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Objective: in the experiment, to investigate the effect of Quercetin on the NO-dependent reactions of isolated vessels involving endothelium and perivascular adipose tissue (PVAT) after a single X-ray irradiation of rats at a sublethal dose. In a clinical study, to investigate the effect of long-term use of Quercetin on the functional state of themicrovascular endothelium in the elderly patients with metabolic syndrome (MS)., Material and Methods: Experimental studies were performed on vascular fragments obtained from adult male rats(7-8 months) of the control group, in animals exposed to a single R-irradiation at a dose of 7 Gy and animals irradiated in the same dose, which received Quercetin orally for 14 days three times a week based on 10 mg/kg bodyweight. Fragments of the thoracic aorta (TA) and mesenteric artery (MA) were cleaned of perivascular adipose tissue (PVAT-) or left uncleaned (PVAT+), and then were cut into rings (up to 2 mm). The amplitude of the contractionof the rings TA and MA under the influence of phenylephrine (PE, 3 x 10-6 M), the amplitude of the contraction of therings TA and MA in the presence of a competitive blocker of NO-synthase methyl ester of N-nitro-L-arginine(L-NAME, 10-5 M), the amplitude of relaxation of the rings TA and MA in the presence of N-acetylcysteine (NAC, 10-4 M)were measured. The clinical study examined 110 patients with MS criteria in accordance with ATP III (2001).Patients in the main group for 3 months received Quercetin from the same manufacturer, 80 mg three times a day,patients in the control group received placebo., Results: Single R-irradiation disrupts the regulation of the contractile function of TA and MA, which is evidenced bychanges in the contractile reactions of isolated fragments of these vessels as a response to the action of vasoactivecompounds. Course use of Quercetin in irradiated rats leads to the normalization of contractile and dilatory vascular responses due to partial correction of NO metabolism in the endothelium and PVAT. For the majority of patients(69 %) who received Quercetin, a post-occlusive hyperemia test showed a statistically significant increase of maximal volumetric velocity of the skin blood flow rate and duration of the recovery period to the baseline, which indicates about improvement of vasomotor vascular endothelial function., Conclusions: Course use of Quercetin improves the functional state of the microvascular endothelium among theelderly people with MS, normalizes contractile and dilatory vascular responses in irradiated rats due to partial correction of NO metabolism in the endothelium and PVAT., (O. V. Korkushko, E. M. Gorban, O. V. Bondarenko, I. A. Antonyuk-Shcheglova, S. S. Naskalova, O. V. Parshykov, N. O. Utko, A. V. Gavalko, V. B. Shatilo, G. V. Duzhak.)

Rationale: Association between different components of metabolic syndrome and the rate of age-related telomere shortening was reported repeatedly, although some findings are inconsistent across studies, suggesting the need for further research on the topic. In the present study, we examined relationships between different components of metabolic syndrome (MetS); glucose tolerance reflected in 2-h post-load plasma glucose (2hPG) levels and age on the leukocyte telomere length (LTL) in Ukraine population. Methods: The study was conducted on the 115 adult individuals residing in the Kyiv region (Ukraine). Among them, 79 were diagnosed with MetS according to the International Diabetes Federation definition. LTL were determined by a qPCR-based method. Multivariate logistic regression (MLR) and artificial neural networks (ANN) modeling were used for the analysis of the results. ROC-analysis was also performed to compare the predictively values of this models. Results: MetS was associated with a high (OR = 3.0 CI 1.3-6.7; p = 0.01) risk of having shorter telomeres that remained significant after adjusting for age, gender and 2hPG levels. Fasting plasma glucose (FPG) levels and other MetS components did not affect the magnitude of the relationship and did not reveal the independent influence of these factors. The level of 2hPG in turn, demonstrated a significant relationship (OR = 1.3 CI 1.0-1.6 per 1 mmol/l; p = 0.04) with LTL regardless of the presence of MetS. The non-linearity of the interactions between age, gender and 2hPG level was revealed by neural network modeling (AUC = 0.76 CI 0.68-0.84). Conclusion: Our study found that impaired glucose tolerance, but not FPG levels, affected the association between LTL and MetS, which may be also indicative for pathophysiological differences in these hyperglycemia categories. 2hPG levels can provide an opportunity for a more accurate diagnostics of MetS and for evaluating the rate of aging in patients with MetS. Further research, however, is needed to verify this assumption.

