[Cerebral microangiopathy in men with obstructive sleep apnea syndrome]. / Tserebral'naya mikroangiopatiya u muzhchin s sindromom obstruktivnogo apnoe sna.

OBJECTIVE: To determine factors associated with the development of small vessel disease (SVD) in patients with obstructive sleep apnea syndrome (OSA). MATERIAL AND METHODS: One hundred and fifty-two patients with risk factors for the development of cerebrovascular diseases were examined. Based on the results of polysomnography, patients were divided into groups with- (n=84) and without (n=68) OSA. The groups were matched by age, prevalence of arterial hypertension and diabetes mellitus. SVD was diagnosed using brain MRI. Laboratory tests included an assessment of parameters of lipid metabolism, glucose metabolism, concentration of C-reactive protein (CRP), levels of homocysteine and creatinine with the calculation of glomerular filtration rate (GFR). RESULTS: Patients with OSA, compared with those without OSA, were characterized by a statistically significant number of gliosis foci, with their large sizes, more frequent changes on the Fazekas scales and the Hassan scale. The most severe degree of damage according to the Hassan scale in patients with OSA was detected more often (55 (66%) and 27 (39%) OR=2.89, 95% CI 1.47-5.67, p=0.002). More pronounced atrophic changes in the brain, an increase in the size of the III ventricle and the index of the anterior horns, significantly lower GFR and higher levels of CRP were noted in the OSA group. Patients with OSA and duration of nocturnal hypoxia for more than 2 minutes were more likely to have hyperintensity of subcortical regions. In patients with OSAS, pronounced manifestations of SMD were associated with a significantly higher level of morning systolic blood pressure (MAP): 140 [120; 150] vs. 127 [120; 130] p=0.029; increased levels of blood homocysteine: 14 [11; 17.8] vs. 13 [9.7; 12.5] p=0.049; a decrease in GFR: 79 [71; 87.3] vs. 89.8 [80.3; 94] p=0.002, respectively. CONCLUSION: OSA and intermittent nocturnal hypoxia are independent risk factors for SMD. A more severe micro-focal vascular lesion in OSA is associated with a decrease in renal filtration function, an increase in morning blood pressure and an elevation in homocysteine level.

Blood Serum Zonulin in Colorectal Cancer, Autoimmune Bowel Diseases, and Irritable Bowel Syndrome.

Zonulin content in blood serum of patients with colorectal cancer (CRC; n=152; 30-84 years) and patients with large bowel adenomas (n=32; 39-82 years) was measured by standardized kit IDK Zonulin ELISA (Immundiagnostik AG). The healthy control group (n=50) comprised volunteers (27 women, 23 men; 25-68 years); pathological control group (n=84) - patients (55 women, 29 men;18-84 years) with irritable bowel syndrome (n=29), Crohn's disease (n=5), and ulcero-necrotic colitis (n=50). In comparison to healthy control group, the level of zonulin was significantly increased in CRC patients (p<0.0000001) and in patients with benign large bowel tumors (p<0.004), as well as in patients with inflammatory intestine diseases and with irritable bowel syndrome (p<0.0002). Zonulin level in blood serum of CRC patients was slightly, but significantly higher (p<0.05) than in the group of pathological control. ROC curve construction revealed that at optimal zonulin cut-off level (52.2 ng/ml), the diagnostic sensitivity of CRC detection was 66.7% and specificity relative to healthy control was 81.8%. The specificity relative to the combined control group (healthy control+non-tumor bowel diseases) was only 68.9%. Thus, no acceptable cut-off levels for differentiation between malignant and benign tumors, as well as between tumor and non-tumor large bowel pathologies were found. Analysis of the associations between serum zonulin level and the main clinical and pathological characteristics of CRC demonstrated that the level of this marker increased with disease progression (p<0.01; Kruskal-Wallis test), but was not associated with individual criteria of the TNM system, tumor localization, histological structure, and malignancy grade.

[The effect of long-term beta-blockers on melatonin secretion, sleep quality, and vascular brain damage]. / Vliyanie dlitel'nogo priema beta-adrenoblokatorov na sekretsiyu melatonina, kachestvo sna i sosudistoe porazhenie golovnogo mozga.

