Impact of CPAP treatment for a short period in moderate-to-severe OSAS patients: a randomized double-blind clinical trial / Impacto do tratamento com CPAP por um curto período em pacientes com SAOS moderada a grave: um estudo clínico duplo-cego randomizado

Abstract Introduction: Obesity is the most frequent reversible agravating factor of obstructive sleep apnea syndrome, with physical activity very important for its control. Continuous positive air pressure during sleep is the ‟gold standard" treatment for obstructive sleep apnea syndrome. Objective: we aimed to investigate if the use of continuous positive air pressure for a short period (7 days), would improve sleep quality, daytime sleepiness, and the disposition for physical activity. Methods: Eighty obstructive sleep apnea syndrome patients were randomly assigned as follows: group I - continuous positive air pressure with a steady pressure of 4cm H2O; group II - ideal therapeutic pressure. After filling out the questionnaires related to the studied variables (International physical activity questionnaire long-form, Epworth sleepiness scale, Pittsburgh sleep quality index), patients underwent a baseline pulmonary function test and continuous positive air pressure titration. After continuous positive air pressure therapy for 4> hours a night for 7 consecutive days, patients returned and filled out new (International physical activity questionnaire long-form, Epworth sleepiness scale, Pittsburgh sleep quality index) forms. New spirometry was carried out. Results: 39 patients completed the study. The mean age was 52 ±11 years old and 28 patients (71.79%) were obese. Both groups were similar for all variables studied at baseline. After Continuous positive air pressure use, patients of group II presented more significant improvements (p< 0.05) for sleep quality and diurnal sleepiness. Time spent with physical activities did not change. Spirometric data were at normal range at baseline. Solely the variable FEF 25%-75% was significantly enhanced (p< 0.05) in group II. Conclusion: Continuous positive air pressure therapy for 1 week, with ideal pressure, improves daytime sleepiness and sleep quality, enhances pulmonary function, but does not change the mean time spent with physical activities.

Resumo Introdução: A obesidade é o fator causal reversível mais frequente da síndrome da apneia obstrutiva do sono, a atividade física é muito importante para o seu controle. A pressão positiva contínua na via aérea, CPAP, durante o sono é o tratamento padrão ouro para essa condição clínica. Objetivo: Avaliar se o uso do CPAP na síndrome da apneia obstrutiva do sono por um curto período (7 dias) melhoraria a qualidade do sono, a sonolência diurna e a disposição para a prática de atividades físicas, além da função pulmonar. Método: Oitenta pacientes com síndrome da apneia obstrutiva do sono foram distribuídos aleatoriamente da seguinte forma: grupo I - CPAP com pressão constante de 4cm H2O; grupo II - pressão terapêutica ideal. Após o preenchimento dos questionários relacionados ao estudo das variáveis (PSQI, ESS e IPAQ-L), os pacientes foram submetidos a teste de função pulmonar basal e titulação da CPAP. Após terapia com CPAP por ≥ 4 horas por noite durante sete dias consecutivos, os pacientes retornaram e preencheram novos questionários PSQI, ESS e IPAQ-L. Nova espirometria foi feita. Resultados: Apenas 39 pacientes completaram o estudo. A média de idade foi de 52 ± 11 anos e 28 pacientes (71,79%) eram obesos. Ambos os grupos eram semelhantes quanto às variáveis avaliadas no início do estudo. Após o uso de CPAP, os pacientes do grupo II apresentaram melhorias mais significantes (p < 0,05) para qualidade do sono e sonolência diurna. O tempo gasto com atividades físicas não mudou. Os dados espirométricos estavam na faixa normal no início do estudo. Apenas a variável FEF 25%-75% aumentou significantemente (p < 0,05) no grupo II. Conclusão: A terapia com CPAP por uma semana, com pressão ideal, melhora a sonolência diurna e a qualidade do sono, melhora a função pulmonar, mas não altera o tempo médio despendido com atividades físicas.

Comparación entre el análisis automático y manual de 301 poligrafías respiratorias domiciliarias con ApneaLink / Comparison between automatic and manual scoring of 301 home respiratory polygraphs with ApneaLink device

Resumen Introducción: El síndrome de apnea obstructiva del sueño (SAOS) se asocia a aumento de morbimortalidad cardiovascular y metabólica, y a mala calidad de vida. Su diagnóstico y tratamiento eficaz mejora la salud individual y pública. Objetivo: evaluar concordancia entre análisis automático versus manual del dispositivo ApneaLink para diagnosticar y clasificar SAOS en pacientes con sospecha clínica. Material y Método: Evaluación retrospectiva de 301 poligrafías respiratorias del HOSCAR. Se mide correlación, acuerdo general y concordancia entre parámetros obtenidos manual y automáticamente usando coeficiente de Pearson, coeficiente de correlación intraclase y gráfico de Bland y Altman. Resultados: En 11,3% de casos el análisis automático interpreto erróneamente la señal de flujo. No hubo diferencias significativas entre índices de apnea-hipopnea automático (AHIa 18,9 ± 17,5) y manual (AHIm 20,8 ± 19,4) r + 0,97 (95% CI: 0,9571 a 0,9728; p < 0,0001) y tampoco entre la saturación mínima de oxígeno automática (82,1 ± 7,6) y manual (83,1 ± 6,8) r + 0,85 (95% CI: 0,8108 a 0,8766; p < 0,0001). No hubo buena correlación entre análisis automático y manual en clasificación de apneas centrales, r + 0,51 (95% CI: 0,4238 a 0,5942; p < 0,0001). Hubo subestimación de gravedad de SAOS por análisis automático: en 11% de casos. Conclusión: El diagnóstico entregado automáticamente por ApneaLink podría aceptarse sin confirmación manual adicional solamente en casos clasificados como severos. Para AHI menores se requeriría confirmación mediante análisis manual de experto.

