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1.
Mol Med Rep ; 23(1)2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33236768

RESUMO

Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) are highly prevalent potential risk factors for systemic disease. Previous studies have reported that COPD and OSA are major independent risk factors for cardio­ or cerebrovascular diseases. The present study aimed to investigate the role of bone marrow mesenchymal stem cells (BMSCs) on vascular injury in a COPD­OSA overlap syndrome (OS) rat model. Rats were randomly divided into three groups: Sham, OS model and BMSC. BMSC localization in major organs was detected via confocal laser fluorescence microscopy, and the aortic tissue pathological changes and related genes were measured using hematoxylin & eosin and Masson staining. Genes associated with vascular endothelial cell injury, including endothelin 1, vascular cell adhesion molecule 1 and endothelial nitric oxide synthase, were detected via reverse transcription­quantitative PCR and western blotting. Apoptosis of vascular endothelial cells was detected using TUNEL and immunofluorescence assays. The endothelial cell marker CD31 in injured vessels was analyzed via immunohistochemistry. BMSCs migrated into the heart, liver, spleen, lung, kidney, brain and aorta in the OS model. The green fluorescence expression of BMSCs demonstrated the highest level in the lung, followed by the aorta. Aortic tissue had a more severe vascular injury and increased apoptosis in the model group compared with the BMSC group. Vascular endothelial cell apoptosis was decreased in the BMSC group compared with the model group. The findings suggested that BMSCs could repair vascular injury by inhibiting endothelial cell damage and apoptosis. These data provide a theoretical basis for the treatment of cardiovascular diseases caused by OS with BMSCs.


Assuntos
Células da Medula Óssea/metabolismo , Transplante de Células-Tronco Mesenquimais , Doença Pulmonar Obstrutiva Crônica/terapia , Apneia Obstrutiva do Sono/terapia , Lesões do Sistema Vascular/terapia , Aloenxertos , Animais , Células da Medula Óssea/patologia , Modelos Animais de Doenças , Feminino , Células-Tronco Mesenquimais , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Ratos , Ratos Sprague-Dawley , Apneia Obstrutiva do Sono/metabolismo , Apneia Obstrutiva do Sono/patologia , Síndrome , Lesões do Sistema Vascular/metabolismo , Lesões do Sistema Vascular/patologia
2.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(4): 455-461, 2020 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-32985158

RESUMO

OBJECTIVE: To investigate the effect of obstructive sleep apnea (OSA) on different sleep stages, and the relationship between N3 stage of non-rapid eye movement sleep and respiratory abnormal events. METHODS: A total of 188 adult patients who underwent overnight polysomnography(PSG)monitoring in Sir Run Run shaw Hospital of Zhejiang University from June 24th to December 26th 2019 were enrolled in the study. OSA patients were classified into 3 groups (mild, moderate and severe) according to the apnea-hypopnea index (AHI). PSG data, AHI and the lowest SPO2 in each stage of sleep were compared among three groups. RESULTS: There was no significant difference in total sleep time and sleep efficiency among patients with different severity of OSA (all P>0.05). The proportion of N3 stage in moderate and severe OSA groups were significantly smaller than that in mild OSA group (all P<0.05). The proportion of N3 stage in severe OSA group was also smaller than that in moderate OSA group (P<0.05). In addition, severe OSA group had a longer latency of N3 stage than mild and moderate OSA groups (all P<0.05). The latency of N3 stage in moderate OSA group was longer than that in mild OSA group (P<0.05). The AHI in N3 stage was markedly lower than that in other sleep stages (all P<0.01), regardless of the severity of OSA. Supine AHI in N3 stage in mild and moderate groups was significantly lower than that in N1, N2 and rapid eye movement (REM) stages (all P<0.01). Supine AHI in N3 stage in severe group was also lower than that in N2 and REM stages (P<0.05 or P<0.01). The lowest SPO2 in N3 stage was significantly higher than that in N1, N2 and REM stages (P<0.05 or P<0.01), regardless of the severity of OSA. CONCLUSIONS: s The proportion of N3 stage is lower in OSA patients, and N3 stage has less sleep respiratory events than non-N3 stages. The results suggest that the increased N3 stage proportion may indicate less severity of OSA.


Assuntos
Apneia Obstrutiva do Sono , Fases do Sono , Adulto , Humanos , Polissonografia , Apneia Obstrutiva do Sono/classificação , Apneia Obstrutiva do Sono/patologia , Sono REM
3.
Sci Rep ; 10(1): 8609, 2020 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-32451401

