Circadian Rhythm of Salivary Cortisol in Obese Adolescents With and Without Apnea: A Pilot Study.

Background and Objective: Obstructive sleep apnea (OSA) and obesity are associated with stress system activation involving the hypothalamic-pituitary-adrenal (HPA) axis in adults, but these effects in childhood and adolescence remain unclear. We examined diurnal salivary cortisol as a measurement of the HPA axis function in obese adolescents with and without OSA and the relationships between cortisol levels, body weight, and parameters of polysomnography (PSG). Methods: After PSG, saliva samples were collected from obese participants (with and without OSA) and lean participants four times over a 24-h period, namely, at 7:00 h (m-sCort), 13:00 h (a-sCort), 19:00 h (e-sCort), and 23:00 h (n-sCort). An enzyme-linked immunosorbent assay (ELISA) was used to measure salivary cortisol levels. The mean values of cortisol levels and fixed-time point diurnal cortisol slope (DCS) were calculated and compared among the three study groups. Correlations between parameters were analyzed using Spearman's correlation coefficients. Results: Obese OSA participants had significantly higher e-sCort and n-sCort levels than both obese non-OSA participants and lean controls. However, m-sCort and a-sCort in these patients had a pronounced upward trend. M-sCort was significantly correlated with both the lowest oxygen saturation (SpO2) and time with SpO2 <90%. Moreover, in the obese OSA group, DCS was significantly flatter than in the other two groups. The a-sCort in obese non-OSA participants was significantly higher than that in the lean control group and, surprisingly, was positively correlated with the apnea/hypopnea index. Additionally, m-sCort was related to body weight. Conclusion: This study provided further evidence for alterations in diurnal cortisol production in obese adolescents, which may indicate a chronically stressed HPA axis. However, there were significant differences in salivary cortisol parameters between participants with and without OSA. Furthermore, patients with OSA had more associations between time-point cortisol levels and OSA-related indices. Nonetheless, this research is a pilot study, and further investigations are necessary.

Sleep Apnea and Serum Serotonin Level Pre- and Post-PAP Therapy: A Preliminary Study.

INTRODUCTION: The high prevalence of obstructive sleep apnea (OSA), which impairs quality of life for numerous patients and leads to various OSA complications, has contributed to the continued interest in this disorder. The role of serotonin (5-HT) in many physiological processes, studies on its connection with the circadian system, and relationship to changes in sleep architecture are insufficient to assess the interaction of this neurotransmitter with nocturnal hypoxia. The aim of this study was to determine changes in sleep patterns and serum serotonin levels before and after positive airway pressure (PAP) therapy in patients with OSA. METHODS: The study involved 30 OSA patients (27 men and 3 women) who were treated with PAP for 3 months. Polysomnography using the GRASS TELEFACTOR (USA) and blood collection were conducted before and after PAP courses. Determination of serum serotonin was performed by high-performance liquid chromatography (HPLC). PAP therapy was performed using an automatic Prisma 20A (Germany) continuous positive airway pressure (CPAP) device. RESULTS: The use of PAP for 3 months revealed a significant improvement as measured by sleep data and serotonin levels (before: apnea index [AI] 17.2 eV/h, after: 2.4 eV/h p = 0.001; SpO2 < 90% - 45.7 min vs. 6.2 min p = 0.001; serotonin 20.3 ng/mL vs. 26.03 ng/mL p = 0.036]. CONCLUSION: Our results demonstrate an improvement in sleep patterns. There was an increase in serum serotonin levels in OSA patients following PAP therapy, which could be an effect of intermittent hypoxia decline, and could be used as criteria for the effectiveness of PAP and an improvement in sleep quality.

CLOCK 3111TT Genotype Is Associated with Increased Total Cholesterol and Low-Density Lipoprotein Levels in Menopausal Women with a Body Mass Index of at Least 25 kg/m2.

Lipid profile comparative analysis was performed to reveal the interdependence of lipids with Circadian locomoter output cycles protein kaput (CLOCK) 3111T/C gene polymorphism in menopausal women with/without a body mass index (BMI) of ≥25 kg/m2. Methods: A total of 193 female volunteers aged 45 to 60 years were divided into two groups: Those with BMI < 25 kg/m2 (control) and those with BMI ≥ 25 kg/m2. Each group was then divided into two subgroups: Those with the CLOCK TT-genotype and those with the CLOCK TC-, CC-genotypes. Lipid metabolism parameters were determined by the enzymatic method. Single-nucleotide polymorphisms (SNPs) were detected via polymerase chain reaction-restriction fragment length polymorphism technology. Results: There were no differences in CLOCK 3111T/C genotypes or allele frequency between the control and main groups. In addition, there were no differences in lipid profile parameters between women of the control group and different CLOCK 3111T/C genotypes. The total cholesterol (p = 0.041) and low-density lipoprotein cholesterol (p = 0.036) levels were higher in the subgroup of women with a BMI ≥ 25 kg/m2 and CLOCK TT-genotype as compared to the subgroup with a BMI ≥ 25 kg/m2 and minor allele 3111C. Conclusions: SNP 3111T/C of the CLOCK gene is not associated with BMI however, data suggest that the minor allele of the CLOCK 3111T/C gene polymorphism may have a protective role in atherogenic lipid levels in women with a BMI greater than or equal to 25 kg/m2.

Lipid peroxidation depends on the clock 3111T/C gene polymorphism in menopausal women with Insomnia.

