The State of the LPO-AOD System and the Relative Length of Telomeric Repeats in the Chromosomes of Blood Leukocytes in Obstructive Sleep Apnea Syndrome.

We analyzed the relative length of telomeric repeats in peripheral blood leukocytes and indicators of oxidative stress in 32 men (mean age 51.2±3.1 years) with obstructive sleep apnea syndrome (OSAS). The control group consisted of volunteers without OSAS. The relative length of telomeres was determined in a DNA sample isolated from venous whole blood samples. The length of telomeric repeats of chromosomes was determined using quantitative real-time PCR (3 times for each DNA sample); albumin served as an internal control. The intensity of LPO processes and antioxidant protection was assessed by conventional spectrophotometric methods. It was found that in patients with OSAS, the relative length of telomeric repeats was lower by 48%, the levels of substrates and products of LPO were higher (double bonds and diene conjugates by 34 and 19%, respectively), and antioxidant protection indicators were lower (concentrations of fat-soluble vitamins α-tocopherol and retinol by 18 and 19.3%, respectively, total antioxidant activity by 32.9%) than in volunteers of the control group. Thus, we can conclude that the nucleotide sequences are reduced in patients with OSAS under conditions of intensified free radical oxidation.

Glutathione Component of Antioxidant Status in Menopausal Women with Insomnia.

The study involved 138 women aged 45-60 years in perimenopause (n=55) and postmenopause (n=83) with insomnia (main groups) and without it (control). The levels of reduced (GSH) and oxidized (GSSG) glutathione and glutathione peroxidase activity were determined in erythrocytes; activities of glutathione S-transferase and glutathione reductase were measured in blood serum. The differences with the control groups were found only in perimenopause: higher glutathione reductase activity and reduced GSSG level and GSH/GSSG ratio in women with insomnia (p<0.05). The results of the comparative analysis between the main groups showed lower glutathione reductase activity, increased GSSG level, and a decrease the GSH/GSSG ratio in the postmenopausal period compared with the perimenopause (p<0.05). These results can be used in choosing the tactics for complex therapy of insomnia in menopausal women to correct free radical homeostasis and prevention of oxidative stress.

Features of the EEG Pattern of Sleep Spindles and Its Diagnostic Significance in Ontogeny.

Analysis of the microstructure of sleep using extended EEG monitoring can provide deep understanding of the neuronal activity of the brain. Sleep spindles (SS) are one of the main EEG patterns occurring during the non-rapid eye movement sleep. SS reflect the process of synchronization and provide sleep initiation and maintenance by suppressing sensory information. SS are associated with a wide range of brain functions, such as memory and neuroplasticity, general intelligence and cognitive performance, which undergo various changes throughout the life. In this review we discuss the features of the formation and regression of SS in humans during ontogeny on the basis of published data of the last 5-6 years and fundamental results of previous studies at the Scientific Centre for Family Health and Human Reproduction Problems that formed the basis of the modern study of neurophysiological phenomena of the wakefulness and sleep. The search for diagnostic patterns and prognostic markers of the pathology of higher nervous activity remains a priority in fundamental studies and medical practice. Modern methods for studying sleep and its EEG patterns are the next step in understanding the neurophysiological aspects of the sleep-wake cycle. This will open prospects for predicting postnatal maturation, understanding the mechanisms of brain neuroplasticity in the "sleep-wakefulness" continuum, which is one of the tasks of modern somnology and neurophysiology.

8-Hydroxy-2'-Deoxyguanosine as an Oxidative Stress Marker in Insomnia.

We performed comparative analysis of 8-hydroxy-2'-deoxyguanosine in women in different climax stages with and without insomnia. The study involved 90 women aged 45 to 60 years divided into perimenopausal (n=30) and postmenopausal (n=60) groups. After questioning using special sleep questionnaires (Insomnia Severity Index, Epworth Sleepiness Scale, Munich Chronotype Questionnaire), the groups were divided into subgroups with insomnia and without it (control). 8-Hydroxy-2'-deoxyguanosine was assayed in blood serum by ELISA. The higher levels of 8-hydroxy-2'-deoxyguanosine in postmenopausal women with insomnia in comparison with the control and perimenopausal patients (p<0.05) attested to oxidative DNA damage in this cohort of patients.

