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We assessed mitochondrial replication, transcription, and function in the upper airways of obstructive sleep apnea (OSA) patients and the effects of uvulopalatopharyngoplasty. Twenty subjects with mild and 40 with moderate to severe OSA requiring uvulopalatopharyngoplasty were included. Mitochondrial transcription factor A (TFAM) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in uvula specimens were assessed by immunohistochemical staining, and their mRNA and protein expression was examined using reverse-transcription polymerase chain reaction and western blotting, respectively. The mitochondrial to nuclear DNA (Mt/N) ratio in the blood, exhaled breath condensate (EBC), and uvula was measured using quantitative reverse-transcription polymerase chain reaction. TFAM and PGC-1α protein concentrations in the plasma and EBC were determined using enzyme-linked immunosorbent assay. All tested parameters were higher in the OSA group than in the control. Three months later, 21 uvulopalatopharyngoplasty-responsive patients with OSA showed decreased TFAM and PGC-1α concentrations and EBC Mt/N ratio while these remained high in 19 uvulopalatopharyngoplasty-unresponsive patients. The OSA group showed severe inflammation, increased mitochondrial replication and transcription-related signaling, and mitochondrial dysfunction in the uvula. Successful OSA treatment using uvulopalatopharyngoplasty restored the TFAM and PGC-1α levels and EBC Mt/N ratio.
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Purpose: Subjects with obstructive sleep apnea (OSA) exhibit systemic and upper airway oxidative stress and inflammation, which cause mitochondrial dysfunction. The intend of this study is to estimate mitochondrial function (mitochondrial DNA/nuclear DNA [Mt/N] ratio) and protein levels of peroxisome proliferator-coactivated receptor gamma co-activator 1-alpha (PGC1-α) in the exhaled breath condensate (EBC) and plasma before and after continuous positive airway pressure (CPAP) treatment. Materials and methods: Twenty healthy individuals (control) and 40 subjects with severe or moderate OSA were recruited to undergo CPAP treatment and evaluation in a sleep study. The Mt/N ratio in the EBC and blood were assayed by quantitative real-time polymerase chain reaction. Enzyme-linked immunosorbent assay was used to measure the protein concentration of PGC1-α in the EBC and plasma. All experiments were performed after 3 months of CPAP treatment in subjects with OSA. Results: We observed no noteworthy differences between the control and treatment groups. Moreover, there were no differences in the Mt/N ratio in the blood and plasma levels of PGC1-α in subjects with OSA before and after treatment. However, the Mt/N ratio and protein levels of PGC1-α in the EBC of OSA subjects were higher than those in the control group and returned to normal levels after CPAP treatment. Conclusions: We successfully treated subjects with OSA by CPAP, which restored the Mt/N ratio and levels of PGC1-α in the EBC.
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Presión de las Vías Aéreas Positiva Contínua , Apnea Obstructiva del Sueño , Humanos , Inflamación , Mitocondrias , Estrés Oxidativo , Apnea Obstructiva del Sueño/terapiaRESUMEN
PURPOSE: Resolvin is a checkpoint controller in inflammation. Matrix metalloproteinase-9 (MMP-9) is an airway remodeling regulator. We evaluated the levels of resolvin and MMP-9 protein in the serum and exhaled breath condensate (EBC) before and after continuous positive airway pressure (CPAP) treatment. METHOD: We enrolled 20 non-OSA snorers and 40 patients with moderate to severe OSA scheduled for CPAP treatment. ELISA was used to assess resolvin and MMP-9 levels in the serum and EBC. All patients underwent sleep assessment at baseline and 3 months after CPAP. RESULTS: There was no between-group difference; moreover, there were no differences in the pre- and post-treatment serum levels of resolvin and MMP-9 in patients with OSA. Compared with non-OSA snorers, patients with OSA had lower resolvin and higher MMP-9 levels in the EBC. After CPAP treatment, the EBC levels of resolvin and MMP-9 in patients with OSA returned to normal. CONCLUSIONS: Successful OSA treatment by CPAP can normalize EBC levels of resolvin and MMP-9.