Diabetes-related conditions such as chronic hyperglycemia and related oxidative stress and inflammation were repeatedly associated with accelerated telomere shortening in epidemiological studies, although some findings are inconsistent. In present study, we aimed to assess the impact of disturbances in glucose metabolism on association between age and leukocyte telomere length (LTL) in the Ukrainian population. The study was conducted on the 119 adult subjects aged between 43 and 87 years residing in the Kyiv region, Ukraine. LTL was determined by a quantitative PCR-based method. LTL was negatively correlated with the measure of abdominal obesity such as waist-hip ratio, as well as with both fasting plasma glucose (FPG) and two-hour post-load glucose (2hPG) levels. Consistently with previous studies, a significant negative association between LTL and age was observed in individuals with normal (<5.6 mmol/L) FPG levels. Unexpectedly, however, no association was found in subjects with impaired glucose metabolism assessed by abnormal FPG or/and 2hPG levels. No association between LTL and age was observed in a logistic regression model; the association between LTL and age became significant after adjusting for FPG level. In the FPG-adjusted model, 1.6-time lower odds to have long telomere length were indicated for each 10 years increase in age. We hypothesize that the attenuation of association between LTL and age in hyperglycemic persons can likely be attributed to the interaction of multidirectional processes determining this relationship., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Shatylo, Valerii B., Tetiana V. Serebrovska, Anna V. Gavalko, Egor Egorov, and Oleg V. Korkushko. Acute hypoxic test in patients with prediabetes. High Alt Med Biol. 17:101-107, 2016.-Prediabetes is a state of impaired carbohydrate metabolism when not all of the symptoms required to label a person as diabetic are present, but blood glucose is higher than in healthy subjects. Recent evidence suggests that intermittent hypoxia training (IHT) might provide a cost-effective strategy for improving metabolic functioning. One of the most important aspects of the successful IHT application is individualized approach to hypoxic dose and regimen prescription. To establish the relationships between indices of carbohydrate metabolism and individual resistance to hypoxia, the acute hypoxic test (AHT, breathing gas mixture with 12% O2 during 20 minutes) was performed in 33 healthy volunteers (mean age, 63.0, range, 44-76; fasting plasma glucose (FPG) less than 5.6 mmol/L and 2 hours postoral glucose tolerance test (OGTT) glycemia less than 7.8 mmol/L) and 30 patients with impaired glucose metabolism (mean age, 65.5, range, 44-75; FPG from 5.6 to 6.9 mmol/L and 2 hours post-OGTT glycemia from 7.8 to 11 mmol/L). Negative correlation was found between the SaO2 level at 20th minute AHT and FPG (r = -0.83; p < 0.01) and insulin (r = -0.27; p < 0.05), as well as 2 hours post-OGTT glucose and insulin levels (r = -0.75 and -0.40, respectively). Longer recovery time and less effective functioning of respiratory and cardiovascular systems were also registered in patients with prediabetes showing that their cardiovascular resilience is impaired compared to normoglycemic controls. These patterns of relationship must be considered when assigning the individual modes of IHT.

To assess organism reaction to dosed hypoxic hypoxia in the human invividuals with pre-diabetic hydrogen metabolism disturbances.Altogether 40 subjects, age range 50-74 years, were examined, including 18 persons with pre-diabetic hydrogen metabolism disturbances and 22 essentially healthy subjects. All of them underwent dosed hypoxic test (breathing gas mixture containing 12 % of oxygen during nearly 20 min. The following monitorings were performed: blood saturation (SpO2), breathing rate, arterial blood pressure and heart rate; and standard glucose tolerance test (GTT) for blood plasma glucose and insulin concentration. The patients with prediabetic hydrogen metabolism disturbances displayed a more significant decrease of SpO2 and less effective functioning of the respiratory and cardiovascular systems during dosed hypoxic test compared with the healthy individuals without hydrogen metabolism disturbances. After redistribution of study subjects relative the degree of SpO2 decrease at dosed hypoxic test in the subgroup with satisfactory resistance to hypoxia (subgroup 1: SpO2 more than 80 %) and with reduced (subgroup 2: SpO2 80 % or less) we have found that the fasting glucose level after 2-hour GTT was significantly higher in subgroup 2 versus subgroup 1. The obtained results indicate the interrelationship between organism reaction to hypoxia, in particular between the degree of arterial hypoxemia during performance of the dosed hypoxic test and the indices of fasting glycemia and at standard GTT. The patients with pre-diabetic hydrogen metabolism disturbances are characterized with lower resistance to hypoxic hypoxia.

The relationship between metabolic syndrome and its individual components, leptin levels and the severity of cognitive impairment in patients of different age with dyscirculatory encephalopathy (DE) and metabolic syndrome (MS) was studied. There were 503 patients aged 45-89 years with DE enrolled into the study, who were divided into two groups: patients without MS (n=198) and with MS (n=305). All patients were divided into three age subgroups. All patients underwent clinical-neurological examination, laboratory tests, high resolution B-mode ultrasound examination, MRI. Cognitive functions were assessed by Mini Mental State Examination (MMSE). In middle age and elderly patients a significant inverse relationship between the total score of MMSE and the level of blood pressure, blood glucose level was found. A direct significant correlation between blood pressure level and a total score of MMSE was revealed in senile patients. The duration of hypertension significantly influenced on the severity of cognitive impairment in patients of middle and old age. The results obtained indicate a definite relationship between the level of leptin in the blood of patients with MS and the state of their cognitive functions. The influence of leptin level on cognitive function in patients with the metabolic syndrome increases with age. Timely and adequate correction of blood pressure, blood glucose and triglycerides may have a positive effect on cognitive function in patients with MS.