Free Radical Oxidation of Lipids as an Indicator of the Effectiveness of CPAP Therapy in Apnea Syndrome.

The processes of free radical lipid oxidation were studied in 47 patients with moderate to severe obstructive sleep apnea syndrome before and after 1-month course of CPAP-therapy (continuous positive airway pressure). The control group consisted of 13 people without clinically confirmed apnea. The material for the study was serum, blood plasma, and erythrocyte hemolysate. The levels of LPO products and antioxidant defense were determined spectrophotometrically and spectrofluorometrically. The changes revealed in patients with obstructive sleep apnea syndrome after CPAP therapy indicate a decrease in the intensity of LPO and restoration of the balance in the "LPO-antioxidant defense" system.

Serum Serotonin as a Biomarker of the Efficacy of PAP-Therapy in Sleep Apnea Syndrome.

Serum serotonin levels were determined by HPLC in 30 patients with diagnosed obstructive sleep apnea syndrome before and after 3-month course of PAP-therapy and in 14 subjects without obstructive sleep apnea symptoms. It was found that elimination of hypoxic conditions was associated with an increase in serotonin level. The results demonstrate the effectiveness of PAP-therapy during sleep and allow assessing the role of serotonin as a potential biomarker of intermittent hypoxia during sleep.

Glutathione system activity in the blood of overweight postmenopausal women.

One of the important components of the antioxidant defense system is the glutathione system, the activity of which, when overweight, changes direction depending on gender and ethnicity. The results of studies involving overweight menopausal women are mixed. The study involved 61 postmenopausal women, who, after clinical and anamnestic examination, were divided into 2 groups: control (BMI = 19-24.9 kg / m2) and overweight group (BMI = 25-29.9 kg/m2). The use of hormone replacement therapy; the use of antioxidant drugs; diseases of endocrine genesis; exacerbation of chronic diseases; premature early menopause; surgical menopause was the exclusion criteria for women from the study. The lipid profile parameters with the calculation of the atherogenic coefficient; reduced and oxidized glutathione levels with the calculation of their ratio, the glutathione S-transferase and glutathione reductase activities were determined in the blood. Overweight women showed an increase in the triacylglycerols (p = 0.041) and cholesterol in very low density lipoproteins levels (p = 0.044). When assessing the glutathione system activity in women of the main group, compared with the control, an increase in the glutathione-S-transferase (p = 0.023) and glutathione reductase (p = 0.022) activities was noted, however, the reduced and oxidized glutathione levels, as well as their ratio did not differ from the control values. The results obtained indicate the activation of the glutathione system enzymatic link in response to changes in lipid status in postmenopausal women with overweight.

Heat Shock Protein HSP70 in Oxidative Stress in Apnea Patients.

We studied the level of heat shock protein HSP70 under conditions of oxidative stress in 47 patients with apnea. The control group included 13 healthy subjects without verified apnea. Blood serum, plasma, and erythrocyte hemolysate were used to determine LPO and anti-oxidant protection components by spectrophotometrical and spectrofluorometrical methods. HSP70 was assayed by ELISA. A direct relationship was established between the intensity of oxidative stress and HSP70 expression in patients with apnea. Quantitative determination of HSP70 can be used as a molecular marker in the early diagnosis and prognosis of the development of various pathological conditions in hypoxia.

[Expression of heat shock proteins HSP70 under oxidative stress.]

Developing oxidative stress inevitably causes damage to cell proteins in need of timely refolding. Synthesis of a group of heat shock proteins is the most ancient and effective mechanism of cell protection. In the course of the whole life of the cell adaptation to a huge number of cytotoxic factors, both xenobiotic and natural origin provide heat shock proteins with polyfunctionality and in terms of the implementation of programmed death acting as either anti - or proapoptogenic factors, or as regulators of the activity of these factors. Studies show the important role of heat shock proteins in adaptation, inflammation, and immune response. Various experimental and clinical studies prove the important role of heat shock proteins in the development of pathophysiological phenomena of oxidative stress, aging, tumor formation, immune reactions. Presented in the review data of domestic and foreign studies on the physiological significance of heat shock proteins, their role in the mechanisms of cell and body stability in General are relevant to modern medicine and biology.