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Presión de las Vías Aéreas Positiva Contínua , Ácidos Docosahexaenoicos/metabolismo , Mediadores de Inflamación/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Apnea Obstructiva del Sueño/metabolismo , Apnea Obstructiva del Sueño/terapia , Ronquido/metabolismo , Ronquido/terapia , Adulto , Pruebas Respiratorias , Femenino , Humanos , Mediadores de Inflamación/sangre , Masculino , Metaloproteinasa 9 de la Matriz/sangre , Persona de Mediana Edad , Apnea Obstructiva del Sueño/sangre , Ronquido/sangre , Resultado del TratamientoRESUMEN
BACKGROUND: Both transforming growth factor ß (TGF-ß) and vascular endothelial growth factor (VEGF) are master regulators of airway remodeling; however, their pathological roles in obstructive sleep apnea (OSA) remain unclear. The aim of the present study was to evaluate the expression of TGF-ß and VEGF protein in the serum and exhaled breath condensate (EBC) before and after continuous positive airway pressure (CPAP) treatment in OSA patients. METHODS: Forty patients with moderate to severe OSA requiring CPAP and 20 healthy subjects were prospectively recruited. The concentrations of TGF-ß and VEGF protein in the serum and EBC were evaluated by enzyme-linked immunosorbent assay. All OSA patients underwent a sleep study that was repeated 3 months after receiving CPAP therapy. RESULTS: Protein concentrations of TGF-ß and VEGF in the serum did not differ between healthy controls and OSA patients before CPAP treatment. There was also no difference in the serum protein concentrations of TGF-ß and VEGF of the OSA patients before and after CPAP treatment. However, both the TGF-ß and VEGF protein concentrations in the EBC were higher in the OSA patients than those in control subjects, and recovered to normal levels after CPAP. CONCLUSIONS: Successful treatment of OSA by CPAP can restore the TGF-ß and VEGF protein concentrations in the EBC.
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Purpose: Chronic asthma is characterized by airway inflammation and remodeling. The aim of this study is to evaluate the effects of aminophylline on airway epithelial-mesenchymal transition (EMT). Materials and methods: Two experimental groups of brown Norway rats that were repeatedly challenged with aerosolized ovalbumin (OA) were given oral aminophylline (OA-aminophylline group) or saline only (OA-saline group). A third group was challenged by saline as a control. The rats were anesthetized and pulmonary function were performed. Immuno-histochemical staining of epithelial markers (zonula occludens-1 (ZO-1)) and mesenchymal markers (vimentin) in the airway were performed. The protein expressions of ZO-1, E-cadherin, vimentin, fibronectine, TGF-ß1, SMAD 2/3, JNK, and p38 MAPK were examined by western blot. Results: Aminophylline had beneficial effects on airway inflammation, and airway remodeling in the OA-aminophylline group compared to the OA-saline group. The OA-saline group had decreased ZO-1 but increased vimentin according to immuno-histochemical staining. The protein expression indicated decreases in ZO-1 and E-cadherin but increases in vimentin, fibronectine, TGF-ß1, SMAD 2/3, JNK, and p38 MAPK in comparison to the other two groups. The OA-aminophylline group had higher ZO-1 but lower vimentin in immuno-histochemical staining compared to the OA-saline group. The protein expression showed higher ZO-1 and E-cadherin but lower vimentin, fibronectine, TGF-ß1, SMAD 2/3, JNK, and p38 MAPK when compared to the OA-saline group. Conclusions: Ovalbumin increases airway remodeling and airway EMT. Aminophylline is effective in preventing airway remodeling and airway EMT in Brown Norway rats after repeated allergen challenge.