In pre-diabetes disorders in which pathogenesis the insulin resistance (IR) plays a leading role, the risk of thrombosis due to increased coagulation factors, decreased concentration of physiological anticoagulants and inhibition of fibrinolysis is increased. Similar changes in the hemostatic system with aging are observed. We investigated the characteristics of the hemostatic system in middle-aged and elderly people with IR in the absence and presence of impaired glucose tolerance (IGT). It is shown that IR in middle-aged and elderly people is accompanied by increased content of plasminogen activator inhibitor type-1, which may lead to potential inhibition of fibrinolysis. An indication of significant prothrombotic changes associated with IR in the elderly are reduced a clotting time of blood plasma in the APTT test and elevated levels of soluble fibrin and D-dimer. Intensity of these changes in the hemostatic system is enhanced in the presence of IGT. The results substantiate need for correction of hemostasis by reducing the IR.

The aim of this study was to investigate the effectiveness of tetrapeptide pankragen-forte in older people with prediabetic state. A total of 150 healthy people of different ages, including 39 young people (20-39 years), 42 people. middle-aged (40-59 years) and 69 older adults (60 years and older). As a result of screening, 69 seniors were selected 12 patients with impaired glucose tolerance, which, for the correction of glucose metabolism used Pankragen-forte as follows: 500 mkg 2 times a day (morning and evening) for 4 weeks. All included surveyed was defined indicator of glycosylated hemoglobin, conducted a standard oral glucose tolerance test with determination of glucose, insulin in plasma glucose and venous blood at 30, 60 and 120 min after ingestion of 75 g glucose. Pro-insulin levels were determined in plasma, venous blood glucose and 30-min OGTT. Also calculated an index of insulin resistance (HOMA-IR), insulin sensitivity index (Matsuda index) and functional activity of β cells of the pancreas (HOMA- %). In 50 percent older people with impaired glucose tolerance use of pankragen forte led to a significant decrease in the concentration of plasma glucose during a standard oral glucose tolerance test, which indicates the normalizing effect of peptide drug in the violation of carbohydrate metabolism, which is consistent with the improvement of the lipid composition of serum blood, endothelial function, decreased platelet aggregation. The use of peptide drug pankragen forte is promising correction prediabetic status in the elderly.

The aim was to study the gastric blood flow due to acid output and enzyme systems of GM. The study included 14 healthy young and 20 healthy elderly people without atrophic changes in GM. Blood flow in microvessels GM was determined by laser Doppler flowmeter, acid output was assessed by 24-hours pH-monitoring, the activity of H(+)-K(+)-ATPase and nitric oxide synthase in biopsies GM was determined by standard biochemical methods. In normal elderly people a significant reduction in blood flow in the microvessels of the secretory zone of GM (large curvature, front and back wall in the body stomach) accompanied by a decrease in the activity of NO-synthase was found. Acid output and activity of H(+)-K(+)-ATPase of parietal cells in the same area do not decreases with age. However, older patients demonstrated a higher level of blood flow in the secretory zone combined with a higher acid output, which indicates that the increase in the level of blood flow values for hydrochloric acid secretion in older people.

This work was undertaken to study tissue oxygen exchange and oxidative processes in the long-lived individuals who were assumed as the physiologically aging individuals. Oxygen tension was assessed in forearm subcutaneous cellular tissue by means of the polarographic method while performing 10 min oxygen inhalation tests (with spontaneous oxygemogram recording) and a 10 min clamping of vessels. The obtained data served as the tissue oxygen exchange indicator. This approach made us possible to evaluate the oxygen delivery and oxygen uptake. To study qualitative characteristics of oxidative processes, we assessed vacat-oxygen of the blood and urine and estimated the underoxidation coefficient proposed by Muller. We have found that tissue respiration intensity falls, the amount of underoxidated products of the blood and urine rises, and the underoxidation coefficient increases in aging. The decrease of tissue oxygen respiration intensity in subcutaneous cellular tissue reflects the development of tissue hypoxia associated with reduced activity of the enzymes, being involved in oxygen exchange. An age-related decrease of tissue perfusion leads to the formation of circulatory hypoxia and also contributes considerably to tissue hypoxia formation. The revealed changes in the tissue oxygen exchange and oxidative processes in the long-livers are generally correspondent to those that can be seen in the people of 80-89 years. This finding speaks in favor of the physiological aging in the long-livers.

We examined two groups of older persons: 30 healthy and 33 patients with type 2 diabetes mellitius. Nocturnal melatonin production was significantly reduced by 70% in patients with DM2 compared to healthy individuals of the corresponding age. In patients with DM2, pancragen significantly decreased glucose level on an empty stomach and in standard glucose tolerance test and reduced plasma concentrations of insulin and insulin resistance index. In patients receiving no pancragen, no changes in carbohydrate metabolism indices were observed. Thus, disturbances in the melatonin-producing function of the pineal gland in elderly individuals contribute to the development of insulin resistance. Administration of the tetrapeptide pancragen is a promising approach to the correction of insulin resistance in elderly individuals.