Abstract Introduction: Obstructive sleep apnea syndrome (OSAS) is associated with increased cardiovascular and metabolic morbidity and mortality, and poor quality of life. Its effective diagnosis and treatment improve individual and public health. Aim: To evaluate concordance between automatic versus manual analysis of the ApneaLink device to diagnose and classify OSAS in patients with clinical suspicion. Material and Method: Retrospective evaluation of 301 respiratory polygraphs from HOSCAR. Correlation, general agreement and concordance between parameters obtained manually and automatically are measured using Pearson's coefficient, intraclass correlation coefficient, and Bland and Altman graph. Results: In 11.3% of cases, the automatic analysis misinterpreted the flow signal. There were no significant differences between automatic (AHIa 18.9 ± 17.5) and manual (AHIm 20.8 ± 19.4) apnea-hypopnea indices r + 0.97 (95% CI:0.9571 to 0.9728, p < 0.0001) and nor between automatic (82.1 ± 7.6) and manual (83.1 ± 6.8) minimum oxygen saturation r + 0.85 (95% CI: 0.8108 to 0.8766, p < 0.0001). There was no good correlation between automatic and manual analysis in the classification of central apneas, r + 0.51(95% CI:0.4238 to 0.5942, p < 0.0001). There was an underestimation of the severity of OSAS by automatic analysis in 11% of cases. Conclusion: The diagnosis delivered automatically by ApneaLink could be accepted without additional manual confirmation only in cases classified as severe. For minors AHI, confirmation through manual expert analysis would be required.

Impacto del síndrome de apneas obstructivas del sueño en accidentes de tránsito en Chile

Resumen Introducción: Existe abundante evidencia para considerar al síndrome de apnea obstructiva del sueño (SAOS) como un factor de riesgo significativo en la ocurrencia de accidentes de tránsito. En el año 2018, los accidentes de tránsito en Chile provocaron 1.507 muertes, 60 mil lesionados, y generaron un costo país de US $5.985 millones al año (2,1% PIB). Sin embargo, se desconoce la prevalencia de SAOS en conductores, ni su impacto en la accidentabilidad a nivel nacional. Objetivo: Estimar la prevalencia de SAOS en conductores nacionales, y su importancia relativa en el número de accidentes, lesionados, muertes y costos asociados. Material y Método: Revisión de la literatura, análisis descriptivo con bases de datos secundarias. Estimación de prevalencia de riesgo de SAOS en conductores nacionales, profesionales, y cálculo de costos asociados a accidentabilidad. Resultados: Se estima prevalencia de SAOS moderado a severo en un 28,6% para conductores nacionales y 30,2% para conductores profesionales. Utilizando un odds ratio de 2,52 (IC 1,84-3,35) como estimador de riesgo, se obtiene un riesgo atribuible porcentual poblacional de 30,28%, que se traduce en que SAOS sería responsable de 27.046 accidentes, 17.545 lesionados, 456 muertes, y un costo país de US $1.812,4 millones al año atribuibles a SAOS para las cifras de accidentabilidad 2018. Conclusión: El presente trabajo es la primera aproximación al tema a nivel chileno. Se requieren estudios de prevalencia de SAOS en conductores para realizar estimaciones más precisas. Impresiona necesario colocar este tema en la agenda pública, por la posible reducción de riesgos.

Abstract Introduction: There is abundant evidence to consider obstructive sleep apnea syndrome (OSAS) as a significant risk factor in the occurrence of traffic accidents. In 2018, traffic accidents in Chile caused 1,507 deaths, 60 thousand injured, and generated a country cost of US $ 5,985 million per year (2.1% GDP). However, the prevalence of OSAS in national drivers, nor its impact on accident rate level is unknown. Aim: To estimate the prevalence of OSAS in Chilean drivers, and their relative importance in the number of accidents, injuries, deaths and associated costs. Material and Method: Literature review, descriptive analysis with secondary databases. Estimation of risk prevalence of OSAS in Chilean drivers, professional drivers, and calculation of costs associated with accident rates. Results: The prevalence of moderate to severe OSAS is estimated at 28,6% for national drivers, 30,2% for professional drivers. Using an OR of 2.52 (CI 1.84-3.35) as a risk estimator), a population attributable risk percentage of 30,28% is obtained, which translates to 27,046 accidents, 17,545 injured, 456 deaths, and a country cost of US $ 1,812.4 million per year attributable to OSAS for accidents in 2018. Conclusion: This paper is the first approach to the subject at the Chilean level. OSAS prevalence studies in drivers are required to make more accurate estimates. It is necessary to place this topic on the public agenda, due to the possible risk reduction.

3-D airway analysis related to facial morphology / Análisis 3-D de la vía aerea relacionado con la morfología facial

The aim of this investigation was to define the volume and area of the airway in subjects with Class II and Class III skeletal deformity. A cross-sectional study was designed including subjects with facial deformity defined by Steiner's analysis in subjects with indication of orthognathic surgery who presented diagnosis by cone beam computerised tomography. We determined the measurements of maximum area, minimum area and volume of the airway. The data were compared using Spearman's test, with statistical significance defined as p<0.05. 115 subjects were included: 61.7 % Class II and 38.3 % Class III, mean age 27.8 years (± 11.6). A significant difference was observed in the area and volume measurements in the groups studied, with significantly smaller measurements found in Class II (p=0.034). The minimum area was 10.4 mm2 smaller in Class II patients than in Class III, while the general volume of the airway was 4.1 mm3 smaller in Class II than in Class III. We may conclude that Class II subjects present a smaller airway volume than Class III subjects.

El objetivo de esta investigación de definir el volumen y área de vía aérea en sujetos con deformidad esqueletal clase II y III. Se diseñó un estudio de corte transversal incluyendo sujetos con deformidad facial definida según análisis de Stainer en sujetos con indicación de cirugía ortognática que presentaran una tomografía computadorizada de haz cónico como elemento diagnóstico; en este examen se determinaron medidas de área mayor, menor de vía aérea y volumen presente; los datos fueron comparados utilizando pruebas estadísticas con el test de spearman considerando el valor de p<0,05 para definir significancia estadística. 115 sujetos fueron incluidos, siendo 61,7 % de tipo clase II y 38,3 % de sujetos clase III, con una edad promedio de 27,8 años (± 11,6). Se observó una diferencia significativa en mediciones de area y volumen en los grupos estudiados, siendo el grupo de clase II significativamente menor (p=0,034). El área de menor tamaño fue 10,4 mm2 en pacientes clase II que en pacientes clase III, mientras que el volumen general de la vía área fue 4,1 menor en los clase II que en los clase III. Es posible concluir que los sujetos de clase II presentan menor volumen de vía área que los sujetos clase III.

