Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0037315 (sleep apnea)
 8,000 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In children with recurrent tonsillitis there may be persistent antigen deposition in tonsil tissue. even between exacerbations. If so, upregulation of immunocompetent cells should occur continuously, in contrast to tonsil tissue from children with tonsillar hypertrophy. The cytokine pattern was studied in cell suspensions prepared from tonsils obtained from 12 children undergoing tonsillectomy. The study group comprised 6 children with recurrent tonsillitis and 6 who had a history of tonsillar hypertrophy causing sleep apnea. Cytokine-producing cells (IL-1alpha, IL-1beta, TNFalpha, IL-6, IL-8, IL-2, IFNgamma, TNFbeta, IL-10 and IL-4) were characterized at the single-cell level by use of cytokine-specific monoclonal antibodies and indirect immunofluorescence technique. A constitutive production of IL-1alpha, IL-1beta, TNFalpha, and IL-8 was found in both groups (10-300/10(5) cells). However, the frequency of spontaneous IL-2, IFNgamma, TNFalpha, IL-6 and IL-10 was consistently low (10 +/- 10 cells) in both groups. Following restimulation by T-cell receptor ligation, using immobilized anti-CD3 mAb, with concentrations chosen so that it did not activate resting cells, increased frequencies of TNFalpha, IL-6, IL-8, IL-2, IFNgamma, IL-4 and 1L-10 synthesizing cells were induced in the recurrent tonsillitis group. Significantly higher incidences of IL-1beta, IL-6 and IL-2 producing cells were found in the recurrent tonsillitis group (60-200/10(5) cells, p <0.05). Microbiological evaluation in the tonsil tissue could not reveal tiny differences between the studied groups regarding bacterial or viral pathogens. However, this does not exclude persistent increased intracellular deposition of microbial antigens as a possible explanation for the elevated incidence of IL-1beta, TNF-alpha, IL-6, IL-8, IL-2, IFNgamma, IL-10 and IL-4 expressing cells noticed in patients with recurrent tonsillitis.
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PMID:Upregulated local cytokine production in recurrent tonsillitis compared with tonsillar hypertrophy. 892 44

Its is well established that sleep apnea (SA) is a health problem of paramount importance because it disrupts sleep and quality of life and may induce serious neuroendocrine and cardiovascular complications. There is little doubt that chronic renal failure is an independent cause of SA. The hypothesis that SA may depend on the accumulation of endogenous opioids still remains to be tested. Cytokines, particularly TNF-alpha and IL-6 which are much elevated in end-stage renal disease (ESRD), may also be implicated in the pathogenesis of SA. Nocturnal hypoxemia is an independent predictor of cardiovascular events in ESRD and the prediction power of this parameter remains strong and substantially unmodified after statistical adjustment for established cardiovascular risk factors in the dialysis population. Left ventricular hypertrophy and dysautonomia appear to be most likely intermediate mechanisms mediating the adverse cardiovascular effects of SA in ESRD.
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PMID:Nocturnal hypoxemia: a neglected cardiovascular risk factor in end-stage renal disease? 1180 69

Sleep is an important component of mammalian homeostasis, vital for survival. Sleep disorders are common in the general population and are associated with significant medical, psychologic, and social disturbances. Sleep, in particular deep sleep, has an inhibitory influence on the HPA axis, whereas activation of the HPA axis or administration of glucocorticoids can lead to arousal and sleeplessness. Insomnia, the most common sleep disorder, is associated with a 24-hour increase of ACTH and cortisol secretion, consistent with a disorder of central nervous system hyperarousal. Sleepiness and fatigue are very prevalent in the general population, and recent studies have demonstrated that the proinflammatory cytokines IL-6 and/or TNF-alpha are elevated in disorders associated with excessive daytime sleepiness, such as sleep apnea, narcolepsy, and idiopathic hypersomnia. Sleep deprivation leads to sleepiness and daytime hypersecretion of IL-6. Combined, these findings suggest that the HPA axis stimulates arousal, while IL-6 and TNF-alpha are possible mediators of excessive daytime sleepiness in humans.
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PMID:Sleep, the hypothalamic-pituitary-adrenal axis, and cytokines: multiple interactions and disturbances in sleep disorders. 1205 86

