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Study objectives Obstructive sleep apnea hypopnea syndrome (OSAHS) is a sleep-related breathing disorder, characterized by excessive daytime sleepiness (EDS), paralleled by intermittent collapse of the upper airway. EDS may be the symptom of OSAHS per se but may also be due to the alteration of central circadian regulation. Irisin is a putative myokine and has been shown to induce BDNF expression in several sites of the brain. BDNF is a key factor regulating photic entrainment and consequent circadian alignment and adaptation to the environment. Therefore, we hypothesized that EDS accompanying OSAHS is reflected by alteration of irisin/BDNF axis. Methods Case history, routine laboratory parameters, serum irisin and BDNF levels, polysomnographic measures and Epworth Sleepiness Scale questionnaire (ESS) were performed in a cohort of OSAHS patients (n = 69). Simple and then multiple linear regression was used to evaluate data. Results We found that EDS reflected by the ESS is associated with higher serum irisin and BDNF levels; β: 1.53; CI: 0.35, 6.15; p = 0.012 and β: 0.014; CI: 0.0.005, 0.023; p = 0.02, respectively. Furthermore, influence of irisin and BDNF was significant even if the model accounted for their interaction (p = 0.006 for the terms serum irisin, serum BDNF and their interaction). Furthermore, a concentration-dependent effect of both serum irisin and BDNF was evidenced with respect to their influence on the ESS. Conclusions These results suggest that the irisin-BDNF axis influences subjective daytime sleepiness in OSAS patients reflected by the ESS. These results further imply the possible disruption of the circadian regulation in OSAHS. Future interventional studies are needed to confirm this observation.

Mixed connective tissue disease (MCTD) is a systemic inflammatory autoimmune disease. The connection between inflammatory measures and atherosclerosis in MCTD has not been described. Paraoxonase (PON) is known to have an antioxidant function. We evaluated lipid profiles and PON activity in patients with MCTD.Thirty-seven patients with MCTD were enrolled. Patients had taken no antihyperlipidemic drugs in the past 2 months. Thirty healthy individuals served as controls. The mean age of patients was 51.2 +/- 9.5 years; disease duration was 11.0 +/- 7.2 years. PON activity was determined with spectrophotometry, von Willebrand factor (vWF) antigen was investigated with the immunoturbidimetry method, and thrombomodulin and antiendothelial cell antibody (AECA) measurements were carried out by ELISA.PON activity in patients with MCTD was significantly lower than in the controls (patients 118.5 +/- 64.6 U/l, controls 188.0 +/- 77.6; p0.001). Arylesterase activity was significantly reduced in patients (p0.001). Reduction of PON activity showed a close correlation with the age of the patients, duration of the disease, and vascular events (eye, cardiac, cerebral). There was a close association between the low PON activity and endothelial cell activation markers (thrombomodulin, vWF, AECA).Our results indicate that in patients with MCTD there is an increased risk for atherosclerosis. In the development of atherosclerosis, besides the elevated levels of cholesterol and triglyceride, reduced PON concentrations and PON activity may play a crucial role.

The aim of this study was to investigate the effect of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor fluvastatin (Flu) on angiotensin II (AII)–stimulated neutrophils of patients with hypercholesterolemia. Results suggest that a 6-week-long Flu administration completely counteracted the AII-induced increase in superoxide anion and leukotriene C4 production of the neutrophils of patients with hypercholesterolemia. However, the failure of signal processing through pertussis toxin–sensitive G protein, the increase in [Ca2+]i in membrane-bound protein kinase C activity, and the increase in neutrophil-bound cholesterol content were only partially restored by Flu. In addition, Flu had no effect on the increased membrane rigidity of the neutrophils of patients with hypercholesterolemia. To sum it up, Flu administration had a beneficial effect on AII-triggered reactive oxygen species generation; it resulted in partial restoration of signaling processes and of membrane composition, but membrane fluidity remained unchanged.