[Lipid status and oxidative stress in menopausal women with obstructive apnea syndrome].

AIM: to assess lipid profile, lipid peroxidation and antioxidant system parameters in peri - and postmenopausal women with obstructive sleep apnea syndrome (OSAS). MATERIALS AND METHODS: 37 perimenopausal women and 43 postmenopausal ones were examined. OSAS diagnosis was made on the basis of the clinical picture and the polysomnography results. In perimenopause, the main group consisted of 18 women, in postmenopausal women - 17. All comparison groups are comparable by age and body mass index. Lipid profile, lipid peroxidation and antioxidant system parameters by spectrophotometric methods were determined. Non - parametric criteria were used to analyze the group differences for the independent samples. RESULTS AND DISCUSSION: The increase of total cholesterol (TC) and low - density lipoprotein cholesterol (LDL-C) levels were observed in perimenopausal women with OSAS as compared to control. The increase of TC, triacylglycerol (TG), LDL-C, very - low - density lipoprotein cholesterol (VLDL-C) levels and decrease of high - density lipoprotein cholesterol (HDL-D) level were found in postmenopausal women with OSAS as compared to control. Accumulation of ketodienes and conjugated trienes in perimenopausal women with OSAS and thiobarbituric acid reactants with a decrease of total antioxidant activity of blood serum in postmenopausal women with OSAS as compared to control was observed. Moreover, postmenopausal women with OSAS have a higher lipid peroxidation substrates and diene conjugates levels with a lower α-tocopherol level and total antioxidant activity compared with perimenopausal patients.The integral indicator of oxidative stress assessment indicates an imbalance in the lipid peroxidation and antioxidant system in menopausal women with OSAS. CONCLUSION: The results obtained indicate a violation of lipid metabolism and the development of oxidative stress in patients with OSAS. This is most pronounced in the postmenopause due to the aggravation of the pathological condition.

Association of 3111T/C Polymorphism of the Clock Gene with Circadian Rhythm of Melatonin in Menopausal Women with Insomnia.

We carried out a comparative analysis of circadian rhythms of melatonin secretion in Caucasian menopausal women with and without insomnia depending on the 3111T/C polymorphism of the Clock gene. Melatonin levels was measured in the saliva 4 times a day (06.00-07.00, 12.00-13.00, 18.00-19.00, and 23.00-00.00 h). Carriers of the TT genotype with insomnia demonstrated significantly higher level of melatonin in the early morning hours compared to the carriers of the minor allele C (12.60±7.58 and 8.98±8.62 pg/ml, respectively, p=0.023). In the control group, no statistically significant differences were revealed. The carriers of the TT genotype with sleep disorders have higher morning melatonin level compared to control group women (12.60±7.58 and 5.48±4.74 pg/ml, respectively, p=0.005) and low nocturnal melatonin level (6.42±4.97 and 12.52±10.40 pg/ml, respectively, p=0.039).

3111T/C Clock Gene Polymorphism in Women with Insomnia.

Comparative analysis of the frequency distributions of genotypes and alleles of 3111T/C Clock gene polymorphism was carried out in climacteric Caucasian women with and without insomnia. Genotype TT is more incident in women with insomnia (55.5% vs. 42.6% in the control). Allele T predominated in the control and study group and its frequency is higher in women with insomnia. The OR for the risk of insomnia realization is 1.78 (95%CI 1.16-2.75). No association between genotypes and complaints of patients with insomnia is detected.

[Oxidative stress in women with insomnia in different stages of menopause]. / Okislitel'nyi stress u zhenshchin s insomniei v raznykh fazakh klimaktericheskogo perioda.