The paper presents the results of randomized comparative study of the efficiency of peptide geroprotector from the pituitary gland in elderly patients with rapidly aging cardiovascular system. Over three years 39 coronary patients received, in addition to basic therapy, regular courses of epithalamin (peptide drug), while 40 coronary patients (control group) received basic therapy alone. Long-term treatment with epithalamin (6 courses over 3 years) decelerated aging of the cardiovascular system, prevented age-associated impairment of physical endurance, normalized circadian rhythm of melatonin production and carbohydrate and lipid metabolism. A significantly lower mortality in the group of patients treated with epithalamin in parallel with basic therapy also indicated a geroprotective effect of the peptide preparation from the pineal gland.

The reaction of cerebral blood flow during breathing with positive end expiratory pressure in elderly people with physiological (24 pers.) and accelerated (26 pers.) aging of the respiratory system were studied. It is shown that in people with accelerated aging of the respiratory system some resistance to expiration improves the efficiency of gas exchange in the lungs. However, breathing with considerable resistance to expiration (15 mm water column) in people with accelerated aging of the respiratory system, causing depression of gas exchange in the lungs. Found that people with accelerated aging of the respiratory system decreased pulmonary gas exchange response to breathing resistance expiration.

In 43 middle age and elderly people without obesity (body mass index of less than 30 kg/m2) we studied the relationship between insulin resistance (IR) and physical performance. It is shown that in healthy elderly IR is associated with a moderate increase of insulin and a small increase in the level of glucose in the blood plasma. In the middle age people, IR has no effect on physical performance. IR in the elderly people is accompanied by the decrease in physical performance due to less economical for hemodynamic load and oxygen consumption. A lower exercise tolerance in elderly people without obesity can be considered not only as a risk factor for insulin resistance, but also as its consequence.

The intermittent normabaric hypoxic training (IHT) is a non-pharmacological method, which due to several positive effects, has been used successfully in treating patients with cardiovascular diseases (CVD). However, the application of this method in the elderly has its own peculiarities because of age-related changes of organism. The article presents the indications and limitations of IHT in elderly people with coronary artery disease, the method of the mode of training in the elderly, as well as displaying the results of our clinical study of the safety and efficacy of IHT in 45 elderly patients with stable angina of I and II functional classes. It is shown that IHT is a safe method, leading to reduction in clinical symptoms of angina and duration of daily myocardial ischemia, normalization of lipid metabolism and increase exercise tolerance. Mechanisms of positive effects of IHT in patients with stable angina of I and II functional classes are an economical functioning of the cardiovascular system, optimization of oxygen consumption, improvement of vasomotor endothelial function due to increased formation of nitric oxide, normalization of microcirculation.

The efficacy and safety of intermittent hypoxia training (IHT) were investigated in healthy, 60- to 74-yr-old men. Fourteen men (Gr 1) who routinely exercised daily for 20 to 30 min were compared with 21 (Gr 2) who avoided exercise. Their submaximal work-load power values before the IHT training were 94 +/- 3.7 and 66 +/- 3.1, respectively. Before and after 10 days of IHT, the ventilatory response to sustained hypoxia (SH; 12% O(2) for 10 min), work capacity (bicycle ergometer), and forearm cutaneous perfusion (laser Doppler) were determined. During SH, no negative electrocardiogram (ECG) changes were observed in either group, and the ventilatory response to SH was unaltered by IHT. In Gr 1, IHT (normobaric rebreathing for 5 min, final Sa(O(2)) = 85% to 86%, followed by 5 min normoxia, 4/day) produced no changes in hemodynamic indixes and work capacity. In Gr 2, IHT decreased blood pressure (BP) by 7.9 +/- 3.1 mmHg (p < 0.05) and increased submaximal work by 11.3% (p < 0.05) and anaerobic threshold by 12.7% (p < 0.05). The increase in HR and BP caused by a 55 W-work load was reduced by 5% and 6.5%, respectively (p < 0.05). Cutaneous perfusion increased by 0.06 +/- 0.04 mL/min/100 g in Gr 1 and by 0.11 +/- 0.04 mL/min/100 g in Gr 2 (p < 0.05). Hyperemia recovery time increased significantly by 15.3 +/- 4.6 sec in Gr 1 and by 25.2 +/- 11.2 sec in Gr 2. Thus, healthy senior men well tolerate IHT as performed in this investigation. In untrained, healthy senior men, IHT had greater positive effects on hemodynamics, microvascular endothelial function, and work capacity.