Obstructive sleep apnoea (OSA) is a very prevalent disorder particularly amongst middle-aged, obese men, although its existence in women as well as in lean individuals is increasingly recognized. Despite the early recognition of the strong association between OSA and obesity, and OSA and cardiovascular problems, sleep apnoea has been treated as a 'local abnormality' of the respiratory track rather than as a 'systemic illness'. In 1997, we first reported that the pro-inflammatory cytokines interleukin (IL)-6 and tumour necrosis factor-alpha (TNF alpha) were elevated in patients with disorders of excessive daytime sleepiness (EDS) and proposed that these cytokines were mediators of daytime sleepiness. Also, we reported a positive correlation between IL-6 or TNF alpha plasma levels and the body mass index (BMI). In subsequent studies, we showed that IL-6, TNF alpha, leptin and insulin levels were elevated in sleep apnoea independently of obesity and that visceral fat, was the primary parameter linked with sleep apnoea. The association of OSA with insulin resistance and diabetes type 2 has been confirmed since then in several epidemiological and clinical studies. Furthermore, our findings that women with polycystic ovary syndrome (PCOS, a condition associated with hyperandrogenism and insulin resistance) were much more likely than controls to have sleep disordered breathing (SDB) and daytime sleepiness support the pathogenetic role of insulin resistance in OSA. Other findings that support the view that sleep apnoea and sleepiness may be manifestations of a serious metabolic disorder, namely the Metabolic or Visceral Obesity Syndrome, include: obesity without sleep apnoea is associated with daytime sleepiness; PCOS and diabetes type 2 are independently associated with EDS after controlling for SDB, obesity and age; and increased prevalence of sleep apnoea in postmenopausal women, with hormonal replacement therapy associated with a significantly reduced risk for OSA. In conclusion, accumulating evidence provides support to our model of the bi-directional, feedforward, pernicious association between sleep apnoea, sleepiness, inflammation and insulin resistance, all promoting atherosclerosis and cardiovascular disease.
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PMID:Metabolic disturbances in obesity versus sleep apnoea: the importance of visceral obesity and insulin resistance. 1282 41

Obesity is an epidemic disease that threatens to inundate health care resources by increasing the incidence of diabetes, heart disease, hypertension, and cancer. These effects of obesity result from two factors: the increased mass of adipose tissue and the increased secretion of pathogenetic products from enlarged fat cells. This concept of the pathogenesis of obesity as a disease allows an easy division of disadvantages of obesity into those produced by the mass of fat and those produced by the metabolic effects of fat cells. In the former category are the social disabilities resulting from the stigma associated with obesity, sleep apnea that results in part from increased parapharyngeal fat deposits, and osteoarthritis resulting from the wear and tear on joints from carrying an increased mass of fat. The second category includes the metabolic factors associated with distant effects of products released from enlarged fat cells. The insulin-resistant state that is so common in obesity probably reflects the effects of increased release of fatty acids from fat cells that are then stored in the liver or muscle. When the secretory capacity of the pancreas is overwhelmed by battling insulin resistance, diabetes develops. The strong association of increased fat, especially visceral fat, with diabetes makes this consequence particularly ominous for health care costs. The release of cytokines, particularly IL-6, from the fat cell may stimulate the proinflammatory state that characterizes obesity. The increased secretion of prothrombin activator inhibitor-1 from fat cells may play a role in the procoagulant state of obesity and, along with changes in endothelial function, may be responsible for the increased risk of cardiovascular disease and hypertension. For cancer, the production of estrogens by the enlarged stromal mass plays a role in the risk for breast cancer. Increased cytokine release may play a role in other forms of proliferative growth. The combined effect of these pathogenetic consequences of increased fat stores is an increased risk of shortened life expectancy.
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PMID:Medical consequences of obesity. 1518 Oct 27

