Erythrocyte Membranes Of Patients Research Articles

Fatty acid composition of blood serum and erythrocyte membranes in men with steatosis and steatohepatitis with normal transaminase activity

Aim. To study the characteristics of the fatty acid (FA) profi le of blood serum and erythrocyte membranes in patients with two forms of fatty liver disease (metabolic + alcoholic): steatosis and steatohepatitis with normal transaminase activity.Materials and methods. We examined 33 men (50.7 ± 9.6 years) with fatty liver disease (metabolic and alcoholic) with fi brosis F ≤ 1 (FibroTest). According to the ActiTest results, patients were divided into groups of steatosis – with minimal (A0–1) activity (n = 17) and steatohepatitis – with moderate/severe (A2–3) necroinfl ammatory activity (n = 16). The FA composition of blood serum and erythrocyte membranes was studied using gas chromatography/mass spectrometry Agilent 7000B (Agilent Technologies, Inc., USA). Methods of unpaired statistics using volcano plot and discriminant analysis based on orthogonal least squares (Orthogonal Partial Least Squares Discriminant Analysis, OPLS-DA), ROC analysis were applied.Results. Volcano plot analysis showed that in patients with fatty liver disease (metabolic and alcoholic) with normal transaminase activity, serum levels of stearic C18:0 (p = 0.016), arachidic C20:0 (p = 0.023), ratio saturated / polyunsaturated fatty acids (PUFA) (p = 0.001) were statistically signifi cantly higher in the steatohepatitis group compared with the steatosis group. The total content in the blood serum of all PUFA (p = 0.003), margaric C17:0 (p = 0.011), the sum of two omega-3 PUFA – eicosapentaenoic acid (C20:5n-3) and docosahexaenoic acid (C22:6n-3) (p = 0.04), the total content of all omega-3 PUFA (p = 0.042) were statistically signifi cantly lower in patients with steatohepatitis. OPLS-DA demonstrated fairly accurate separation of steatohepatitis and steatosis using individual FA and their ratios. When individual FA and their ratios were included in the analysis, a model was obtained with AUC = 0.827 (95% confi dence interval 0.499–1.0), sensitivity 82.2% and specifi city 80.7%.Conclusion. FA in blood serum and erythrocyte membranes appear to be promising biomarkers of steatohepatitis with normal levels of transaminases.

Жирные кислоты мембран эритроцитов в дифференцировании пациентов с жировой болезнью печени алкогольного, неалкогольного и смешанного генеза

The purpose of the study: to study the possibilities of using fatty acids of erythrocyte membranes in differentiating patients with fatty liver disease of alcoholic, non-alcoholic and mixed genesis (metabolic + alcohol). Material and methods. 38 men (average age 47.5 ± 2.9 years) with non-alcoholic fatty liver disease (NAFLD); 31 men with alcoholic fatty liver disease (AFLD) (45.1 ± 3.1 years) and 30 men (48.2 ± 3.2 years) with fatty liver disease of mixed genesis (metabolic + alcoholic) were examined. The degree of fibrosis in the groups did not exceed grade I. The composition and levels of the fatty acids (FA) of erythrocyte,s membranes were studied using gas chromatography/mass spectrometry, a system based on three Agilent 7000B quadrupoles (USA). Results. The levels of elaidic, 9-palmitoleic, eicosapentaenoic fatty acids were higher (p = 0.041–0.058), and the content of margaric, stearic and alpha-linolenic acids (p = 0.043–0.05) were lower in alcoholic genesis compared with non-alcoholic. The use of a panel of fatty acids – C18:1;t9, C17:0, C18:0, C18:3 n-3, C16:1;9, C20:5 n-3 – provided high diagnostic accuracy with an AUC of 0.914, sensitivity of 81%, specificity of 93% when distinguishing NAFLD from AFLD. It was found that the total content of unsaturated, monounsaturated, levels of arachidonic (n-6), oleic, eicosapentaenoic (n-3), palmitoleic, elaidic, the total content of two n-3 PUFA – eicosapentaenoic and docosahexaenoic in patients with mixed-genesis fatty liver disease were statistically significantly higher, and the levels of stearic, the total content of saturated, arachinic and the ratios of saturated FA/unsaturated FA, saturated FA/polyunsaturated FA were lower than in patients with non–alcoholic fatty liver disease (p = 0.000004–0.04). In patients with fatty liver disease of mixed genesis, the total content of monounsaturated FA, especially oleic and palmitoleic, linoleic (n-6) and saturated lauric, were significantly higher, and the levels of saturated FA arachinic, stearic, SFA/USFA, SFA/PUFA ratios were lower than in AFLD (p = 0.0009–0.06). Conclusion. The revealed differences in the levels of fatty acids of erythrocyte membranes in patients with fatty liver disease of various origins are probably associated with the main etiological factor and can be used to develop new diagnostic methods and targets for therapy.

