Complementary roles of gasotransmitters CO and H2S in sleep apnea.
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ABSTRACT:
SUBMITTER: Peng YJ
PROVIDER: S-EPMC5307452 | biostudies-other | 2017 Feb
REPOSITORIES: biostudies-other
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Project description:This study examines the relationship between sleep apnea and glucose metabolism. Physiological studies have demonstrated that 5 days of exposure to intermittent hypoxia (similar to what occurs with sleep apnea) leads to significant improvements in glucose tolerance. Therefore, this study investigates the hypothesis that intermittent hypoxia may lead to upregulation of some novel peptide(s) that have a powerful glucose lowering action. Keywords: other
2003-07-16 | GSE480 | GEO
Project description:Study objectivesObstructive sleep apnea (OSA) is associated with increased morbidity and mortality, and treatment with positive airway pressure (PAP) is cost-effective. However, the optimal diagnostic strategy remains a subject of debate. Prior modeling studies have not consistently supported the widely held assumption that home sleep testing (HST) is cost-effective.MethodsWe modeled four strategies: (1) treat no one; (2) treat everyone empirically; (3) treat those testing positive during in-laboratory polysomnography (PSG) via in-laboratory titration; and (4) treat those testing positive during HST with auto-PAP. The population was assumed to lack independent reasons for in-laboratory PSG (such as insomnia, periodic limb movements in sleep, complex apnea). We considered the third-party payer perspective, via both standard (quality-adjusted) and pure cost methods.ResultsThe preferred strategy depended on three key factors: pretest probability of OSA, cost of untreated OSA, and time horizon. At low prevalence and low cost of untreated OSA, the treat no one strategy was favored, whereas empiric treatment was favored for high prevalence and high cost of untreated OSA. In-laboratory backup for failures in the at-home strategy increased the preference for the at-home strategy. Without laboratory backup in the at-home arm, the in-laboratory strategy was increasingly preferred at longer time horizons.ConclusionUsing a model framework that captures a broad range of clinical possibilities, the optimal diagnostic approach to uncomplicated OSA depends on pretest probability, cost of untreated OSA, and time horizon. Estimating each of these critical factors remains a challenge warranting further investigation.
| S-EPMC4773629 | biostudies-literature
Project description:Rationale: Obstructive sleep apnea (OSA) has been associated with metabolic dysregulation and systemic inflammation. This may be due to pathophysiologic effects of OSA on visceral adipose tissue. We sought to assess the transcriptional consequences of OSA on adipocytes by utilizing pathway-focused analyses. Methods: Patients scheduled to undergo ventral hernia repair surgery were recruited to wear a portable home sleep monitor for two nights prior to surgery. Visceral fat biopsies were obtained intra-operatively. RNA was extracted and whole-genome expression profiling was performed. Gene Set Enrichment Analysis (GSEA) was used to identify curated gene sets that were differentially enriched in OSA subjects. Network analysis was applied to a select set of highly enriched pathways. Results: 10 patients with OSA and 8 control subjects were recruited. There were no differences in age, gender, body mass index between the two groups, but the OSA subjects had a significantly higher respiratory disturbance index (19.2 vs. 0.6, P-value 0.05) and worse hypoxemia (minimum oxygen saturation 79.7% vs. 87.8%, P-value < 0.001). GSEA identified a number of gene sets up-regulated in adipose tissue of OSA patients including the pro-inflammatory NF-M-NM-:B pathway and the proteolytic ubiquitin/proteasome module. A critical metabolic pathway, the peroxisome proliferator-activated receptor (PPAR), was down-regulated in subjects with OSA. Network analysis linked members of these modules together and identified regulatory hubs. Conclusions: OSA is associated with alterations in visceral fat gene expression. Pathway-based network analysis highlighted perturbations in several key pathways whose coordinated interactions may contribute to the metabolic dysregulation observed in this complex disorder. Total RNA from visceral fat of 18 subjects (10 OSA, 8 Control) was hybridized to 18 Affymetrix Genechip Human Gene 1.0 ST microarrays.
2012-09-01 | E-GEOD-38792 | biostudies-arrayexpress
Project description:Rationale: Obstructive sleep apnea (OSA) has been associated with metabolic dysregulation and systemic inflammation. This may be due to pathophysiologic effects of OSA on visceral adipose tissue. We sought to assess the transcriptional consequences of OSA on adipocytes by utilizing pathway-focused analyses. Methods: Patients scheduled to undergo ventral hernia repair surgery were recruited to wear a portable home sleep monitor for two nights prior to surgery. Visceral fat biopsies were obtained intra-operatively. RNA was extracted and whole-genome expression profiling was performed. Gene Set Enrichment Analysis (GSEA) was used to identify curated gene sets that were differentially enriched in OSA subjects. Network analysis was applied to a select set of highly enriched pathways. Results: 10 patients with OSA and 8 control subjects were recruited. There were no differences in age, gender, body mass index between the two groups, but the OSA subjects had a significantly higher respiratory disturbance index (19.2 vs. 0.6, P-value 0.05) and worse hypoxemia (minimum oxygen saturation 79.7% vs. 87.8%, P-value < 0.001). GSEA identified a number of gene sets up-regulated in adipose tissue of OSA patients including the pro-inflammatory NF-κB pathway and the proteolytic ubiquitin/proteasome module. A critical metabolic pathway, the peroxisome proliferator-activated receptor (PPAR), was down-regulated in subjects with OSA. Network analysis linked members of these modules together and identified regulatory hubs. Conclusions: OSA is associated with alterations in visceral fat gene expression. Pathway-based network analysis highlighted perturbations in several key pathways whose coordinated interactions may contribute to the metabolic dysregulation observed in this complex disorder.