RESUMO

Continuous positive airway pressure (CPAP) treatment results in nearly complete remission of symptoms of obstructive sleep apnoea (OSA); however, its effect on OSA comorbidities including cardiovascular diseases remains contradictory. Here we investigated the short- and long-term effect of CPAP treatment on matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in patients with severe OSA. Serum levels of 7 MMPs and 3 TIMPs were followed in OSA patients (n = 28) with an apnoea-hypopnoea index of ≥30 events/h at the time of diagnosis and at control visits (2 months, 6 months and 5 years) after initiation of fixed-pressure CPAP treatment. The first few months of CPAP therapy resulted in significant decrease of MMP-8 and MMP-9 levels (MMP-8: 146 (79-237) vs. 287 (170-560) pg/mL; MMP-9: 10.1 (7.1-14.1) vs. 12.7 (10.4-15.6) ng/mL, p < 0.05 for each at 2 months), while the rest of the panel remained unchanged as compared to baseline values. In contrast, at 5 years, despite of uninterrupted CPAP treatment and excellent adherence the levels of MMP-8, MMP-9 and TIMPs significantly increased (p < 0.05). Our data suggest that initiation of CPAP therapy leads to a decrease in the level of key MMPs in the short-term; however, this effect is not sustained over the long-term.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas , Metaloproteinases da Matriz/sangue , Apneia Obstrutiva do Sono/terapia , Inibidores Teciduais de Metaloproteinases/sangue , Adulto , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/patologia , Resultado do Tratamento
4.
Sci Rep ; 10(1): 8524, 2020 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-32444630

RESUMO

Obstructive sleep apnea (OSA) is associated with increasing risk of recurrent stroke and mortality. Nasogastric tubes used by dysphagic stroke patients may interfere with nasal continuous positive airway pressure (CPAP) due to air leakage. This study was evaluated the effects and short-term tolerability of high-flow nasal cannula (HFNC) therapy for OSA in stroke patients with nasogastric intubation. The HFNC titration study was performed in post-acute ischemic stroke patients with nasogastric intubation and OSA. Then, participants were treated with HFNC therapy in the ward for one week. Eleven participants (eight males) who were all elderly with a median age of 72 (IQR 67-82) years and a body mass index of 23.5 (IQR 22.0-26.6) completed the titration study. The HFNC therapy at a flow rate up to 50~60 L/min significantly decreased the apnea-hypopnea index from 52.0 events/h (IQR 29.9-61.9) to 26.5 events/h (IQR 3.3-34.6) and the total arousal index from 34.6 (IQR 18.6-42.3) to 15.0 (IQR 10.3-25.4). The oxygen desaturation index was also significantly decreased from 53.0 events/h (IQR 37.0-72.8) to 16.2 events/h (IQR 0.8-20.1), accompanied by a significant improvement in the minimum SpO2 level. Finally, only three participants tolerated flow rates of 50~60 L/minute in one-week treatment period. Conclusively, HFNC therapy at therapeutic flow rate is effective at reducing the OSA severity in post-acute ischemic stroke patients with nasogastric intubation. Owing to the suboptimal acceptance, HFNC might be a temporary treatment option, and CPAP therapy is suggested after the nasogastric tube is removed.


Assuntos
Isquemia Encefálica/complicações , Cânula , Nutrição Enteral , Intubação Intratraqueal , Oxigenoterapia/métodos , Apneia Obstrutiva do Sono/terapia , Acidente Vascular Cerebral/complicações , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Oxigenoterapia/instrumentação , Respiração Artificial , Apneia Obstrutiva do Sono/etiologia , Apneia Obstrutiva do Sono/patologia
5.
Cardiovasc Pathol ; 47: 107221, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32371340

RESUMO

Unexpected sudden cardiac death (SCD), sudden infant death syndrome (SIDS) and sudden intrauterine unexplained death (SIUD) are major unsolved, devastating forms of death that occur frequently. Obstructive sleep apnea (OSA) has been associated with increased cardiovascular and cerebrovascular morbidity and mortality, including sudden cardiac death (SCD). This editorial will review the pathology of SCD, including sudden infant death syndrome (SIDS) and sudden intrauterine unexplained death (SIUD); OSA with its cardiovascular consequences; the possible link between SCD and OSA, discussing the potential mechanisms underlying these two frequent, but yet overlooked pathologies. Finally, the possible preventive benefits of treating OSA and identifying patients at common risk for OSA and SCD and SIDS-SIUD to prevent unexpected deaths will be discussed. Post-mortem examination is of great importance in every case of SCD sine materia, with examination of the brainstem and cardiac conduction system on serial sections, when general autopsy fails, but it should be stressed that also the investigations of patients suffering from OSA should focus on the possibility of pathological findings in common with cases of SCD.


Assuntos
Tronco Encefálico/patologia , Morte Súbita Cardíaca/patologia , Morte Fetal/etiologia , Sistema de Condução Cardíaco/patologia , Apneia Obstrutiva do Sono/patologia , Morte Súbita do Lactente/patologia , Tronco Encefálico/imunologia , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/prevenção & controle , Feminino , Morte Fetal/prevenção & controle , Sistema de Condução Cardíaco/imunologia , Humanos , Lactente , Recém-Nascido , Mediadores da Inflamação/imunologia , Gravidez , Prognóstico , Fatores de Risco , Apneia Obstrutiva do Sono/imunologia , Apneia Obstrutiva do Sono/mortalidade , Apneia Obstrutiva do Sono/terapia , Morte Súbita do Lactente/epidemiologia , Morte Súbita do Lactente/imunologia , Morte Súbita do Lactente/prevenção & controle
6.
Sci Rep ; 10(1): 6846, 2020 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-32321999