AIM: To investigate of a lipid peroxidation (LPO) process and the antioxidant defense system (ADS) in peri- and postmenopausal women with insomnia. SUBJECTS AND METHODS: 47 perimenopausal women and 71 postmenopausal ones were examined. Each group was divided into 2 subgroups: 1) individuals with insomnia and 2) controls. LPO-ADS spectrophotometric studies were used in the investigation. RESULTS: There was an increase in the serum levels of ketodienes and conjugated trienes and a decrease in those of α-tocopherol and retinol in postmenopause versus in perimenopause. In insomnia, there was a rise in the level of ketodienes and conjugated trienes in perimenopause; LPO substrates with conjugated double bonds, diene conjugates, and thiobarbituric acid-active products in postmenopause. The indicators of ADS do not differ from those in the controls. The integral indicator of oxidative stress assessment suggests that there is a LPO-ADS imbalance in the menopausal women with insomnia, which is most pronounced in postmenopause. CONCLUSION: The findings suggest that the patients with insomnia develop oxidative stress that is more marked in postmenopause.

[Impact of CPAP therapy on erectile function during sleep and testosterone level in men with sleep apnea syndrome].

The article presents the results of a polysomnographic study with simultaneous monitoring spontaneous nocturnal erections - Nocturnal Penile Tumescences (NPT) in 69 men with age-related androgen deficiency (AAD). Of these, 45 patients were diagnosed with obstructive sleep apnea syndrome (OSAS). In 34 of the 45 patients with OSAS, regimens of non-invasive ventilation with positive-positive airway pressure (CPAP) were selected. Titration was carried out using automatic CPAP-devices for 2 months. The control group (n=24) comprised men with AAD, matched by the "copy-pair" type without clinical manifestations of respiratory disturbances during sleep. Extreme fragmentation of sleep with a significant predominance of the 1st and 2nd stages of the slow sleep phase, the deficiency of deep sleep stages and the significant shortening of the fast sleep phase was leveled by using a constant positive pressure in the upper respiratory tract. CPAP-therapy produced the phenomenon of a "rebound" of slow-wave sleep and fast-sleep phase. Before treatment, men with OSAS had a disruptive pattern of NPT (quantitative and qualitative characteristics). CPAP-therapy resulted in its recovery and maximum preservation relative to fast sleep phase time boundaries. However, the trend towards increasing testosterone levels was not significant, which requires additional testosterone replacement therapy concurrently with CPAP therapy in patients with OSAS and AAD.

[Serum Myokines Levels in Patients with Endogenous Cushing Syndrome and Acromegaly: Cross-Sectional Case−Control Study].

Background: Myokines are produced and released by muscle cells in response to muscular contractions. Endogenous Cushing syndrome (CS) and acromegaly cause significant changes in muscle tissue leading to atrophy or hypertrophy. However, there is no data whether these endocrine abnormalities influence myokine secretion. Aims: To evaluate serum levels of myostatin, interleukin-6 (IL6) and irisin in patients with CS and acromegaly. Materials and Methods: Fasting serum samples were taken and stored in aliquot at ≤-20°C from consecutive subjects with clinically evident and biochemically confirmed active CS, acromegaly and healthy volunteers matched by age, sex and body mass index (BMI). Commercially available kits were used to assay serum myokine levels. Grip strength was measured by a dynamometer. Insulin-like growth factor-1 (IGF1) was measured by immunochemiluminescence assay (Liaison), twenty-four hours urine free cortisol (24hUFC) ­ by immunochemiluminescence assay (Vitros ECi), salivary free cortisol ­ by electrochemiluminescence assay (Cobas). One-way ANOVA was utilized to assess the difference between groups. Results: We enrolled 88 subjects: 30 patients suffered from CS (group 1), 28 ­ acromegaly (2) and 30 matched healthy controls (3) with no difference among the groups in sex, age and BMI (p=0.492, 0.062 and 0.174 respectively). Mean 24hUFC in subjects with CS and mean IGF1 in subjects with acromegaly were significantly higher as compared to other groups (p<0.001). Right-hand grip strength was lower in patients with CS as compared to both patients with acromegaly and healthy subjects (p=0.04). However, among these young adults we did not find statistically significant differences in measured myokines levels: irisin ­ p=0.15; IL6 ­ p=0.34; myostatin ­ p=0.50. There was a significant correlation between myostatin and irisin in the whole group of people and in every separately analyzed subset of patients (p<0.001), but no correlation was found between any measured myokines and 24hUFC or IGF1. Conclusions: Hypercortisolism or supraphysiological IGF1 levels do not significantly influence serum levels of myostatin, IL6 and irisin in young adults.