La cirugía ortognática en el tratamiento del síndrome de apnea obstructiva del sueño / Orthognathic surgery in the treatment of obstructive sleep apnea syndrome

RESUMEN Introducción: El síndrome de apnea obstructiva del sueño provoca somnolencia diurna; incide negativamente sobre el sistema cardiovascular y disminuye la calidad de vida. La cirugía ortognática provoca cambios en el espacio aéreo faríngeo, por lo que ha sido empleada en el tratamiento de dicho síndrome. Objetivo: Caracterizar las técnicas en cirugía ortognática más empleadas en el tratamiento del síndrome de apnea obstructiva del sueño, sus influencias sobre la vía aérea faríngea y efectividad terapéutica. Métodos: Se realizó una revisión de la literatura científica desde diciembre del 2016 a junio del 2017 a través de los buscadores de información y plataformas SciELO, Medline, Pubmed y Hinari. Los descriptores empleados para la búsqueda fueron cirugía ortognática, síndrome de apnea obstructiva del sueño, vía aérea faríngea, avance máxilo mandibular y sus combinaciones. Se obtuvieron 127 artículos de los que se seleccionaron 28 por su contenido, actualidad y objetividad. Análisis e integración de la información: El adelanto quirúrgico del maxilar, mandíbula, mentón o sus combinaciones minimiza los efectos del síndrome de apnea obstructiva del sueño. Es recomendable la cirugía bimaxilar en la corrección de las clases III esqueletales para atenuar posibles efectos perjudiciales sobre la vía aérea por la retroposición mandibular aislada. Conclusiones: La cirugía ortognática de avance, incrementa el espacio faríngeo y mejora la calidad del sueño. Los movimientos de retroposición pueden tener efecto inverso, aspecto importante en la corrección de las clases III esqueletales(AU)

ABSTRACT Introduction: Obstructive sleep apnea syndrome causes daytime sleepiness, affects the cardiovascular system and reduces the quality of life. Since orthognathic surgery brings about changes in the pharyngeal airway space, it has been used to treat this syndrome. Objective: Characterize the orthognathic surgery techniques most commonly used to treat obstructive sleep apnea syndrome, their impact on the pharyngeal airway and their therapeutic effectiveness. Methods: A bibliographic review was conducted from December 2016 to June 2017 using the search engines and platforms SciELO, Medline, Pubmed and Hinari. The search words used were orthognathic surgery, obstructive sleep apnea syndrome, pharyngeal airway, maxillomandibular advancement, and combinations thereof. Of the 127 papers obtained, 28 were selected based on their content, topicality and objectivity. Data analysis and integration: Surgical advancement of the maxilla, mandible, chin or combinations thereof minimizes the effects of obstructive sleep apnea syndrome. Bimaxillary surgery is recommended to correct skeletal class III malocclusion so as to lessen potential damaging effects on the airway caused by isolated mandibular retroposition. Conclusions: Advancement orthognathic surgery broadens the pharyngeal airway space and improves the quality of sleep. The fact that retroposition movements may have an opposite effect is an important aspect to be considered in the correction of skeletal class III malocclusions(AU)

Effects of fluoride exposure on microRNA-200c expression and its target in human osteoblast Saos-2 cells / 中华地方病学杂志

Objective To investigate the effect of fluoride exposure on expression of miRNA (miR)-200c and its target in human osteoblast Saos-2 cells.Methods Saos-2 cells were cultured in DMEM/F-12 medium and treated with fluoride (sodium fluoride,NaF).There were two groups including:control group (0 mg/L) and fluoride group (4 mg/L).Cells were harvested after 48 hours of culture with fluoride.The expression of miR-200c,the mRNA of alkaline phosphatase (ALP),osteocalcin (BGP),the target phosphatase and tensin homolog deleted on chromosome ten (PTEN) and dual-specific phosphatase 1 (DUSP1) of miR-200c was detected by qRT-PCR.The protein expression of PTEN and DUSP1 was detected by Western blotting.Results The expressions of ALP,BGP mRNA and miR-200c in Saos-2 cells in the fluoride group (23.60 ± 1.87,9.41 ± 0.94,8.61 ± 0.26) were higher than those in the control group (1.00 ± 0.11,1.00 ± 0.07,1.00 ± 0.12).The differences were statistically significant (t =-24.084,-18.388,-8.687,P ＜ 0.05).The mRNA expressions of PTEN and DUSP1 in the fluoride group (0.63 ± 0.02,0.38 ± 0.02) were lower than those in the control group (1.02 ± 0.24,1.02 ± 0.24).The differences were statistically significant (t =3.327,5.454,P ＜ 0.05).The protein expressions of PTEN and DUSP1 in Saos-2 cells in the fluoride group (1.19 ± 0.10,0.83 ± 0.07) were lower than those in the control group (1.81 ± 0.14,1.44 ± 0.25).The differences were statistically significant (t =6.250,4.171,P ＜ 0.05).Conclusion Exposure to fluorine may increase the expression of miR-200c in Saos-2 cells,and fluorine may act on PTEN and DUSP1 through miR-200c,downregulates the mRNA and protein expression levels of PTEN and DUSP1.

