Results of the study of the pathophysiological effects of dysregulation of free-radical processes: deadlock or a new impulse?

The review presents the results of the authors' work of many years and the data of foreign studies, indicating the importance of free radical processes in etiology and pathogenesis of atherosclerosis. The justification of the idea that oxidative stress in atherosclerosis develops more often during disorders of carbohydrate metabolism, contributing to emergence of carbonyl stress in diabetes. It is hypothesized that there is a single molecular mechanism of primary pro-atherogenic injuries of vessel walls in atherosclerosis and diabetes, which enhances the formation of carbonyl-modified low-density lipoproteins, accumulating in the foam cells. The results of recent studies indicate that oxidatively modified LDL involved not only the primary injury to the vessel walls, but also provoked the development of endothelial dysfunction, so that once again raises the issue of the need for the use of antioxidants to prevent injuries in vascular walls. It can be assumed that the result of years of intensive research of free radical process mechanisms in atherosclerosis and diabetes will be the development of new drugs for the combined therapy of these diseases that can be disposed not only reactive oxygen species and organic free radicals and reactive carbonyls, which are clearly playing an important role in the development of pro-atherogenic injuries

Oxidative stress in hyperthermia

Oxidative stress is a risk factor for disease development and cardiovascular system, diabetes, neurodegenerative diseases, etc. The resulting product is thus free radical lipid peroxidation - malondialdehyde (MDA) is atherogenic modification of low density lipoproteins (LDL), so that they acquire the ability to be rapidly accumulated in the cells of the vessel walls, causing pre-aterosklerotic lipoid damages. The aim of this study was to investigate the effect of high temperature (one of the environmental factors) for key operating parameters: the content of secondary products of free radical oxidation polyene lipids - mDa in blood plasma and erythrocyte antioxidant activity of key enzymes. Hyperthermia was triggered in practically healthy volunteers (6 males, 22-46years). The analysis was made using a recording spectrophotometer Hitachi-557 (Japan). The statistical analysis was performed using the non-parametric Wilcoxon-test (Attestat program). MDA levels in the blood plasma, the activity of key antioxidant enzymes in erythrocytes were determined through divided intervals in study participants. A significant increase in MDA content (62 %) and reduction of catalase activity (11 %) and glutathione peroxidase (19 %) were revealed after 30 days in the conditions of hyperthermia test

Clearance of carbonyl-modified lipoproteins from the bloodstream of rabbits

We have suggested that the molecular mechanism of vascular wall damage in diabetes is not substantially different from that in atherosclerosis. Thus, it can be assumed that aldehyde-modified LDL should be eliminated from the blood stream with much greater speed than non-oxidized LDL. In the available literature there is information about the clearance of native human LDL from the bloodstream, whereas information on the clearance of the aldehyde-modified LDL in animals or humans was not found. Based on this, the present work is devoted to the clearance of aldehyde-modified LDL of rabbits and humans introduced into the bloodstream of rabbits. We investigated the clearance of glyoxal-, methylglyoxal- and MDA-modified LDL from the bloodstream of rabbits. We used biotinylated LDL of rabbit blood plasma and FITC-labeled LDL of human blood plasma. LDL was isolated with preparative ultracentrifugation in NaBr gradient. It was shown that glyoxal- and methylglyoxal-modified LDL of rabbits and humans circulated in the bloodstream for the same time as native LDL while MDA-modified LDL was rapidly eliminated from the bloodstream. The data obtained indicated the possibility of greater atherogenic potential of glyoxal- and methylglyoxal-modified LDL as they circulate in the bloodstream for a rather long time. At the same time, MDA-modified LDL is likely to be exposed to enhanced elimination by macrophages after their "linkage" to blood cells

Modification of low-density lipoproteins by low molecular weight carbonyl products of free-radical oxidation of lipids and carbohydrates plays a key role in atherosclerotic lesion of the vascular wall and in endothelial dysfunction