RESUMO

Obstructive sleep apnea (OSA) is a common sleep disorder associated with obesity. Emerging evidence suggest that OSA increases the risk of cardiovascular morbidity and mortality partly via accelerating the process of cellular aging. Thus, we sought to examine the effects of intermittent hypoxia (IH), a hallmark of OSA, on senescence in human white preadipocytes. We demonstrate that chronic IH is associated with an increased generation of mitochondrial reactive oxygen species along with increased prevalence of cells with nuclear localization of γH2AX & p16. A higher prevalence of cells positive for senescence-associated ß-galactosidase activity was also evident with chronic IH exposure. Intervention with aspirin, atorvastatin or renin-angiotensin system (RAS) inhibitors effectively attenuated IH-mediated senescence-like phenotype. Importantly, the validity of in vitro findings was confirmed by examination of the subcutaneous abdominal adipose tissue which showed that OSA patients had a significantly higher percentage of cells with nuclear localization of γH2AX & p16 than non-OSA individuals (20.1 ± 10.8% vs. 10.3 ± 2.7%, Padjusted < 0.001). Furthermore, the frequency of dual positive γH2AX & p16 nuclei in adipose tissue of OSA patients receiving statin, aspirin, and/or RAS inhibitors was comparable to non-OSA individuals. This study identifies chronic IH as a trigger of senescence-like phenotype in preadipocytes. Together, our data suggest that OSA may be considered as a senescence-related disorder.


Assuntos
Adipócitos Brancos/metabolismo , Senescência Celular , Apneia Obstrutiva do Sono/metabolismo , Adipócitos Brancos/patologia , Hipóxia Celular , Doença Crônica , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Histonas/metabolismo , Humanos , Masculino , Espécies Reativas de Oxigênio/metabolismo , Apneia Obstrutiva do Sono/patologia
7.
Biochim Biophys Acta Mol Basis Dis ; 1866(6): 165753, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32126269

RESUMO

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is associated to intermittent hypoxia (IH) and is an aggravating factor of non-alcoholic fatty liver disease (NAFLD). We investigated the effects of hypoxia in both in vitro and in vivo models of NAFLD. METHODS: Primary rat hepatocytes treated with free fatty acids (FFA) were subjected to chemically induced hypoxia (CH) using the hypoxia-inducible factor-1 alpha (HIF-1α) stabilizer cobalt chloride (CoCl2). Triglyceride (TG) content, mitochondrial superoxide production, cell death rates, cytokine and inflammasome components gene expression and protein levels of cleaved caspase-1 were assessed. Also, Kupffer cells (KC) were treated with conditioned medium (CM) and extracellular vehicles (EVs) from hypoxic fat-laden hepatic cells. The choline deficient L-amino acid defined (CDAA)-feeding model used to assess the effects of IH on experimental NAFLD in vivo. RESULTS: Hypoxia induced HIF-1α in cells and animals. Hepatocytes exposed to FFA and CoCl2 exhibited increased TG content and higher cell death rates as well as increased mitochondrial superoxide production and mRNA levels of pro-inflammatory cytokines and of inflammasome-components interleukin-1ß, NLRP3 and ASC. Protein levels of cleaved caspase-1 increased in CH-exposed hepatocytes. CM and EVs from hypoxic fat-laden hepatic cells evoked a pro-inflammatory phenotype in KC. Livers from CDAA-fed mice exposed to IH exhibited increased mRNA levels of pro-inflammatory and inflammasome genes and increased levels of cleaved caspase-1. CONCLUSION: Hypoxia promotes inflammatory signals including inflammasome/caspase-1 activation in fat-laden hepatocytes and contributes to cellular crosstalk with KC by release of EVs. These mechanisms may underlie the aggravating effect of OSAS on NAFLD. [Abstract word count: 257].


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Hipóxia/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Hepatopatia Gordurosa não Alcoólica/genética , Apneia Obstrutiva do Sono/genética , Animais , Caspase 1/genética , Deficiência de Colina/genética , Deficiência de Colina/metabolismo , Deficiência de Colina/patologia , Cobalto/toxicidade , Modelos Animais de Doenças , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/patologia , Ácidos Graxos não Esterificados/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Hipóxia/induzido quimicamente , Hipóxia/metabolismo , Hipóxia/patologia , Inflamassomos/genética , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Interleucina-1beta/genética , Macrófagos do Fígado/metabolismo , Macrófagos do Fígado/patologia , Camundongos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Ratos , Apneia Obstrutiva do Sono/etiologia , Apneia Obstrutiva do Sono/metabolismo , Apneia Obstrutiva do Sono/patologia , Triglicerídeos/genética
8.
J Glaucoma ; 29(5): 337-343, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32134828