The aim of the study was to investigate, whether the degree of metabolic risk factors for atherosclerotic complications in a very rare kind of obesity, the Multiple Symmetrical Lipomatosis, also known as the Launois-Bensaude Syndrome (LBS), are comparable or different from "simple" truncal obesity. 10 patients with LBS (Body mass index 34.4 +/- 1.8 kg/m(2), age: 62 +/- 3 yrs) were compared with 19 BMI - matched patients with "simple" truncal obesity and obstructive sleep apnoea syndrome (OSAS) and 20 BMI- matched patients with "simple" truncal obesity without OSAS. Markers of subclinical inflammation and thrombocyte activation (sCD62p = soluble p-selectin, highly sensitive C-Reactive protein = CRP, Interleukin-6 = IL-6, ICAM-1 = Intracellular Adhesion Molecule-1, Vascular Cell Adhesion Molecule = VCAM -1, leptin), as well as adiponectin and resistin were studied. The prevalence of atherogenic risk factors as hypertension (80%), type 2 diabetes (30%), OSAS (50%), smoking (30%) and alcohol abuse (80%) was high in the (obese) LBS group. The markers of subclinical inflammation and thrombocyte activation showed an indifferent picture with lower levels of circulating IL-6 and sCD62p, comparable CRP and higher ICAM-1 and VCAM-1 than in controls. Leptin and adiponectin were higher than in controls. However, the accumulation of "classic" cardiovascular risk factors in the LBS group was well reflected by the presence of symptomatic cardiovascular disease in 3 of the 10 LBS patients, putting LBS patients - if obese - at an atherosclerotic risk at least comparable to obese persons.
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PMID:Adiponectin, resistin and subclinical inflammation--the metabolic burden in Launois Bensaude Syndrome, a rare form of obesity. 1744 28

Clock genes regulate mammalian circadian rhythms, and dysfunction of clock genes can contribute to various disorders. To investigate whether obstructive sleep apnoea syndrome (OSAS) influences clock gene function, the present authors examined Period1 (Per1) mRNA expression in vitro and in vivo. In eight healthy subjects and eight OSAS patients, plasma noradrenaline, serum interleukin (IL)-6, high-sensitivity C-reactive protein (hsCRP) and Per1 mRNA expression in peripheral whole blood were measured. Expression of Per1 mRNA in cultured cells was examined under IL-6 or noradrenaline stimulation in vitro. After noradrenaline was administered to mice in vivo, Per1 mRNA expression in the brain was examined. The concentrations of serum IL-6, hsCRP and plasma noradrenaline were elevated in OSAS patients, but improved by continuous positive airway pressure (CPAP) therapy. Per1 mRNA expression in the peripheral blood significantly decreased at 02:00 h by CPAP in OSAS patients. Stimulation with IL-6 did not directly induce Per1 mRNA in vitro. Administration of noradrenaline induced Per1 mRNA in the cerebral cortex of mice in vivo. The current study revealed that obstructive sleep apnoea syndrome caused clock gene dysfunction, and continuous positive airway pressure helped to improve it. Sympathetic activation and elevation of the plasma noradrenaline concentration in obstructive sleep apnoea syndrome may be one of the factors involved in disorders of Period1 mRNA expression.
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PMID:Clock gene dysfunction in patients with obstructive sleep apnoea syndrome. 1859 31

There is increasing evidence that inflammation plays an important role in the development of cardiovascular complications in patients with obstructive sleep apnoea (OSA). No previous works have studied levels of soluble tumour necrosis factor-alpha receptor (sTNFR)-1 in patients with OSA. The aims of the present study were to examine serum levels of sTNFR-1 and the effect of nasal continuous positive airway pressure (CPAP) in patients with OSA. A prospective, randomised, placebo-controlled crossover study was performed. In total, 30 consecutive newly diagnosed OSA patients (apnoea/hypopnoea index 43.8+/-27.0 events x h(-1)) and 15 healthy obese patients were selected. Urinary levels of norepinephrine and epinephrine, as well as plasma sTNFR-1, tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and leukotriene (LT)B(4) levels were obtained at baseline and after 3 months of CPAP or sham CPAP. Nocturnal urinary levels of norepinephrine, epinephrine and sTNFR-1 (1,053+/-269 versus 820+/-166 pg x mL(-1)) were significantly higher in OSA patients. There were no significant differences in plasma levels of IL-6, LTB(4), or TNF-alpha between the two study groups. There were no significant differences in blood pressure, urinary catecholamine levels, or plasma IL-6, LTB(4) and TNF-alpha levels after both treatment modalities. However, after 3 months of effective CPAP usage, sTNFR-1 levels were significantly reduced (1,053+/-269 versus 899+/-254 pg x mL(-1)). Obstructive sleep apnoea patients have higher levels of soluble tumour necrosis factor-alpha receptor 1 than individuals without OSA; soluble tumour necrosis factor-alpha receptor 1 levels are lowered by continuous positive airway pressure therapy. These findings further corroborate a potential role of inflammation in the natural history of obstructive sleep apnoea.
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PMID:CPAP decreases plasma levels of soluble tumour necrosis factor-alpha receptor 1 in obstructive sleep apnoea. 1850 32

