Tumor Necrosis Factor-alpha Expression in Uvular Tissues Differs Between Snorers and Apneic Patients
ABSTRACT Inflammatory changes such as subepithelial edema and excessive inflammatory cell infiltration have been observed in uvular tissues of obstructive sleep apnea (OSA) subjects. The levels of proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha and interleukin-6 are elevated in the serum of apneic patients and have been proposed as mediators of muscle weakness. TNF-alpha has been shown to affect diaphragm contractility in mice and rabbit in vivo.
To assess total and compartmental TNF-alpha expression in uvular tissues of apneic and nonapneic patients.
Uvular tissues were collected from 14 snorers without sleep disorders breathing, 14 subjects with OSA (OSA 1 group) whose body mass index (BMI) was similar to that of snorers, and 12 additional obese OSA subjects (OSA 2 group) who underwent an uvulopalatopharyngoplasty. Sections were examined using immunohistochemistry and Western blot analysis. TNF-alpha expression was evaluated in the musculus uvulae (MU), epithelial layer, and perimuscular tissues from proximal uvular sections.
TNF-alpha was more highly expressed in whole uvular protein extracts of apneic groups than in snorers ([mean +/- SEM] snorers, 100.5 +/- 3.0%; OSA 1 group, 127.1 +/- 6.9%; OSA 2 group, 140.7 +/- 11.0%; p = 0.01). In the muscular area, TNF-alpha levels were higher in the more obese OSA subjects than in the other two groups (snorers, 100.3 +/- 3%; OSA 1 group, 107.4 +/- 0.7%; OSA 2 group, 124.1 +/- 4.2%; p = 0.007). In the muscular area, TNF-alpha was correlated with BMI, but no relationship was found with the apnea-hypopnea index.
We conclude that MU is the major TNF-alpha source in uvular tissue and that TNF-alpha is more highly expressed in the heaviest OSA patients compared to less obese OSA patients and nonapneic snorers.
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ABSTRACT: A general model of the multiple-winding coupled inductor is described, in which all parameters can be directly measured. The magnetics and the resulting cross-regulation models are employed in a tutorial explanation of the mechanisms by which leakage inductances and effective turns ratios affect cross regulation and discontinuous conduction mode boundaries in a multiple-output converter with arbitrary number of outputs. Analytical results are found for the discontinuous mode boundaries and for the steady-state characteristics when one of the outputs operates in discontinuous conduction mode. Three basic approaches to coupled-inductor design are compared: near-ideal coupling, practical moderate coupling, and the zero-ripple approach. It is shown that the best cross regulation can be obtained via the zero-ripple approach with relatively loose coupling in applications where there is at least one output whose load current variations are relatively small so that all windings can always operate in continuous conduction mode. The conclusions are supported by experimental resultsIEEE Transactions on Power Electronics 08/2000; DOI:10.1109/63.849030 · 5.73 Impact Factor
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ABSTRACT: Recurrent infective tonsillitis (RI) and obstructive sleep apnea (OSA) are the major indications for adenotonsillectomy (T&A) in children. However, little is known on the determinants of lymphadenoid tissue proliferation in the pediatric upper airway. To develop an in vitro culture system allowing for assessment of tonsillar or adenoidal proliferation under basal or stimulated conditions. Tonsils surgically removed from pediatric patients with obstructive sleep apnea and recurrent tonsillitis during T&A, were dissociated using standard methods. Whole cell tonsillar cultures were either maintained in normal medium or stimulated with lipopolysaccharide (25 microg/mL) and concanavalin A (10 microg/mL) for 24 hours (stimulated conditions [STIM]). Cellular proliferation was evaluated by [3H]thymidine incorporation. In parallel, supernatants were collected after 48 hours, and concentration of cytokines was measured using standard enzyme-linked immunosorbent assay procedures. Basal proliferative rates were increased in the OSA group (305.2 +/- 40.6 cpm; n = 31) compared to RI group (232.8 +/- 31.9 cpm; n = 26; P < .001). No significant differences in proliferative rates emerged after STIM between OSA and RI. Furthermore, basal TNF-alpha, IL-6, and IL-8 concentrations in the supernatant were increased in OSA-derived cultures compared to RI, but IL-8 was higher after STIM in RI, while IL-6 remained increased in OSA. The proliferative rates and concentrations of inflammatory mediators in tonsillar cell cultures from children with OSA and RI suggest that lymphadenoid tissue proliferation in these two conditions may be regulated by different mechanisms. This novel method may allow for future development of specific therapeutic interventions aimed at curtailing and reversing tonsillar and adenoidal hypertrophy in children in a disease-specific manner.The Laryngoscope 05/2009; 119(5):1005-10. DOI:10.1002/lary.20147 · 2.03 Impact Factor
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ABSTRACT: Normalisation of eosinophil counts in sputum of asthmatic patients reduces eosinophilic exacerbations. However, the effect of this strategy on airway remodelling remains to be determined. We compared bronchial inflammation and collagen deposition after 2 yrs of treatment guided by either sputum eosinophils (sputum strategy, SS) or by clinical criteria (clinical strategy, CS). As a pilot study, 20 mild asthmatic patients were randomly assigned to CS or SS strategies. Bronchial biopsies were obtained when minimum treatment needed to maintain control was identified and this was continued for 2 yrs. Biopsies were immunostained for inflammatory cells, mucin 5A (MUC5A) and collagen. The mean dose of inhaled corticosteroids at the start and end of the study was similar in both SS and CS groups. Forced expiratory volume in 1 s increased in both groups at the study end. In SS, mucosal lymphocyte and eosinophil counts, but not neutrophils, were reduced at the end of the study. In CS, only activated eosinophil and neutrophil counts decreased. MUC5A staining decreased in SS but not CS. No change in collagen deposition underneath the basement membrane was observed in either strategy. Treatment strategies that normalise sputum eosinophils also reduce mucosal inflammatory cells and MUC5A expression, but do not change subepithelial collagen deposition in mild to moderate asthma.European Respiratory Journal 08/2009; 35(1):48-53. DOI:10.1183/09031936.00130008 · 7.13 Impact Factor