2012-09-01 | GSE38792 | GEO
Project description:Sleep apnea is a prevalent respiratory disease in which episodic cessation of breathing causes intermittent hypoxia. Patients with sleep apnea and rodents exposed to intermittent hypoxia exhibit hypertension. The carotid body senses changes in blood O2 concentrations, and an enhanced carotid body chemosensory reflex contributes to hypertension in sleep apnea patients. A rodent model of intermittent hypoxia that mimics blood O2 saturation profiles of patients with sleep apnea has shown that increased generation of reactive oxygen species (ROS) in the carotid body enhances the chemosensory reflex and triggers hypertension. CO generated by heme oxygenase-2 (HO-2) induces a signaling pathway that inhibits hydrogen sulfide (H2S) production by cystathionine γ-lyase (CSE), leading to suppression of carotid body activity. We found that ROS inhibited CO generation by HO-2 in the carotid body and liver through a mechanism that required Cys(265) in the heme regulatory motif of heterologously expressed HO-2. We showed that ROS induced by intermittent hypoxia inhibited CO production and increased H2S concentrations in the carotid body, which stimulated its neural activity. In rodents, blockade of H2S synthesis by CSE, by either pharmacologic or genetic approaches, inhibited carotid body activation and hypertension induced by intermittent hypoxia. Thus, our results indicate that oxidant-induced inactivation of HO-2, which leads to increased CSE-dependent H2S production in the carotid body, is a critical trigger of hypertension in rodents exposed to intermittent hypoxia.
| S-EPMC5505181 | biostudies-literature
Project description:Humans have five RecQ helicases, whereas simpler organisms have only one. Little is known about whether and how these RecQ helicases co-operate and/or complement each other in response to cellular stress. Here we show that RECQL5 associates longer at laser-induced DNA double-strand breaks in the absence of Werner syndrome (WRN) protein, and that it interacts physically and functionally with WRN both in vivo and in vitro. RECQL5 co-operates with WRN on synthetic stalled replication fork-like structures and stimulates its helicase activity on DNA fork duplexes. Both RECQL5 and WRN re-localize from the nucleolus into the nucleus after replicative stress and significantly associate with each other during S-phase. Further, we show that RECQL5 is essential for cell survival in the absence of WRN. Loss of both RECQL5 and WRN severely compromises DNA replication, accumulates genomic instability and ultimately leads to cell death. Collectively, our results indicate that RECQL5 plays both co-operative and complementary roles with WRN. This is an early demonstration of a significant functional interplay and a novel synthetic lethal interaction among the human RecQ helicases.
| S-EPMC3553943 | biostudies-literature
Project description:Humans have five RecQ helicases, whereas simpler organisms have only one. Little is known about whether and how these RecQ helicases co-operate and/or complement each other in response to cellular stress. Here we show that RECQL5 associates longer at laser-induced DNA double-strand breaks in the absence of Werner syndrome (WRN) protein, and that it interacts physically and functionally with WRN both in vivo and in vitro. RECQL5 co-operates with WRN on synthetic stalled replication fork-like structures and stimulates its helicase activity on DNA fork duplexes. Both RECQL5 and WRN re-localize from the nucleolus into the nucleus after replicative stress and significantly associate with each other during S-phase. Further, we show that RECQL5 is essential for cell survival in the absence of WRN. Loss of both RECQL5 and WRN severely compromises DNA replication, accumulates genomic instability and ultimately leads to cell death. Collectively, our results indicate that RECQL5 plays both co-operative and complementary roles with WRN. This is an early demonstration of a significant functional interplay and a novel synthetic lethal interaction among the human RecQ helicases.