Features of the fatty acid profile of erythrocyte membranes in patients with fatty liver disease of alcoholic genesis

Introduction. Alcoholic steatosis, which is a reversible condition, is currently considered a significant risk factor for the progression of diffuse liver pathology, therefore understanding of its mechanisms at the molecular level is essential.Aim. To study the features of the fatty acid profile of erythrocyte membranes in patients with fatty liver disease of alcoholic origin for possible use of fatty acids (FAs) as biomarkers and potential therapeutic targets.Materials and methods. A total of 31 men with alcoholic fatty liver disease (AFLD) (average age of 45.1 ± 17.1 years) and 28 men of comparable age without AFLD and symptomatic pathology of internal organs were examined. The FA composition and levels of erythrocyte membranes (ER) were studied using Agilent 7000B (USA) triple quadrupole gas chromatography/mass spectrometry.Results and discussion. A higher level of a range of saturated FAs (lauric, margaric, pentadecane), monounsaturated FAs (MUFAs), which are additional factors for the progression of AFLD (palmitoleic, total monounsaturated acids), n-6/n-3 polyun-saturated FAs ratio (PUFAs), alpha-linolenic FA was detected in patients with AFL vs the control group (p = 0.00002–0.05). In contrast, the levels of arachidic and docosahexaenoic acids, total eicosapentaenoic and docosahexaenoic n-3 PUFAs, and total n-3 PUFAs were lower in patients with AFLD than in healthy men (p = 0.003–0.01), which is associated with increased ethanol induced adipose tissue lipolysis via PDE3B-AMPK axis. The use of FAs panel (C16:1;9, sum MUFA, n-6/n-3 PUFA, C22:6n3, C20:0) to distinguish patients with AFLD from healthy ones ensured high levels of sensitivity (79%), and specificity (81%) (AUC 0.808). Multidirectional associations of FA levels in erythrocyte membranes with each other and liver tests and lipid profile results were revealed.Conclusion. Thus, the features of erythrocytes membrane FAs in patients with AFLD and the potential to use them as biomarkers for differentiation of people with AFLD from healthy individuals have been identified.

Βeta-adrenergic receptor reactivity of erythrocyte membranes in patients with left or right atrial dilatation against the background of atrial fibrillation

Hyperactivation of the sympathoadrenal system (SAS) leads to desensitization of β1-adrenergic receptors (β1-AR). This contributes to aggravation of myocardial contractile dysfunction and development of arrhythmias, including atrial fibrillation (AF). An indirect indicator of the viability of β1-AR is β-adrenergic receptor reactivity of erythrocyte membranes (β-ARM).Aim. To evaluate β-ARM in patients with different forms of AF, including left (LAD) or right (RAD) atrial dilation.Materials and methods. The sample included 38 patients, 65.8% of whom had paroxysmal AF, 21% had persistent AF, and 13.2% had long-standing persistent AF. All patients received surgical treatment for AF by radiofrequency ablation or cryoablation. LAD was detected in 39.4% of patients, RAD – in 34.2% of patients. Βeta-ARM was determined before treatment, as well as at 3 days and at 12 months after ablation.Results. The groups of patients with different forms of AF, as well as patients with LAD / RAD and without it showed comparable values of β-ARM at different measurement periods. In the group of patients without LAD / RAD, β-ARM increased 3 days after ablation compared to β-ARM before the treatment (p = 0.002 / p = 0.004) and returned to the pre-treatment level after 3 months. At the same time, in the group of patients with LAD / RAD, β-ARM did not significantly change before the ablation and in different periods after it.Conclusion. In patients with AF without LAD / RAD, we detected an increase in β-ARM 3 days after the ablation compared to the level before the treatment and a decrease in the intensity of SAS 3 months after the surgery. In the presence of LAD / RAD, no changes in the β-ARM were revealed.

