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1.
Life Sci ; 239: 117020, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31678553

RESUMO

AIMS: Obstructive sleep apnea (OSA) combined with type 2 diabetes (T2DM) may lead to cognitive dysfunction. We previously reported that cognitive impairment is exacerbated in KKAy mice exposed to intermittent hypoxia (IH), during which the DNA binding protein HMGB1 mediates hippocampal neuronal apoptosis by maintaining microglia-associated neuroinflammation, but the underlying mechanism remains largely unknown. MATERIALS AND METHODS: We performed immunofluorescence, Western blotting, and immunohistochemistry experiments in mouse hippocampal tissues and HT22 cells. KKAy type 2 diabetes model mice and normal C57BL/6J mice were exposed to IH or intermittent normoxia. HT22 cells were cultured in high glucose medium and exposed to IH or intermittent normoxia. We transfected HMGB1 siRNA into HT22 cells and then treated them with high glucose combined with intermittent hypoxia. KEY FINDINGS: In conclusion, IH aggravated apoptosis and autophagy defects in T2DM mice, and increased the protein expression of HMGB1 and TLR4. This was also confirmed in HG + IH-treated hippocampal HT22 cells. HMGB1 siRNA can significantly reduce the protein expression of HMGB1 and TLR4, reverse neuronal apoptosis and enhance autophagy. SIGNIFICANCE: We believe that HMGB1 is a key factor in the regulation of hippocampal neuronal apoptosis and autophagy defects in T2DM combined with OSA. Targeting HMGB1/TLR4 signaling as a novel approach may delay or prevent the increased apoptosis and decreased autophagy induced by T2DM combined with OSA, and may ultimately improve cognitive dysfunction.


Assuntos
Apoptose/genética , Autofagia/genética , Diabetes Mellitus Tipo 2/patologia , Proteína HMGB1/genética , Hipocampo/patologia , Neurônios/patologia , Apneia Obstrutiva do Sono/patologia , Receptor 4 Toll-Like/genética , Animais , Hipóxia Celular , Diabetes Mellitus Tipo 2/complicações , Masculino , Camundongos , Camundongos Endogâmicos C57BL , RNA Interferente Pequeno/farmacologia , Transdução de Sinais/genética , Apneia Obstrutiva do Sono/complicações
2.
Expert Opin Pharmacother ; 20(16): 1981-1991, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31487204

RESUMO

Introduction: Obstructive sleep apneas are a frequent clinical condition in which there are momentary interruptions or reductions in breathing activity. To date, the gold standard therapy is the use of Continous Positive Airway Pressure (CPAP). But, due to the relatevely high frequency of poor compliant patients, there is the need to research possible pharmacological treatments for obstructive apnea (OSA). Areas covered: A recent study divided OSA into four major phenotypes. With this characterization in hand, the authors have reviewed the pharmacological treatments present to date according to the different phenotypes in which they could be used. Afterwards, they analyzed the efficacy of different medicaments for the therapy of the residual (despite CPAP treatment) excessive day-time sleepiness (EDS) that often afflicts OSA' patients. Expert opinion: Different drug classes have been evaluated, with some positive results. However, there is still the need to better define treatment strategies for every single phenotype. This underlines the importance to avoid considering the pathology like a single entity without any differences between each single form. The authors are concerned about the risk that, treating only EDS, patients could reduce their compliance to CPAP, thus not reducing the cardiovascular risk associated with OSA.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas , Apneia Obstrutiva do Sono/terapia , Antidepressivos/uso terapêutico , Depressores do Apetite/uso terapêutico , Inibidores da Anidrase Carbônica/uso terapêutico , Humanos , Mandíbula/anatomia & histologia , Fenótipo , Apneia Obstrutiva do Sono/tratamento farmacológico , Apneia Obstrutiva do Sono/patologia
3.
J Bras Pneumol ; 45(4): e20180264, 2019 Aug 15.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31432889

RESUMO

OBJECTIVE: To determine whether airway narrowing during obstructive events occurs predominantly at the retropalatal level and results from dynamic changes in the lateral pharyngeal walls and in tongue position. METHODS: We evaluated 11 patients with severe obstructive sleep apnea (OSA) and 7 healthy controls without OSA during wakefulness and during natural sleep (documented by full polysomnography). Using fast multidetector CT, we obtained images of the upper airway in the waking and sleep states. RESULTS: Upper airway narrowing during sleep was significantly greater at the retropalatal level than at the retroglossal level in the OSA group (p < 0.001) and in the control group (p < 0.05). The retropalatal airway volume was smaller in the OSA group than in the control group during wakefulness (p < 0.05) and decreased significantly from wakefulness to sleep only among the OSA group subjects. Retropalatal pharyngeal narrowing was attributed to reductions in the anteroposterior diameter (p = 0.001) and lateral diameter (p = 0.006), which correlated with an increase in lateral pharyngeal wall volume (p = 0.001) and posterior displacement of the tongue (p = 0.001), respectively. Retroglossal pharyngeal narrowing during sleep did not occur in the OSA group subjects. CONCLUSIONS: In patients with OSA, upper airway narrowing during sleep occurs predominantly at the retropalatal level, affecting the anteroposterior and lateral dimensions, being associated with lateral pharyngeal wall enlargement and posterior tongue displacement.