A comparative analysis of lipid peroxidation processes and antioxidant defense system in Caucasian menopausal women with/without insomnia depending on the genotype of Clock 3111T/C gene polymorphism was performed. Two hundred and fourteen Caucasian menopausal women divided into control (without insomnia) and main group (with insomnia) were examined. Lipid peroxidation (conjugated dienes, thiobarbituric acid reactants) and antioxidant defense system parameters (?-tocopherol, retinol, reduced and oxidized glutathione, glutathione S-transferase, glutathione peroxidase, glutathione reductase, superoxide dismutase) were determined by spectrofluorophotometer and immunoenzymometric methods. Patients with insomnia carriers of the TT-genotype had a significantly higher thiobarbituric acid reactants level and glutathione peroxidase activity as compared to group with insomnia carriers of the minor 3111C-allele (p < .05). A comparative analysis of the parameters in the women of the main and control groups showed higher conjugated dienes, thiobarbituric acid reactants levels and lower retinol, reduced glutathione levels, glutathione reductase activity in women with insomnia carriers of the TT-genotype (p < .05). The carriers of the minor allele with insomnia had a higher conjugated dienes levels and lower glutathione peroxidase activity as compared to control (p < .05). Thus, lipid peroxidation and antioxidant system parameters in Caucasian menopausal women with insomnia depend on the Clock 3111T/C gene polymorphism.

Association of the melatonin circadian rhythms with clock 3111T/C gene polymorphism in Caucasian and Asian menopausal women with insomnia.

A comparative analysis of melatonin circadian rhythms in Caucasian (incoming population) and Asian (indigenous population) menopausal women with/without sleep disorders depending on the genotype of Clock 3111T/C gene polymorphism was realized.The melatonin level in the saliva was determined four times a day (6:00-7:00, 12:00-13:00, 18:00-19:00, 23:00-00:00 h). The Caucasian women-carriers of the TT-genotype with insomnia as compared to control group-had a higher morning melatonin level and a lower night melatonin level. The Asian women with TT-genotype and insomnia had a lower levels of melatonin as compared to control at daytime, evening and night. A significantly higher melatonin level in the early morning hours was detected in the Caucasian women-carriers of the TT-genotype with insomnia as compared to group womencarriers of the minor 3111C-allele. There were no statistically significant differences in the circadian rhythms of melatonin in the Asian women depending on the genotype of the Clock 3111T/C polymorphism. An assumption with respect to the protective role of the minor allele 3111C in the development of insomnia associated with the displacement of melatonin circadian rhythms in the representatives of the incoming population was made.

Obstructive Sleep Apnea and Hypertension in Adolescents: Effect on Neurobehavioral and Cognitive Functioning.

Background. There are limited published data in regard to the relationship between obstructive sleep apnea (OSA) and hypertension and neurobehavioral and mental status in adolescence. The aim of our study was to evaluate neurobehavioral patterns and cognitive functions in adolescents with hypertension according to absence or presence of OSA. Methods. This was a retrospective cohort study completed at the Scientific Center for Family Health and Human Reproduction Problems. Participants included adolescents aged 14-17 years and referred for 24-hour ambulance blood pressure monitoring (ABPM) and polysomnographic (PSG) studies between 2007 and 2009, inclusive. Results. 18 hypertensive OSA (the 1st group) and 20 hypertensive non-OSA adolescents (the 2nd group) were included in the study. Significant changes of neurobehavioral functioning in OSA patients were shown. Cognitive abilities also were impaired. Verbal and visual memory indexes and attention index were 2.1 and 2.2 times lower, accordingly, in the 1st group than in the 2nd group (P < 0.05). Speech index was significantly 2.8 times lower in OSA patients than in non-OSA patients (P < 0.05). In hypertensive OSA adolescents more significant Spearman correlations between classic sleep parameters and cognitive measures were found compared to patients without OSA. Conclusions. These results suggest that OSA is closely associated with neurobehavioral and cognitive functioning in hypertensive adolescents.

Antioxidant status in peri- and postmenopausal women.

Menopause is a risk factor for oxidative stress. The aim of our study is to assess antioxidant system parameters (α-tocopherol, retinol, reduced glutathione, total antioxidant activity) in peri- and postmenopausal women. The antioxidant defense activity by estimation of total antioxidant activity, α-tocopherol, retinol, oxidized and reduced glutathione levels was studied in women of reproductive age (n=37), in perimenopausal (n=41) and postmenopausal women (n=41). In our study we used spectrofluorofotometer methods. Statistical analysis was performed by non-parametric tests with p<0.05 as the level of significance. The results of our study showed the decrease of α-tocopherol and retinol concentrations and the increase of oxidized glutathione level in blood serum both in perimenopausal and postmenopausal women, the total antioxidant activity of blood serum was decreased in postmenopausal women only. The results of our study demonstrate that decrease of antioxidant defense system resources depends on the menopausal phase.

Sleep-disordered breathing in 15-year-old boy with arterial hypertension.

Obstructive sleep apnea/hypopnea syndrome (OSA/HS) is the basis of the spectrum of sleep-disordered breathing (SDB) and is a condition characterized by the presence of snoring, repetitive partial upper airway obstruction (hypopnea) and/or intermittent complete obstruction (apnea), long enough to cause reduce the level of oxygen in the blood (desaturation), fragmented sleep and excessive daytime sleepiness. It is known that OSA/HS in the middle and older age predisposes to arterial hypertension (AH). We discuss a case of 15-year-old boy with AH and OSA/HS. He was treated on nasal continuous positive pressure in the upper airway (nasal CPAP) with good results.