ИНТЕНСИВНОСТЬ СВОБОДНО-РАДИКАЛЬНЫХ ПРОЦЕССОВ И СТРУКТУРНО-ДИНАМИЧЕСКИЕ ПА-РАМЕТРЫ МЕМБРАН ЭРИТРОЦИТОВ БОЛЬНЫХ САХАРНЫМ ДИАБЕТОМ 2 ТИПА

The World Health Organization has recognized diabetes mellitus (DM) as one of the four major noncommunicable diseases that lead to early disability and mortality among the population. Oxidative stress, which contributes to the intensification of free radical processes (FRP), can be considered as a universal nonspecific mechanism of DM2 pathogenesis. De-spite numerous studies, questions about the mechanisms of development of oxidative stress and its influence on the physicochemical state of biological membranes still remain open. The aim of this work is to study the intensity of free radical processes and the structural and dynamic characteristics of blood erythrocyte membranes in patients with type 2 diabetes mellitus (DM2). The study included male patients with type 2 diabetes aged 55 to 70 years who did not have other acute and chronic diseases in the acute stage. The content of glucose, glycated hemoglobin, markers of oxidative stress (MDA and carbonyl groups) was determined in the blood of patients. The structural and dynamic parameters of erythrocyte membranes were determined using fluorescent probe pyrene. It was found that an increase in blood glucose levels in patients with DM2 increases the content of markers of lipid peroxidation (MDA) and oxidative modification of proteins (carbonyl groups). Oxidative damage to lipids and proteins of erythrocyte membranes in decompensated DM2 changes their structural and dynamic properties: they increase the microviscosity of the lipid bilayer and the polarity of its phospholipids, and promote conformational rearrangements in membrane proteins. Close correlations were found between the level of glucose, the content of CRP products in the blood, and the structural and dynamic parameters of erythrocyte membrane

СТРУКТУРНО-ФУНКЦИОНАЛЬНОЕ СОСТОЯНИЕ БЕЛКОВ В ЭРИТРОЦИТАРНЫХ МЕМБРАНАХ ПАЦИЕНТОВ С АРТЕРИАЛЬНОЙ ГИПЕРТЕНЗИЕЙ

Objective. To study the structural and functional state of proteins in erythrocyte membranes of AH patients with asymptomatic brain lesions (ABL) and AH patients without brain lesions who suffered from cerebrovascular accident (CVA). Methods. The study included 47 patients diagnosed with AH. The study groups were formed based on the detected neuroimaging changes in the brain and analysis of the structural and functional state of proteins in the membranes of erythrocytes in patients with AH. The following groups were identified: 1-рatients with AH without BL 2-patients with AH and ABL 3-patients with previous cerebrovascular accident Results. A comparative analysis of abnormalities of structural and functional state of proteins in erythrocyte membranes in patients with AH without brain lesions, in patients with AH with asymptomatic brain lesions visualized by MRI, and patients who suffered from cerebrovascular accident showed the following: 1. In patients with AH with asymptomatic brain lesions, and in those suffered from cerebrovascular accident, the value of the maximum reaction rate (Vmax) of AChE in erythrocyte membranes was significantly reduced in comparison with the values of this parameter in patients with AH without brain lesions (Figure 1). 2. The value of Michaelis constant (MC) for AChE in isolated erythrocyte membranes of patients with AH without brain lesions and with asymptomatic brain lesions is increased compared with the group of patients with a history of cerebrovascular accident (Figure 2). Conclusion. In patients with hypertension, the structural and functional state of proteins in erythrocyte membranes is disturbed, depending on the severity of the damage to the brain.

The Role of Na+/K+-ATPase in the Development of Hyponatrenemia under Conditions of Hypoxic Stress in Patients with SARS-CoV-2 Infection.

We studied laboratory parameters of patients with COVID-19 against the background of chronic pathologies (cardiovascular pathologies, obesity, type 2 diabetes melitus, and cardiovascular pathologies with allergy to statins). A decrease in pH and a shift in the electrolyte balance of blood plasma were revealed in all studied groups and were most pronounced in patients with cardiovascular pathologies with allergy to statin. It was found that low pH promotes destruction of lipid components of the erythrocyte membranes in patients with chronic pathologies, which was seen from a decrease in Na+/K+-ATPase activity and significant hyponatrenemia. In patients with cardiovascular pathologies and allergy to statins, erythrocyte membranes were most sensitive to a decrease in pH, while erythrocyte membranes of obese patients showed the greatest resistance to low pH and oxidative stress.