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Aminofilina/farmacología , Pruebas de Provocación Bronquial , Transición Epitelial-Mesenquimal/efectos de los fármacos , Remodelación de las Vías Aéreas (Respiratorias)/efectos de los fármacos , Aminofilina/uso terapéutico , Animales , Broncodilatadores/farmacología , Inflamación/tratamiento farmacológico , Ovalbúmina/farmacología , Ratas , Sistema Respiratorio/patologíaRESUMEN
OBJECTIVES: The increased cardiovascular risk seen in patients with obstructive sleep apnea (OSA) may be due to combination of oxidative stress, systemic inflammation and damage to leukocyte telomere length (LTL) seen with aging. Another molecule, Sirtuin 1 (SIRT1), a histone/protein deacetylase, regulates endothelial nitric oxide synthase and is involved in different aspects of cardiovascular disease, aging and stress resistance. The aim of this study was to evaluate the effects of mandibular advancement device (MAD) on the circulating LTL and SIRT1 protein level in peripheral blood mononuclear cells (PBMCs) in patients with OSA. MATERIALS AND METHODS: Forty patients with moderately severe to severe OSA who desired MAD and 20 healthy controls were prospectively enrolled. The LTL was measured by quantitative polymerase chain reaction while SIRT1 protein levels in PBMC was assessed using a Sirtuin 1 ELISA Kit. All study subjects underwent baseline sleep study, with OSA patients having repeat testing at 3 months after MAD. RESULTS: Compared to healthy subjects, patients with OSA at baseline had lower LTL and SIRT1 protein levels in PBMC. After 3 months of MAD, 24 OSA patients, designated as MAD responders, median (range) LTL increased from (0.556 [0.393-0.748]) to (0.708 [0.533-0.893]) and SIRT1 protein levels in PBMC increased from 0.58 ± 0.23 pg/µg of total protein to 0.95 ± 0.26 pg/µg of total protein. For the 16 MAD unresponsive patients, LTL and SIRT1 protein levels remained low. CONCLUSIONS: Successful treatment of OSA with MAD can restore LTL and SIRT1 protein levels in PBMC. CLINICAL RELEVANCE: LTL and SIRT1 protein levels in PBMC can be improved following effective treatment of OSA using MAD.
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Avance Mandibular , Sirtuina 1/genética , Apnea Obstructiva del Sueño/terapia , Telómero/ultraestructura , Femenino , Humanos , Leucocitos Mononucleares , Masculino , Apnea Obstructiva del Sueño/genéticaRESUMEN
Exhaled breath condensate (EBC) has been used to examine airway inflammation and oxidative stress. This study aimed to evaluate if there were abnormal Sirtuin 1 (SIRT1) protein and tumor necrosis factor (TNF)-α levels in EBC and to determine if these levels could be improved after nasal continuous positive airway pressure (CPAP) treatment. Thirty-five patients with moderately severe to severe obstructive sleep apnea syndrome (OSAS) who wanted nasal CPAP treatment and 20 healthy controls were prospectively enrolled. The EBC SIRT1 protein levels and EBC TNF-α protein levels were assessed by ELISA. All patients underwent sleep studies that were repeated 3 months after nasal CPAP treatment in patients with OSAS. Results showed that in OSAS before nasal CPAP treatment, the EBC SIRT1 protein levels were lower than that in normal subjects, whereas the EBC TNF-α protein levels were higher. After nasal CPAP treatment, the EBC SIRT1 levels increased and EBC TNF-α levels decreased. In conclusion, successful treatment of OSAS by nasal CPAP can normalize the levels of EBC SIRT1 and EBC TNF-α.
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Presión de las Vías Aéreas Positiva Contínua , Sirtuina 1/metabolismo , Apnea Obstructiva del Sueño/metabolismo , Apnea Obstructiva del Sueño/terapia , Factor de Necrosis Tumoral alfa/metabolismo , Adulto , Biomarcadores/metabolismo , Pruebas Respiratorias , Ensayo de Inmunoadsorción Enzimática , Espiración , Femenino , Humanos , Leucocitos/metabolismo , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
BACKGROUND: Sirtuin 1 (SIRT1), a histone/protein deacetylase, has been implicated in aging, metabolism, and stress resistance. SIRT1 regulates endothelial nitric oxide (NO) synthase, restores NO availability, and is involved in different aspects of cardiovascular disease. The aim of this study was to evaluate any abnormalities with regard to SIRT1 protein level in the blood, SIRT1 activity, and impaired endothelial function in patients with obstructive sleep apnea syndrome (OSAS). We also investigated whether or not OSAS patients who received nasal continuous positive airway pressure (CPAP) treatment showed improvements in the levels of SIRT1. METHODS: Thirty-five patients with moderately severe to severe OSAS who requested nasal CPAP treatment and 20 healthy controls were prospectively enrolled. The SIRT1 protein levels in blood and its activity, and the serum levels of nitric oxide derivative (NO x ) were assessed. All subjects participated in sleep studies, which were repeated 3 months after nasal CPAP treatment in the patients with OSAS. RESULTS: In the patients with OSAS, the level of SIRT1 in the blood, its activity, and that of NO x was lower than those of normal subjects before nasal CPAP treatment. After nasal CPAP treatment, the level of SIRT1 in the blood and its activity increased from 0.55 ± 0.32 pg/µg of total protein and 3085.53 ± 1071.57 arbitrary fluorescence units (AFUs)/µg of total protein to 1.13 ± 0.43 pg/µg of total protein and 5344.65 ± 1579.71 AFUs/µg of total protein. The serum levels of NO x in the patients with OSAS increased from 16.36 ± 5.78 to 25.94 ± 5.17 µM. CONCLUSIONS: Successful treatment for OSAS with nasal CPAP can restore blood levels of the SIRT1 protein and its activity and serum levels of NO x .