The review presents evidence of the participation of low-density lipoproteins (LDL) modified by low molecular weight dicarbonyl compounds formed during freeradical oxidation of lipids (malondialdehyde) and carbohydrates in the development of endothelial dysfunction and atherosclerotic vascular lesions. The authors believe that it is they, and not oxidized (hydroperoxide-containing) LDL, that are the main factors of pathogenesis. The role of dicarbonyl-modified LDL in LOX-1 dependent induction of processes leading to the development of endothelial dysfunction is discussed. The results of studies proving that damage to the glycocalyx (a layer of macromolecules that prevent the development of endothelial dysfunction) covering the luminal surface of the endothelium is caused by hyperproduction of reactive oxygen species. Ways of pharmacological correction of free-radical oxidation processes are discussed, due to which inhibition of atherogenesis and diabetogenesis can be achieved

Regulation of free radical processes in healthy volunteers during experimental hyperthermia and in patients with coronary artery disease during summer heat waves

Background. In view of the worsening forecast for global temperature rise worldwide, it seems relevant to study the effects of abnormal heat waves on systemic regulatory processes in people with chronic diseases, in particular coronary artery disease (CAD).Aims. This study aimed to investigate the effect of hyperthermia on oxidative stress parameters in patients with various severity of CAD and in healthy subjects.Materials and methods. We studied the level of malonic dialdehyde (MDA) and the activity of Cu,Zn-containing superoxide dismutase (Cu,Zn-SOD) in healthy subjects under conditions of 30-day long simulated hyperthermia and in patients with different severity of CAD after the summer heat wavesResults. We revealed signs of oxidative stress in healthy volunteers during model hyperthermia that manifested as an increase in content of MDA in blood plasma. At the  same time we observed increasing activity of Cu,Zn-SOD in erythrocytes that  utilizes reactive oxygen species. The increase of Cu,Zn-SOD activity started with a certain latency what also can be explained by de novo enzyme biosynthesis induction. We also studied oxidative stress parameters in patients at high and moderate cardiovascular risk according to the SCORE risk chart with uncomplicated CAD course and in patients with complicated CAD with severe coronary damage according to angiography during the summer heat waves. We observed accumulation of MDA in blood plasma and increasing activity of erythrocyte Cu,Zn-SOD in patients with uncomplicated CAD. At the same time we noted that accumulation of MDA in blood plasma was not followed by any increase in activity of red blood cell Cu,Zn-SOD in patients with severe complicated CAD. This fact indicates dysregulation of free radical processes in patients with severe course of CAD during the heat waves.Conclusions. The dysregulation of free-radical processes in patients with a severe clinical course of CAD has been revealed

Сholesterol lowering therapy and low density lipoprotein peroxidation during atherosclerosis

атеросклероз, статины, липопротеины низкой плотност

The Language of Consumer Society: Communicative Role of Thing

In this paper an attempt is made to examine the function of things in today's consumer society with its specific language objectified in everyday consumer practices. The main idea of consumption today is not to satisfy material needs, but to establish and maintain cultural exchange. Things in modern society are considered to be a new instrument of communication with its specific norms and codes. The authors consider the language of things on the macro- and micro-levels, projecting it onto the norms and rules of the natural language. In spite of the total illusion of abundance of goods in consumer society people are not free in their choice, use and combination of things, as the structure of the consumer society's language (like that of the natural language) determines the structure of thinking. This paper reveals the smallest parts of the language of things (graphemes in the natural language) with examples of small parts of things that can give the whole information about the thing. Brands play a decisive role in the processes of choosing, buying and amassing things