Changes in the compound zeta potential of erythrocyte membranes in patients with arterial hypertension and obesity

The development of microcirculatory disorders is considered to be one of the earliest changes in the cardiovascular system with a combination of arterial hypertension (AH) and obesity. The rheological properties of blood play a significant role in the system of microcirculation. An important place in changing the rheological characteristics of blood is largely assigned to erythrocytes. Aggregation of erythrocytes is closely related to the magnitude of the surface-bound charge of their membranes or zeta potential of erythrocyte membranes. Purpose. To study the state of compound zeta potential of erythrocyte membranes in patients with hypertension and obesity. Material and methods. The study included 112 patients with AH and Index of Mass Corporal more than 30 kg/m2 (main group); the control group consisted of 25 people without AH and obesity. All patients of the main group received standard antihypertensive, lipid-lowering and hypoglycemic therapy to achieve the target levels of the indices under correction. Results. The level of compound zeta potential of erythrocyte membranes in patients with AH and obesity was significantly lower than in the control group and amounted to 1.57 ± 0.06 × 107 and 1.67 ± 0.03 × 107, respectively (p < 0.05). At the same time, in patients of the main group with an increase in AH, lower indices were noted. In patients with AH and obesity, a significant inverse correlation was found between the compound zeta potential of erythrocyte membranes and the degree of hypertension, which indicates a negative effect of hypertension on the rheological properties of blood at the microvasculature level. A correlation analysis was carried out to evaluate the association between Index of Mass Corporal and zeta potential of erythrocyte membranes in obese hypertensive patients. A negative direct correlation was revealed (r = 0.7, p < 0.05). Conclusion: a decrease in the total charge of erythrocytes can be considered as an early sign of microrheological disorders in patients with a controlled course of arterial hypertension and obesity.

Changes in the spectrum of protein components and the concentration of phospholipids of the erythrocyte membrane in patients with ulcerative colitis

Ulcerative colitis is a chronic inflammatory bowel disease with unclear etiology. An insufficient amount of data on the etiopathogenetic mechanisms of the disease creates opportunities to research them at the cellular level, including the membrane level. Since the functional state of the cytoplasmic membrane largely depends on protein-lipid interactions, we studied the effect of the proportional ratio of three proteins (glucose transporter, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and glutathione-S-transferase (GST)) on the level of phosphatidylethanolamine and phosphatidylcholine in the erythrocyte membrane of patients with ulcerative colitis during an acute attack. The study involved 51 patients with ulcerative colitis during the acute attack and 26 clinically healthy individuals. The groups are comparable by gender and age to study the proteins of the cytoplasmic membrane, Laemmli electrophoresis technique in polyacrylamide gel was used, followed by an assessment of the intensity of protein bands staining on electropherograms. Phospholipid fractions were obtained using thin-layer chromatography and their content was assessed using the Mathcad 2001 Professional system. Statistical processing was carried out by the program Statistica 10.0 for Windows. Changes of phosphatidylcholine and phosphatidylethanolcholine levels in patients and healthy individuals are not of the same type and are interrelated with changes in the proportion of membrane proteins of the glucose transporter, GAPDH and GST. The proportions of proteins that affect the level of phospholipids have calculated. In patients with ulcerative colitis, a decrease in the level of the studied membrane lipids have revealed in comparison with the clinically healthy group, in addition, an increase in the proportion of the glucose transporter and a decrease in the proportion of GST have noted. In addition, the relationship between an increase in the level of the cytoplasmic membrane phospholipids in ulcerative colitis and a change in the proportion of GAFDH in a smaller direction, which slows down the process of glucose oxidation, was determined. The obtained data confirm the strengthening of the processes of antioxidant protection and the increased need for energy supply of the cell membrane in patients with ulcerative colitis during an acute attack.

Validation and application of a protocol for the extraction and quantitative analysis of sphingomyelin in erythrocyte membranes of patients with non-alcoholic fatty liver disease

Validation and application of a protocol for the extraction and quantitative analysis of sphingomyelin in erythrocyte membranes of patients with non-alcoholic fatty liver disease

Serum and erythrocyte membrane fatty acid levels may be used as biomarkers to assess the severity of NAFLD