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Presión de las Vías Aéreas Positiva Contínua , Endotelio Vascular/metabolismo , Óxido Nítrico/metabolismo , Sirtuina 1/metabolismo , Apnea Obstructiva del Sueño/terapia , Adulto , Estudios de Casos y Controles , Endotelio Vascular/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polisomnografía , Estudios Prospectivos , Apnea Obstructiva del Sueño/metabolismo , Apnea Obstructiva del Sueño/fisiopatologíaRESUMEN
OBJECTIVES: This study evaluated the effects of mandibular advancement device (MAD) on serum levels of nitric oxide derivatives and endothelial function by endothelium-dependent flow-mediated dilation (FMD) in obstructive sleep apnea syndrome (OSAS). METHODS: Thirty patients with moderately severe-to-severe OSAS who desired MAD and 15 healthy controls were prospectively enrolled. FMD was measured by high-resolution B-mode ultrasonography, while serum NO x level from peripheral blood samples was measured by ELISA. All subjects participated in the sleep studies, which were repeated 2 months after MAD in OSAS patients. RESULTS: Serum NO x level and FMD were lower in patients with OSAS than in controls prior to MAD. Serum NO x levels in 19 of 30 patients with OSAS, the designated MAD responders, increased from 11.8 ± 5.8 µM pre-MAD to 22.7 ± 4.9 µM post-MAD. The FMD increased from 5.9 ± 4.6 pre-MAD to 10.5 ± 4.8 post-MAD. For the 11 unresponsive patients, serum NO x and FMD remained impaired after MAD. CONCLUSIONS: Successful treatment of OSAS with MAD can restore serum levels of NO x and FMD. CLINICAL RELEVANCE: Endothelial function can be improved following effective treatment of OSAS using MAD.
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Endotelio Vascular/fisiopatología , Avance Mandibular/instrumentación , Síndromes de la Apnea del Sueño/fisiopatología , HumanosRESUMEN
PURPOSE: This study aims to study the effects of depression and demoralization on suicidal ideation and to determine the feasibility of the Distress Thermometer as a screening tool for patients with cancer who experience depression and demoralization, and thus to establish a model screening process for suicide prevention. METHODS: Purposive sampling was used to invite inpatients and outpatients with lung cancer, leukemia, and lymphoma. Two hundred participants completed the questionnaire, which included the Distress Thermometer (DT), Patient Health Questionnaire-9 (PHQ-9), Demoralization Scale-Mandarin Version (DS-MV), and Beck Scale for Suicide Ideation. All data obtained were analyzed using SPSS 18.0 and SAS 9.3. RESULTS: Tobit regression analysis showed that demoralization influenced suicidal ideation more than depression did (t = 2.84, p < 0.01). When PHQ-9 ≥ 10 and DS-MV ≥42 were used as criteria for the DT, receiver operating characteristic analysis revealed that the AUC values were 0.77-0.79, with optimal cutoff points for both of DT ≥5; sensitivity 76.9 and 80.6 %, respectively; and specificity of 73.9 and 72.2 %, respectively. CONCLUSIONS: Demoralization had more influence on suicidal ideation than depression did. Therefore, attention should be paid to highly demoralized patients with cancer or high demoralization comorbid with depression for the purposes of suicide evaluation and prevention. The DT scale (with a cutoff of ≥5 points) has discriminative ability as a screening tool for demoralization or depression and can also be used in clinical settings for the preliminary screening of patients with cancer and high suicide risk.