47 elderly patients aged 60-74 with stable exertional angina of I-II functional classes and 2a type dislipidemia have been observed. The authors studied the efficacy of hypocholesteremic diet (HD) including soya-based food in comparison with the use of HD without soya-based food. Patients of the main group were prescribed HD, soya-based food (29 g of soya protein per day) and medications of a based therapy during four weeks. Patients of the control group were given HD and medications of a based therapy during the same period. The use of HD with soya-based food decreased considerably frequency and duration of exertional angina attack, increased the tolerance to physical activity resulted in more considerable decrease in concentration of blood serum common cholesterin and cholesterin of low density lipoprotein in comparison with indices of patients of the control group. Soya-based food together with HD in patients with disturbed tolerance to glucose normalized the tolerance test to glucose.

In contrast to young people, changes in the rhythms of parameters manifested in elderly and senile chronic coronary patients in inversion (decreased T cell count in the peripheral blood, values of lymphocyte blastogenesis test with phytohemagglutinin, and phagocytic index in the fall), monotony (B cell count in the peripheral blood), decreased amplitude of serum hydrocortisone, and desynchronization. The levels of thymic serum factor and IgG were higher in the fall than in the spring, but the seasonal difference leveled after 2.5 years of observation. On the other hand, the rhythms of changes in the thymic serum factor and hydrocortisone were retained in patients with chronic coronary disease after 6 courses of epithalamin by the optimal protocol (period of observation 30 months) and blood T cell count increased in the fall. Improvement of the rhythms of the parameters was associated with a benign clinical course of the disease.

The majority of the adaptation processes to hypoxia is based on transcriptional regulation by hypoxia-inducible factors--HIFs. Recently the allele polymorphism of oxygen-dependent degradation domain of HIF-lalpha has been described. It consists in the replacement of cytosine for thymine in 1772 location (C1772-->T). The physiological significance of such replacement is obscure. In the investigation of 26 healthy elderly subjects (58.5 +/- 0.7 yr) we tried to verify whether HIF-lalpha polymorphism in exon 12 may identify individual features of adaptation to intermittent hypoxia training (IHT) (isocapnic hypoxic rebreathing technique, 5-min sessions with 5 min rest intervals, 3 times daily during 10 days). The distribution of HIF-l alpha genotypes for C1772-->T were studied by using the polymerase chain reaction and restriction analysis. We detected that all subjects from the group had C/C genotype. Meanwhile, the broad spectrum of adaptive reactions to IHT was observed, from the best adaptation up to disadaptation. IHT enhanced HVRs in the range of 167% - 5%, blood malon dialdehyde content varied from a decrease by 46% up to an increase by 88%, the changes of superoxide dismutase activity varied from +64% to -56% etc. These results suggest that the C1772-->T polymorphism in HIF- 1alpha does not contribute to individual peculiarities of adaptation to IHT. Because the activity of HIF-lalpha is regulated by multiple steps including the transcriptional level, the effect of the polymorphism in enother exons on the adaptive reactions remains to be elucidated.

In the course of aging both monkeys and people reveal decreased night and average daily level of melatonin in the blood plasma and reduced hormone circadian rhythm amplitude, which evidence the disorder of the pineal gland melatonin releasing function. Peptide preparations of the pineal gland (Epithalamin--a complex of peptides isolated from the pineal gland and Epitalon--synthetic tetrapeptide) recover night release of endogenous melatonin and lead to the normalization of the hormone circadian rhythm in the blood plasma. In elderly people Epithalamin and Epitalon modulate pineal gland functional state: people with pineal gland functional insufficiency report an increase of night melatonin level. The preparations of the pineal gland, effectively increasing melatonin concentration and having no side effects, can be used in clinical geriatric practice.

A 12-year randomized clinical study of epithalamine (pineal gland peptide preparation) was carried out in elderly patients with coronary disease and accelerated aging of the cardiovascular system. Long-term treatment with epithalamine decreased the functional age and degree of cardiovascular aging; exercise tolerance increased. After 12 years the number of elderly subjects dead in the group treated by epithalamine was 28% lower than in the control group, despite the same basic therapy. Cardiovascular mortality was 2-fold lower in patients treated by epithalamine; the incidence of cardiovascular failure and respiratory diseases was 2-fold lower in this group. Long-term treatment with epithalamine was associated with a geroprotective effect on the long-term life prognosis in elderly subjects with accelerated aging.

Age peculiarities of cardiorespiratory system reactions on isocapnic hypoxia (inhalation of gas mixture of 12% O2) have been investigated. It has been stated that breathing with hypoxic mixture resulted in more significant shift of O2 blood saturation, AP and autonomic balance in the elderly people (p < 0.05) comparing to the young people. It testifies to a greater intensity of sympathoadrenal system at hypoxic stress in elderly people that confirms the decrease of their tolerance to hypoxia.

The effect of epithalamin on circadian rhythms of thymic serum factor titers and melatonin concentrations in the blood of elderly people was studied. Course treatment with epithalamin modulated the rhythm of the thymic endocrine function. The increase in the titer of thymic serum factor at night coincided with the increase in blood melatonin concentration and shift of its acrophase to 3.00, which was characteristic of young people. In elderly people with preserved nocturnal peak of the thymic serum factor titer before therapy the nocturnal (3.00) concentration of melatonin was high and did not change after drug therapy. The correlation between melatonin concentration and titer of thymic serum factor increased after epithalamin treatment.