The aim of this work is to study the possibility of using blood serum (BS) fatty acids (FA) and erythrocytes (ER) as diagnostic markers of the severity of NAFLD. Materials and methods. We examined 52 patients with NAFLD (51.8 ± 3.9 years), confirmed by the NLFS index, and 20 apparently healthy men (49.2 ± 4.5 years). The degree of liver fibrosis was established by indirect elastometry (FibroScan® 502 Echosens, France). 27 patients had an initial degree of fibrosis (F0-1), 25 had severe fibrosis (F2-4). The study of the composition of fatty acids of Er and BS was carried out using a GC / MS system based on three Agilent 7000B quadrupoles (USA). Results. Significant differences in the levels of fatty acids in blood serum and erythrocyte membranes in patients with NAFLD were revealed, associated with the degree of fibrosis and necroinflammatory activity. To distinguish between mild and severe fibrosis in NAFLD, the levels of saturated fatty acids (myristic, pentadecane, margarine) and omega-3 PUFAs (eicosapentaenoic, docosapentaenoic, docosahexaenoic) were found to be significant (p = 0.002-0.0003). Saturated and monounsaturated FAs (palmitelaidic, palmitoleic, vaccenic) played a key role in differentiating the degree of necroinflammatory activity (minimal versus pronounced) (p = 0.03-0.005). The created diagnostic panels (FA of blood serum and erythrocyte membranes) made it possible to differentiate patients with NAFLD with varying degrees of fibrosis. Correlations of FA levels in erythrocyte membranes and blood serum with manifestations of metabolic syndrome, indicators of liver damage in patients with NAFLD were revealed. Conclusions. The established differences in fatty acid profiles of blood serum and erythrocyte membranes in patients with NAFLD, associated with the degree of fibrosis, necroinflammatory activity, manifestations of metabolic syndrome and indicators of liver damage, should be considered as promising biomarkers for assessing the severity of NAFLD.

787P Endotoxicosis and properties of erythrocyte membranes in patients with cervical cancer receiving combination therapy with dendritic cell-based immunotherapy

The efficacy of antitumor treatment depends on the function of proteins and structural components of cells. We studied the effect of immunotherapy with dendritic cell vaccine (DCV) as a part of combination therapy on the functional status of albumin, endogenous intoxication and structural and functional properties of erythrocyte membranes.

STUDIES OF ALTERATIONS OF THE CELLULAR MEMBRANE BARRIER FUNCTION AT LARYNGEAL CANCER

Introduction. Cellular membrane barrier alterations lead to metabolic and functional disorders. However, in the case of laryngeal cancer (LC) they are insufficiently studied.
 The aim of the study – to learn the nature of the interaction of erythrocyte membranes with introduced spin probes as an indicator of changes in the barrier function of membranes at LC.
 Research Methods. Samples of the erythrocyte membranes from 40 patients with LC stages II and III and 20 healthy volunteers were probed by EPR with AdTEMPO test. Microviscosity of erythrocyte membranes was determined by the τeff and the decreasing in RSSI. The content of MWM was identified in the blood plasma and in erythrocyte. The partition coefficient between blood plasma proteins and erythrocyte glycocalyx was calculated. SCEM was evaluated by amount of unabsorbed methylene blue.
 Results and Discussion. It was established that LC patient’s endogenous intoxication is characterized by excessive accumulation of the total pool of MWM both in blood plasma and glycocalyx of erythrocyte. SCEM was significantly decreased in samples of both LC stages in comparison to control. The most apparent decline in τeff was observed prior to washing of erythrocytes for 5 min after probe insertion. The deceleration after 60 min was observed only in LC stage II. The value of τeff was at control values levels after washing of erythrocytes of LC stage II 5 min after probe insertion and was significantly reduced in stage III LC in comparison to control. RSSI in samples both stage of patients prior to and after washing of erythrocytes was on average 1.5-fold higher than that of control.
 Conclusions. It was established that the LC patient’s endogenous intoxication is characterized by excessive accumulation of the total pool of MWM both in blood plasma and glycocalyx of erythrocytes, activation of catabolic processes in plasma, redistribution of MWM between the pool of erythrocyte proteins, which corresponds to the second stage of endotoxicosis. The reduction of the SCEM is shown, which is a manifestation of pathological changes in the surface functional activity of erythrocyte membranes. The effectiveness of AdTEMPO for the eva­luation of microviscosity of erythrocyte membranes in patients with LC was confirmed.