Circadian rhythm of pineal melatonin production is paced by the thalamus suprachiasmatic nucleus (SCN) depending on the lighting conditions via signal transduction to pinealocytes beta-receptors. Melatonin is a natural regulator of many physiological processes, and the decrease of its synthesis leads to various diseases, in particular, insomnia and metabolic disorders. It is known that administration of beta-blockers reduces melatonin production, but the data showing clinical significance of melatonin reduction associated with beta-blockers administration are still contradictory. OBJECTIVE: The influence of long-term administration of beta-blockers to melatonin synthesis, sleep quality and vascular brain damage. MATERIALS AND METHODS: The main study group included 114 patients, aged 47-83, with cardiovascular diseases, who were under a complex therapy with long-term administration of beta-blockers. The comparison group included 110 patients with cardiovascular diseases, similar in age and sex, who did not receive beta-blockers in their complex therapy. The circadian dynamics of melatonin synthesis was observed by excretion of 6-sulfatoxymelatonin (6-SM), the major metabolite of melatonin, in three urinary samples (day, evening, night). All the patients underwent night polysomnography to assess the severity of sleep disorders. The severity of vascular brain damage was assessed using magnetic resonance imaging. RESULTS: The analyses showed large variability in individual values of 6-SM circadian excretion of patients with cardiovascular diseases (from 0.9 to 133 µg/24h with a mid-point 16.8 µg/24h). A considerable decrease of 6-SM circadian excretion is detected in the group of patients taking beta-blockers comparing to those not Me [q 25; q 75]: 12.8 [6.2; 21.1] and 24.0 [12.5; 41.5] µg/24h, respectively (p<0.001), with no differences in sleep values and severity of vascular brain damage. Comparing subgroups of patients with 6-SM circadian excretion lower and higher than 16.8 µg/24h showed a significant increase of sleep latency, decrease of rapid eye movement sleep (REM sleep), increasing number of gliosis foci in white matter of the brain with higher values of leptin, leptin/adiponectin ratio and glycohemoglobin in the group of patients with 6-SM circadian excretion ≤16.8 µg/24h. CONCLUSION: A low level of endogenous melatonin is a risk factor for development of sleep structure and quality disorders, vascular white matter brain damages with a higher risk for metabolic disorders. Long-term beta-blockers administration decrease endogenous melatonin synthesis to 50% increasing the risk for insomnia and vascular brain damage, mostly in patients with lower initial level of 6-SM circadian excretion.: melatonin, 6-sulfatoxymelatonin, beta-blockers, insomnia, vascular white matter brain damage, leptin, adiponectin.

[A role of insomnia in the development of silent cerebral infarctions]. / Rol' insomnii v razvitii nemykh infarktov mozga.

AIM: To investigate the relationship between insomnia, hemostatic abnormalities and silent cerebral infarctions. MATERIAL AND METHODS: A complex study of 76 male patients, aged 40-85, with vascular risk factors was carried out. Magnetic resonance imaging (MRI) data was used to verify presence of silent cerebral infarctions; the presence and severity of insomnia were determined using questionnaires and polysomnography. Laboratory diagnosis included a complete assessment of hemostatic system with thrombodynamics test. RESULTS: Patients were divided into 2 groups according the MRI data. The 1st group included 20 men with less than 4 silent cerebral infarctions, the 2nd group 56 men with multiple silent cerebral infarctions - from 5 to 25. Chronic insomnia was diagnosed in 35 (46%) of patients, more frequently in the second group (25% and 54% respectively, p<0.05). The group of patients with multiple silent infarctions demonstrated a loss of sleep efficiency and hypercoagulation with an increased rate of clot growth in thrombodynamics test. Correlation analysis confirmed the dependence between sleep efficiency and quantity of vascular sites, sleep efficiency and clot growth rate. CONCLUSION: The more severe plasma haemostasis disorder in patients with multiple silent infarctions and relation between insomnia severity and plasma haemostasis activation suggest that insomnia can be an additional risk factor of arteriole thrombosis.

[Disturbances in melatonin secretion and the efficacy of replacement therapy in sleep disorders]. / Narushenie sekretsii melatonina i éffektivnost' zamestitel'noi terapii pri rasstroistvakh sna.

The review presents data on the dependence of endogenous melatonin synthesis on the time of day, age, pineal gland size, lighting conditions, administration of beta-blockers and a number of other medications. The results of studies on parasecretion and efficacy of exogenous melatonin use in sleep-wake cycle disturbances, insomnia, neurodegeneration, diabetes mellitus and oncological diseases are discussed.

[The clinical/laboratory support for using melatonin in chronic cerebrovascular diseases and metabolic syndrome]. / Kliniko-laboratornoe obosnovanie primeneniia melatonina pri khronicheskikh tserebrovaskuliarnykh zabolevaniiakh i metabolicheskom sindrome.