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Depresión , Neoplasias/psicología , Estrés Psicológico , Ideación Suicida , Prevención del Suicidio , Adulto , Anciano , Área Bajo la Curva , Depresión/diagnóstico , Depresión/etiología , Depresión/fisiopatología , Estudios de Factibilidad , Femenino , Humanos , Masculino , Tamizaje Masivo/métodos , Persona de Mediana Edad , Pacientes Ambulatorios/psicología , Pacientes Ambulatorios/estadística & datos numéricos , Análisis de Regresión , Medición de Riesgo/métodos , Factores Socioeconómicos , Estrés Psicológico/diagnóstico , Estrés Psicológico/etiología , Estrés Psicológico/fisiopatología , Suicidio/psicología , Encuestas y Cuestionarios , TaiwánRESUMEN
OBJECTIVES: This study evaluated the effects of uvulopalatopharyngoplasty (UPPP) on serum leptin levels and endothelial function in patients with obstructive sleep apnea syndrome (OSAS). METHODS: Fifteen healthy subjects and 35 patients with moderate to severe OSAS who desired UPPP were prospectively enrolled. The serum levels of leptin and nitric oxide derivative (NOx) from their peripheral blood samples were measured by enzyme-linked immunosorbent assay. All subjects participated in sleep studies, which were repeated 3 months after UPPP in the patients with OSAS. RESULTS: Before UPPP, the patients with OSAS had a higher serum level of leptin and a lower NOx level than did the control subjects. The serum leptin levels in the 17 of the 35 patients with OSAS who were surgical responders decreased from 24.2 ± 6.1 ng/mL before operation to 15.9 ± 6.0 ng/mL after operation. The serum NOx levels in these 17 patients increased from 18.5 ± 7.5 µmol/L before operation to 27.3 ± 8.2 µmol/L after operation. In the 18 patients who were unresponsive to surgery, the serum leptin and NOx levels remained impaired after the UPPP. CONCLUSIONS: Successful treatment of OSAS with UPPP leads to the normalization of serum leptin and NOx levels.
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Endotelio Vascular/fisiopatología , Leptina/sangre , Paladar Blando/cirugía , Faringe/cirugía , Apnea Obstructiva del Sueño/sangre , Apnea Obstructiva del Sueño/cirugía , Úvula/cirugía , Adulto , Biomarcadores/sangre , Índice de Masa Corporal , Femenino , Depuradores de Radicales Libres/sangre , Humanos , Masculino , Óxido Nítrico/sangre , Obesidad/complicaciones , Procedimientos Quirúrgicos Otorrinolaringológicos/métodos , Polisomnografía , Estudios Prospectivos , Procedimientos de Cirugía Plástica/métodos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/fisiopatología , Resultado del TratamientoRESUMEN
BACKGROUND: Chronic asthma is characterized by airway inflammation and remodeling. OBJECTIVE: This study aimed to evaluate the effects of zileuton on bronchial hyperresponsiveness, airway inflammation and airway smooth muscle (ASM) remodeling. METHODS: Two experimental groups of brown Norway rats sensitized and repeatedly challenged with aerosolized ovalbumin (OA) were given oral zileuton (OA-zileuton group) and oral saline only (OA-saline group). A third, control group was sensitized and challenged by saline. The rats were anesthetized and paralyzed. Pulmonary function tests were performed at baseline and after varying doses of acetylcholine. Bronchoalveolar lavage fluid and lung tissues were examined. RESULTS: Zileuton had beneficial effects on pulmonary function, airway inflammation and ASM remodeling in the OA-zileuton group compared to the OA-saline group. Zileuton inhibited an OA-stimulated increase in ASM by inhibiting hypertrophy, hyperplasia and increased extracellular matrix via the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, thereby reducing cyclin D1 expression and attenuating bronchial hyperresponsiveness. CONCLUSION: OA increases airway inflammation and ASM mass. Zileuton effectively prevents bronchial hyperresponsiveness, airway inflammation and ASM remodeling in sensitized rats through the PI3K/Akt pathway, which reduces cyclin D1 expression.
