adjusting titration and titration using a predictive equation - with full-night manual titration used as the benchmark. We also investigated the reliability of the two methods in patients with obstructive sleep apnea syndrome (OSAS). METHODS: Twenty consecutive adult patients with OSAS who had successful, full-night manual and auto-adjusting CPAP titration participated in this study. The titration pressure level was calculated with a previously developed predictive equation based on body mass index and apnea-hypopnea index. RESULTS: The mean titration pressure levels obtained with the manual, auto-adjusting, and predictive equation methods were 9.0 +/- 3.6, 9.4 +/- 3.0, and 8.1 +/- 1.6 cm H2O,respectively. There was a significant difference in the concordance within the range of +/- 2 cm H2O (p = 0.019) between both the auto-adjusting titration and the titration using the predictive equation compared to the full-night manual titration. However, there was no significant difference in the concordance within the range of +/- 1 cm H2O (p > 0.999). CONCLUSIONS: When compared to full-night manual titration as the standard method, auto-adjusting titration appears to be more reliable than using a predictive equation for determining the optimal CPAP level in patients with OSAS.
Assuntos
Pressão Positiva Contínua nas Vias Aéreas/métodos , Apneia Obstrutiva do Sono/terapia , Adulto , Índice de Massa Corporal , Pressão Positiva Contínua nas Vias Aéreas/instrumentação , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PolissonografiaRESUMO
Background: Altered innate defense mechanisms, including an imbalance between oxidants and antioxidants release, have been implicated in the pathogenesis of chronic rhinosinusitis (CRS). The aim of this study is to investigate whether oxidative stress may attenuate the secretion of anti-viral interferons in human sinonasal mucosa. Methods: The levels of H2O2 in nasal secretion were increased in patients with CRS with nasal polyps, compared with that of CRS patients without nasal polyps and control subjects. Normal sinonasal epithelial cells derived from healthy subjects were cultured under an air-liquid interface. The cultured cells were infected with rhinovirus 16 (RV 16) or treated with poly (I: C), TLR3 agonist, after being pretreated with an oxidative stressor, H2O2 or antioxidant, N-acetylcysteine (NAC). Thereafter, the expression levels of type I (IFN-ß) and type III (IFN-λ1 and λ2) interferons and interferon-stimulated genes (ISGs) were evaluated with RT-qPCR, ELISA, and western blot. Results: The data showed that the production of type I (IFN-ß) and type III (IFN-λ1 and λ2) interferons and ISGs was upregulated in cells infected with RV 16 or treated with poly (I: C). However, their up-regulated expression was attenuated in cells pretreated with H2O2, but not inhibited in cells pretreated with NAC. In line with these data, the up-regulated expression of TLR3, RIG-1, MDA5, and IRF3 was reduced in cells pretreated with H2O2, but not attenuated in cells treated with NAC. Furthermore, cells transfected with Nrf2 siRNA showed decreased secretion of anti-viral interferons whereas sulforaphane treatment enhanced the secretory capacity of antiviral interferons. Conclusions: These results suggest that the production of RV16-induced antiviral interferons may be attenuated by oxidative stress.
Assuntos
Interferon Tipo I , Pólipos Nasais , Humanos , Antivirais/farmacologia , Peróxido de Hidrogênio , Rhinovirus , Receptor 3 Toll-Like , Células Epiteliais , Acetilcisteína/farmacologia , AntioxidantesRESUMO
We aimed to evaluate the association between periodontitis in the upper jaw and chronic rhinosinusitis (CRS) using the nationwide Korean National Health and Nutrition Examination Survey (KNHANES) data. In this cross-sectional study, data of KNHANES participants enrolled between 2008 and 2012 were reviewed. Periodontitis of the upper teeth was diagnosed by dentists according to the community periodontal index with standardized methods. CRS was diagnosed by otorhinolaryngologists according to the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 with nasal endoscopy findings. We also evaluated the association between periodontitis and CRS according to smoking and drinking status. Univariate and multivariate logistic regression analyses were performed. Overall, 28,761 participants were eligible for analysis, and 210 were diagnosed with CRS. Periodontitis was associated with CRS diagnosis (odds ratio [OR] = 1.391, 95% confidence interval [CI] = 1.013-1.912). Non-drinkers showed no significant association between periodontitis and CRS (OR = 1.142, 95% CI 0.746-1.749). However, among drinkers, periodontitis was significantly associated with CRS (OR = 1.733, 95% CI 1.091-2.753). The number of smokers with CRS was not statistically sufficient and a logistic regression model based on smoking status could not be generated. Individuals with periodontitis in the upper jaw may need to consult an otorhinolaryngologist for comorbid CRS especially according to drinking status.