AIM: To evaluate a role of melatonin deficiency in the metabolic syndrome and chronic cerebral ischemia (CCI). MATERIAL AND METHODS: One hundred and seventy-nine men, aged 45-75 years, with CCI and components of metabolic syndrome (MS) were examined. Intima-media thickness (IMT) in the carotid arteries and cerebrovascular reactivity was assessed by the results of duplex scanning and hypercapnic test. Cholesterol spectrum parameters, glucose metabolism, inflammatory mediators, markers of lipid metabolism were measured in the blood serum. Daily changes in melatonin production were determined by measuring 6-SMT, a melatonin metabolite, in morning, evening and night urine. RESULTS AND CONCLUSION: The levels of total 6-SMT excretion were 17.2 [10.01; 36.8] mcg/day. Patients with the values <10.01 and >36.8 mcg/day significantly differed by the PAI-1, leptin/adiponectin ratio, IMT and cerebrovascular activity. The combination of 4 or 5 MS components was identified in 19 (42%) patients with low 6-SMT excretion and only in 7 (15%) with high excretion (OR=3.9; 95% CI 1.3-12.2; p=0.01). Thus, the low level of endogenic melatonin and disturbances of circadian dynamics of its synthesis with the decrease in the night and increase in the evening portions are the risk factors for MS and CCI. Addition of melatonin in the complex treatment of CCI associated with MS and the low level of endogenic melatonin is pathogenetically explained.

[FROM THEORY TO PRACTICE. THE ROLE OF QUALITY CONTROL OF ANALYTICAL STAGE OF STUDIES IN INCREASING CLINICAL INFORMATIVENESS OF LABORATORY TESTS].

Nowadays, improving accuracy and clinical informativeness of results of studies is one of main directions of development of laboratory. The article presents originally developed algorithm of evaluation of quality of immunochemical studies in part related to analytical stage. The case of application in practice of the results of such evaluation is presented.

[Influence of smoking on the cerebral hemodynamics and biochemical blood indices in chronic insufficiency of brain circulation]. / Vliianie kureniia na tserebral'nuiu gemodinamiku i biokhimicheskie pokazateli krovi pri khronicheskoi nedostatochnosti mozgovogo krovoobrashcheniia.

The influence of smoking on cerebral hemodynamics and biochemical blood indices has been studied in 50 male patients with chronic insufficiency of brain circulation (CIBC), aged 40-50 years, divided into 2 groups: smoking (n=26) and nonsmoking (n=24). Smoking was shown to play a substantial role in the development of discirculatory encephalopathy with atrophic brain changes, causing metabolic disturbances (a shift of acid-basic balance towards acidosis) and microcirculation disorders due to altered cerebrovascular reactivity. These alterations develop previously to hemodynamically significant atherosclerotic arteries lesion and emerge irrespective of the presence of atherosclerotic vascular changes, atherogenic shifts of lipid metabolism, disturbances of free-radical processes and platelet aggregation.

[Chromosomal aberrations and parameters of oxidative stress in Chernobyl clean-up workers in a remote period after ionizing radiation]. / Khromosomnye aberratsii i pokazateli okislitel'nogo stressa u likvidatorov posledstvii avarii na Chernobyl'skoi AES v otdalennom periode posle deistviia ioniziruiushchei radiatsii.

This investigation was performed to test a supposition about the influence of disturbances in antioxidative system on cytogenetical parameters in Chernobyl' clean-up workers. It was shown that some cytogenetical parameters straightly correlated with the parameters of oxidative stress, while other cytogenetical parameters show just reverse correlations. Apparently, these relationships are not of cause-and-effect type, but they reflect a complex processes occurring in humans for a long period after radiation exposure.

[Oxidative modification of blood plasma proteins in elderly people with vascular dementia]. / Okislitel'naia modifikatsiia belkov plazmy krovi u pozhilykh liudei s sosudistoi dementsiei.

We examined the spontaneous and metal-ion-catalyzed oxidative modification plasma blood proteins in the group of healthy adults and elderly ones and patients with vascular dementia (mild and severe). We determined the spectrophotometric measurement of 2,4-dinitrophenylhydrazone derivatives formed by reactions with protein carbonyls. The level of metal-ion-catalyzed oxidation proteins in the aged patients both with and without dementia was high in comparison to the healthy adults. The patients with severe dementia showed lower amount of 2,4-dinitrophenylhydrazone deriviates. Low levels of metal-ion-catalysed protein oxidation strongly correlated with the degree of psychoorganic disturbances. The elderly persons with both and without dementia showed a high level of plasma nonenzymatic H2O2 scavenging in comparison with the healthy adult ones. We discovered an imbalance between enzymatic and nonenzymatic components of the antioxidant system. The latter indicates that the oxidative modification of brain tissue proteins probably plays an important role in aging and mental disorders.