The importance of clinical monitoring for compliance with Continuous Positive Airway Pressure / A importância do seguimento clínico para adesão ao CPAP

Abstract Introduction: Obstructive sleep apnea syndrome is currently a public health problem of great importance. When misdiagnosed or improperly treated, it can lead to serious consequences on patients' quality of life. The gold standard treatment for cases of obstructive sleep apnea syndrome, especially in mild to severe and symptomatic cases, is continuous positive airway pressure therapy. Compliance with continuous positive airway pressure therapy is directly dependent on the active participation of the patient, which can be influenced by several factors. Objective: The objective of this study is to describe the factors related to compliance with continuous positive airway pressure therapy, and to analyze which associated factors directly influence the efficiency of the treatment. Methods: Patients who received continuous positive airway pressure therapy through the Municipal Health Department of the city of Ribeirão Preto were recruited. A structured questionnaire was administered to the patients. Compliance with continuous positive airway pressure therapy was assessed by average hours of continuous positive airway pressure therapy usage per night. Patients with good compliance (patients using continuous positive airway pressure therapy ≥4 h/night) were compared to those with poor compliance (patients using <4 h/night). Results: 138 patients were analyzed: 77 (55.8%) were considered compliant while 61 (44.2%) were non-compliant. The comparison between the two groups showed that regular monitoring by a specialist considerably improved compliance with continuous positive airway pressure therapy (odds ratio, OR = 2.62). Conclusion: Compliance with continuous positive airway pressure therapy is related to educational components, which can be enhanced with continuous and individualized care to patients with obstructive sleep apnea syndrome.

Resumo Introdução: Síndrome da apneia obstrutiva do sono (SAOS) é, atualmente, um problema de saúde pública de suma importância. Quando mal diagnosticada ou tratada inadequadamente, pode levar a sérias consequências na qualidade de vida do paciente. O tratamento padrão-ouro para casos de SAOS, principalmente nos casos moderados a grave e sintomáticos, é o CPAP (Continuous Positive Airway Pressure). A adesão ao CPAP depende diretamente da participação ativa do paciente, que pode ser influenciada por vários fatores. Objetivo: O objetivo deste estudo é descrever os fatores relacionados à adesão ao CPAP e analisar quais fatores associados influenciam diretamente na eficiência do tratamento. Método: Foram recrutados pacientes que receberam CPAP pela Secretaria Municipal de Saúde de Ribeirão Preto. Um questionário estruturado foi aplicado ao paciente. A adesão ao CPAP foi avaliada pela média de horas de uso do CPAP por noite. Pacientes com boa adesão (pacientes em uso de CPAP ≥4 horas/noite) foram comparados aos com má adesão (pacientes em uso < 4 horas/noite). Resultados: No estudo, 138 pacientes foram analisados: 77 (55,8%) foram considerados aderentes e 61 (44,2%) foram não aderentes. A comparação entre os dois grupos demonstrou que o seguimento regular com especialista melhorou consideravelmente a adesão ao CPAP (odds ratio, OR = 2,62). Conclusão: A adesão ao CPAP está relacionada a componentes educacionais, que podem ser aprimorados com assistência contínua e individualizada ao paciente com SAOS.

Knockdown of tissue transglutaminase in SaOS-2 cell line inhibits its osteoblastic differentiation and mineralization / 中国实验动物学报

Objective To investigate whether TG2 plays an important role in the osteoblast differentiation and mineralization.Methods TG2 mRNA of SaOS-2 cells was knocked down using a lentivirus stably expressing short-hairpin ( sh) RNA targeting TG2.Then the cells were cultured in osteo-inductive medium for 14 d to measure mineralization and for 7 d to measure the levels of osteoblastic differentiation markers including ALP activity and mRNA of collagen I, osteocalcin ( OCN) and BMP-2.The wild-type SaOS-2 cells and scrambled shRNA-transducted SaOS-2 cells served as the controls. Results The controls displayed an increasing trend of the level of ALP activity and mRNA of collagen I, osteocalcin and BMP-2,and notable mineralization at 14 d.When TG2 was knocked down, ALP activity, mRNA of collagen I, osteocalcin and BMP-2 at 7d,and mineralization at 14 d were all significantly lower in comparison with the corresponding values in the controls.Conclusion TG2 is involved in the differentiation and mineralization of osteoblasts in vitro.

Influences different functional groups on the biological characteristics of the osteosarcoma Saos-2 cell line / 医学研究生学报

Objective Microenvironment plays important roles in the proliferation , viability, and apoptosis of tumor cells. This study was to investigate the effects of different functional groups on the biological characteristics of the osteosarcoma Saos -2 cell line in vitro. Methods Using self-assembled monolayers of alkanethiols on gold , we prepared different terminal chemical groups , including methyl (-CH3 ) , amino (-NH2 ) , hydroxyl (-OH) , and carboxyl (-COOH ) .We determined the similar density of different functional groups by contact angle measurement and x-ray photoelectron spectroscopy , and observed the effects of different functional groups on the adhesion , proliferation, viability, and apoptosis of the osteosarcoma Saos-2 cells by fluorescence microscopy , CCK-8 as-say, flow cytometry, and scan electron microscopy (SEM). Results The surface of -COOH and -NH2 promoted the adhesion and proliferation of the of the Saos-2 cells, with a good compatibility , while that of -CH3 was unfavorable for their adhesion and proliferation and even increased their apoptosis . The promoting effects of the functional groups on the adhesion and proliferation of the cells were listed in the following order: -COOH ≥ -NH2 >-OH -CH3 , while their toxicity and apoptosis-increasing effect ranked as -CH3 -OH >-NH2 >-COOH. Conclusion The-CH3 group inhibits the adhesion and proliferation and promotes the apoptosis of Saos-2 cells, which has provided some evidence for the surface design of biomaterials.