Assuntos
Periodontite , Sinusite , Humanos , Inquéritos Nutricionais , Estudos Transversais , Índice Periodontal , Periodontite/complicações , Periodontite/epidemiologia , Comorbidade , Sinusite/complicações , Sinusite/epidemiologia , Sinusite/diagnóstico , Doença CrônicaRESUMO
BACKGROUND: Myofibroblasts are detected in nasal polyps and are involved in nasal polyp formation by inducing extracellular matrix accumulation. Reactive oxygen species (ROS) are released during the differentiation of fibroblasts to myofibroblasts. The purpose of this study was to investigate ROS production and nicotinamide adenine dinucleotide phosphate oxidase (NOX) expression in nasal polyp-derived fibroblasts (NPDFs) and to evaluate whether ROS from NOX mediates transforming growth factor (TGF)-ß1-induced production of alpha smooth-muscle actin (α-SMA) and collagen production. METHODS: NPDFs were incubated and treated with TGF-ß1. The mRNA expression of NOXs, α-SMA, and collagen type I and IV was determined by reverse transcription-polymerase chain reaction, and the expression of α-SMA protein was determined by immunofluorescence microscopy. The amount of total soluble collagen production was analyzed by the SirCol assay. The ROS generation of cells was investigated using the 2',7'-dichlorfluorescein-diacetate. The fluorescence was captured by fluorescent microscope and measured using a fluorometer. RESULTS: Stimulation with TGF-ß1 increased ROS production by NPDFs compared with NPDFs not treated with TGF-ß1. Stimulation with TGF-ß1 increased the expression of NOX4 mRNA most potently among various Nox enzymes. siNOX4 was able to decrease the level of ROS production. Myofibroblast differentiation and the production of collagen in NPDFs were prevented by inhibition of ROS generation with diphenyliodonium, N-acetylcysteine, ebselen, and siNox4. CONCLUSIONS: This study showed that NOX4 and ROS have a role in myofibroblast differentiation and collagen production of TGF-ß1-induced NPDFs and that these processes are inhibited by the elimination of ROS.
Assuntos
Fibroblastos/efeitos dos fármacos , NADPH Oxidases/antagonistas & inibidores , Pólipos Nasais/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Acetilcisteína/farmacologia , Actinas/antagonistas & inibidores , Actinas/biossíntese , Adulto , Azóis/farmacologia , Compostos de Bifenilo/farmacologia , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Colágeno Tipo I/antagonistas & inibidores , Colágeno Tipo I/biossíntese , Colágeno Tipo IV/antagonistas & inibidores , Colágeno Tipo IV/biossíntese , Feminino , Fibroblastos/metabolismo , Fibroblastos/patologia , Fluoresceínas , Corantes Fluorescentes , Expressão Gênica/efeitos dos fármacos , Humanos , Isoindóis , Masculino , Microscopia de Fluorescência , NADPH Oxidase 4 , NADPH Oxidases/genética , Pólipos Nasais/patologia , Oniocompostos/farmacologia , Compostos Organosselênicos/farmacologia , RNA Interferente Pequeno/genética , Espécies Reativas de Oxigênio/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: The aim of this study was to evaluate the role of suppressor of cytokine signaling (SOCS) molecules, SOCS1 and SOCS3, which act as negative regulators of cytokine signaling in various allergic diseases, in patients with mild and moderate/severe persistent allergic rhinitis. METHODS: The expression and distribution pattern of SOCS1 and SOCS3 were analyzed in nasal mucosa and peripheral blood mononuclear cells (PBMC) of healthy controls, and patients with mild and moderate/severe persistent allergic rhinitis using RT-PCR, immunohistochemistry and Western blotting. IL-4, IL-13, IL-15 and IFN-γ expression was also analyzed in the nasal mucosa of each individual using RT-PCR and Western blotting. RESULTS: SOCS1 and SOCS3 mRNA and protein expression was significantly increased in the nasal mucosa and PBMC of patients with mild and moderate/severe persistent allergic rhinitis compared with healthy controls. In healthy and allergic nasal mucosa, they were commonly localized to the epithelium, submucosal glands and endothelium, showing stronger staining intensity in mild and moderate/severe persistent allergic nasal mucosa than in healthy nasal mucosa. Tissue levels of IL-4 and IL-13 were increased in moderate/severe persistent allergic nasal mucosa whereas IL-15 and IFN-γ were decreased in moderate/severe persistent allergic nasal mucosa. CONCLUSIONS: Upregulation of SOCS1 and SOCS3 in mild and moderate/severe persistent allergic rhinitis suggests that SOCS proteins may be important regulators in the pathogenesis of allergic rhinitis and play a role as molecular determinants of allergic rhinitis persistence.