THE INFLUENCE OF HYPOLIPIDEMIC THERAPY ON THE LEVEL OF MODIFIED LOW DENSITY LIPOPROTEIDES

Aim. To assess the influence of coronary heart disease patients (CHD) therapy with statins or PCSK9 inhibitors influence on the level of oxidatively modified low density lipoproteides (LDL) and activity of erythrocyte Se-glutathione peroxidase (GSH-Px).Material and methods. To the study, CHD patients were included (9-10 males per group), who during 6 months were undergoing statin therapy — 40 mg per day of pravastatin (group 1) or 0,4 mg per day of cerivastatin (group 2), as the therapy with PCSK9 inhibitor — 420 mg per month evolocumab (group 3) during 1 year. The level of lipohydroperoxide in LDL (LOOH-LDL) was measured in the groups 1 and 2 with the modified method and usage of Fe-xilenolorange; content of oxidized LDL (oxLDL) in the group 3 — with immune chemistry method (assays Mercodia, Sweden). Activeness of GSH-Px in all groups was assessed with the modified methods bound with glutathione reductase system and tret-buthyl hydroperoxide as a substrate.Results. Simultaneously with the decrease of LDL cholesterol in the groups 1 and 2 there was significant increase (in the group 2 — 6-7 times in 3-6 months of therapy) of the level of LOOH-LDL. In the group 2 there was marked significant decrease of GSH-Px activity beginning from the month 3. In the group 3, with decreased LDL cholesterol there was significant decline in oxLDL with changed activity of GSH-Px.Conclusion. Statins, effectively decreasing the level of LDL cholesterol, simultaneously induce the oxidation of LDL and decrease the activity of GSH-Px. Inhibitor PCSK9 not only does effectively decrease the level of LDL cholesterol, but also the content of oxLDL, not leading to decreased GSH-Px activity

Telomere length as a biomarker of the risk of cardiovascular complications in patients with coronary heart disease

Aim. To study the effect of oxidative stress and telomere length in the chromosomes of blood leukocytes in patients with coronary heart disease (CHD) on the development of cardiovascular complications. Materials and methods. In 119 patients with CHD, the level of oxidatively modified low-density lipoproteins (ox-LDL) in blood plasma and the length of telomeres in nuclear blood cells were determined during the examination. After 5 years, a telephone survey of patients (or their relatives) was conducted to obtain data on the presence of cardiovascular complications. Telomere length was determined using quantitative real-time PCR, and the level of ox-LDL was determined by immunochemical method. Results. It was found that reducing the length of telomeres in patients with CHD increases the risk of subsequent development of cardiovascular complications. A strong negative correlation was found between the level of ox-LDL and telomere length in the group of examined CHD patients who had cardiovascular complications after 5 years. Conclusion. CHD patients with short telomere length and high levels of ox-LDL have an increased risk of cardiovascular complications during 5 years

AN ADAPTOGEN USAGE IN OUTPATIENT PRACTICE TO IMPROVE CARDIOVASCULAR ADAPTATION TO ABNORMAL CLIMATIC CONDITIONS (THE HEAT)

Aim. To evaluate the drug implied to improve the metabolic resistance to stress (adaptogen), Qudesan®, on its influence on cardiovascular system, psychological status and life quality of patients with average to high cardiovascular risk in the extreme climatic conditions (the summer heat).Material and methods. We included 60 patients; for 30 of those the Qudesan® 40 gtts. qd was added to standard drug therapy; other 30 patients were controls. We measured office BP, potassium and sodium concentrations; malonic dialdehyde (MDA), superoxidedysmutase (SOD) in erythrocytes. Then the relation of MDA/SOD was calculate. Patients also completed the questionnaire made up for this study. Results. In the Qudesan® group during the heat period we found lowering of SBP (А -13,8 mmHg, p=0,02), DBP (А -4,5 mmHg, p=0,05) and PWV (А -0,8 m/s, p=0,05) absent in the control. Also in Qudesan® group the concentration of sodium starts to increase during the heat period (А +1,0 mM/l, p=0,008). This increase becomes significant by september (А +1,7 mM/l, p=0,008) and is probably adaptive. The level of MDA (p<0,05) and MDA/SOD relation, the signs of "antioxydant potential", in blood were increasing significantly during the summer heat only in control group. The complaints on heart rhythm disorders (p=0,04) and on CHF worsening (p=0,09) after the end of heat period were more common in control group. That is the Qudesan® shows adaptogenic effect and can be used to improve adaptability during the heat period and its switching to cloder time in patients with compensated CVD