Effects of RNA Interfering of MBP-1 on Proliferation of Saos-2 Cell Line / 中国医科大学学报

Objective To investigate the effects of c?myc promoter binding protein 1(MBP?1)gene on the proliferation of human Saos?2 osteo?sarcoma cells in vitro. Methods Saos?2 cells were divided into three groups:blank control group(untransfected cells),negative group(cells transfected with missense sequence)and experimental group(cells transfected with MBP?1 shRNA). Two MBP?1 shRNA sequences and one neg?ative control shRNA sequence were designed ,synthesized and cloned into pSIREN?retroQ plasma. Then the recombinant plasmids were construct?ed and transfected into human Saos?2 osteosarcoma cells by Lipofectamine 2000. The expressions of MBP?1 mRNA and protein in Saos?2 cells were detected by real?time PCR and Western blot ,respectively. The effects of altered expression of MBP?1 on cell proliferation were measured by CCK?8 cell proliferation assay. The expressions of cyclin D1 and cyclin E in Saos?2 were determined by Western blot. Results PCR and sequenc?ing results indicated that the recombinant plasmids pSIREN?retroQ was constructed. The relative expression level of MBP?1 mRNA in the MBP?1 siRNA transfection group was significantly decreased than that in blank control group(P<0.05). Compared with the blank control group,the ex?pression levels of MBP?1 protein in the experimental group also significantly decreased. The proliferation abilities of Saos?2 cells at 48,72,and 96 hours after MBP?1 siRNA transfection were significantly increased than those in the blank control group(P<0.05). Compared with the blank con?trol group,the expression levels of cyclin D1 and cyclin E protein in the experimental group also significantly increased(P<0.05). Conclusion Knockdown of the expression of MBP?1 gene promotes the proliferation of human Saos?2 osteosarcoma cells. MBP?1 gene may become the new tar?get of gene therapy for osteosarcoma.

Celastrol induces caspase-dependent apoptosis through ROS/JNK path-way in Saos-2 cells / 中国病理生理杂志

AIM:ToexploretheeffectofcelastrolonapoptosisofSaos-2cellsanditsmechanism.METH-ODS:Saos-2 cells were treated with various concentrations of celastrol , and the cell viability was measured by MTT assay . Apoptosis and reactive oxygen species ( ROS) production were determined by flow cytometry .The protein levels of cleaved caspase-9, cleaved caspase-3 and phosphorylated JNK were evaluated by Western blot .RESULTS:The viability of Saos-2 cells was significantly inhibited by celastrol .Celastrol significantly induced apoptosis of Saos-2 cells.Celastrol signifi-cantly induced ROS production in the Saos-2 cells.Western blot analysis demonstrated that celastrol significantly increased the protein levels of cleaved caspase-9, cleaved caspase-3 and phosphorylated JNK in the Saos-2 cells.CONCLUSION:Celastrol induces caspase-dependent apoptosis through ROS/JNK pathway in Saos-2 cells.

The obstructibe sleep apnea screening in patients with epilepsy / Triagem da síndrome da apneia obstrutiva do sono em pacientes com eplepsia

Objectives: To estimate the accuracy of some obstructive sleep apnea (OSA) screening clinical methods in patients with epilepsy (PWE), besides to report OSA screening issues by literature review. Methods: 98 adult PWE were prospectively screened for OSA. The Berlin questionnaire (BQ) performance was compared to the Epworth sleepiness scale (ESS), as well as with some questions about snore from Basic Nordic Sleep Questionnaire (BNSQ), anthropometrical characteristics (BMI, neck circumference-NC), besides variables related to epilepsy by means of the diagnostic odds ratio (OR). Results: It was found a remarkable OR for OSA regarding snore frequency (OR=11.2/CI95%=4.2-30/p<0.001), loud snoring (OR=10.7/ CI95%=3.6-28.6/p<0.001) and time of snoring in years (OR=14.4 /CI95%=1.6-127.6/p<0.000), BMI(OR=4.1/CI95%=1.8- 9.7/p=0.001), male neck circumference (NC) (OR=4.7/CI95%=1.5-14.9/p=0.006), female NC (OR=5.5 /CI95%=1.3-22.7/ p=0.015) and generalized epilepsy (OR=3.1/CI95%=1.3-7.1/ p=0.009). Conclusions: These questions may help clinicians identify OSA in PWE and the selection of the patients for carrying out polysomnography registration. They can be used for the construction of a predictive rule for the diagnosis of OSA in PWE.The generalized seizure is important for OSA's screening and there is necessity of the better study of this relationship...

Objetivos: Estimar acurácia de alguns métodos clínicos de triagem para Síndrome de Apneia Obstrutiva do Sono (SAOS) em pessoas com epilepsia (PCE) e rever literatura sobre assunto. Métodos: 98 PCE adultas foram prospectivamente triadas para SAOS. O Questionário Clínico de Berlim (QB) foi comparado através da razão de chances (RC) a: Escala de Sonolência de Epworth (ESE), algumas questões sobre ronco do Questionário Escandinavo Básico do Sono (QEBS), características antropométricas (IMC, circunferência do pescoço (CP), além de variáveis relacionadas a epilepsia. Resultados: Foram encontradas RC significativas para o diagnóstico de SAOS em: frequência de roncos (RC=11.2/IC95%=4.2-30/p<0.001), volume de ronco (RC=10.7/IC95%=3.6-28.6/p<0.001), tempo de ronco em anos (RC=14.4/IC95%=1.6-127.6/p<0.000), IMC(RC=4.1/IC95%=1.8-9.7/p=0.001), CP masculina (RC=4.7/IC95%=1.5-14.9/p=0.006), CP feminina (RC=5.5/ IC95%=1.3-22.7/p=0.015) e epilepsia generalizada (RC=3.1/IC95%=1.3-7.1/p=0.009). Conclusões: Estas questões ajudam o clínico no diagnóstico de SAOS e a seleção dos pacientes para a realização de polissonografia. Elas podem colaborar para construção de uma regra preditiva para diagnóstico de SAOS em PCE. O tipo de crise generalizada é relevante e pode servir para o rastreamento de SAOS e há necessidade de melhor avaliação desta relação...