Circadian rhythm of plasma melatonin concentrations in healthy elderly subjects was studied before and after a course treatment with Epithalamin (peptide preparation from the pineal gland). Epithalamin modulated the melatonin-producing function of the pineal gland. During the dark period plasma melatonin concentration increased in subjects with initially lowered activity of the pineal gland, while in subjects with normal epiphyseal function plasma melatonin concentration tended to decrease.

Age dynamics of the critical points of an exercise in 240 apparently healthy men aged 18-95 years was investigated. It is shown that linear decrease of a level of critical load capacity, maximum oxygen consumption, thresholds of anaerobic exchange and decompensated metabolic acidosis takes place in aged individuals. The equations of linear regression of changes in these parameters with age are presented. Using the method of factor analysis it is demonstrated that in healthy men variability of critical points of physical activity is age-dependent. Age factor determines 58% of maximum oxygen consumption variability, 62% of decompensated metabolic acidosis variability and 51% of anaerobic exchange variability. At the same time 23% of maximum oxygen consumption variability, 26% of threshold of decompensated metabolic acidosis variability and 33% of threshold of anaerobic exchange variability depends on physical activity level.

Circadian rhythms of pineal gland melatonin-forming function were studied in healthy elderly people (n=31, age range 60-74 years). The blood plasma melatonin concentration was determined by means of radioimmune method at 3.00, 9.00, 15.00 and 21.00. The study revealed two types of circadian rhythms of plasma melatonin concentration: a high-amplitude (29%) and a low-amplitude (71%) ones. The high-amplitude rhythm of melatonin-forming pineal gland function was observed in elderly people with a higher physical working ability and a lower functional age of cardiovascular system. It is advisable to conduct the correction of pineal gland melatonin-forming function in elderly people with low-amplitude circadian rhythm of plasma melatonin concentration.

The study of predictors of the development of arrhythmia in elderly age people with IHD is an important task requiring the thorough investigation. The presence of late potentials of ventricles (LPV) is considered presently as one of the most highly informative parameters indicating an electrical inhomogeneity of myocardium, which would result in cardiac rhythm disturbance. The presence of early, late ventricle potentials as well as a dispersion of QT, QRS and T intervals are believed to be the predictors of arrhythmia along with other indices. The study focused on determining a frequency of such predictors among patients of 60-74 y.o. with various clinical picture of IHD. 300 patients were observed: 120 of them with IHD, 100--additionally having essential hypertension, 60--PICS (postinfarction cardiosclerosis), 20--HF. 20 people aged 60-89 formed the control group. The registration of LPV, EPV as well as QT, QRS and T dispersion was carried out by means of Megacart electrocardiograph (produced by "Siemens" company, Germany). The findings are the following: 48 % of the patients with IHD were found with LPV, 33%--with EPV (early potentials of ventricles). LPV is also more frequently met in the patients with IHD complicated with heart failure (HF) and hypertension; dispersion of QRS and T is for sure higher in patients with IHD and HF.

Taking into consideration age-related changes in endothelium, the ability of endothelium to produce vasoactive substances has been studied in healthy subjects of various age. Under experimental conditions, the activity of constitutive and inducible NO-synthase has been studied as well. The clinical part of the study involved investigation of 38 healthy subjects aged 60-79. The study has been designed to investigate vasomotor function of the endothelium, the levels of endothelin-1, NO2, prostacyclin, thromboxan, the level of adhesive molecules and inhibitor of tissue plasminogen activator. The levels of endothelial and inducible NO-synthases in tissues of the myocardium and the aorta has been investigated in healthy rats of various age. The data obtained show a decrease in the production of relaxation factors: NO and prostacyclin with aging. An important mechanism of deterioration of NO-synthesizing function of the endothelium is a decrease in endothelial NOS activity. The synthesis of endothelial vasoconstricting agents increased with ageing. This in combination with decreased production of vasodilating substances results in deterioration of defence properties of the endothelium. The increase in titer of adhesive molecules and inhibitors of tissue plasminogen activator testifies to age-dependent deterioration of anti-inflammatory and antithrombotic activities of the endothelium.

General characteristics and mechanisms of effects of nitric oxide (NO) and its role in the development of pathology are reviewed. Presented are the data about NO participation in the regulation of circulation and cardiovascular system; NO-dependent mechanism of regulation of cardiovascular reactivity against the background of dysfunction of endothelium; cGMP-independent mechanism of NO effect upon Ca homeostasis and the sensitivity of myofibrils of smooth muscle cells to Ca ions; pharmacological correction of disturbances of NO metabolism and related endothelial dysfunction; role of age changes of the endothelial function in the development of cardiovascular pathology.