Assuntos
Tomografia Computadorizada Multidetectores/métodos , Doenças Faríngeas/diagnóstico por imagem , Doenças Respiratórias/diagnóstico por imagem , Apneia Obstrutiva do Sono/diagnóstico por imagem , Língua/diagnóstico por imagem , Adulto , Idoso , Estudos de Casos e Controles , Humanos , Masculino , Pessoa de Meia-Idade , Palato/diagnóstico por imagem , Palato/patologia , Palato/fisiopatologia , Doenças Faríngeas/patologia , Doenças Faríngeas/fisiopatologia , Faringe/diagnóstico por imagem , Faringe/patologia , Faringe/fisiopatologia , Polissonografia , Valores de Referência , Doenças Respiratórias/patologia , Doenças Respiratórias/fisiopatologia , Apneia Obstrutiva do Sono/patologia , Apneia Obstrutiva do Sono/fisiopatologia , Língua/patologia , Língua/fisiopatologia , Vigília/fisiologia
4.
Physiol Res ; 68(3): 445-455, 2019 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-31301730

RESUMO

Obstructive sleep apnea (OSA) has been demonstrated to be implicated in disorder of insulin secretion and diabetes mellitus. In this study, we aimed to evaluate the protective role of tempol, a powerful antioxidant, in chronic intermittent hypoxia (IH)-induced pancreatic injury. The rat model of OSA was established by IH exposure. The pathological changes, increased blood-glucose level, and raised proinsulin/insulin ratio in pancreatic tissues of rats received IH were effectively relieved by tempol delivery. In addition, the enhanced levels of pro-inflammatory cytokines, TNF-alpha, IL-1beta, IL-6, and inflammatory mediators, PGE2, cyclooxygenase-2 (COX-2), NO, and inducible nitric oxide synthase (iNOS) in pancreatic tissue were suppressed by tempol. Moreover, tempol inhibited IH-induced apoptosis in pancreatic tissue as evidenced by upregulated Bcl-2 level, and downregulated Bax and cleaved caspase-3 levels. Finally, the abnormal activation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) signaling pathways induced by IH was restrained by tempol administration. In summary, our study demonstrates that tempol relieves IH-induced pancreatic injury by inhibiting inflammatory response and apoptosis, which provides theoretical basis for tempol as an effective treatment for OSA-induced pancreatic injury.


Assuntos
Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Óxidos N-Cíclicos/uso terapêutico , Hipóxia/tratamento farmacológico , Mediadores da Inflamação/antagonistas & inibidores , Pâncreas/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Apoptose/fisiologia , Óxidos N-Cíclicos/farmacologia , Hipóxia/metabolismo , Hipóxia/patologia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Pâncreas/metabolismo , Pâncreas/patologia , Ratos , Ratos Wistar , Apneia Obstrutiva do Sono/tratamento farmacológico , Apneia Obstrutiva do Sono/metabolismo , Apneia Obstrutiva do Sono/patologia , Marcadores de Spin
5.
Biomed Res Int ; 2019: 9174218, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31346526

RESUMO

Background: Intermittent hypoxia (IH) induced by obstructive sleep apnea (OSA) is a leading factor affecting cardiovascular fibrosis. Under IH condition, smooth muscle cells (SMAs) respond by dedifferentiation, which is associated with vascular remodelling. The expression of prolyl 4-hydroxylase domain protein 3 (PHD3) increases under hypoxia. However, the role of PHD3 in OSA-induced SMA dedifferentiation and cardiovascular fibrosis remains uncertain. Methods: We explored the mechanism of cardiovascular remodelling in C57BL/6 mice exposed to IH for 3 months and investigated the mechanism of PHD3 in improving the remodelling in vivo and vitro. Results: In vivo remodelling showed that IH induced cardiovascular fibrosis via SMC dedifferentiation and that fibrosis improved when PHD3 was overexpressed. In vitro remodelling showed that IH induced SMA dedifferentiation, which secretes much collagen I. PHD3 overexpression in cultured SMCs reversed the dedifferentiation by degrading and inactivating HIF-1α. Conclusion: OSA-induced cardiovascular fibrosis was associated with SMC dedifferentiation, and PHD3 overexpression may benefit its prevention by reversing the dedifferentiation. Therefore, PHD3 overexpression has therapeutic potential in disease treatment.


Assuntos
Cardiomiopatias/genética , Fibrose/genética , Pró-Colágeno-Prolina Dioxigenase/genética , Apneia Obstrutiva do Sono/genética , Animais , Cardiomiopatias/etiologia , Cardiomiopatias/patologia , Desdiferenciação Celular/genética , Hipóxia Celular/genética , Modelos Animais de Doenças , Fibrose/etiologia , Fibrose/patologia , Regulação da Expressão Gênica/genética , Humanos , Camundongos , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/patologia
6.
Curr Med Sci ; 39(4): 568-575, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31346992