Síndrome da apneia obstrutiva do sono (Saos) e sonolência diurna excessiva (SDE): influência sobre os riscos e eventos de queda em idosos / Obstructive sleep apnea syndrome (OSA) and excessive daytime sleepiness (EDS): influence about the risks and falling events in elderly people

INTRODUÇÃO: Muitos países vêm experimentando o processo de envelhecimento populacional e a consequente elevação das doenças associadas a ele, como dificuldade de manter o equilíbrio, perdas na qualidade do sono e síndrome da apneia obstrutiva do sono (Saos). OBJETIVOS:Investigar a correlação entre a Saos e sonolência diurna excessiva (SDE) com os riscos e eventos de quedas em indivíduos idosos. MATERIAIS E MÉTODOS:Estudo descritivo, comparativo, de corte transversal com amostra de 75 indivíduos com idade igual ou superior a 60 anos, gêneros masculino e feminino. Foram utilizados o mini-exame do estado mental; escalas de depressão geriátrica simplificada; de sonolência de epworth; de avaliação do equilíbrio de tinneti; índice de massa corporal (IMC); registros estabilométricos das oscilações posturais ântero-posterior (AP) e médio-lateral (ML). RESULTADOS: Maior prevalência de Saos no gênero masculino. Não foi encontrada correlação com significância estatística (Pearson, p ≤ 0,01) entre as variáveis IMC e estabilometria. Não houve correlação estatisticamente significativa (ANOVA, p ≤ 0,05) entre IMC (subgrupos normal, sobrepeso, graus I, II, III, e IV) e estabilometria; entre os graus de severidade de Saos e estabilometria; entre dados estabilométricos de subgrupos de IMC e mesmo grau de severidade de Saos; entre dados estabilométricos de subgrupos de IMC e diferentes graus de Saos; entre os diferentes graus de Saos (GC, G1), (GC e G2), subgrupos de IMC e registros estabilométricos. CONCLUSÃO: Não foram encontrados resultados que corroborassem a hipótese de proporcionalidade entre graus de severidade de Saos, IMC e registro estabilométrico.

INTRODUCTION:Many countries are experiencing population aging process, and the consequent rise of diseases associated with it as difficulty maintaining balance, loss in quality of sleep apnea syndrome and obstructive sleep apnea (OSA). OBJECTIVES: Investigating the correlation between obstructive sleep apnea (OSA) and excessive daytime sleepiness (EDS) associated to the risks and falling events in elderly people. MATERIALS AND METHODS: A descriptive, comparative cross-sectional research was done using a convenience sample of 75 individuals aged over 60 years, men and women. The procedures were performed: application of the mini-mental state examination; simplified geriatric depression scale, Epworth sleepiness scale; Tinneti assessment scale balance; weight and height measuring; calculation of body mass index (BMI), three stabilometric records of the postural oscillation on front-to-back (FB) and side-to-side ways (SS). RESULTS: Higher prevalence of OSA in men. The correlations made between variables BMI and stabilometry found no statistically significant correlation (Pearson’s, p ≤ 0.01). For the other statistical calculations it was used the method one way ANOVA (p ≤ 0.05). It was decided to divide the BMI (normal subgroups, I, the overweight class, II, III and IV) and relate it to stabilometry; was the correlation between the severity of OSA and stabilometry without regard to BMI; was also made to correlate the data stabilometric subgroups of BMI with the same degree of severity of OSA; correlation was performed between the data subsets stabilometric BMI and different degrees of OSA, and all those who showed no statistical significance. When correlated with different degrees of OSA group (G1), (GC and G2) and BMI subgroups with stabilometric records, no statistically significant correlation was established. CONCLUSION: It was not possible to determine quantitative values of the variables that promote the prevention of falling events in elderly people.

Oropharyngeal examination as a predictor of obstructive sleep apnea: pilot study of gag reflex and palatal reflex / Avaliação orofaríngea como preditor da apneia obstrutiva do sono: estudo piloto dos reflexos nauseoso e palatal

Obstructive sleep apnea (OSA) has high prevalence and may cause serious comorbities. The aim of this trial was to show if simple noninvasive methods such as gag reflex and palatal reflex are prospective multivariate assessments of predictor variables for OSA. METHOD: We evaluate gag reflex and palatal reflex, of fifty-five adult patients, and their subsequent overnight polysomnography. RESULTS: Forty-one participants presented obstructive sleep apnea. The most relevant findings in our study were: [1] absence of gag reflex on patients with severe obstructive apnea (p=0.001); [2] absence of palatal reflex on moderate obstructive apnea patients (p=0.02). CONCLUSION: Gag reflex and palatal reflex, a simple noninvasive test regularly performed in a systematic neurological examination can disclose the impact of the local neurogenic injury associated to snoring and/or obstructive sleep apnea syndrome.

A síndrome da apneia obstrutiva do sono (SAOS) possui alta prevalência e pode causar sérias comorbidades. O objetivo deste estudo foi mostrar se métodos não invasivos como os reflexos nauseoso e palatal podem ser avaliações prospectivas multivariadas preditoras para SAOS. MÉTODO: Avaliamos os reflexos palatal e nauseoso em 55 pacientes adultos, com exame polissonográfico subsequente. RESULTADOS: 41 pacientes apresentaram SAOS. Os achados mais relevantes em nosso estudo foram: [1] ausência do reflexo nauseoso em pacientes com SAOS grave (p=0,001); [2] ausência do reflexo palatal em pacientes com SAOS moderada (p=0,02). CONCLUSÃO: Os reflexos nauseoso e palatal, um simples exame não invasivo, aplicado em uma avaliação neurológica rotineira, pode revelar o impacto de lesões neurogênicas locais associadas ao ronco e/ou a SAOS.

Riesgo cardiovascular en adultos con síndrome de apnea obstructiva del sueño: a 25 años de los primeros estudios de asociación / Cardiovascular risk among adults with obstructive sleep apnea syndrome

Las enfermedades cardiovasculares y los trastornos respiratorios durante el sueño representan un grave problema de salud pública en México y el mundo. En los últimos 25 años se han realizado estudios que demuestran que el síndrome de apnea obstructiva del sueño (SAOS) es un factor de riesgo independiente para hipertensión arterial sistémica, cardiopatía isquémica y enfermedad vascular cerebral. Se ha descrito también otras asociaciones con hipertensión arterial pulmonar, arritmias, muerte súbita durante el sueño e insuficiencia cardiaca. El tratamiento con presión positiva continua en la vía aérea en pacientes con SAOS ha mostrado tener un efecto positivo sobre la prevención primaria y secundaria de las principales enfermedades cardiovasculares. En este manuscrito revisamos la evidencia epidemiológica que relaciona el SAOS con incremento en el riesgo cardiovascular y proponemos algunas estrategias para hacer frente al creciente problema del SAOS en su asociación con enfermedades cardiovasculares.