Forty-eight elderly patients with IHD and paroxysmal atrial fibrillation were studied to determine circadian pattern of arrhythmia onset. The data were obtained by detailed interview and analysis of medical documents. The found variations were fitted to cosinusoidal function with a period of 24 hours Y = 9.75 + 3.5cos(2 pi t/24 + 0.2) (R2 = 0.69; F = 10.2; P < 0.01; two first coefficients of equation are significant by t-test, P < 0.01), the peak of arrhythmia onset was observed about midnight. 59.8% of overall number of episodes developed at dark period of day (P < 0.05). Findings testify that time periods of arrhythmia onset increase in number with disease evolution. It may be an additional criterion of paroxysmal atrial fibrillation transformation into its permanent form.

The purpose of the research was to investigate the peculiarities of ventilatory reaction to hypoxia with the elderly and old people. 27 practically healthy young (20-35 years), 24 elderly (60-74 years) and old (older 74 years) people were examined. The influence of hypoxia on the gas exchange was investigated during the respiration of gas mixtures with 17% and 12.5% of oxygen content (during 12 minutes), that corresponds to 1500 m and 4000 m above sea level. The parameters of ventilating function of the lung were determined on the spirograf CT-1M. Oxygen tension in arterial blood (PaO2) was determined with the device "AVL" by "OMNI" (Austria). The curves of ventilating dependence on PaO2 for the young and old people are plotted using the mathematical model. It was shown, that with aging the "steepness" of curve's dependence on the ventilatory answer from the degree of hypoxemia decreases, that testifies to the decrease of chemoreflex sensitivity.

Taking into account the prerequisites existing in elderly people for disturbances in metabolism of polyunsaturated fatty acids (PUFA) which are risk factors of cardiovascular pathology, we studied the content of separate fractions of fatty acids (FA) in erythrocyte membrane of practically healthy people aged over 60. Seventeen practically healthy subjects aged 60-74 were investigated. All of them have been under long-term observation at the Institute of gerontology, AMS of Ukraine. A thorough preliminary examination proved them to be free from any pathology which might affect the results of studying the lipid composition of erythrocyte membrane. Twenty healthy subjects aged 20-29 served as controls. The fractions of FA as well as HDL and LDL were determined in erythrocyte membrane. In elderly healthy people the results obtained have shown a statistically significant decrease in the content of unsaturated FA and PUFA in erythrocyte membrane. The level of PUSFA decreased due to both omega-6 and omega-3 fractions as well as at the expense of their precursors. However, the decrease in the level of omega-3 fraction was more pronounced. As evidenced by a decrease in the content of unsaturated FA and PUFA in lipoproteins of both high and low density, the disturbance of PUFA transport by lipoproteins is one of the mechanisms of the decrease in PUFA level in the erythrocyte membrane.

The aim of the study was to investigate the peculiarities of tissue oxygen provision on the level of microcirculatory bed and to determine the significance of the indices taken separatively in pathogenesis of hypoxia in practically healthy elderly people. The study comprised 30 practically healthy people aged 60-74. It included investigation of oxygen tension in peripheral tissues, skin and bulbar microcirculation, functional state of endothelium in the group of elderly healthy people. The results obtained were compared with analogous data obtained in practically healthy young subjects. The tissue oxygen provision was found to decrease with age.

The study comprised 45 healthy subjects aged 60-74. It was designed to examine the state of skin and bulbar microcirculation using the method of television capillaroscopy. The functional state of endothelial microvessels was studied with the help of laser doppler flowmeter by means of functional tests with postocclusion hyperaemia and intradermal injection of epinephrine solution in the dose of 0.1 ml (1.10-6 mol/l). The platelets aggregation activity was studied using the method of turbidimetry. The blood viscosity and functional state of erythrocytes were determined with the help of rotary viscosimeter at the shift velocity of 10 to 200s-1 with estimating the erythrocytes deformability and aggregation indexes. Oxygen saturation of the subcutaneous fat fibers was studied by polarography. It has been found that the increase of adrenalin-induction aggregation of platelets, the decrease of erythrocyte deformation and the endothelium synthesis disturbance caused relaxing factors play role in the circulatory hypoxia development.

The aim of this study was to assess age-related morpho-functional peculiarities of the heart on the basis of investigating the chrono-inotropic dependence of left ventricular [LV] myocardium. The results of this investigation are of importance for geriatric practice. They are necessary for determining the markers and elaborating the quantitative criteria of detecting the early stages of heart failure and finding the ways to its correction in elderly people. Twenty subjects aged 20-35 and forty four subjects aged 60-74 without clinical symptoms of cardiovascular pathology were investigated by means of stress-echocardiography. The indices of systolic and diastolic functions of the heart were studied by means of the transesophageal atrial electric pacing (TAEP) at baseline and at each frequency of pacing with the assessment of degree and type of LV myocardium hypertrophy. In all of the subjects investigated the results of TAEP were negative, i.e. they showed no signs of coronary insufficiency. In elderly people the increment values of contraction and relaxation velocity indices at the same pacing frequency were significantly lower (P < 0.05) in comparison with ones obtained in younger subjects. In elderly people a decrease of the maximal relaxation velocity occurred at submaximal age-related heart rate (on the average 135 beats/min) as compared to intermediate pacing frequencies whereas in younger subjects a further increment of this value continued. The LV hypertrophy developing with ageing plays on the one hand a compensatory role but on the other hand it deteriorates the diastolic function. The inefficiency of work of the old heart while pacing is an important factor limiting functional capabilities of the heart.