Indicators of adrenergic reactivity of erythrocyte membranes in patients with myocardial infarction and nonobstructive atherosclerosis of the coronary arteries after 1 year

Abstract Funding Acknowledgements Type of funding sources: None. Background We hypothesized that MINOCA patients have distinctive features of sympatho-adrenal system (SAS) activation in comparison with patients with stenosis atherosclerosis which can play a significant role in the development of ischemic events at the time of the index hospitalization and after 1 year. Aim To study the parameters of β-adrenoreception of cell membranes in patients with MINOCA compared with patients with AMI and single-vessel coronary artery disease after 1 year. Material and methods: The study is non-randomized open controlled. Adrenergic reactivity of the body was assessed by the method for assessing the β-adrenergic reactivity of erythrocyte membranes (β-ARM) for studying the parameters of adrenergic reception of cell membranes. This parameter (β-ARM) was studied upon admission, at days 2, 4 and 7 and 1 year after AMI. The normal level of β- ARM <20 rel.units. Results The study included 40 patients with AMI (19 patients in the main group and 21 patients in the control group). Three patients (15.7%) with diagnosed acute myocarditis were excluded from the analysis. The median age in the main and control groups was 66 (54; 70) years and 59 (55; 65) years, respectively. These groups were different at the admission in such parameters: in smoking frequency (31,3% vs 52.3%), history of angina pectoris (62,5% vs 28,5%), time of admission to the hospital (390 min. vs 180 min.) and thrombolytic therapy at the prehospital phase (3% vs 11%), p < 0,05. The median β-ARM in MINOCA patients upon admission was 41.7 (29.0; 61.5) rel. units, 1 day - 48.6 (38.5; 57.3) rel. units, 4 days - 49, 4 (39.0; 63.3) rel. units, 7 days - 53.5 (35.2; 67.7) rel. units, after 1 year - 35.7 (25.5; 42.6) rel. units. In the control group, the median β-ARM upon admission was 52.5 (25.4; 64.5) rel. units, 1 day –51.6 (28.3; 56.9) rel. units, 4 days - 48, 5 (34.9; 61.2) rel. units, 7 days - 45.1 (32.2; 68.9) rel. units, after 1 year - 20.8 (14.8; 29.3). In MINOCA patients β-ARM indices in the early postinfarction period statistically higher than the 1 year: at 1, 2, 4 days, p <0.05, on day 7 no differences were found (p = 0.34). A dynamic comparison of β-ARM indicators in the control group at the time of the index hospitalization and through 1 year revealed differences at all days early postinfarction period, p <0.05. In the control group, the β-ARM indicator reached normal values by 1-year follow-up period. In MINOCA patients, β-ARM indices after 1 year were statistically higher than in the control group, p = 0.008. Conclusions: The β - ARM indices in MINOCA patients after 1 year from the ischemic event are higher than in the control group. In dynamics, the β - ARM indices statistically decreased in the control group, but did’n change in MINOCA patients. Despite the use of a beta-blocker in MINOCA patients, increased SAS activity persists; therefore, β-APM values did’n change significantly after 1 year.

Differences in fatty acid profi les of erythrocyte membranes related to tumor localization in colorectal cancer (pilot study)

Aim of work is to study the compositional features of fatty acids (FA) of erythrocyte membranes in patients with diff erent localization of the tumor in colorectal cancer (CRC). Materials and methods . Using a chromatography-mass spectrometric system (GC/MS) Agilent 7000B based on three quadrupoles (USA), the composition of erythrocyte (Er) membranes of 129 patients with CRC was studied: (average age 63.2±9.4 years, of which 68 men and 61 women; 25 with proximal, 98 with distal tumor localization) and 35 people in the comparison group. Results . A greater degree of decrease in the levels of saturated, monounsaturated FAs (MUFAs), and, conversely, an increase in the levels of polyunsaturated FAs (PUFAs) in patients with distal tumor localization compared to healthy ones, was established than the same ratio in the pair “proximal localization of tumor RCC — healthy”. A greater degree of increase in the level of omega-3 PUFAs was noted than omega-6, which aff ected the ratio n-6 / n-3, which was signifi cantly reduced in cancer patients, to a greater extent with distal tumor localization. The most signifi cant for distinguishing tumors located in diff erent parts of the intestine were: saturated fatty acids — myristic C14:0 (p<0,001) and pentadecanoic C15:0 (p=0,012), omega-3 a-linolenic (C18:3; n-3) (p=0,02), whose levels were signifi cantly higher and, conversely, most of the omega-6 PUFAs (C18:2 n-6, C20:3 n-6, C20:4 n-6) and one omega-3 PUFAs — C22:6 n-3 (p<0,05), whose levels were signifi cantly lower with proximal localization of the tumor than with distal. Conclusion . The results obtained indicate the importance of taking into account the localization of the tumor in patients with CRC when conducti ng studies of metabolic profiles.