RESUMO

PRéCIS:: This study found an association between thinner superotemporal retinal nerve fiber layer (RNFL) and obstructive sleep apnea (OSA). However, the lack of association of sleep apnea with other disc measures does not support a link with glaucoma. AIM: Previous findings on the link between OSA and increased glaucoma risk have been inconsistent. In a community-based study of middle-aged and older adults, we explored for differences in optic disc measures that may resemble preclinical glaucomatous changes in relation to OSA status and severity. METHODS: A total of 865 participants (46 to 67 y; 45% male) underwent an at-home sleep study during which their apnea-hypopnea index (AHI) and sleep oxygen saturation level were measured. Participants were determined to have no OSA (AHI<5 events/h), mild (AHI 5 to 15), moderate (AHI 16 to 30), or severe OSA (AHI>30). At a 6-year follow-up visit, the optic discs of both eyes were imaged using spectral domain optic coherence tomography to measure the Bruch membrane opening-minimum rim widths and RNFL thicknesses. RESULTS: On the basis of the AHI, 411 participants (48%) had OSA, of whom 92 (11% of total sample) and 26 (3%) had moderate and severe OSA, respectively. In the multivariate analysis, participants with severe OSA had thinner RNFL superotemporally than those without OSA or with mild OSA (P<0.001 and 0.001, respectively). In addition, superotemporal RNFL was inversely associated with AHI (P=0.004) and sleep time with oxygen saturation level <90% (P=0.005). There was no association between OSA measures and Bruch membrane opening-minimum rim widths. CONCLUSIONS: Our findings do not provide strong evidence of a link between measures of OSA and the optic disc. However, the association between increased OSA severity and thinner superotemporal RNFL has been reported consistently in previous studies and thus warrants further evaluation.


Assuntos
Fibras Nervosas/patologia , Disco Óptico/patologia , Células Ganglionares da Retina/patologia , Apneia Obstrutiva do Sono/patologia , Idoso , Lâmina Basilar da Corioide/patologia , Feminino , Glaucoma/complicações , Humanos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Polissonografia , Tomografia de Coerência Óptica
9.
Int J Mol Sci ; 21(3)2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32028672

RESUMO

The purpose of this study is to explore the anti-inflammatory role of microRNAs (miR)-21 and miR-23 targeting the TLR/TNF-α pathway in response to chronic intermittent hypoxia with re-oxygenation (IHR) injury in patients with obstructive sleep apnea (OSA). Gene expression levels of the miR-21/23a, and their predicted target genes were assessed in peripheral blood mononuclear cells from 40 treatment-naive severe OSA patients, and 20 matched subjects with primary snoring (PS). Human monocytic THP-1 cell lines were induced to undergo apoptosis under IHR exposures, and transfected with miR-21-5p mimic. Both miR-21-5p and miR-23-3p gene expressions were decreased in OSA patients as compared with that in PS subjects, while TNF-α gene expression was increased. Both miR-21-5p and miR-23-3p gene expressions were negatively correlated with apnea hypopnea index and oxygen desaturation index, while TNF-α gene expression positively correlated with apnea hypopnea index. In vitro IHR treatment resulted in decreased miR-21-5p and miR-23-3p expressions. Apoptosis, cytotoxicity, and gene expressions of their predicted target genes-including TNF-α, ELF2, NFAT5, HIF-2α, IL6, IL6R, EDNRB, and TLR4-were all increased in response to IHR, while all were reversed with miR-21-5p mimic transfection under IHR condition. The findings provide biological insight into mechanisms by which IHR-suppressed miRs protect cell apoptosis via inhibit inflammation, and indicate that over-expression of the miR-21-5p may be a new therapy for OSA.


Assuntos
Apoptose , Hipóxia/patologia , MicroRNAs/genética , Oxigênio/metabolismo , Apneia Obstrutiva do Sono/patologia , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Hipóxia/genética , Hipóxia/metabolismo , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Leucócitos Mononucleares , Masculino , Pessoa de Meia-Idade , Transdução de Sinais , Apneia Obstrutiva do Sono/genética , Apneia Obstrutiva do Sono/metabolismo , Ronco/genética , Ronco/metabolismo , Ronco/patologia , Receptor 4 Toll-Like/genética , Fator de Necrose Tumoral alfa/genética
10.
Sci Rep ; 10(1): 2101, 2020 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-32034229

RESUMO

Lateral pharyngeal wall appears to be a critical culprit of obstructive sleep apnea (OSA) subjects and relocation pharyngoplasty has been expected to be a promising surgical option to correct retropalatal circumferential narrowing in OSA patients. The purpose of our study is to evaluate the therapeutic outcomes of relocation pharyngoplasty and its clinical effectiveness in OSA patients with retropalatal circumferential narrowing. We performed relocation pharyngoplasty combined with nasal surgery in 133 OSA patients with the following characteristics: apnea-hypopnea index (AHI) over 10, retropalatal circumferential narrowing greater than grade I when awake, and redundant soft tissue around the lateral pharyngeal wall. The analysis of surgical success rate was performed with the data of 68 subjects who underwent pre and postoperative polysomnography. The objective success rate of relocation pharyngoplasty was 52.9%, and significant reduction of mean AHI with improvement of lowest SpO2 was seen in 69% of patients 3 months after the surgery. The median AHI was decreased from preoperative 37.3 to postoperative 21.4. Median lowest SpO2 changed from 78.4 to 84.1%. Total sleep time, daytime sleepiness, and visual analogue scale for snoring showed improvement as well. Postoperative complications including pain or bleeding were minimal in 133 subjects and a few patients complained of subtle taste loss. Our data demonstrate that relocation pharyngoplasty can be a favorable surgical option fighting against retropalatal circumferential narrowing.