Cardiovascular diseases and sleep-disordered breathing have been recognized as a public health problem in Mexico and worldwide. These two groups of disorders are closely associated and the evidence accumulated over the last 25 years indicates that obstructive sleep apnea syndrome (OSAS) is an independent risk factor in systemic arterial hypertension, coronary artery disease and stroke. Other associations have also been described, linking these disorders with pulmonary hypertension, cardiac arrhythmias, sudden death during sleep and congestive heart failure. Treatment with continuous positive airway pressure in patients with OSAS has proven to be an efficient primary and secondary cardiovascular prevention strategy. This article reviews the epidemiological evidence that links OSAS with increased cardiovascular risk, and proposes strategies designed to address this growing health problem.

Establishment of a methotrexate-resistant cell line of human osteosarcoma and its biological characteristics / 肿瘤

Objective: To establish a methotrexate (MTX)-resistant human osteosarcoma cell line (Saos-2/MTX1 and Saos-2/MTX2) Lived from the Saos-2 cell line and observe its biological characters. Methods: Saos-2 cells were pulse-exposed to MTX with gradually increased dosage. Both MTX-resistant human osteosarcoma cell lines (Saos-2/MTX1 and Saos-2/MTX2) were established after 178 days. The sensitivity of the Saos-2, Saos-2/MTX1, and Saos-2/MTX2 cell lines to MTX, cisplatin (DDP), doxorubicin (ADM), ifosfamide (IFO), epirubicine (EPI), pirarubicin (PTH), and paclitaxel (PTX) was measured by MTT assay. The morphological and ultra-structural changes of the cells were observed by optical microscopy and transmission electronic microscopy. The cell proliferation ability was calculated from the growth curve. The cell cycle distribution was analyzed by flow cytometry. Results: The MTX-resistant human osteosarcoma cell lines, Saos-2/MTX1 and Saos-2/MTX2, were established after 178 d induction. The resistance indexes to MTX were 4.87 and 12.73 times than that of Saos-2, respectively. The two cell lines had cross resistance to ADM, EPI, PTH and TAXOL and were still sensitive to DDP (P > 0.05). Optical microscopy showed the volume of Saos-2/MTX1 and Saos-2/MTX2 cells were enlarged and the number of poly-nucleus cells was increased. Transmission electronic microscopy revealed the cell process was decreased and the nucleoli were increased. Cell proliferation curve and flow cytometry demonstrated that the proliferation abilities of Saos-2/MTX 1 and Saos-2/MTX 2 cells were decreased significantly and the proportion of cells in S phase was reduced (P < 0.05). Conclusion: We establish two MTX-resistant human osteosarcoma cell lines (Saos-2/MTX1 and Saos-2/MTX2) and observe their biological characteristics. It provides a new experimental model for further studying the mechanism of MTX-resistance.

Gene Expression Changes of Drug-resistant Saos-2 Cells Induced by Anticancer Drug / 대한해부학회지

During the treatment of cancers, especially with anticancer drugs, the recurrence of cancer is the most important factor for survival rate. The most common cause of the recurrence is the resistance of cells to anticancer drugs. To explore and analyze the changes of gene expression during the induction of resistance by anticancer drugs in human osteogenic cancer cell line Saos-2. The drug resistance was induced with adriamycin, cisplatin or vincristine at 10(-7) M concentration of each and cDNA microarray was performed. Total RNA was purified from Saos-2, adriamycin-resistant (Saos-2AdR), cisplatin-resistant (Saos-2CpR) and vincristine-resistant (Saos-2VcR) and expressed genes were investigated with a Affymetrix Human HG-U133Plus2.0 GeneChip(TM). The genes of anticancer drug resistant cells that showed more than 2.5 fold expression change than Saos-2 were selected for differential expression. Four hundred seventeen genes were selected for Saos-2 vs Saos-2AdR. Two thousand five hundred thirty six genes were selected for Saos-2 vs Saos-2CpR. Two hundred twenty five genes were selected for Saos-2 vs Saos-2VcR. Eighty seven genes were selected for common differential expression. The results showed that many genes were changed in expression during the acquiring of resistance to anticancer drugs but most of genes were not in common among the three anticancer durg-resistant Saos-2. This means the different anticancer drug takes the different mechanism for acquiring resistance to anticancer drug even we use same cells.

Expression and functional characterization of amino acid transport system L in Saos2 human osteogenic sarcoma cells

inhibitor, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH). The affinity of [14C]L-leucine uptake and the inhibition profiles of [14C]L-leucine uptake by various amino acids in the Saos2 cells were comparable with those for the LAT1 expressed in Xenopus oocytes. The majority of [14C]Lleucine uptake is, therefore, mediated by LAT1 in the Saos2 cells. These results suggest that the transports of neutral amino acids including several essential amino acids into Saos2 human osteogenic sarcoma cells are for the most part mediated by LAT1. Therefore, the Saos2 human osteogenic sarcoma cells are excellent tools for examine the properties of LAT1. Moreover, the specific inhibition of LAT1 in tumor cells might be a new rationale for anti-tumor therapy.

The effect of rhBMP-2 on delta12-PGJ2 induced osteoblastic differentiation and mineralization / 대한치주과학회지