Morphological investigation of gastric mucosa was done in 85 patients of various age with duodenal ulcer disease using visual-analogue scale of the modified classification of the Sidney system (1996). In all the patients there was revealed chronic gastritis, possessing age morphological peculiarities. The frequency of infectionizing with Helicobacter pylori is reduced with the age increased.

Health effects of fermented milks have been associated with the metabolic activity of lactic acid bacteria in the gastrointestinal tract. It has been proposed that an increased excretion of urea nitrogen via microbial protein may decrease the workload on kidneys and liver. Therefore, a study was carried out in healthy elderly human subjects to investigate the incorporation of [15N2]urea nitrogen into plasma and fecal proteins and amino acids. Over a period of 10 d 13 healthy elderly subjects ingested daily a freeze-dried microbial preparation which contained different genera of lactic acid bacteria and is used to produce fermented milk products. One of the strains was originally isolated from stool samples of elderly people from the Caucasus region (Lactobacillus plantarum). No stimulation of fecal protein-nitrogen excretion and no increase in 15N-abundances in fecal protein was measured following the administration of the viable microbial preparation and a [15N2]urea bolus. Tentatively, it was concluded that this may have been caused by the inability of the microbial culture to survive the gastro-intestinal passage and (or) by the absence of additional fermentable carbohydrates in the diet as energy source for bacterial protein synthesis in the large intestine. However, using a highly sensitive GC-C-IRMS method we observed a significant incorporation of 15N into plasma protein amino acids. 15N-Enrichments in single amino acids were found according to their participation in transamination reactions. The slight enrichment of lysine which is not transaminated in mammalian tissues may indicate a microbial synthesis and absorption of bacterial lysine.

With the purpose of examining particular characteristics of filling of the left ventricle in elderly IHD patients we evaluated essentially healthy persons, both young and of greater age, and elderly IND patients (exertional angina, II-III functional class), 20 subjects in each of the three groups of examines, by echocardiography followed by the echocardiograms processing on a computer. The greatest age-related changes were found for the phase of early filling. Also noted in IHD patients was a relatively prolonged atrial systole and shortened time of filling, reduction in the value for the index "duration of slow filling/duration of fast filling", increase in the volume rate of blood filling in the phase of slow filling.

The changes of hormonal and autonomic nervous systems in trained and untrained elderly people were studied. An exercise tolerance test was used as a model of physical stress. Elderly people were more sensitive to the influence of stress factors. The hemodynamic reaction at the same workload was more economical in trained subjects. Also, the reaction of the autonomic nervous system and pituitary-adrenal system was less pronounced in trained elderly people. It was established that physical training in aging increases the resistance to stress.

The indices of lung ventilation and biomechanics of breathing were determined in 48 patients with chronic obstructive bronchitis (COB) aged 60-79 and 45 healthy subjects of the same age. Inpatients with COB a rise of lung ventilation, work of breathing, ventilation equivalent, positive reaction to oxygen, a decrease of maximal breathing capacity and reserve of breathing take place that reflect excessive and uneffective ventilation, limitation of its functional performance. These specific features are due to an increase in the total lung capacity at the expense of residual volume against a decrease of vital capacity with diminution of alveolar ventilation to lung ventilation ratio. But of decisive significance was disturbance of bronchial patency manifesting in a decrease of Tiffeneau index, midexpiratory flow, respiratory flows in forced respiration, especially in expiratory phase, concavity of flow-volume curve to volume axis, a rise of bronchial resistance.

Healthy young and elderly men were examined with the aim to study age peculiarities of energy provision during physical load (PhL). Changes in concentration of glucose and free fatty acids (FFA) under PhL of various intensity and duration was analyzed. It is found out that the load with force corresponding to the anaerobic threshold (AT) level of young people causes a marked drop of glucose concentration in blood accompanied by development of subjective fatigue feeling, which led to loading termination in elderly people. After such a loading a tardy restoration of glucose and FFA concentration was observed in elderly persons. Young persons during 45 min of PhL on the AT level demonstrated no evident signs of fatigue. In elderly persons long-term PhL on the individual AT level caused similar changes in glucose and FFA concentration as in young people. However, in elderly persons a slower transmission of energy formation from glucose oxidation to FFA oxidation during PhL was observed. It is quite possible that PhL on the AT level corresponds to functional potentialities of the energy provision system of working muscles in elderly people.

30 healthy 60- to 89-year-old subjects and 20 young ones (20 to 31 years) were given orally ammonium chloride 125 mg/kg. The signs of subsequent metabolic acidosis were more obvious in older subjects and they lasted longer. In young subjects, the intake of ammonium chloride induced a considerable hyperventilation.