Assuntos
Procedimentos Cirúrgicos Otorrinolaringológicos/métodos , Palato Mole/cirurgia , Faringe/cirurgia , Apneia Obstrutiva do Sono/cirurgia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Palato Mole/patologia , Polissonografia , Apneia Obstrutiva do Sono/etiologia , Apneia Obstrutiva do Sono/patologia , Resultado do Tratamento , Adulto Jovem
11.
Sci Rep ; 10(1): 1854, 2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-32024881

RESUMO

The purpose of this study was to evaluate whether obstructive sleep apnea (OSA)-related chronic intermittent hypoxia (CIH) influences lung cancer progression and to elucidate the associated mechanisms in a mouse model of lung cancer. C57/BL6 mice in a CIH group were exposed to intermittent hypoxia for two weeks after tumor induction and compared with control mice (room air). Hypoxia inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF) and metastasis-related matrix metalloproteinases (MMP) were measured. The expression levels of several hypoxia-related pathway proteins including HIF-1α, Wnt/ß-catenin, the nuclear factor erythroid 2-related factor 2 (Nrf2) and mammalian target of rapamycin-ERK were measured by western blot. The number (P < 0.01) and volume (P < 0.05) of tumors were increased in the CIH group. The activity of MMP-2 was enhanced after CIH treatment. The level of VEGF was increased significantly in the CIH group (p < 0.05). ß-catenin and Nrf2 were translocated to the nucleus and the levels of downstream effectors of Wnt/ß-catenin signaling increased after IH exposure. CIH enhanced proliferative and migratory properties of tumors in a mouse model of lung cancer. ß-catenin and Nrf2 appeared to be crucial mediators of tumor growth.


Assuntos
Hipóxia/patologia , Neoplasias Pulmonares/patologia , Animais , Proliferação de Células/fisiologia , Modelos Animais de Doenças , Progressão da Doença , Hipóxia/metabolismo , Neoplasias Pulmonares/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais/fisiologia , Apneia Obstrutiva do Sono/metabolismo , Apneia Obstrutiva do Sono/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , beta Catenina/metabolismo
12.
Sci Rep ; 10(1): 34, 2020 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-31913307

RESUMO

The aim of the study was to compare REM-dependent and REM-independent, obstructive sleep apnea syndrome (OSA) patients in relation to their daily sleepiness assessed by Epworth sleepiness scale (ESS). The study included 1863 consecutive patients, who were referred to a sleep centre with a presumed diagnosis of OSA. Following polysomnography, 292 patients fulfilled criteria for either REM-dependent OSA (REM-OSA, n = 102) or REM-independent OSA (nREM-OSA, n = 190). Both study groups were matched regarding sex and age. REM-OSA group had two times lower median apnoea-hypopnea index (AHI) compared to nREM-OSA (p < 0.001), yet day-time sleepiness measured by ESS was similar: median score 9.0 (6.0-11.0) and 8.0 (4.8-11.0), p = 0.109, respectively. Subsequent post-hoc ANCOVA analysis, with covariates (BMI, percent of total sleep time spent in REM stage, percent of total sleep time spent in the supine position), has shown statistically significant difference between study groups regarding AHI (p < 0.001) and no difference regarding ESS score (p = 0.063). Despite two times lower AHI, patients with REM-OSA present with similar day-time sleepiness as those with REM independent OSA. Daily sleepiness may be stronger associated with apneas/hypopneas occurring in REM than nREM sleep.


Assuntos
Distúrbios do Sono por Sonolência Excessiva/complicações , Polissonografia/métodos , Índice de Gravidade de Doença , Apneia Obstrutiva do Sono/etiologia , Sonolência , Vigília/fisiologia , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Apneia Obstrutiva do Sono/patologia , Fases do Sono , Sono REM
13.
J Sleep Res ; 29(2): e12958, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31782212

RESUMO

Obstructive sleep apnea (OSA) is a widely prevalent disorder that can affect cognitive function. The relationship between cognitive function and OSA is known to be affected by an individual's premorbid cognitive ability. Tools to measure premorbid intelligence across OSA disease severity have not been validated. This brief report aims to establish if the National Adult Reading Test (NART) provides a stable estimate of premorbid intelligence across levels of OSA disease severity. We examined if NART scores varied systematically across levels of untreated OSA severity (defined according to the apnea-hypopnea index [AHI]) and mean oxygen saturation in sleep clinic (n = 121) and community samples (n = 398) using regression analysis. Simple linear regression was used to predict NART scores based on the AHI. NART-estimated premorbid IQ scores without demographics did not vary systematically with AHI (F < 1; ß = 0.01) or mean SpO2 (F < 1; ß = 0.12). NART-estimated premorbid IQ scores with added demographic information also did not vary systematically with AHI (F < 1; ß = -0.01) or mean SpO2 (F < 1; ß = 0.15). This preliminary examination shows that the NART provides a stable estimate of premorbid intelligence across untreated OSA disease severity, as demarcated by AHI or mean nocturnal SpO2 .