[Gender Features of Radical Oxidation of Lipids in Menopausal Women and Men in Andropause].

Aims: Our aim was to assess lipid peroxidation ­ antioxidant protection in menopausal women and men in andropause and to compare these processes in different gender and age groups. Materials and Methods: 74 women and 37 men were examined. This study was a prospective, randomized cohort study. Women were divided into perimenopausal group (n=22, mean age 49.03±3.13), postmenopausal group (n=15, mean age 54.43±4.54) and control (n=37, mean age 34±1.2). Men were divided into a group of andropause (n=20, mean age 50.38±2.63) and control (n=17, mean age 35.21±4.75). Body mass index in the main and control groups was comparable. Questionnaires, clinical examination, assessment of the lipid peroxidation-antioxidant defense system, and the calculation of oxidative stress ratio were conducted to all participants of the study. Results: In women from the reproductive phase transition to its extinction increases content of compounds with conjugated double bonds by 22% (p<0.05) in perimenopause and by 27% (p<0.05) in postmenopause, increases content of the ketodienes and coupled trienes by 21% (p<0.05) in perimenopause relative to the control group and reduced by 27% (p<0.05) in postmenopausal women relative to the group of perimenopause. The antioxidant system in women observed the following changes: decrease in the α-tocopherol levels in postmenopausal women by 37% relative to control and by 22% (p<0.05) to compare perimenopause; reduction of retinol level by 29% (p<0.05) in the perimenopause and by 39% (p<0.05) in postmenopause relative to control, increasing of the content of GSSG by 18% (p<0.05) in postmenopause to compare control. When comparing groups of men statistically significant differences were not found. When comparing the groups according to gender, we revealed in men the increased content of compounds with conjugated double bonds by 38% (p<0.05), the GSSG by 13% (p<0.05), reduced content of the ketodienes and coupled trienes by 43% (p<0,05), α-tocopherol by 24% (p<0.05), SOD activity by 9% (p<0.05).Coefficient oxidative stress in perimenopausal women was 2,5, in postmenopausal ­ 3,48, in andropause ­ 0,97. Conclusions: Expressed lipid peroxidation activity is more physiological in andropause than in menopause. Men in andropause have large functional reserves and adaptive capacity than menopausal women.

[Gender characteristics of the structural organization of sleep in obstructive sleep apnea syndrome]. / Gendernye osobennosti strukturnoi organizatsii sna pri sindrome apnoe.

AIM: To reveal gender characteristics of the sleep structure in obstructive sleep apnea syndrome (OSAS) during polysomnographic monitoring (PSGM). SUBJECTS AND METHODS: According to the results of a pre-survey using an apnea screening questionnaire, the investigation included 58 women (body mass index (BMI), 38.2±2.1 kg/m2) and 75 men (BMI, 34.2±1.8 kg/m2), aged 50-55 years, who complained about snoring, sleep apnea, and daytime hypersomnia. Copy-pair groups were formed and compared after objectively confirming the diagnosis by PSGM made at a specialized sleep laboratory, by applying the GRASS-TELEFACTOR Twin PSG system (Comet) with an integrated SPM-1 sleep module (USA) in accordance with the standard procedure. The International Sleep Disorder Classification (2005) was used to diagnose apnea and to estimate its severity. RESULTS: According to the results of PSGM, the men and women were divided into 3 groups, by using the generally accepted OSAS severity scale. Comparative analysis revealed differences in sleep structure parameters with the equal severity of OSAS in the men and women. These differences were characterized by a more marked fragmentariness, impaired cyclicity, and the appearance of the basic specific phenomenon of impaired integrated activity of somnogenic structures - an alpha-delta sleep phenomenon in the men versus the women. There were increases in the time of rapid eye movement (REM) sleep, in that of awakening at night after falling asleep, and in sleep latency in the women with a simultaneous decrease in the total effectiveness of sleep compared to that in the men with the equal-severity OSAS. CONCLUSION: The found gender differences in the sleep structure may be ascribed to the compensatory mechanisms in the function of brain somnogenic structures in the women and the preponderance of REM sleep is a compensatory adaptive response of the sleep homeostatic system, which necessitates further investigations in this area.