Intranasal corticosteroids (CS) are potentially useful interventions for children with obstructive sleep apnoea (OSA), and may reduce lymphadenoid tissue size in the upper airway. The present authors hypothesised that CS would reduce cellular proliferation and the production of pro-inflammatory cytokines in a tonsil/adenoid mixed-cell culture system. Dissociated tonsils or adenoids harvested intra-operatively from children with polysomnographically diagnosed OSA were cultured in control medium (CO) or after stimulation with lipopolysaccharide and concanavalin A (STIM), and incubated with dexamethasone (DEX; 10(-5)-10(-7) M), fluticasone (FLU; 10(-5)-10(-14) M) and budesonide (BUD; 10(-4)-10(-14) M). Proliferation and apoptosis were assessed, and supernatants were assayed for the cytokines tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-8. STIM increased tonsillar and adenoidal proliferation compared with CO (1,976+/-133 versus 404+/-69 counts min(-1); n = 54). DEX, FLU and BUD reduced cellular proliferation rates, and exhibited dose-dependent effects, with the potency being FLU>BUD>DEX (n = 25 per group). Conversely, CS increased cellular apoptosis (n = 20 per group). Furthermore, TNF-alpha, IL-8 and IL-6 concentrations in the supernatant were increased by STIM, and markedly reduced by all CS (n = 48 per group). Whole tissue cell cultures of adenoids and tonsils provide a useful approach for in vitro assessment of therapeutic efficacy of corticosteroids in the management of lymphadenoid hypertrophy that underlies obstructive sleep apnoea in children.
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PMID:Corticosteroids suppress in vitro tonsillar proliferation in children with obstructive sleep apnoea. 1904 10

Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea syndrome represent two of the most prevalent chronic respiratory disorders in clinical practice, and cardiovascular diseases represent a major comorbidity in each disorder. The two disorders coexist (overlap syndrome) in approximately 1% of adults but asymptomatic lower airway obstruction together with sleep-disordered breathing is more prevalent. Although obstructive sleep apnea syndrome has similar prevalence in COPD as the general population, and vice versa, factors such as body mass index and smoking influence relationships. Nocturnal oxygen desaturation develops in COPD, independent of apnea/hypopnea, and is more severe in the overlap syndrome, thus predisposing to pulmonary hypertension. Furthermore, upper airway flow limitation contributes to nocturnal desaturation in COPD without apnea/hypopnea. Evidence of systemic inflammation in COPD and sleep apnea, involving C-reactive protein and IL-6, in addition to nuclear factor-kappaB-dependent pathways involving tumor necrosis factor-alpha and IL-8, provides insight into potential basic interactions between both disorders. Furthermore, oxidative stress develops in each disorder, in addition to activation and/or dysfunction of circulating leukocytes. These findings are clinically relevant because systemic inflammation may contribute to the pathogenesis of cardiovascular diseases and the cell/molecular pathways involved are similar to those identified in COPD and sleep apnea. However, the pathophysiological and clinical significance of systemic inflammation in COPD and sleep apnea is not proven, and thus, studies of patients with the overlap syndrome should provide insight into the mechanisms of systemic inflammation in COPD and sleep apnea, in addition to potential relationships with cardiovascular disease.
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PMID:Chronic obstructive pulmonary disease and obstructive sleep apnea: overlaps in pathophysiology, systemic inflammation, and cardiovascular disease. 1962 78


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