Assuntos
Cognição/fisiologia , Testes de Inteligência/normas , Apneia Obstrutiva do Sono/complicações , Escalas de Wechsler/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Apneia Obstrutiva do Sono/patologia
14.
J Sleep Res ; 29(2): e12956, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31808986

RESUMO

Whole blood carbonic anhydrase activity (CAa) is increased in patients with obstructive sleep apnea (OSA). Our study investigated the influence of positive airway pressure (PAP) or CA inhibitor acetazolamide (ACT) therapy on CAa, OSA and blood pressure. Thirty-three OSA patients (21 hypertensive, body mass index (BMI) 37 ± 7 kg/m2 and apnea-hypopnea index (AHI) of 47 ± 31 events/hr) were followed-up after PAP treatment (compliance, 4.7 ± 1.5 hr/day; duration, median 6 [IQR 6,6] months) (Cohort A). A second OSA Cohort (B) contained nine hypertensive patients (BMI, 29 ± 4 kg/m2 ; AHI, 39 ± 20 events/hr) with 2-week treatment of ACT, PAP or ACT + PAP in an open crossover study. CAa was assessed at baseline and at the end of each treatment period. In Cohort A, baseline CAa was higher in hypertensive, compared with normotensive, patients (1,033 ± 204 versus 861 ± 201 units, p = .028). PAP treatment reduced systolic/diastolic blood pressure but not CAa (-9 ± 11/-5 ± 7 mmHg and -20 ± 289 units, p < .001, <.001 and .70). In Cohort B, blood pressure was reduced in both ACT-treated groups (-10 ± 10/-5 ± 7 mmHg, p = .043 and .019; and -5 ± 5/-13 ± 13 mmHg, p < .001 and .009). AHI was reduced in both groups: ACT only, -17 ± 9 events/hr p = .001; and ACT + PAP, -39 ± 19 events/hr, p < .001. PAP did not change CAa (p = .98) but activity tended to decrease after ACT with or without PAP (p = .081 and .056). CAa is elevated in hypertensive OSA patients. Long-term PAP reduced blood pressure without affecting CAa. ACT reduced blood pressure and CAa. Increased CAa may constitute a physiological characteristic in OSA, contributing to comorbid hypertension.


Assuntos
Anidrases Carbônicas/efeitos adversos , Pressão Positiva Contínua nas Vias Aéreas/métodos , Hipertensão/etiologia , Polissonografia/métodos , Apneia Obstrutiva do Sono/fisiopatologia , Anidrases Carbônicas/sangue , Estudos de Coortes , Estudos Cross-Over , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Apneia Obstrutiva do Sono/patologia , Apneia Obstrutiva do Sono/terapia
15.
J Clin Endocrinol Metab ; 105(1)2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31612224

RESUMO

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is common in active acromegaly and negatively influences quality of life, morbidity, and mortality. This prospective study with 3 predetermined timepoints and a standardized treatment protocol investigates changes in sleep parameters during the first 2.5 years of acromegaly treatment. METHODS: Before initiation of acromegaly treatment (medical pretreatment followed by surgery), polysomnography (PSG) was performed in 27 consecutive patients with treatment-naive acromegaly. PSG was repeated after 1 year (N = 24) and 2.5 years (N = 23), and anthropometric and biochemical parameters were obtained. RESULTS: At baseline, 74.1% of the patients was diagnosed with OSAS. The respiratory disturbance index (RDI; P = 0.001), oxygen desaturation index (ODI; P = 0.001), lowest oxygen saturation (LSaO2; P = 0.007) and the Epworth Sleepiness Scale (ESS; P < 0.001) improved significantly during treatment, with the greatest improvement in the first year. After 2.5 years of treatment, all patients had controlled acromegaly. Of the 16 patients with repeated PSG and OSAS at baseline, 11 (68.8%) were cured of OSAS. Changes in RDI, ODI, LSaO2, and ESS correlated with insulin-like growth factor 1 levels. CONCLUSION: OSAS has a high prevalence in active acromegaly. There is a substantial decrease in prevalence and severity of OSAS following acromegaly treatment, with the largest improvement during the first year. Most patients recover from OSAS following surgical or biochemical control of the acromegaly. Therefore, a PSG is advised after diagnosis of acromegaly. When OSAS is present, it should be treated and PSG should be repeated during acromegaly treatment.