[The results of the drug therapy of the ischemic syndrome in arteriosclerosis obliterans]. / Rezul'taty medikamentoznoi terapii ishemicheskogo sindroma pri obliteriruiushchem ateroskleroze.

A thorough investigation of 120 patients with obliterating atherosclerosis of lower extremities, treated conservatively at a hospital and observed for 5 years have shown that such a treatment was most effective in patients with the initial stages of the disease. The mechanisms of positive effects is based on the dilatation of the peripheral arteries and the resulting decrease of the peripheral resistance of the vessels, improved cardiac activity, activation of microcirculation and tissue respiration. An important result of the treatment is an increased rate of the oxygen consumption by the tissues in the ischemic zone. It determines the pathogenetic direction of the therapy which leads to a delayed progress of the disease in 20% of the patients and improves the patient's state in 57% of cases.

[Activation of the processes of lipid peroxidation in the small-intestinal mucosa and liver in peritonitis and possible ways of their correction by a complex infusion-detoxification therapy]. / Aktivatsiia protsessov perekisnogo okisleniia lipidov v slizistoi tonkoi kishki i pecheni pri peritonite i vozmozhnye puti ikh korrektsii kompleksnoi infuzionno-detoksikatsionnoi terapiei.

Possibilities of lipid peroxidation (LPO) correction by infusion-detoxication therapy in peritonitis were studied in an experiment on 160 white rats and during clinical treatment of 88 patients with general peritonitis. It was shown that peritonitis development in rats was attended by an increase of LPO products--malonic dialdehyde and diene conjugates, in the hepatic tissue and small intestine mucosa, while the activity of antioxidant defense elements--superoxide dismutase and fat-soluble antioxidants, decreased. It was noted that LPO became normal after intravenous administration of exogenous superoxide dismutase (6 mg/kg) and the blood substitute Mafusol containing Krebs cycle substrate--sodium fumarate (9 ml/kg). Inclusion of Mafusol into the combined therapy of patients with general peritonitis contributed to the reduction of malonic dialdehyde and diene conjugate levels in the blood, normalization of its acid-base state, diminution of medium mass molecule content. Similar normalization of LPO was not recorded when lactosol was used. It has been concluded that blood substitute Mafusol used in the combined therapy of patients with general peritonitis significantly raises the treatment effectiveness.

[Effects of impulse hydrodynamic influences on blood cells in vitro and in vivo]. / Vliianie impul'snykh gidrodinamicheskikh vozdeistvii na kletki krovi in vitro i in vivo.

Impulse hydrodynamic influences (IHDI) resulted in an increase of accumulation of acridine organ, degranulation of neutrophils, decrease in adenylate cyclase and Na+, K+, Mg2(+)-dependent ATPase activities in the white blood cells of man and rat in vitro and in vivo. It was found that the cell's response to one-fold IHDI was more pronounced than to 5-fold IHDI. It was suggested that in certain conditions IHDI could lead to a decrease in reactivity of white blood cells.

[Treatment of gunshot wounds of soft tissues]. / Lechenie ognestrel'nykh ran miagkikh tkanei.

The authors have determined principal directions of a complex and successive action on the wound process taking into account its phasic character and new ideas as the dynamics of zonal disturbances of microcirculation around the gunshot wound. The use of the systemic treatment of 44 patients with gunshot wounds of soft tissues allowed the period of treatment to become 1.5 times shorter and the amount of suppurations was 4 times less.

[Viability of tissues of the extremities and surgical tactics in stage IV arteriosclerosis obliterans]. / Zhiznesposobnost' tkanei konechnosti i khirurgicheskaia taktika pri IV stadii obliteriruiushchego ateroskleroza.

Amputation of the extremity was performed in 26 of 52 patients with the IV stage obliterating atherosclerosis. Clinical severity of the disease was confronted with results of special investigations. Three groups of such patients are described: with traumatic necroses, with ischemic necroses and with necrotic ischemia (criteria of its irreversibility are presented). Surgical tactics of treatment in the first group of patients may include sympathectomy with necrectomy. The outcome of treatment of the second group patients is determined by the efficiency of reconstructive operations. Amputation of the extremity is indicated to patients of the third group.