RESUMO

The possible relationship between lung cancer and nocturnal intermittent hypoxia, apnea and daytime sleepiness, especially the possible relationship between the occurrence and progression of lung cancer and obstructive sleep apnea syndrome (OSAS) was explored. Forty-five cases of primary lung cancer suitable for surgical resection at the Third Affiliated Hospital of Kunming Medical University between January 2017 and December 2017 were recruited (lung cancer group), and there were 45 patients in the control group who had no significant differences in age, sex and other general data from lung cancer group. The analyzed covariates included general situation, snore score, the Epworth Sleeping Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), apnea and hypopneas index (AHI), oxygen desaturation index 4 (ODI4), lowest arterial oxygen saturation [LSpO2 (%)], oxygen below 90% of the time [T90% (min)], the percentage of the total recorded time spend below 90% oxygen saturation (TS90%), to explore the possible relationship between lung cancer and above indicators. The participants were followed up for one year. The results showed that: (1) There was significant difference in body mass index (BMI), ESS, AHI, T90% (min), TS90%, ODI4, snore score and LSpO2 (%) between lung cancer group and control group (P<0.05). There was no statistically significant difference in age, gender, PSQI score, incidence of concurrent hypertension, diabetes and coronary heart disease (CHD), and smoking history between the two groups (P>0.05); (2) Patients in the lung cancer group were divided into OSAS subgroup and non-OSAS subgroup according to the international standard for the diagnosis of OSAS. There was significant difference in BMI, age, staging, incidence of concurrent hypertension and concurrent CHD, snore score, ESS score, T90% (min), TS90%, ODI4 and LSpO2 (%) between OSAS subgroup and non-OSAS subgroup (P<0.05). There was no statistically significant difference in gender, PSQI score, incidence of concurrent diabetes, smoking history and lung cancer type between the two groups (P>0.05); (3) AHI was strongly negatively correlated with the LSpO2 (%) and positively with ESS, staging, snoring score, T90% (min), TS90%, ODI4 and BMI (P<0.05); (4) There were 3 deaths, 5 cases of recurrence, and 4 cases of metastasis in OSAS subgroup; and there was 1 death, 4 cases of recurrence and 2 cases of metastasis in non-OSAS subgroup during the follow-up period of one year, respectively. There was no significant difference in mortality, recurrence rate and metastasis rate between the two subgroups, and the total rate of deterioration in OSAS subgroup was significantly increased compared to the non-OSAS subgroup (P<0.05). It was concluded that the patients with lung cancer are prone to nocturnal hypoxemia, apnea, snoring and daytime sleepiness compared to control group. The incidence of OSAS in patients with lung cancer was higher, and the difference in the hypoxemia-related indicators was statistically significant. The mortality, recurrence rate, and metastasis rate increases in lung cancer patients with OSAS during the one-year follow-up period, suggesting that OSAS may be a contributing factor to the occurrence and progression of lung cancer.


Assuntos
Apneia/epidemiologia , Hipóxia/epidemiologia , Neoplasias Pulmonares/epidemiologia , Apneia Obstrutiva do Sono/epidemiologia , Adulto , Idoso , Apneia/complicações , Apneia/metabolismo , Apneia/patologia , Índice de Massa Corporal , Progressão da Doença , Feminino , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Hipertensão/metabolismo , Hipertensão/patologia , Hipóxia/metabolismo , Hipóxia/patologia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Oxigênio/metabolismo , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/metabolismo , Apneia Obstrutiva do Sono/patologia , Sonolência
7.
PLoS One ; 14(6): e0217138, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31216297

RESUMO

STUDY OBJECTIVES: Vascular damage must be diagnosed early in patients with hypertension. In this regard, endothelial dysfunction (ED) is an early sign of vascular disease and a predictor of cardiovascular diseases. In obstructive sleep apnea (OSA), intermittent hypoxia triggers ED, but mechanisms are not clear. In this context, it has been described that BK channels regulates arterial tone and that chronic and intermittent hypoxia downregulates the expression of the BK channel ß1-subunit facilitating vasoconstriction. Thus, we investigated the relationship among hypoxemia, ED, and mRNA expression of the ß1-subunit in patients with severe OSA. We aimed to assess (1) ED in non-hypertensive patients with OSA using laser-Doppler flowmetry, (2) BK ß1-subunit mRNA expression, and (3) the impact of continuous positive airway pressure (CPAP) treatment on ED and ß1-subunit regulation. METHODS: OSA patients underwent 24-hour blood pressure monitoring to exclude hypertension. Laser-Doppler flowmetry was performed to assess ED, and ß1-subunit mRNA expression was evaluated using a blood test of peripheral blood leukocytes at baseline and after 3 months of CPAP treatment. RESULTS: In normotensive patients with OSA, endothelial function correlated with the severity of OSA. CPAP improved endothelial function in normotensive OSA patients and the speed of the arterial response was significantly correlated with ß1-subunit mRNA expression. ß1-subunit mRNA expression at baseline correlated inversely with its change after CPAP. CONCLUSIONS: Sleep apnea is related to ED in normotensive patients with OSA. CPAP therapy improves endothelial function and regulates ß1-subunit mRNA expression.