Assuntos
Acromegalia/complicações , Acromegalia/epidemiologia , Acromegalia/terapia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/patologia , Acromegalia/diagnóstico , Adenoma/complicações , Adenoma/epidemiologia , Adenoma/terapia , Adulto , Idoso , Estudos de Casos e Controles , Progressão da Doença , Agonistas de Dopamina/uso terapêutico , Feminino , Adenoma Hipofisário Secretor de Hormônio do Crescimento/complicações , Adenoma Hipofisário Secretor de Hormônio do Crescimento/epidemiologia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/terapia , Hormônio do Crescimento Humano/análogos & derivados , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Polissonografia , Prevalência , Prognóstico , Apneia Obstrutiva do Sono/diagnóstico , Sonolência , Resultado do Tratamento
16.
Sci Rep ; 9(1): 18664, 2019 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-31819149

RESUMO

Several studies have recently investigated the contribution of genetic factors in obstructive sleep apnea (OSA). Patients with OSA suffer from a reduction in nitric oxide (NO) serum level. This study investigated rs841, A930G p22phox, and rs1799983 polymorphisms in three critical genes involved in NO formation. A total of 94 patients with OSA and 100 healthy controls were enrolled into the study. Results showed there was no association between rs841, A930G p22phox and rs1799983 polymorphism and the risk of OSA (P = 0.51, P = 0.4 and P = 0.33, respectively). Moreover, rs841 GA genotype had a reverse relationship with the severity of OSA (P = 0.005). On the other hand, rs841 GA and A930G p22phox AA genotypes had a protective effect on daytime sleepiness in OSA patients (P = 0.01and P = 0.02, respectively). Additionally, the combination of rs841 and A930G p22phox (AG/AG and AG/AA) genotypes was significantly associated with a reduction in daytime sleepiness in OSA patients (P = 0.03 and P = 0.03, respectively). According to the results of our study, GA genotype of rs841 and GA/AA genotypes of A930G p22phox polymorphisms significantly reduced the severity of the problem and daytime sleepiness in OSA patients.


Assuntos
GTP Cicloidrolase/genética , Predisposição Genética para Doença , Óxido Nítrico/genética , Apneia Obstrutiva do Sono/genética , Adulto , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/metabolismo , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Apneia Obstrutiva do Sono/patologia
17.
Int J Mol Sci ; 20(24)2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31835632

RESUMO

Pediatric obstructive sleep apnea (P-OSA) is associated with neurocognitive deficits and endothelial dysfunction, suggesting the possibility that disruption of the blood-brain barrier (BBB) may underlie these morbidities. Extracellular vesicles (EVs), which include exosomes, are small particles involved in cell-cell communications via different mechanisms and could play a role in OSA-associated end-organ injury. To examine the roles of EVs in BBB dysfunction, we recruited three groups of children: (a) absence of OSA or cognitive deficits (CL, n = 6), (b) OSA but no evidence of cognitive deficits (OSA-NC(-), n = 12), and (c) OSA with evidence of neurocognitive deficits (OSA-NC(+), n = 12). All children were age-, gender-, ethnicity-, and BMI-z-score-matched, and those with OSA were also apnea-hypopnea index (AHI)-matched. Plasma EVs were characterized, quantified, and applied on multiple endothelial cell types (HCAEC, HIAEC, human HMVEC-D, HMVEC-C, HMVEC-L, and hCMEC/D3) while measuring monolayer barrier integrity and wound-healing responses. EVs from OSA children induced significant declines in hCMEC/D3 transendothelial impedance compared to CL (p < 0.001), and such changes were greater in NC(+) compared to NC(-) (p < 0.01). The effects of EVs from each group on wound healing for HCAEC, HIAEC, HMVED-d, and hCMEC/D3 cells were similar, but exhibited significant differences across the three groups, with evidence of disrupted wound healing in P-OSA. However, wound healing in HMVEC-C was only affected by NC(+) (p < 0.01 vs. NC(-) or controls (CO). Furthermore, no significant differences emerged in HMVEC-L cell wound healing across all three groups. We conclude that circulating plasma EVs in P-OSA disrupt the integrity of the BBB and exert adverse effects on endothelial wound healing, particularly among OSA-NC(+) children, while also exhibiting endothelial cell type selectivity. Thus, circulating EVs cargo may play important roles in the emergence of end-organ morbidity in pediatric OSA.


Assuntos
Barreira Hematoencefálica/patologia , Células Endoteliais/patologia , Vesículas Extracelulares/metabolismo , Plasma/metabolismo , Apneia Obstrutiva do Sono/metabolismo , Barreira Hematoencefálica/metabolismo , Comunicação Celular , Células Cultivadas , Criança , Pré-Escolar , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Feminino , Humanos , Masculino , Apneia Obstrutiva do Sono/patologia , Apneia Obstrutiva do Sono/psicologia , Cicatrização
18.
Sci Rep ; 9(1): 17722, 2019 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-31776365

