Circadian rhythms in blood pressure, heart rate, hormones, and on polysomnographic parameters in severe obstructive sleep apnea syndrome patients: effect of continuous positive airway pressure.

INTRODUCTION: Seventeen male patients with severe obstructive sleep apnea syndrome (OSAS; apnea-hypopnea index>30/h) were monitored by polysomnography in the sleep lab before and after about 8 weeks of continuous positive airway pressure (CPAP). Twelve of the patients were hypertensive, but treated by antihypertensive drugs. The circadian rhythms in blood pressure (BP) and heart rate were determined by ambulatory BP monitoring and motor activity was monitored by a motion logger. As the sympathetic tone is reported to be increased in sleep apnea, the circadian rhythm in plasma norepinephrine was studied in parallel and as a marker rhythm of the biological clock plasma melatonin was determined around the clock by radioimmunoassay. RESULTS: Level and rhythm in BP and heart rate were not significantly affected by CPAP in this group of patients, but the number of dippers increased after CPAP intervention. The high 24 h plasma values of norepinephrine were lowered by CPAP therapy. In contrast, melatonin values were disturbed in OSAS patients with a loss in nocturnal increase; this pattern was not corrected by CPAP. Sleep functions (deep sleep, slow wave sleep, rapid eye movement sleep, arousal index, apnea-hypopnea index, desaturation index) were disturbed in OSAS patients as monitored by polysomnography and were significantly improved by CPAP therapy. CONCLUSION: The study indicates that BP-controlled hypertensive patients with OSAS can additionally benefit from CPAP therapy by increasing the number of dippers. This treatment significantly improved sleep functions and OSAS symptoms. In addition, arousal movements at night were also reduced and the high sympathetic tone during early morning hours was also decreased. However, there is still an indication of a disturbed function of the biological clock as the loss in the rhythm in plasma melatonin was not corrected by CPAP.

Novel stabilin-1 interacting chitinase-like protein (SI-CLP) is up-regulated in alternatively activated macrophages and secreted via lysosomal pathway.

Mammalian Glyco_18-domain-containing proteins include catalytically active chitinases and chitinase-like proteins with cytokine activity involved in host defense and Th2-type inflammatory reactions. Here, we describe a novel human Glyco_18-domain-containing protein, SI-CLP, as an interacting partner of the endocytic/sorting receptor stabilin-1. Similarly to the chitinase-like cytokines YKL-39, YKL-40, and YM1/2, SI-CLP lacks a chitin-binding domain and catalytic amino acids. Using a novel mAb 1C11, we demonstrated that SI-CLP is sorted into late endosomes and secretory lysosomes in human alternatively activated macrophages. The direct interaction of SI-CLP with stabilin-1, their colocalization in the trans-Golgi network, and the reduced sorting of SI-CLP into lysosomes in macrophages treated with stabilin-1 siRNA suggest that stabilin-1 is involved in intracellular sorting of SI-CLP. Expression of SI-CLP in macrophages was strongly up-regulated by the Th2 cytokine IL-4 and by dexamethasone. This effect was suppressed by IFNgamma but not affected by IL-10. In contrast, expression of YKL-40 was induced by IFNgamma and suppressed by dexamethasone. Macrophages treated with IL-4 secreted SI-CLP, while costimulation with dexamethasone blocked secretion and resulted in intracellular accumulation of SI-CLP. The 1C11 mAb detected SI-CLP in human bronchoalveolar lavage and peripheral-blood leukocytes (PBLs), and can be used to analyze the role of SI-CLP in human disorders.