Assuntos
Endotélio Vascular/patologia , Regulação da Expressão Gênica , Subunidades beta do Canal de Potássio Ativado por Cálcio de Condutância Alta/genética , Apneia Obstrutiva do Sono/genética , Apneia Obstrutiva do Sono/patologia , Adulto , Idoso , Pressão Positiva Contínua nas Vias Aéreas , Feminino , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/terapia
8.
Turk J Med Sci ; 49(3): 939-944, 2019 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-31195789

RESUMO

Background/aim: To prepare a porcine model of obstructive sleep apnea-hypopnea syndrome (OSAHS) and observe the pathological and hemodynamic changes in the common carotid artery. Materials and methods: Twelve male miniature pigs were randomly divided into the model and control group (n = 6). Pigs in the model group were kept in an air-flow negative pressure chamber at 0.96 ± 0.01 kPa, and the air oxygen content, temperature, and humidity were kept at normal culture conditions in both groups. After pigs in the model group presented symptoms of OSAHS, changes in the hemodynamics and morphology of the carotid artery were analyzed using color Doppler, and light and electron microscopy. Results: An animal model of OSAHS was successfully created. The internal diameter of the carotid artery of pigs in the model group was decreased, while the intima thickness, peak-systolic mean velocity, and resistance index were increased when compared to the control group (P < 0.05). The results of the light and electron microscopy revealed an incomplete elastic plate, increased media thickness, irregular morphology of the smooth muscle cells, increased collagen fiber bundles, partially disordered elastic fibers, and smooth muscle layers. The quantitative analysis showed significantly increased elastic fibers in the media of the carotid artery in the model group (P < 0.01). Conclusion: Pathological changes in the tissue structure and hemodynamics in the negative pressure-induced pig OSAHS model were observed. We suggest that alterations in the upper airway pressure during OSAHS may lead to cardiovascular conditions through its pathological effects on the carotid artery.


Assuntos
Artéria Carótida Primitiva , Hemodinâmica/fisiologia , Apneia Obstrutiva do Sono , Animais , Artéria Carótida Primitiva/fisiologia , Artéria Carótida Primitiva/fisiopatologia , Modelos Animais de Doenças , Masculino , Apneia Obstrutiva do Sono/patologia , Apneia Obstrutiva do Sono/fisiopatologia , Suínos , Porco Miniatura
9.
PLoS One ; 14(5): e0216607, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31116781

RESUMO

BACKGROUND: This study aims to investigate the role of FPR 1/2/3 expressions in patients with obstructive sleep apnea (OSA). METHOD: We made cross-sectional comparisons of FPR1/2/3 expressions of blood neutrophil, M1/M2a monocyte, and natural killer (NK) cell between 16 healthy subjects (HS), 16 primary snoring (PS) subjects, 46 treatment-naive OSA patients, and 18 severe OSA patients under long-term continuous positive airway pressure treatment (severe OSA on CPAP). RESULTS: FPR1 expressions on neutrophil were increased in treatment-naive OSA and severe OSA on CPAP groups versus either HS or PS. FPR2 expressions on neutrophil were decreased in treatment-naive OSA versus HS, and returned to normal in severe OSA on CPAP group. FPR1/FPR2 expression ratio on neutrophil was increased in treatment-naive OSA versus either HS or PS. Serum lipoxin A4, resolvin D1 levels, and FPR3 expressions of M1, M2a and NK cells were all decreased in treatment-naive OSA versus HS. OSA patients with hypertension had decreased FPR2 expressions on neutrophil and FPR3 expressions of NK cell. FPR1 expression, FPR1/FPR2 expression ratio on neutrophil, and FPR3 expression of M1 cell were all reversed after > 6-month CPAP treatment in 9 selected patients. In vitro intermittent hypoxia with re-oxygenation treatment in THP-1 cells resulted in increased FPR1/FPR2 expression ratio of M1 cells, and increased FPR1/FPR3 expression ratio of M2a cells. CONCLUSIONS: FPR1 over-expression and insufficiency of FPR2 and FPR3 in association with defective lipoxin A4 and resolving D1 production were associated with disease severity of OSA and its adverse consequences.


Assuntos
Ácidos Docosa-Hexaenoicos/sangue , Lipoxinas/sangue , Receptores de Formil Peptídeo/sangue , Receptores de Lipoxinas/sangue , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/patologia , Células Sanguíneas/metabolismo , Estudos de Casos e Controles , Estudos Transversais , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Neutrófilos/metabolismo , Apneia Obstrutiva do Sono/imunologia
10.
Ann Otol Rhinol Laryngol ; 128(10): 938-948, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31091983

RESUMO

OBJECTIVE: Obstructive sleep apnea/hypopnea syndrome (OSA) could compromise oxygenation of the optic nerve and cause glaucomatous optic neuropathy; however, there were no studies to investigate the changes of visual function and retinal microstructures in OSA patients after upper airway surgery. We aim to assess the changes in the visual sensitivity and retinal fiber layer thickness in OSA patients before and after surgery. METHODS: This prospective single-blind study enrolled patients with OSA from a tertiary academic medical center who had unsuccessful conservative therapy and then underwent surgery. The patients were referred for comprehensive ophthalmologic evaluation at baseline and 6 months after OSA surgery. The polysomnographic findings were collected pre- and postoperatively. Visual sensitivities on standard automated perimetry (SAP) were assessed. Peripapillary retinal nerve fiber layer (RNFL) thickness and macular layer (ML) thickness parameters were measured by spectral-domain optical coherence tomography (OCT). RESULTS: A total of 108 OSA patients were enrolled. Six months after surgery, the major parameters of polysomnography (PSG), mean deviation, and pattern standard deviation of SAP significantly improved in these OSA patients. Regarding the OCT parameters, thickness of ML in the nasal-outer, superior-inner, temporal-inner, inferior-inner, nasal-inner sectors, and total ML thickness significantly increased 6 months after upper airway surgery in the severe OSA group (apnea/hypopnea index ⩾30 per hour). CONCLUSION: The visual sensitivities on SAP, ML thickness on OCT, and oxygenation status on PSG significantly improved 6 months after upper airway surgery in patients with severe OSA. Upper airway surgery may ameliorate the microstructures of the retina in patients with severe OSA.