Prostaglandin plays a significant role in the local control of bone metabolism associated with periodontal disease. delta12-PGJ2 is a natural PGD2 metabolite that is formed in vivo in the presence of plasma. It is known for delta12-PGJ2 to stimulate calcification in osteoblastic cells. Bone morphogenetic protein(BMP) stimulated osteoblastic differentiation in various types of cells and greatly enhanced healing of bony defects. The purpose of this study was to evaluate the effect of rhBMP-2 on delta12-PGJ2 induced osteoblastic differentiation and mineralization in vitro. A human osteosarcoma cells line Saos-2 were cultured. In the test groups, 10-7M of delta12-PGJ2 or mixture of 10-8M of delta12-PGJ2 and 100ng/ml of rhBMP-2 or 100ng/ml of rhBMP-2 were added to culture media. After 1 day, 2 days and 4 days of culture period, the cell number was measured. Alkaline phosphatase activity was measure at 3 days. Reverse transcription polymerase chain reaction(RT-PCR) was performed to determine the expression of mRNA of bone matrix protein at 8 hours, 1 day and 7 days. The ability to produce mineralized nodules in rat osteoblasts(MC3T3-E1) was evaluated at 21 days. The results were as follows : 1. rhBMP-2 or mixture of rhBMP-2 and delta12-PGJ2 inhibited cell proliferation of human osteosarcoma cells. 2. rhBMP-2 or mixture of rhBMP-2 and delta12-PGJ2 stimulated alkaline phosphatase activity significantly higher than delta12-PGJ2 alone. 3. rhBMP-2 or mixture of rhBMP-2 and delta12-PGJ2 stimulated mineralization compared to delta12-PGJ2 alone. 4. mRNA of alkaline phosphatase, BMP-2, cbfa 1, Type I collagen were detected in the group treated with delta12-PGJ2/rhBMP-2, rhBMP-2 alone, delta12-PGJ2 alone. These results show that mixture of delta12-PGJ2 and rhBMP-2 causes more bone formation than delta12-PGJ2 alone while the bone formation effects of mixture of delta12-PGJ2 and rhBMP-2 are less than those of rhBMP-2 alone. Further researches would be necessary to clarify the interactions of these agents.

Complicaciones factores de riesgo asociados amorbimortalidad en pacientes peediátricos que son operados de adenoamigdalectomía con síndrome de apnea obstructiva del sueño

Introducción: Reconocer las complicaciones quirúrgicas en niños con adenoamigdalectomía y síndrome de apnea obstructiva del sueño es de suma importancia, así como valorar la severidad del índice de apnea/hipoapnea con desaturación en sueño movimiento ocular rápido. Se requiere indicar tratamiento médico, no farmacológico, de ventilación no invasiva con presión positiva, previo a la cirugía y disminuir las complicaciones cardiovasculares respiratorias. Material y métodos: Estudio observacional, cohorte, longitudinal, descriptivo y prospectivo. La cohorte estuvo constituida por 124 niños menores de 15 años posoperados de adenoamigdalectomía y síndrome de apnea obstructiva del sueño que ingresaron a la Unidad de Cuidados Intensivos Respiratorios del Instituto Nacional de Enfermedades Respiratorias de junio de 2000 a agosto de 2001. La estadística inferencial aplicada fue la prueba exacta de Fisher, Chi cuadrada, progresión logística e intervalo de confianza 95%. Resultados: El sexo más afectado fue el masculino con relación 2:1. La edad mínima fue 13 meses y máxima 168 meses, el peso en kilogramos fue 25.0±9.9, la comorbilidad asociada fue la obesidad (26.6%), asma (8.9%) y neurología (3.2%). La gravedad de la apnea en el síndrome de apnea obstructiva del sueño leve fue 62.1%, moderado 21% y grave 16.9%, con promedio de índice de apnea 21.6, desviación estándar 32.7, con mínima 1.3 a máxima 175 por hora. La incidencia de complicaciones transoperatorias fue 12.9%; la más frecuente, la hipertensión arterial sistémica de 6.5%, falla para extubar al enfermo en quirófano, 4.8%, de las respiratorias, estridor, sibilancias y ventilación mecánica asistida, 9.7%, de las cardiovasculares, hipertensión arterial, 4% que requirió uso de vasodilatador sistémico y analgésicos. En el análisis univariado las variables que tuvieron asociación con la presencia de complicaciones, se encontró que la presencia de comorbilidad (p<0.017) falla para poder extubar al enfermo en quirófano, y la presencia de complicaciones transoperatorias (p<0.002) mostraron significancia estadística; la obesidad (p>0.08) mostró tendencia hacia la significancia. Conclusiones: Las complicaciones posoperatorias de adenoamigdalectomía en pacientes con síndrome de apnea obstructiva del sueño son del tipo cardiovascular respiratorias en comparación con aquellos niños que no tienen síndrome de apnea obstructiva del sueño y se operan de adenoamigdalectomía. La comorbilidad fue la variable independiente en el preoperatorio que mostró asociación estadística con la presencia de complicaciones posoperatorias, el uso y tiempo ± 30 días de ventilación no invasiva con presión positiva donde ninguno se complicó.

Background: It is very important to recognize in pediatric patients with OSAS and adenotonsilar hypertrophy the severity of the apnea/hypoapnea index and SpO2 desaturation during REM sleep, because, in case of surgical intervention, non-pharmacologic medical treatment with CPAP or Bilevel positive pressure ventilation will be necessary prior to surgery to dismiss perioperative complications. Methods: Observational, cohort, longitudinal, descriptive and prospective study. We included 124 children under 15 years of age in postsurgical period, who were admitted to IRCU between June 2000 and August 2001. We applied Fisher's exact test, Chi square, logistic progression and CI value of 95%. Result: Gender relation was M/F: 2:1, boys being more affected. The youngest patients were 13 months and the oldest 168 months; weight in kilograms was 25±9.9; percentages of associated comorbility were: obesity 26.6%, asthma 8.9% and 3.2% for neurological disorders. OSAS severity percentages were: 62.1% for mild; 21% for moderate and 16.9% for severe. Mean apnea index was 21.6 (SD32.7; min 1.3 max 175/hour). Perioperative complications were: systemic arterial hypertension, 6.5%; weaning failure, 4.8%; strider, wheezing and AMV: 9.7%; in addition, 4% of the patients with SAH needed vasodilatation intravenous therapy and analgesic. Univariate analyses showed strong association of morbidity with obesity (p>0.08), weaning failure in the OR and other trans-operative complications (p<0.002), and comorbility (p<0.017). Conclusions: Postoperative cardiovascular and respiratory complications of adeno-amygdalectomy were common (23%) in these OSAS patients compared to children without OSAS. Comorbility was strongly associated with perioperative complication. Treatment with CPAP or Bilevel positive pressure ventilation before surgical intervention decreased respiratory and cardiovascular complications.