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Remodelación de las Vías Aéreas (Respiratorias)/efectos de los fármacos , Alérgenos/administración & dosificación , Asma/tratamiento farmacológico , Hidroxiurea/análogos & derivados , Antagonistas de Leucotrieno/uso terapéutico , Pulmón/patología , Remodelación de las Vías Aéreas (Respiratorias)/inmunología , Animales , Asma/inmunología , Asma/metabolismo , Asma/patología , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Evaluación Preclínica de Medicamentos , Hidroxiurea/farmacología , Hidroxiurea/uso terapéutico , Antagonistas de Leucotrieno/farmacología , Pulmón/efectos de los fármacos , Pulmón/inmunología , Sistema de Señalización de MAP Quinasas , Masculino , Fosfatidilinositol 3-Quinasas/metabolismo , Ratas , Pruebas de Función Respiratoria , Linfocitos T/metabolismoRESUMEN
Obesity, particularly severe central obesity, affects respiratory physiology both at rest and during exercise. Reductions in expiratory reserve volume, functional residual capacity, respiratory system compliance and impaired respiratory system mechanics produce a restrictive ventilatory defect. Low functional residual capacity and reductions in expiratory reserve volume increase the risk of expiratory flow limitation and airway closure during quiet breathing. Consequently, obesity may cause expiratory flow limitation and the development of intrinsic positive end expiratory pressure, especially in the supine position. This increases the work of breathing by imposing a threshold load on the respiratory muscles leading to dyspnoea. Marked reductions in expiratory reserve volume may lead to ventilation distribution abnormalities, with closure of airways in the dependent zones of the lungs, inducing ventilation perfusion mismatch and gas exchange abnormalities. Obesity may also impair upper airway mechanical function and neuromuscular strength, and increase oxygen consumption, which in turn, increase the work of breathing and impair ventilatory drive. The combination of ventilatory impairment, excess CO(2) production and reduced ventilatory drive predisposes obese individuals to obesity hypoventilation syndrome.
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Obesidad/complicaciones , Obesidad/fisiopatología , Trastornos Respiratorios/etiología , Respiración , Resistencia de las Vías Respiratorias/fisiología , Animales , Disnea/etiología , Disnea/fisiopatología , Ejercicio Físico/fisiología , Femenino , Humanos , Masculino , Neurotransmisores/fisiología , Consumo de Oxígeno/fisiología , Ratas , Trastornos Respiratorios/fisiopatología , Músculos Respiratorios/fisiopatología , Sistema Respiratorio/fisiopatología , Síndromes de la Apnea del Sueño/etiología , Síndromes de la Apnea del Sueño/fisiopatología , Trabajo Respiratorio/fisiologíaRESUMEN
Erlotinib, an EGFR tyrosine kinase inhibitor, can inhibit the proliferation and survival of cancer cells. It has been widely used to treat non-small cell lung cancer. This study aimed to evaluate the effects of erlotinib on bronchial hyperresponsiveness, airway inflammation, and airway remodeling in sensitized, ovalbumin-challenged rats. Two experimental groups of Brown-Norway rats were sensitized and repeatedly challenged by breathing aerosolized ovalbumin. Since Day 1, one group was given oral erlotinib (OA-erlotinib group) while the other group was given only oral saline (OA-saline group). The control group was sensitized and challenged using saline. All were anesthetized and paralyzed, and pulmonary function tests conducted at baseline and after provocation with varying doses of acetylcholine. Lung tissues were examined for airway inflammation, airway remodeling, and Th2-related cytokine mRNA expression. Results showed that the OA-erlotinib group had better pulmonary function and less airway inflammation, Th2-related cytokines and their mRNA expression, and airway remodeling compared to the OA-saline group. In conclusion, erlotinib effectively prevents bronchial hyperreactivity, airway inflammation, Th2-related cytokine mRNA expression, and airway remodeling after sensitization and repeated allergen challenge in Brown-Norway rats.