Assuntos
Macula Lutea/patologia , Retina/patologia , Apneia Obstrutiva do Sono/patologia , Apneia Obstrutiva do Sono/cirurgia , Adulto , Feminino , Humanos , Macula Lutea/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Polissonografia , Estudos Prospectivos , Retina/diagnóstico por imagem , Método Simples-Cego , Apneia Obstrutiva do Sono/diagnóstico por imagem , Apneia Obstrutiva do Sono/fisiopatologia , Tomografia de Coerência Óptica
11.
Oxid Med Cell Longev ; 2019: 7415212, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30984338

RESUMO

Obstructive sleep apnea (OSA) can cause intermittent changes in blood oxygen saturation, resulting in the generation of many reactive oxygen species (ROS). To discover new antioxidants and clarify the endoplasmic reticulum (ER) stress involved in cardiac injury in OSA, we established a chronic intermittent hypoxia (CIH) rat model with a fraction of inspired O2 (FiO2) ranging from 21% to 9%, 20 times/h for 8 h/day, and the rats were treated with H2-O2 mixture (67% hydrogen and 33% oxygen) for 2 h/day for 35 days. Our results showed that H2-O2 mixture remarkably improved cardiac dysfunction and myocardial fibrosis. We found that H2-O2 mixture inhalation declined ER stress-induced apoptosis via three major response pathways: PERK-eIF2α-ATF4, IRE 1-XBP1, and ATF 6. Furthermore, we revealed that H2-O2 mixture blocked c-Jun N-terminal kinase- (JNK-) MAPK activation, increased the ratio of Bcl-2/Bax, and inhibited caspase 3 cleavage to protect against CIH-induced cardiac apoptosis. In addition, H2-O2 mixture considerably decreased ROS levels via upregulating superoxide dismutase (SOD) and glutathione (GSH) as well as downregulating NADPH oxidase (NOX 2) expression in the hearts of CIH rats. All the results demonstrated that H2-O2 mixture significantly reduced ER stress and apoptosis and that H2 might be an efficient antioxidant against the oxidative stress injury induced by CIH.


Assuntos
Hipóxia Celular/fisiologia , Cardiopatias/terapia , Hidrogênio/uso terapêutico , Miocárdio/patologia , Oxigênio/uso terapêutico , Apneia Obstrutiva do Sono/terapia , Animais , Apoptose , Modelos Animais de Doenças , Cardiopatias/patologia , Humanos , Hidrogênio/farmacologia , Masculino , Oxigênio/farmacologia , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio , Apneia Obstrutiva do Sono/diagnóstico por imagem , Apneia Obstrutiva do Sono/patologia
13.
Int J Pediatr Otorhinolaryngol ; 122: 133-137, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31022683

RESUMO

OBJECTIVE: Rhinitis is an acute or chronic inflammatory condition due to several causes (i.e. infections, allergens). There are controversial results that point out the role of nasal inflammation in primary snoring and obstructive sleep apnoea syndrome (OSAS). METHODS: The aim of the present investigation is to study the nasal cytology in 58 children aged from 1 to 15 affected by sleep disordered breathing. RESULTS: Inflammation of the nasal mucous was found in 88% of children. The most frequent problems were infectious rhinitis (36%), followed by non-allergic rhinitis (28%) and allergic rhinitis (21%). Infectious rhinitis was found in 31% of children with primary snoring and 41% with OSAS. Allergic rhinitis was found in 35% of children with primary snoring, and 6% with OSAS. Non-allergic rhinitis was found in 19% of children with primary snoring, and 34% with OSAS. Bacteria was found in 59% of children with OSAS and 46% in children with primary snoring. CONCLUSION: the most prevalent forms of rhinitis in primary snoring were the allergic rhinitis, and in OSAS group were the non-allergic rhinitis. Bacteria were equally distributed in primary snoring and OSAS children. The nasal cytology provided interesting information that can be used to plan possible treatment strategies.