[Features of the sleep pattern during pregnancy].

AIM: To evaluate the qualitative characteristics of a sleep in pregnant women in the 3rd term of the physiological pregnancy by a questionnaire survey. MATERIALS AND METHODS: We have demonstrated questionnaire survey data of 400 pregnant women (mean age 27.5 +/- 8.2 years) in the 3rd term of pregnancy. Questioning conducted using the scale PSQI (PITTSBURGH SLEEP QUALITY INDEX--Pittsburgh Sleep Quality Assessment Questionnaire), EPWORTH SLEEPINESS SCALE (sleepiness questionnaire Epfort's) and screening questionnaire to identify obstructive sleep apnea. RESULTS: We have determined that 78% of pregnant women to complain about sleep disorders, namely obstructive sleep disordered breathing, insomnia, "restless legs" syndrome, and combinations thereof. The frequency of sleep disorders increases as pregnancy progresses. Obstructive sleep disordered breathing increases with 10.12% in the 1st term to 31.7% in the 3rd term, insomnia--from 14.3% in the 1st term to 37.6% in the 3rd term. In pregnancy increases of sleep latency (from 14.3 to 44.9 minutes), and reduced the duration of a sleep (from 8.7 to 7.8 hours). CONCLUSIONS: high frequency of sleep disorders in pregnancy requires early pathogenetic prevention of pathological conditions, both in the mother and in the fetus.

[Evaluation of erectile function during the night in men with obstructive sleep apnea syndrome: new possibilities of modern sleep medicine].

Currently, the relationship between the sleep and erectile function (EF) is not in doubt; therefore, evaluation of this relationship in the context of sleep medicine (somnology) is the most informative diagnostic method. The article presents the results of polysomnography with the option of simultaneous monitoring of spontaneous episodes of nocturnal erections in 51 men aged 46-55 years without complaints of violation of the EF. The main group (n = 37) consisted of patients with obstructive sleep apnea syndrome (OSAS). The violation of pattern (quantitative and qualitative characteristics) of nocturnal episodes of spontaneous erections in this group of men was revealed, which was regarded as the initial (pre-clinical) manifestation of erectile dysfunction. Thus, modern diagnostic capabilities of sleep medicine allow to effectively evaluate the EF in patients with OSAS and timely assign pathogenetically justified therapy.

[The experience with the application of the non-medication methods for the treatment of essential arterial hypertension in the adolescents presenting with obstructive sleep apnea/hypopnea syndrome].

The present study was designed to estimate the effectiveness of non-invasive auxiliary lung ventilation under continuous positive airway pressure (CPAP therapy) and phototherapy applied for the treatment of adolescents presenting with essential arterial hypertension and obstructive sleep apnea/hypopnea. It was shown that CPAP therapy decreased the level of arterial pressure (AP) either to normal or to high normal values in accordance with the patients' gender and age. It was confirmed that phototherapy produced beneficial effect on the system of circadian rhythms in the patients with essential hypertension. These findings give reason to recommend the combined application of the above methods for the treatment of adolescents with essential hypertension and obstructive sleep apnea/hypopnea. The proposed treatment makes it possible to decrease arterial pressure due to the correction of obstructive breathing disorders in sleep and to normalize the circadian rhythm system in the adolescents suffering from essential hypertension and obstructive sleep apnea/hypopnea. The clinical application of this method would permit to reduce morbidity, the incidence of disability, and mortality from complications developing in adulthood.