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Remodelación de las Vías Aéreas (Respiratorias)/efectos de los fármacos , Hiperreactividad Bronquial/prevención & control , Neumonía/prevención & control , Inhibidores de Proteínas Quinasas/farmacología , Quinazolinas/farmacología , Alérgenos/inmunología , Animales , Hiperreactividad Bronquial/inmunología , Clorhidrato de Erlotinib , Inmunohistoquímica , Ovalbúmina/inmunología , Neumonía/inmunología , Ratas , Ratas Endogámicas BN , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
To evaluate the prevalence of obstructive sleep apnea (OSA) and to clarify sleep characteristics in patients with mucopolysaccharidoses (MPS), we performed overnight polysomnographic studies in 24 patients (22 males and 2 females; 3 with MPS I, 15 with MPS II, 1 with MPS III, 1 with MPS IV, and 4 with MPS VI; mean age, 10.8 ± 6.0 years; age range, 2.0-23.7 years; 2 patients ≥18 years of age). The nadir arterial oxygen saturation (SaO(2) ) was 74.5 ± 12.3%, and the average percentage of sleep time with an SaO(2) of <95% was 39.4%. The percentages of total sleep time spent in sleep stages N1, N2, N3, and R were 18.6 ± 10.8%, 50.3 ± 7.6%, 14.8 ± 8.1%, and 15.3 ± 4.6%, respectively. The respiratory disturbance index (RDI) was 21.8 ± 20.4/hr, and obstructive apnea-hypopnea index (OAHI) and central apnea index were 21.4 ± 19.9/hr and 0.4 ± 0.6/hr, respectively. The desaturation index was 17.6 ± 17.8/hr. All patients had some degree of OSA. For 22 children, the disorder was mild (OAHI 1.5-5) in 2, moderate (OAHI 5-10) in 7, and severe (OAHI > 10) in 13. Two patients with MPS II who received enzyme replacement therapy had reductions in RDI after treatment (38.9-10.8 and 3.5-2.0, respectively). The prevalence of moderate to severe OSA was 88% (21/24) in patients with MPS. The overnight polysomnography will help to determine the abnormalities of breathing during sleep more precisely and urge the clinicians to take necessary action for patients with severe manifestations.
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Mucopolisacaridosis/complicaciones , Apnea Obstructiva del Sueño/diagnóstico , Adolescente , Adulto , Factores de Edad , Niño , Preescolar , Terapia de Reemplazo Enzimático , Femenino , Humanos , Masculino , Mucopolisacaridosis/terapia , Oxígeno/sangre , Polisomnografía , Pubertad , Índice de Severidad de la Enfermedad , Apnea Obstructiva del Sueño/etiología , Adulto JovenRESUMEN
BACKGROUND: Serum levels of high mobility group box-1 protein (HMGB1) are increased in a variety of inflammatory disorders. Obstructive sleep apnea syndrome (OSAS) is associated with inflammation secondary to chronic intermittent hypoxia, but HMGB1 levels in treated and untreated OSAS have not been evaluated. METHODS: Twenty healthy subjects and 30 subjects with moderately severe or severe OSAS who desired nasal continuous positive airway pressure (CPAP) treatment were enrolled. Serum levels of HMGB1 and nitric oxide derivative (NO(x)) from peripheral blood samples were measured, and all subjects underwent a sleep study. These studies were repeated 2 months after nasal CPAP treatment in the patients with OSAS. RESULTS: In OSAS before nasal CPAP treatment, the serum level of HMGB1 was higher but that of NO(x) was lower than those levels of normal subjects. The HMGB1 levels correlated negatively with NO(x) levels in subjects with OSAS. After nasal CPAP treatment, the HMGB1 and NO(x) returned to normal levels. CONCLUSION: Elevated HMGB1 levels and reduced NO(x) levels in patients with OSAS normalized after nasal CPAP treatment.
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Presión de las Vías Aéreas Positiva Contínua/métodos , Proteína HMGB1/sangre , Apnea Obstructiva del Sueño/terapia , Biomarcadores/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Óxido Nítrico/sangre , Apnea Obstructiva del Sueño/sangre , Resultado del TratamientoRESUMEN
OBJECTIVES: This study evaluates the effects of uvulopalatopharyngoplasty (UPPP) on serum levels of nitric oxide derivatives (NO(x)) and endothelial function by endothelium dependent flow-mediated dilation (FMD) in obstructive sleep apnea syndrome (OSAS). STUDY DESIGN: Prospective study. SUBJECTS AND METHODS: Fifteen healthy subjects and 30 subjects with moderately severe to severe OSAS who desired UPPP were prospectively enrolled. FMD was measured by high-resolution B-mode ultrasonography; serum level of NO(x) from peripheral blood samples was also measured. All subjects participated in sleep studies. These studies were repeated 3 months after UPPP in OSAS patients. RESULTS: For healthy patients, there was no difference in serum level of NO(x) and FMD between baseline and 3 months later. The serum levels of NO(x) in 14 of 30 patients with OSAS - designated surgical responders - increased from 13.9 +/- 5.5 microM preoperation to 28.9 +/- 8.2 microM postoperatively. FMD increased from 5.2 +/- 5.0 preoperatively to 10.0 +/- 4.7 postoperatively. For the 16 unresponsive patients, serum NOx and FMD remained impaired after UPPP. CONCLUSION: Successful treatment of OSAS with UPPP leads to restoration of FMD and normal serum levels of NO(x).