Assuntos
Mucosa Nasal/patologia , Rinite Alérgica/patologia , Apneia Obstrutiva do Sono/patologia , Ronco/etiologia , Ronco/patologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Rinite Alérgica/complicações , Apneia Obstrutiva do Sono/microbiologia
14.
Clin Biochem ; 68: 24-29, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30928393

RESUMO

BACKGROUND: Acute coronary syndrome (ACS) is a major cause of death and closely related with obstructive sleep apnea (OSA). Our hypothesis is that several cardiovascular-related biomarkers could have a differential prognostic value for ACS severity in patients with OSA, and could also help (individually or combined) in the detection of OSA in patients after a coronary event. METHODS: Up to 361 consecutive individuals admitted due to ACS were included in the study. All of them were evaluated for ACS severity (Killip score, number of diseased vessels, ejection fraction) and further classified as OSA or non-OSA. Medical records were registered and eleven blood biomarkers were measured, including heart-type fatty acid-binding globulin, N-terminal pro-brain natriuretic peptide, matrix metalloproteinase-9 (MMP9), placental growth factor (PlGF) and high-sensitivity C-reactive protein. Odds ratios of every biomarker for ACS severity-related parameters were calculated and adjusted for age, gender, body-mass index (BMI), hypertension, diabetes, smoking and drinking. The use of clinical measures and biomarkers for the diagnosis of OSA in ACS patients was evaluated both alone and combined using ROC curves. RESULTS: Several biomarkers showed a significant association with ACS severity, which remained after adjusting for OSA and other potentially confounding variables. The mathematical combination of age, BMI, PlGF and MMP9 showed an area under the ROC curve (AUC) for OSA identification of 0.741, which was greater than any individual parameter or combination assessed: AUC(BMI):0.687, AUC(age):0.576, AUC(PlGF):0.584, AUC(MMP9):0.555. CONCLUSIONS: The usefulness of biomarkers in the assessment of ACS severity was independent of OSA and the other variables evaluated. In patients admitted after a coronary event, the combination of clinical measures and biomarkers showed a significant discriminating power for the detection of OSA. CLINICAL TRIAL REGISTRATION: NCT01335087 (clinicaltrials.gov).


Assuntos
Biomarcadores/sangue , Síndromes da Apneia do Sono/sangue , Apneia Obstrutiva do Sono/sangue , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/patologia , Algoritmos , Área Sob a Curva , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , Feminino , Humanos , Masculino , Prognóstico , Síndromes da Apneia do Sono/patologia , Apneia Obstrutiva do Sono/patologia
15.
Oxid Med Cell Longev ; 2019: 4862760, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30863480

RESUMO

Objective: The aim of this study was to establish a 3T3-L1 adipocyte model and ApoE-/- mouse model of intermittent hypoxia (IH) composite abnormal glucose metabolism (AGM) in vitro and in vivo and explore their synergistic damage effect leading to atherosclerosis (AS) and the influence of SREBP-1 signaling molecule-related mechanisms. Methods: Mature 3T3-L1 adipocytes were cultured with complete culture medium containing DEX 1 × 106 mol/L for 96 h to establish an AGM-3T3-L1 adipocyte model. Then, AGM-3T3-L1 adipocytes were treated with IH for 0 cycles, 2 cycles, 4 cycles, 8 cycles, 16 cycles, and 32 cycles and sustained hypoxia (SH). ApoE-/- mice were treated with high-fat diet and injection of STZ solution to establish an AGM-ApoE-/- mouse model. A total of 16 AGM-ApoE-/- mice were randomly and averagely divided into the normoxic control group (NC) and model group (CIH). AGM-ApoE-/- mice of the CIH group were treated with IH, which meant that the oxygen concentration fell to 10 ± 0.5% in the first 90 seconds of one cycle and then increased to 21 ± 0.5% in the later 90 seconds, continuous for eight hours per day (09 : 00-17 : 00) with a total of eight weeks. Eight C57BL/6J mice were used as the blank control group (Con) which was fed with conventional diet. qPCR and Western blotting were used to detect the expression level of SREBP-1c, FAS, and IRS-1. Oil Red O staining was used to compare the plaque of the aorta among each mouse group. Results: As a result, within 32 cycles of IH, mRNA and protein expression levels of SREBP-1c and FAS in AGM-3T3-L1 adipocytes were elevated with the increase in IH cycles; the mRNA expression of IRS-1 was decreased after IH 32 cycles and lower than that of the SH group. For the study in vivo, Oil Red O staining showed a more obvious AS aortic plaque in the CIH group. After CIH treatment of 4 w and 8 w, fasting blood glucose (FBG) of the NC group and CIH group was higher than that of the Con group, and the insulin level of the CIH group was higher than that of the Con group after IH treatment of 8 w. The expressions of the IRS-1 mRNA level in the aorta, skeletal muscle, and liver of the CIH group were lower than those in the Con group. The mRNA and protein expression of SREBP-1c and its downstream molecule FAS in the aorta, skeletal muscle, and liver significantly enhanced in the CIH group in contrast with those in the Con group. Conclusion: The CIH composite AGM could promote the progress of AS, which might be related to the modulation of the expression of SREBP-1-related molecular pathways.