Effect of Antioxidant Preparation «Mexidol» on the Protein Components of the Erythrocyte Cytoplasmic Membrane in Patients with Ulcerative Colitis

Background . Ulcerative colitis is a colon disease accompanied by a systemic inflammatory response with the development of oxidative stress, which leads to structural and functional changes in cell membranes. There are no data on the qualitative and quantitative changes in the protein components of the cytoplasmic membrane in ulcerative colitis under the influence of the antioxidant, membrane-stabilizing drug Mexidol. The article presents the data of our own research, the purpose of which is to study the nature of changes in protein components in the erythrocyte membrane in vitro when exposed to Mexidol (the active substance is oxymethylethyl peridine succinate) in patients with ulcerative colitis during an acute attack. Materials and methods . The study involved 51 patients with ulcerative colitis during the exacerbation period and 30 clinically healthy individuals comparable by sex and age. Ten major protein components of the erythrocyte membrane were evaluated. Results . As a result of the regression analysis, it was shown that in the group of clinically healthy individuals, almost all structural proteins are to varying degrees linked to proteins by glucose transporters and the enzyme glutathione-S-transferase and in patients with ulcerative colitis, the connection of protein components of membrane channels with spectrines is lost. Incubation of red blood cells of patients with ulcerative colitis in a solution of Mexidol in vitro did not affect the protein components of the erythrocyte cytoplasmic membrane. At the same time, in ulcerative colitis patients there was a restoration of spectrin connections with anion transport proteins and a glucose transporter, which were not detected in the initial state. Conclusion . The effect of Mexidol in vitro on the erythrocyte membranes of patients with ulcerative colitis was accompanied by the restoration of structural and functional protein bonds, which can be considered as a beneficial effect of this drug on the erythrocyte membrane under the conditions of the studied pathology.

Арония черноплодная (Aronia melanocarpa) как источник соединений с потенциальной геропротекторной активностью

Арония черноплодная (Aronia melanocarpa (Micht.) Elliot) известна как ценная плодовая культура. В статье представлен обзор эффектов экстрактов стеблей, листьев и ягод A. melanocarpa на продолжительность жизни модельных организмов, а также потенциальных последствий применения экстрактов аронии для организма в целом. Анализ литературы показывает, что экстракт аронии черноплодной способствует увеличению продолжительности жизни и является потенциальным геропротектором.

Association of polymorphic variants of ADRB1 gene with contractile myocardial dysfunction and erythrocyte adrenoreactivity in patients with rhythm disorders

Aim. To study the association of the rs1801252 (A145G, Ser49Gly) and rs1801253 polymorphic variants (G1165C, Gly389Arg) of the p1-adrenoreceptor ADRB1 gene with the clinical manifestations of chronic heart failure (CHF) and the adrenoreactivity of their erythrocyte membranes in patients with cardiac arrhythmias. Material and methods . The study included 47 patients with atrial fibrillation and I-III FC CHF. A standard clinical examination of patients was performed, including a six-minute walk test and an echocardiographic study. The rs1801252 (A145G, Ser49Gly), rs 1801253 (G1165C, Gly389Arg) polymorphic variants of the p1-adrenoceptor ADRB1 gene and p-adrenoreactivity of erythrocyte membranes were determined. Results. A statistically significant inverse correlation of p-adrenoreactivity of erythrocyte membranes with the left ventricular ejection fraction (r=-0,336, p=0,021) and a direct correlation with the end-systolic volume (r=0,320, p=0,039) were defined. Depending on the FC of CHF, there was a pronounced tendency (p=0,058) of p-adrenoreactivity increasing. In patients with I FC — 25,88 (12,07; 46,37) relative units, II FC — 30,54 (14,50; 43,36) relative units, III FC — 3774 (33,67; 41,81) relative units. Diastolic dysfunction in patients was combined with a decrease in the adrenoreactivity of the organism. The median of p-adrenoreactivity of erythrocyte membranes in the group of patients with diastolic dysfunction was significantly (p=0,021) higher (33,04 (16,30; 4729) relative units) than in the group without diastolic dysfunction (15,91 (11,10; 26,47) relative units). In the studied sample, there were no statistically significant differences in the frequency of diastolic dysfunction in carriers of different genotypes of the rs1801252 and rs1801253 polymorphic variants of the ADRB1 gene (p=1,0 and p=0,058, respectively). An association (p=0,042) of a carrier of the homozygous 145AA rs1801252 genotype with high p-adrenoreactivity of erythrocyte membranes (32,5 (14,6; 473) relative units) was detected in comparison with the heterozygous 145AG genotype (16,3 (11,7; 31,5) relative units). In the studied sample, there was no statistically significant association of p-adrenoreactivity with the carrier of homozygous and heterozygous genotypes of the rs1801253 variant of the ADRB1 gene. Conclusion. The studied rs1801252 and rs1801253 variants of the ADRB1 gene have different associations with impaired diastolic function of the myocardium and desensitization of erythrocyte p-adrenoreceptors.