| S-EPMC5415880 | biostudies-literature
Project description:Study objectivesThe aim of the study was to investigate the effect of ambient temperature on sleep, sleep apnea, and morning alertness in patients with obstructive sleep apnea.DesignRandomized controlled trial.SettingIn-hospital investigations.ParticipantsForty patients with obstructive sleep apnea naïve to treatment, with an apnea-hypopnea index of 10-30.InterventionsThree different nights in room temperatures of 16°C, 20°C, and 24°C.MeasurementsOvernight polysomnography and Karolinska Sleepiness Scale.ResultsThe obstructive apnea-hypopnea index was 30 ± 17 at 16°C room temperature, 28 ± 17 at 20°C, and 24 ± 18 at 24°C. The obstructive apnea-hypopnea index was higher at 16°C room temperature versus 24°C (P = 0.001) and at 20°C room temperature versus 24°C (P = 0.033). Total sleep time was a mean of 30 min longer (P = 0.009), mean sleep efficiency was higher (77 ± 11% versus 71 ± 13% respectively, P = 0.012), and the patients were significantly more alert according to the Karolinska Sleepiness Scale (P < 0.028) in the morning at 16°C room temperature versus 24°C. The amount of sleep in different sleep stages was not affected by room temperature.ConclusionsUntreated patients with obstructive sleep apnea sleep longer, have better sleep efficiency, and are more alert in the morning after a night's sleep at 16°C room temperature compared with 24°C, but obstructive sleep apnea is more severe at 16°C and 20°C compared with 24°C.Clinical trial informationThis study is registered in ClinicalTrials.gov number NCT00544752.
| S-EPMC3296793 | biostudies-literature
Project description:BackgroundObstructive sleep apnea (OSA) and insomnia are commonly co-occurring conditions that amplify morbidity and complicates the management of affected patients. Unfortunately, previous research provides limited guidance as to what constitutes the best and most practical management approach for this comorbid patient group. Some preliminary studies show that when cognitive behavioral insomnia therapy (CBT-I) is combined with standard OSA therapies for these patients, outcomes are improved. However, the dearth of trained providers capable of delivering CBT-I has long served as a pragmatic barrier to the widespread use of this therapy in clinical practice. The emergence of sophisticated online CBT-I (OCBT-I) programs could improve access, showing promising reductions in insomnia severity. Given its putative scalability and apparent efficacy, some have argued OCBT-I should represent a 1st-stage intervention in a broader stepped care model that allocates more intensive and less assessable therapist-delivered CBT-I (TCBT-I) only to those who show an inadequate response to lower intensity OCBT-I. However, the efficacy of OCBT-I as a 1st-stage therapy within a broader stepped care management strategy for insomnia comorbid with OSA has yet to be tested with comorbid OSA/insomnia patients.Methods/designThis dual-site randomized clinical trial will use a Sequential Multiple Assignment Randomized Trial (SMART) design to test a stepped care model relative to standard positive airway pressure (PAP) therapy and determine if (1) augmentation of PAP therapy with OCBT-I improves short-term outcomes of comorbid OSA/insomnia and (2) providing a higher intensity 2nd-stage CBT-I to patients who show sub-optimal short-term outcomes with OCBT-I+PAP improves short and longer-term outcomes. After completing baseline assessment, the comorbid OSA/insomnia patients enrolled will be randomized to a 1st-stage therapy that includes usual care PAP + OCBT-I or UC (usual care PAP + sleep hygiene education). Insomnia will be reassessed after 8 weeks. OCBT-I recipients who meet "remission" criteria (defined as an Insomnia Severity Index score < 10) will continue PAP but will not be offered any additional insomnia intervention and will complete study outcome measures again after an additional 8 weeks and at 3 and 6 month follow-ups. OCBT-I recipients classified as "unremitted" after 8 weeks of treatment will be re-randomized to a 2nd-stage treatment consisting of continued, extended access to OCBT-I or a switch to TCBT-I. Those receiving the 2nd-stage intervention as well as the UC group will be reassessed after another 8 weeks and at 3- and 6-month follow-up time points. The primary outcome will be insomnia remission. Secondary outcomes will include subjective and objective sleep data, including sleep time, sleep efficiency, fatigue ratings, PAP adherence, sleepiness ratings, sleep/wake functioning ratings, and objective daytime alertness.DiscussionThis study will provide new information about optimal interventions for patients with comorbid OSA and insomnia to inform future clinical decision-making processes.Trial registrationClinicalTrials.gov, NCT03109210 , registered on April 12, 2017, prospectively registered.
| S-EPMC9509569 | biostudies-literature
Project description:Scientific investigations in the past few decades have supported the important role of sleep in various domains of health. Sleep apnea is a highly prevalent yet underdiagnosed sleep disorder representing a valid cardiovascular risk factor, particularly for hypertension. While several studies have demonstrated the benefits of sleep apnea treatment on subclinical cardiovascular measures, there is a paucity of studies proving reduction of cardiovascular events and mortality. Sufficient and high-quality sleep is also important in the maintenance of cardiovascular health. Future investigations should focus on improving identification of patients at greatest risk of adverse cardiovascular s sequalae of sleep apnea and testing the therapeutic benefit of sleep apnea treatment in this vulnerable group.
| S-EPMC7375706 | biostudies-literature