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Endotelio Vascular/fisiopatología , Óxido Nítrico/análogos & derivados , Óxido Nítrico/sangre , Procedimientos Quirúrgicos Otorrinolaringológicos , Apnea Obstructiva del Sueño/fisiopatología , Apnea Obstructiva del Sueño/cirugía , Adulto , Femenino , Humanos , Masculino , Procedimientos Quirúrgicos Otorrinolaringológicos/métodos , Hueso Paladar/cirugía , Faringe/cirugía , Polisomnografía , Úvula/cirugíaRESUMEN
Kyphoscoliosis is one of the causes of restrictive lung disease. It can lead to chronic hypercapnic respiratory failure and hypoxaemia. The benefits of long term intermittent nocturnal non-invasive positive pressure ventilation (NIPPV) to these patients have been shown in regard to improved vital capacity, total lung capacity, muscle strength and daytime oxygenation. In our case, we found long term intermittent nocturnal NIPPV also had a beneficial effect on exercise capacity and pulmonary hypertension. This is good for patients with kyphoscoliosis not only in terms of their survival but also for their quality of life. We recommend long term intermittent nocturnal NIPPV as a routine intervention for severe kyphoscoliosis with hypoxaemia, and transthoracic echocardiography as a routine evaluation tool for determining the response of pulmonary hypertension to management.
RESUMEN
BACKGROUND: Upper airways in patients with obstructive sleep apnea syndrome (OSAS) are more likely narrower than those of normal subjects, a factor in increasing the work of breathing (WOB) in these individuals. OBJECTIVES: To evaluate WOB while sitting and while supine, both awake and during stage 2 sleep, in patients with hypercapnic or eucapnic OSAS. METHOD: Twenty normal control subjects without OSAS, 20 patients with eucapnic moderate or severe OSAS and another 8 patients with hypercapnic severe OSAS were studied. WOB was measured by esophageal manometry with the subjects seated and then with the subjects supine, both while awake and during stage 2 sleep. RESULTS: In both the control and the eucapnic group, WOB was normal in the sitting position. When the eucapnic subjects lay supine, their WOB increased, both while awake and asleep. In contrast, the hypercapnic subjects had an abnormally high WOB both sitting and supine, whether awake or asleep. CONCLUSION: WOB was increased in subjects with hypercapnic OSAS in both the sitting and supine positions. While eucapnic individuals with OSAS have increased WOB when supine, it is normal when they are sitting upright.
Asunto(s)
Hipercapnia/fisiopatología , Mecánica Respiratoria , Síndromes de la Apnea del Sueño/fisiopatología , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Postura , SueñoRESUMEN
To evaluate the effect of erythromycin on bronchial hyperreactivity, inflammation, and T-cell related cytokine mRNA expression in rats sensitized to ovalbumin, three experimental groups of 10 brown Norway rats each were sensitized by breathing aerosolized ovalbumin. From day 1 to day 15, one group was given oral erythromycin 80 mg/kg/day, another group oral erythromycin 20mg/kg/day, and the third group oral saline only. A fourth control group of 10 rats breathed aerosolized saline. After sensitization, the three experimental groups were provoked by breathing ovalbumin, with the controls again breathing saline. The rats were then anesthetized and paralyzed, and pulmonary function tests were performed at baseline and after varying doses of acetylcholine. Bronchoalveolar lavage (BAL) fluid and lung tissues were examined for expression of mRNA for T-cell cytokines. Our results showed that erythromycin had no beneficial effects on pulmonary function and lung inflammation in the two erythromycin-treated experimental groups compared with the saline experimental group. Th2-related cytokines and their mRNA expression in the three experimental groups were higher than in controls but did not differ among the experimental groups. In conclusion, erythromycin does not prevent bronchial hyperreactivity or an inflammatory response in ovalbumin-sensitized rats.