Assuntos
Mucosa Nasal/metabolismo , Rinite Alérgica Perene/metabolismo , Proteínas Supressoras da Sinalização de Citocina/biossíntese , Adulto , Citocinas/biossíntese , Feminino , Humanos , Imunoglobulina E/sangue , Leucócitos Mononucleares/metabolismo , Masculino , Índice de Gravidade de Doença , Proteína 1 Supressora da Sinalização de Citocina , Proteína 3 Supressora da Sinalização de Citocinas , Regulação para CimaRESUMO
To determine whether surgery influences cardiovascular autonomic modulation in obstructive sleep apnoea syndrome (OSAS), the present study was performed to evaluate the effect of upper airway (UA) surgery on heart rate variability (HRV) using frequency domain analysis for patient groups who have had either successful or unsuccessful surgery. We compared body mass index (BMI), polysomnographic [apnoea index (AI), apnoea-hypopnoea index (AHI), minimum SaO(2)] and HRV [very low frequency (VLF) power, low frequency (LF) power, high frequency (HF) power, HF/LF ratio, LFnu = LF/(LF + HF), HFnu = HF/(LF + HF)] parameters between the unsuccessful (n = 14) and successful (n = 22) surgical groups before and after UA surgery. Significant changes were observed for the successful patient group with respect to mean AI (from 29.1 ± 21.3 to 2.0 ± 3.2 events h(-1), P < 0.001), AHI (from 38.6 ± 20.0 to 5.6 ± 5.1 events h(-1), P < 0.001), minimum SaO(2) (from 73.3 ± 12.7 to 86.3 ± 6.5%, P < 0.001), VLF power (from 25599 ± 12906 to 20014 ± 9839 ms(2), P = 0.013), LF power (from 17293 ± 7278 to 14155 ± 4980 ms(2), P = 0.016), LFnu (from 0.700 ± 0.104 to 0.646 ± 0.128, P = 0.031) and HFnu (from 0.300 ± 0.104 to 0.354 ± 0.128, P = 0.031); however, mean BMI, HF power and LF/HF ratio did not change significantly after UA surgery. No significant changes were observed in the unsuccessful surgical group. Successful UA surgery may improve cardiac sympathetic and parasympathetic modulation in patients with OSAS.
Assuntos
Frequência Cardíaca/fisiologia , Apneia Obstrutiva do Sono/cirurgia , Adulto , Índice de Massa Corporal , Feminino , Humanos , Masculino , Nariz/cirurgia , Faringe/cirurgia , Polissonografia , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
INTRODUCTION: Central compartment atopic disease (CCAD) has recently been suggested as a phenotype of chronic rhinosinusitis (CRS). This study aims to investigate the prevalence of the radiologic CCAD phenotype in CRS within a pediatric population and identify its ability to predict comorbid allergy and asthma. METHODS: Computed tomography and endoscopic examination were conducted on pediatric patients with CRS either with or without nasal polyps. Allergen sensitization was determined with the multiple-allergen simultaneous test and skin prick test. Serum total immunoglobulin E (IgE), peripheral blood eosinophil percentage, and presence of asthma were also evaluated. RESULTS: A total of 82 pediatric patients were enrolled. Overall, 55 (67.1%) of the participants demonstrated aeroallergen sensitization, and 31 (18.9%) of the 164 sides of sinuses were radiologically defined to fit the CCAD phenotype. Patients having CRS with the CCAD phenotype had a higher prevalence of aeroallergen sensitization (87.1% vs 62.4%, P = .008), particularly house dust mite (74.2% vs 53.4%, P = .035), and a higher incidence of asthma (16.1% vs 3.8%, P = .010). Additionally, patients having CRS with the CCAD phenotype demonstrated a high serum total IgE levels (51.6% vs 30.1%, P = .023) in comparison to patients having CRS without CCAD. CONCLUSION: In pediatric CRS, the radiological CCAD phenotype was associated with allergen sensitization and asthma. Furthermore, the CCAD phenotype was associated with high serum total IgE levels, suggesting allergy etiology should be considered with this type of pediatric patients with CRS.