Assuntos
Aterosclerose/metabolismo , Hipóxia Celular/fisiologia , Glucose/metabolismo , Apneia Obstrutiva do Sono/complicações , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Animais , Modelos Animais de Doenças , Masculino , Camundongos , Apneia Obstrutiva do Sono/patologia
16.
Korean J Radiol ; 20(4): 631-640, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30887745

RESUMO

OBJECTIVE: To evaluate the value of airway computed tomography (CT) in patients with obstructive sleep apnea (OSA) as a predictor of cerebrocardiovascular disease (CCVD) clinically, by quantitatively analyzing carotid arterial calcification (CarAC). MATERIALS AND METHODS: This study included 287 patients aged 40-80 years, who had undergone both polysomnography (PSG) and airway CT between March 2011 and October 2015. The carotid arterial calcium score (CarACS) was quantified using the modified Agatston method on each upper airway CT. The OSA severity was categorized as normal, mild, moderate, and severe using the PSG results. Clinical characteristics, comorbid diseases, and lipid profiles of all patients were analyzed, and the prevalence of CCVDs was investigated during the follow up period (52.2 ± 16.0 months). RESULTS: CCVD occurred in 27 patients (9.3%) at the end of follow-up, and the CCVD-present groups showed a significantly older mean age (57.5 years vs. 54.2 years), higher prevalence of hypertension (59% vs. 34%) and CarAC (51.9% vs. 20.8%), whereas sex, other comorbid diseases, and severity of OSA were not significantly different from the CCVD-absent group. A univariate analysis showed that age, hypertension, incidence of CarAC, and CarACS were risk factors for the occurrence of CCVD events. In a multivariate analysis, the incidence of CarAC was the only independent risk factor for CCVD. CONCLUSION: CarAC is an independent risk factor for CCVD, whereas the severity of OSA is not a contributory risk factor in patients with OSA. Therefore, additional analysis of CarACS based on airway CT scans may be useful for predicting CCVD.


Assuntos
Cálcio/análise , Artérias Carótidas/química , Transtornos Cerebrovasculares/diagnóstico , Apneia Obstrutiva do Sono/patologia , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Artérias Carótidas/metabolismo , Transtornos Cerebrovasculares/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Polissonografia , Fatores de Risco , Índice de Gravidade de Doença , Apneia Obstrutiva do Sono/complicações
17.
Blood Press ; 28(3): 173-183, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30836778

RESUMO

BACKGROUND: Arterial hypertension is associated with obstructive sleep apnoea, poor quality and duration of sleep, which might contribute to hypertension-mediated organ damage. METHODS: We investigated the presence of insomnia, restless legs syndrome, and obstructive sleep apnoea using validated questionnaires (Insomnia Severity Index, Restless Legs Syndrome Rating Scale, and STOP-Bang), and their relationship with hypertension-mediated organ damage, in hypertensive patients. RESULTS: In 159 consecutive consenting hypertensive patients [age 47(11) years, median and (interquartile range), body mass index 25.5(5.9) kg/m2, office systolic and diastolic blood pressure 144(23)/92(12) mmHg], the STOP-Bang, but not the other scores, predicted cardiac remodelling: compared to patients with a STOP-Bang score < 3, those at high risk of obstructive sleep apnoea showed higher left ventricular mass index [49.8(11.9) vs. 43.3(11.9) g/m2.7, p < 0.0001], left atrium volume [25.7(2.5) vs. 25.0(2.8) ml/m2, p = 0.003], and aortic root diameter [33.6(3.0) vs. 33.0(3.7) mm, p < 0.0001]. They did not differ for microalbuminuria and estimated glomerular filtration rate. At multivariate analysis, after adjustment for office systolic blood pressure values, the STOP-Bang score remained a predictor of left ventricular mass index; while the Insomnia Severity Index and restless legs syndrome risk score had no predictive value. However, a significant interaction between STOP-Bang and Restless Legs Syndrome Rating Scale scores in determining left ventricular remodelling was found. CONCLUSIONS: In consecutive hypertensive stage I patients the STOP-Bang questionnaire allowed identification of a high-risk cohort featuring a more prominent cardiac damage. Hence, this inexpensive tool can be useful for risk stratification purposes in municipalities with limited access to health care resources.


Assuntos
Traumatismos Cardíacos/etiologia , Hipertensão/complicações , Apneia Obstrutiva do Sono/complicações , Adulto , Feminino , Coração , Humanos , Rim/lesões , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Síndromes da Apneia do Sono/complicações , Síndromes da Apneia do Sono/patologia , Apneia Obstrutiva do Sono/patologia , Inquéritos e Questionários
18.
Heart Vessels ; 34(8): 1266-1279, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30790035

RESUMO

Obstructive sleep apnea (OSA) is associated with coronary artery disease (CAD) and with an increased risk for myocardial infarction, stroke or death due to cardiovascular disease. Optical frequency-domain imaging (OFDI) is a useful modality for evaluating the characteristics of atherosclerotic plaque. The purpose of the study was to use OFDI to investigate the association of OSA with coronary plaque characteristics in patients undergoing percutaneous coronary intervention (PCI). We retrospectively analyzed OFDI data for coronary artery plaques from 15 patients with OSA and 35 non-OSA patients treated between October 2015 and October 2018. Plaque morphology was evaluated for 70 lesions, including 21 from patients with OSA and 49 from non-OSA patients. Compared with the non-OSA group, patients with OSA had significantly higher prevalences of thinned cap fibroatheroma (TCFA) (67% vs. 35%, P = 0.014) and microchannels (86% vs. 55%, P = 0.014); a significantly higher mean lipid index (1392 ± 982 vs. 817 ± 699, P = 0.021), macrophage grade (8.4 ± 6.4 vs. 4.8 ± 4.5, P = 0.030), and maximum number of microchannels (1.5 ± 1.0 vs. 0.7 ± 0.7, P = 0.001); and a significantly lower mean minimum fibrous cap thickness (69.4 ± 28.7 vs. 96.1 ± 51.8 µm, P = 0.008). This OFDI analysis suggests that OSA is associated with unstable plaque characteristics in patients with CAD. More intensive medical management for stabilization of coronary atherosclerotic plaque is required in patients with OSA.