RESUMO

The aim of this study was to assess associations between fat pad areas at various anatomic levels and the sites of lateral wall collapse and disease severity in adult patients with obstructive sleep apnea (OSA). Forty-one patients with OSA who prospectively underwent drug-induced sleep computed tomography were included. Areas of parapharyngeal fat pads and degrees of lateral wall collapse at three representative anatomic levels (nasopharynx, oropharynx, and subglosso-supraglottis), and apnea-hypopnea index (AHI) were measured. In the subglosso-supraglottic region, the parapharyngeal fat pad area in 17 (41%) patients with complete lateral wall collapse was significantly larger than that in 24 (59%) patients without complete collapse (median, 236.0 mm2 vs 153.0 mm2; P = 0.02). In multivariate regression analysis, the parapharyngeal fat pad area at the subglosso-supraglottic level (ß = 0.02; P = 0.01) and body mass index (ß = 3.24; P = 0.01) were independently associated with AHI. Our preliminary results supported that parapharyngeal fat pads at the subglosso-supraglottic level may be involved in the development of lateral wall collapse and then determine the severity of OSA. Further studies are warranted to investigate the effect of reducing parapharyngeal fat pads in the treatment of OSA.


Assuntos
Tecido Adiposo/diagnóstico por imagem , Glote/diagnóstico por imagem , Faringe/diagnóstico por imagem , Apneia Obstrutiva do Sono/diagnóstico por imagem , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Apneia Obstrutiva do Sono/patologia
19.
Mol Med Rep ; 20(5): 4665-4673, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702032

RESUMO

Bone marrow­derived mesenchymal stem cells (BMSCs) possess potential therapeutic properties for treating patients with chronic obstructive pulmonary disease (COPD), which is characterized by emphysema and obstructive sleep apnea (OSA). However, their effects on overlap syndrome (OS) remain unclear. We investigated the potential therapeutic effects and possible mechanisms of BMSC transplantation in OS rats. To generate the OS model in rats, the animals underwent daily exposure to cigarette smoke and intermittent hypoxia. BMSCs were intravenously injected into rats. At 4 weeks post­transplantation, the severity of emphysema was assessed by lung hematoxylin and eosin (H&E) staining. The levels of oxidative stress and the malondialdehyde (MDA) and superoxide dismutase (SOD) contents in serum and lung were detected. The apoptosis of alveolar septal cells was also detected by TUNEL assay. Finally, we determined the expression of CD31 and VWF in lung tissues by an immunohistochemical (IHC) assay. It was found that BMSCs were able to migrate to the injured lung and aorta tissues. In lung tissues, transplanted BMSCs, some of which had differentiated into endotheliocytes, were found in the alveolar walls. The mean linear intercept (MLI) and pathological scores were higher and the mean alveolar number (MAN) was lower in the OS group than these parameters in the control group. These values were significantly reduced in the OS+BMSC group compared to those in the OS group. The MDA content was decreased and SOD activity was increased in the OS+BMSC group compared to those in the OS group. The apoptotic index of alveolar wall cells in the OS group was higher than that in the OS+BMSC group. The expression levels of CD31 and VWF in alveolar wall cells in the OS group were lower than those in the OS+BMSC group. These results indicate that BMSCs may inhibit the progression of emphysema in the OS model by differentiating into endotheliocytes and suppressing the apoptosis of endotheliocytes and oxidative stress. There is a possibility that the release of growth factors and structural support may be a determinant for the regenerative effects observed following treatment with BMSCs.


Assuntos
Células da Medula Óssea/metabolismo , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Doença Pulmonar Obstrutiva Crônica , Apneia Obstrutiva do Sono , Aloenxertos , Animais , Células da Medula Óssea/patologia , Modelos Animais de Doenças , Células-Tronco Mesenquimais/patologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Doença Pulmonar Obstrutiva Crônica/terapia , Ratos , Ratos Sprague-Dawley , Apneia Obstrutiva do Sono/metabolismo , Apneia Obstrutiva do Sono/patologia , Apneia Obstrutiva do Sono/terapia
20.
Brain Behav ; 9(12): e01482, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31749327

RESUMO

BACKGROUND: There is some evidence that obstructive sleep apnea (OSA) patients have white matter integrity abnormality in the corpus callosum (CC). However, whether the CC subregions are differentially affected in OSA is largely unknown. METHODS: Twenty patients with OSA and 24 well-matched healthy controls were enrolled and underwent diffusion tensor imaging (DTI) and clinical and cognitive assessments. DTI tractography was used to reconstruct the CC which was divided into five subregions. Intergroup differences in multiple diffusion metrics of each CC subregion and their correlations with clinical and cognitive parameters were tested. RESULTS: In comparison with healthy controls, OSA patients exhibited white matter integrity alterations in the anterior CC, characterized by increased radial diffusivity (RD) in the subregion 1 and decreased fractional anisotropy (FA) along with increased mean diffusivity (MD) and RD in the subregion 2. Moreover, we found that the lower microstructural integrity in the anterior CC was correlated with worse prospective memory and sustained attention in OSA patients. CONCLUSIONS: These findings indicate that the selective impairments of the anterior CC may help clarify the neural correlates of cognitive impairments in OSA.


Assuntos
Disfunção Cognitiva , Corpo Caloso , Apneia Obstrutiva do Sono , Adulto , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/patologia , Substância Branca/fisiopatologia
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