Effect of Hyperglycemia on the Total Surface Charge of the Erythrocyte Membrane in Patients with Metabolic Syndrome

Aim. To study the effect of hyperglycemia on the total surface charge of the erythrocyte membrane (SCEM) in patients with metabolic syndrome (MS).Material and methods. 112 MS patients were examined (45 men and 67 women) (mean age 61.4±7.2 years, average MS duration 8.7±5.2 years). The level of SCEM was determined by adsorption of a positive cationic dye (cationic blue O) on the surface of the plasma membrane of erythrocytes to completely neutralize their negative charge, followed by photometry of the solution and calculation of the number of charges on the cell surface of erythrocytes.Results. In the main group of patients with MS, abdominal obesity was observed in 100% of patients, arterial hypertension – in 73%, hyperglycemia – in 75%, dyslipidemia – in 80%. The level of glycated hemoglobin (HbA1c) was determined in all patients with MS, which was 7.3±1.9%. Patients with MS were conditionally divided according to the level of HbA1c into 2 groups (group 1 – HbA1c from 6.6 to 7.8%, group 2 – more than 7.8%). In MS patients with hyperglycemia, the SCEM values were significantly lower than in the group of patients without hyperglycemia (1.58±0.05×107 and 1.64±0.03×107, respectively; p=0.001)., Significant negative correlations between SCEM and the fasting blood glucose level, hyperglycemia duration, HbA1c level were found in patients with MS.Conclusion. SCEM indices reliably depended on the presence, severity and duration of hyperglycemia, which indicated the effect of impaired carbohydrate metabolism on the state of electric charge of erythrocyte membranes and, therefore, on the mechanisms of microvascular blood flow, thereby contributing to the development of vascular changes in patients with MS.

Lipids and mental disorders: Evidence, uncertainties and perspectives

Brain is an organ with the highest lipid concentration in the body. Cellular membrane lipids can affect both the positioning and the functioning of membrane proteins, thus regulating several cell actions. Changes in the lipid composition of cell membrane can modulate the microenvironment and consequently the function of its proteins, e.g. neurotransmission. Some of the first studies on the subject have shown a negative correlation between serum cholesterol levels and depression, suicidality and behavioral disorders. Several studies -but not all- have found decreased concentrations of ω-3 polyunsaturated fatty acids (ω-3-PUFA) in plasma or erythrocyte membranes of patients with depression, bipolar disorder or after a suicide attempt. In some cases, positive results after their administration have been reported. The effect of ω-3-PUFA in affective disorders is attributed to their action on neurotransmission, neuroplasticity as well as to their anti-inflammatory and anti-oxidative properties. Besides, decreased levels of ω-3-PUFA have been found in erythrocytes or platelets of schizophrenic patients. Some studies have shown in schizophrenics an increased rate of membrane phospholipids breakdown and a decreased ratio of ω-3-PUFA incorporation in phospholipids, possibly because of increased activity of phospholipase A2, an enzyme with crucial role in signaling transduction. Deficient dietetic ingestion of ω-3-PUFA may increase the risk for development of schizophrenia, while a diet rich in ω-3-PUFA may have a preventive role for the disease or improve its course. Although there is no evidence for their action as a monotherapy, they may be useful as an add-on therapy to drug treatment. Some authors suggest that abnormal sphingolipid metabolism, leading to accumulation of ceramides, may be responsible for the development of mood and anxiety disorders, as well as for induction of inflammation or oxidative stress, mechanisms possibly responsible for the physical symptoms of depression. Some drugs seem to combine inhibition of sphingomyelinase (an enzyme catalyzing the production of ceramides) and antidepressant effect. Despite the multitude of related studies, many aspects of the subject remain obscure. Current research focuses on the validity of preventive (especially in the perinatal period) or therapeutic administration of ω-3-PUFA as well as to the pharmacological manipulation of enzymes involved in lipid metabolism (e.g. sphingomyelinase) for the treatment of psychiatric disorders.