Assuntos
Doença da Artéria Coronariana/etiologia , Intervenção Coronária Percutânea , Placa Aterosclerótica/complicações , Apneia Obstrutiva do Sono/complicações , Idoso , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/patologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/patologia , Polissonografia , Estudos Retrospectivos , Apneia Obstrutiva do Sono/patologia , Tomografia de Coerência Óptica
19.
PLoS One ; 14(2): e0212317, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30794596

RESUMO

The study aims to examine drug-induced sleep endoscopy (DISE) in the decision-making process of pediatric obstructive sleep apnea (OSA) patients with small tonsils. This was a retrospective study of children who underwent awake flexible endoscopy, DISE, and adenoidectomy with/without tonsillectomy at the Shanghai Children's Medical Center between 03/2015 and 12/2016. Tonsillectomy was performed for tonsillar obstruction found by DISE. Adenoidectomy was performed for all children. Cardio-pulmonary coupling (CPC) and oximetry were observed before/after surgery. The study included 126 children: 56 (44.4%) with grade 2 tonsils and 70 (55.6%) with grade 1. Mean age was 5.7±3.2 (range, 2.8-10.4) years and mean BMI of 15.7±5.5 kg/m2. Unexpectedly, DISE showed tonsillar obstruction in 57 (45.2%) children, including 44 (78.6%) with grade 2 tonsils and 13 (18.6%) with grade 1. Therefore, DISE-directed tonsillectomy was performed for 57 patients. There was an improvement in respiratory disturbance index (RDI) and oxygen saturation nadir in the DISE (P = 0.0007, P = 0.037) and control (P = 0.001, P = 0.023) groups 6 months after surgery, but RDI improvement was better in the DISE group compared with controls 1 year after surgery (P = 0.042). DISE is a good way to determine the necessity of tonsillectomy in pediatric OSA patients with small tonsils.


Assuntos
Adenoidectomia/métodos , Tonsila Faríngea/cirurgia , Anestésicos Intravenosos/administração & dosagem , Endoscopia/métodos , Tonsila Palatina/cirurgia , Apneia Obstrutiva do Sono/cirurgia , Tonsilectomia/métodos , Tonsila Faríngea/patologia , Criança , Pré-Escolar , China , Feminino , Humanos , Masculino , Tonsila Palatina/patologia , Estudos Retrospectivos , Apneia Obstrutiva do Sono/patologia
20.
PLoS One ; 14(2): e0211455, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30707735

RESUMO

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a relentlessly progressive lung disease with a fatal prognosis to whose rapid evolution multiple comorbidities may contribute, one of the most common being obstructive sleep apnea (OSA). There are several potential factors and conditions for the emergence of a cognitive deficit in relation to IPF or associated morbidities. OBJECTIVES: The goals of this study were to assess cognition in patients with IPF in stable phase and to identify clinical cognition modifiers. METHODS: In a cross-sectional study, 23 patients with IPF were evaluated using Montreal Cognitive Assessment (MoCA), an instrument for detecting mild cognitive impairments and were screened for OSA through overnight cardiorespiratory polygraphy and for anxiety and depression with three specific scale (Generalized Anxiety Disorder 7-item scale: GAD-7; the Patient Health Questionnaire: PHQ-9; Hospital Anxiety and Depression Scale: HADS). RESULTS: MoCA score was lower in patients with IPF when compared to controls subjects (24 [21,26] vs. 27 [26,28], p = 0.003) but not as significantly as in COPD patients (21 [18.8,23.3], p<0.0001). OSA was diagnosed in 19 (82.6%) IPF patients, 12 patients showed the presence of moderate-severe forms (63.15%). IPF patients with cognitive impairment (MoCA<23) exhibit a higher severity of OSA (apneea hypopnea index-AHI: 33.0±19.1 vs. 12.44±8.2, p = 0.018), and a higher Epworth score (7.1±3.3 vs. 4.3±1.8, p = 0.013). Anxiety and depression scores were not correlated with MoCA results. CONCLUSIONS: Impaired cognition in patients with IPF is mild and affect the areas of visuospatial abilities, language and working memory. OSA could be a possible predictor of IPF cognition deficit. Given the high prevalence of multiple types of sleep disorders in IPF patients, these should be investigated at least by cardiorespiratory polygraphy.


Assuntos
Fibrose Pulmonar Idiopática/patologia , Apneia Obstrutiva do Sono/patologia , Idoso , Disfunção Cognitiva/complicações , Disfunção Cognitiva/diagnóstico , Estudos Transversais , Feminino , Humanos , Fibrose Pulmonar Idiopática/complicações , Masculino , Memória de Curto Prazo , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/diagnóstico , Percepção Espacial
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